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A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19
CHEN Jun,LIU Danping,LIU Li,LIU Ping,XU Qingnian,XIA Lu,LING Yun,HUANG Dan,SONG Shuli,ZHANG Dandan,QIAN Zhiping,LI Tao,SHEN Yinzhong,LU Hongzhou
J Zhejiang Univ (Med Sci)    2020, 49 (2): 215-219.   DOI: 10.3785/j.issn.1008-9292.2020.03.03
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Objective: To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19). Methods: We prospectively enrolled 30 treatment-naïve patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1:1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517). Results: One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1, 9) days in HCQ group, which is comparable to that in the control group [2 (1, 4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0, 2) day after hospitalization, which was also comparable to that in the control group [1 (0, 3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05). Conclusions: The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.

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Management of COVID-19: the Zhejiang experience
XU Kaijin,CAI Hongliu,SHEN Yihong,NI Qin,CHEN Yu,HU Shaohua,LI Jianping,WANG Huafen,YU Liang,HUANG He,QIU Yunqing,WEI Guoqing,FANG Qiang,ZHOU Jianying,SHENG Jifang,LIANG Tingbo,LI Lanjuan
J Zhejiang Univ (Med Sci)    2020, 49 (2): 147-157.   DOI: 10.3785/j.issn.1008-9292.2020.02.02
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The current epidemic situation of coronavirus disease 2019 (COVID-19) still remained severe. As the National Clinical Research Center for Infectious Diseases, the First Affiliated Hospital of Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang province. Based on the present expert consensus carried out by National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on "Four-Anti and Two-Balance" for clinical practice. The "Four-Anti and Two-Balance" strategy included antivirus, anti-shock, anti-hyoxemia, anti-secondary infection, and maintaining of water, electrolyte and acid base balance and microecological balance. Meanwhile, integrated multidisciplinary personalized treatment was recommended to improve therapeutic effect. The importance of early viralogical detection, dynamic monitoring of inflammatory indexes and chest radiograph was emphasized in clinical decision-making. Sputum was observed with the highest positive rate of RT-PCR results. Viral nucleic acids could be detected in 10%patients' blood samples at acute period and 50%of patients had positive RT-PCR results in their feces. We also isolated alive viral strains from feces, indicating potential infectiousness of feces.Dynamic cytokine detection was necessary to timely identifying cytokine storms and application of artificial liver blood purification system. The "Four-Anti and Two-Balance" strategy effectively increased cure rate and reduced mortality. Early antiviral treatment could alleviate disease severity and prevent illness progression, and we found lopinavir/ritonavir combined with abidol showed antiviral effects in COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system could rapidly remove inflammatory mediators and block cytokine storm.Moreover, it also favored the balance of fluid, electrolyte and acid-base and thus improved treatment efficacy in critical illness. For cases of severe illness, early and also short period of moderate glucocorticoid was supported. Patients with oxygenation index below 200 mmHg should be transferred to intensive medical center. Conservative oxygen therapy was preferred and noninvasive ventilation was not recommended. Patients with mechanical ventilation should be strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was not recommended except for patients with long course of disease, repeated fever and elevated procalcitonin (PCT), meanwhile secondary fungal infection should be concerned.Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased probiotics such as Lactobacillus and Bifidobacterium, so nutritional and gastrointestinal function should be assessed for all patients.Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infection due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established dynamic assessment and warning for psychological crisis. We also integrated Chinese medicine in treatment to promote disease rehabilitation through classification methods of traditional Chinese medicine. We optimized nursing process for severe patients to promote their rehabilitation. It remained unclear about viral clearance pattern after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, two weeks' quarantine for discharged patients was required and a regular following up was also needed.The Zhejiang experience and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work was warranted to improve strategies of prevention, diagnosis and treatment for COVID-19.

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Study on the epidemic development of COVID-19 in Hubei province by a modified SEIR model
CAO Shengli,FENG Peihua,SHI Pengpeng
J Zhejiang Univ (Med Sci)    2020, 49 (2): 178-184.   DOI: 10.3785/j.issn.1008-9292.2020.02.05
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Objective: To establish a SEIR epidemic dynamics model that can be used to evaluate the COVID-19 epidemic, and to predict and evaluate the COVID-19 epidemic in Hubei province using the proposed model. Methods: COVID-19 SEIR transmission dynamics model was established, which took transmission ability in latent period and tracking quarantine interventions into consideration. Based on the epidemic data of Hubei province from January 23, 2020 to February 24, 2020, the parameters of the newly established modified SEIR model were fitted. By using Euler integral algorithm to solve the modified SEIR dynamics model, the epidemic situation in Hubei province was analyzed, and the impact of prevention and control measures such as quarantine and centralized treatment on the epidemic development was discussed. Results: The theoretical estimation of the epidemic situation by the modified SEIR epidemic dynamics model is in good agreement with the actual situation in Hubei province. Theoretical analysis showed that prevention and control quarantine and medical follow-up quarantine played an important inhibitory effect on the outbreak of the epidemic.The centralized treatment played a key role in the rapid decline in the number of infected people. In addition, it is suggested that individuals should improve their prevention awareness and take strict self-protection measures to curb the increase in infected people. Conclusion: The modified SEIR model is reliable in the evaluation of COVID-19 epidemic in Hubei province, which provides a theoretical reference for the decision-making of epidemic interventions.

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Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)
CHEN Zhimin,FU Junfen,SHU Qiang,WANG Wei,CHEN Yinghu,HUA Chunzhen,LI Fubang,LIN Ru,TANG Lanfang,WANG Tianlin,WANG Yingshuo,XU Weize,YANG Zihao,YE Sheng,YUAN Tianming,ZHANG Chenmei,ZHANG Yuanyuan
J Zhejiang Univ (Med Sci)    2020, 49 (2): 139-146.   DOI: 10.3785/j.issn.1008-9292.2020.02.01
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The coronavirus disease 2019 (COVID-19) has caused a global pandemic. All people including children are generally susceptible to COVID-19, but the condition is relatively mild for children. The diagnosis of COVID-19 is largely based on the epidemiological evidence and clinical manifestations, and confirmed by positive detection of virus nucleic acid in respiratory samples. The main symptoms of COVID-19 in children are fever and cough; the total number of white blood cell count is usually normal or decreased; the chest imaging is characterized by interstitial pneumonia, which is similar to other respiratory virus infections and Mycoplasma pneumoniae infections. Early identification, early isolation, early diagnosis and early treatment are important for clinical management. The treatment of mild or moderate type of child COVID-19 is mainly symptomatic. For severe and critical ill cases, the oxygen therapy, antiviral drugs, antibacterial drugs, glucocorticoids, mechanical ventilation or even extracorporeal membrane oxygenation (ECMO) may be adopted, and the treatment plan should be adjusted timely through multi-disciplinary cooperation.

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Dynamic changes of chest CT imaging in patients with COVID-19
WANG Jincheng,LIU Jinpeng,WANG Yuanyuan,LIU Wei,CHEN Xiaoqun,SUN Chao,SHEN Xiaoyong,WANG Qidong,WU Yaping,LIANG Wenjie,RUAN Lingxiang
J Zhejiang Univ (Med Sci)    2020, 49 (2): 191-197.   DOI: 10.3785/j.issn.1008-9292.2020.02.03
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Objective: To analyze the dynamic changes of chest CT images of patients with coronavirus disease 2019 (COVID-19). Methods: Fifty-two cases of COVID-19 were admitted in the First Affiliated Hospital of Zhejiang University School of Medicine. The consecutive chest CT scans were followed up for all patients with an average of 4 scans performed per patient during the hospitalization. The shortest interval between each scan was 2 days and the longest was 7 days. The shape, number and distribution of lung shadows, as well as the characteristics of the lesions on the CT images were reviewed. Results: The obvious shadows infiltrating the lungs were shown on CT images in 50 cases, for other 2 cases there was no abnormal changes in the lungs during the first CT examination. Ground-glass opacities (GGO) were found in 48 cases (92.3%), and 19 cases (36.5%) had patchy consolidation and sub-consolidation, which were accompanied with air bronchi sign in 17 cases (32.7%). Forty one cases (78.8%) showed a thickened leaflet interval, 4 cases (7.6%) had a small number of fibrous stripes. During hospitalization, GGO lesions in COVID-19 patients gradually became rare, the fibrous strip shadows increased and it became the most common imaging manifestation. The lesions rapidly progressed in 39 cases (75.0%) within 6-9 days after admission. On days 10-14 of admission, the lesions distinctly resolved in 40 cases (76.9%). Conclusion: The chest CT images of patients with COVID-19 have certain characteristics with dynamic changes, which are of value for monitoring disease progress and clinical treatment.

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Pharmaceutical care for severe and critically ill patients with COVID-19
JIANG Saiping,LI Lu,RU Renping,ZHANG Chunhong,RAO Yuefeng,LIN Bin,WANG Rongrong,CHEN Na,WANG Xiaojuan,CAI Hongliu,SHENG Jifang,ZHOU Jianying,LU Xiaoyang,QIU Yunqing
J Zhejiang Univ (Med Sci)    2020, 49 (2): 158-169.   DOI: 10.3785/j.issn.1008-9292.2020.03.01
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Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6), and Management of COVID-19: the Zhejiang experience, we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.

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Diagnostic efficacy of three test kits for SARS-CoV-2 nucleic acid detection
SHEN Lihua,HUANG Fei,CHEN Xiang,XIONG Zuan,YANG Xiaoyu,LI Hui,CHENG Feng,GUO Jian,GONG Guofu
J Zhejiang Univ (Med Sci)    2020, 49 (2): 185-190.   DOI: 10.3785/j.issn.1008-9292.2020.03.09
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Objective: To compare the diagnostic efficacy among three RT-PCR test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection. Methods: The throat swab samples from 40 hospitalized patients clinically diagnosed as coronavirus disease 2019 (COVID-19) and 16 hospitalized non-COVID-19 patients were recruited. The SARS-CoV-2 nucleic acid was detected in throat swab samples with RT-PCR test kits from Sansure Biotech ("Sansure" for short), Jiangsu Bioperfectus Technologies ("Bioperfectus" for short) and BGI Genomics ("BGI" for short). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Kappa value were analyzed. The viral nucleic acid was extracted from the throat swab samples by one-step cleavage and magnetic bead methods, and the efficacy of two extraction methods was also compared. The results of magnetic bead method for nucleic acid extraction by two different extractors (Sansure Natch CS S12C Fully Automated Nucleic Acid Extraction System vs. Tianlong NP968-C Nucleic Acid Extractor) were also compared. Results: The sensitivity, specificity, PPV, NPV and kappa value were 95.00%, 87.50%, 95.00%, 87.50%and 0.825 for Sansure kit; 90.00%, 87.50%, 94.74%, 77.78%and 0.747 for the Bioperfectus kit, and 82.50%, 81.25%, 91.67%, 65.00%and 0.593 for the BGI kit, respectively. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by one-step cleavage and magnetic bead methods were 95.24%, 100.00%, 96.43%and 0.909, respectively, but the one-step cleavage method took only 25 min, while the magnetic bead method required 180 min. The positive, negative and total coincident rates and kappa value of viral nucleic acid detection results using the samples extracted by the two different nucleic acid extractors were 85.00%, 100.00%, 89.29% and 0.764, respectively. Conclusion: The detection efficacy for SARS-CoV-2 nucleic acid by the Sansure kit is relatively higher and the one-step cleavage method has advantages of convenient operation and less time consuming.

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CT imaging features of patients with different clinical types of COVID-19
ZHONG Qi,LI Zhi,SHEN Xiaoyong,XU Kaijin,SHEN Yihong,FANG Qiang,CHEN Feng,LIANG Tingbo
J Zhejiang Univ (Med Sci)    2020, 49 (2): 198-202.   DOI: 10.3785/j.issn.1008-9292.2020.03.05
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Objective: To investigate the CT findings of patients with different clinical types of coronavirus disease 2019 (COVID-19). Methods: A total of 67 patients diagnosed as COVID-19 by nucleic acid testing were collected and divided into 4 groups according to the clinical stages based on Diagnosis and treatment of novel coronavirus pneumonia (trial version 6). The CT imaging characteristics were analyzed among patients with different clinical types. Results: Among 67 patients, 3(4.5%) were mild, 35 (52.2%) were moderate, 22 (32.8%) were severe, and 7(10.4%) were critical ill. No significant abnormality in chest CT imaging in mild patients. The 35 cases of moderate type included 3 (8.6%) single lesions, the 22 cases of severe cases included 1 (4.5%) single lesion and the rest cases were with multiple lesions. CT images of moderate patients were mainly manifested by solid plaque shadow and halo sign (18/35, 51.4%); while fibrous strip shadow with ground glass shadow was more frequent in severe cases (7/22, 31.8%). Consolidation shadow as the main lesion was observed in 7 cases, and all of them were severe or critical ill patients. Conclusion: CT images of patients with different clinical types of COVID-19 have characteristic manifestations, and solid shadow may predict severe and critical illness.

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Clinical observation of 6 severe COVID-19 patients treated with plasma exchange or tocilizumab
LUO Song,YANG Lijuan,WANG Chun,LIU Chuanmiao,LI Dianming
J Zhejiang Univ (Med Sci)    2020, 49 (2): 227-231.   DOI: 10.3785/j.issn.1008-9292.2020.03.06
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Objective: To observe the clinical effect of plasma exchange and tocilizumab in treatment of patients with severe coronavirus disease 2019 (COVID-19). Methods: Six patients with severe COVID-19 admitted in First Affiliated Hospital of Bengbu Medical College from January 25 to February 25, 2020. Three patients were treated with plasma exchange and three patients were treated with tocilizumab. The effect on excessive inflammatory reaction of plasma exchange and tocilizumab was observed. Results: The C-reactive protein (CRP) and IL-6 levels were significantly decreased and the lymphocyte and prothrombin time were improved in 3 patients after treatment with plasma exchange; while inflammation level was not significantly decreased, and lymphocyte and prothrombin time did not improve in 3 patients treated with tocilizumab. Conclusion: For severe COVID-19 patients with strong inflammatory reaction, plasma exchange may be preferred.

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Principles and suggestions on biosafety protection of biological specimen preservation during prevalence of COVID-19
ZHANG Xiaoyan,SUN Wei,SHANG Shiqiang,MAO Jianhua,FU Junfen,SHU Qiang,JIANG Kewen
J Zhejiang Univ (Med Sci)    2020, 49 (2): 170-177.   DOI: 10.3785/j.issn.1008-9292.2020.02.04
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Coronavirus disease 2019 (COVID-19) is a grade B infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In pace with the spreading of the disease, biosafety risk of the biological specimen preservation in biobanks has been significantly increased and biosafety protection during biological specimen preservation become increasingly important. According to the related national rules and the corresponding guidelines of Chinese Medical Association, this paper introduced the etiology about SARS-CoV-2, epidemiology about COVID-19, and the biosafety protection principles of individuals and biological specimen storage places in the process of personal protection, protection of collection, transport, handling, preservation, detection, post-detection disposal and emergencies of biological specimen. Emphasized to carry out a strict biosafety-risk assessment on biological specimen basing on virus load information, infectivity, and sample type (possible contact transmission, aerosol transmission, and fecal oral transmission).

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Anesthesia management in cesarean section for patient with COVID-19: a case report
KANG Xianhui,ZHANG Rong,HE Huiliang,YAO Yongxing,ZHENG Yueying,WEN Xiaohong,ZHU Shengmei
J Zhejiang Univ (Med Sci)    2020, 49 (2): 249-252.   DOI: 10.3785/j.issn.1008-9292.2020.03.04
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Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.

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Roles of multidisciplinary team in diagnosis and treatment of suspected cases of COVID-19
DING Shubo,YU Shi'an,CHEN Haijun,ZHANG Dehe,XU Yejin,ZHU Dan,CHENG Kun
J Zhejiang Univ (Med Sci)    2020, 49 (2): 209-214.   DOI: 10.3785/j.issn.1008-9292.2020.03.15
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Objective: To analyze the roles of multidisciplinary team (MDT) in the diagnosis and treatment of suspected cases of coronavirus disease 2019 (COVID-19). Methods: The clinical data of 48 patients with suspected COVID-19 admitted in Jinhua Municipal Central Hospital from January 21, 2020 to March 20, 2020 were retrospectively analyzed. Results: In the 48 suspected cases, 18 were diagnosed with COVID-19, and 30 were excluded. Each of the confirmed cases were discussed among MDT for 2 to 12 times with an average of (4.7±3.2) times; while for non-COVID-19 patients were discussed for 2 to 4 times with an average of (2.3±0.6) times. With the guidance of MDT, one COVID-19 patient was transferred to designated provincial hospital after effective treatment; one patient complicated with acute cholecystitis underwent gallbladder puncture and drainage; and COVID-19 was excluded in a highly suspected patient after alveolar lavage fluid examination. Except one transferred patient, all 17 confirmed COVID-19 patients were cured and discharged. There was no cross-infection occurred in suspected patients during the hospitalization. There were no deaths and no medical staff infections. Conclusion: The efficiency of diagnosis and treatment for suspected COVID-19 patients can be improved with MDT, particularly for complicated cases.

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Clinical analysis of suspected COVID-19 patients with anxiety and depression
LI Xin,DAI Tian,WANG Hong,SHI Junnian,YUAN Wei,LI Jing,CHEN Lijun,ZHANG Tianming,ZHANG Shanshan,KONG Yan,YUE Ning,SHI Hui,HE Yuping,HU Huifang,LIU Furong,YANG Caixia
J Zhejiang Univ (Med Sci)    2020, 49 (2): 203-208.   DOI: 10.3785/j.issn.1008-9292.2020.03.02
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Objective: To explore the risk factors of anxiety and depression in patients with suspected coronavirus disease 2019 (COVID-19) so as to achieve early intervention and better clinical prognosis. Methods: Seventy-six patients with suspected COVID-19 in fever isolation wards of Second Hospital of Lanzhou University were enrolled From January 31, 2020 to February 22, 2020. Their clinical baseline data were collected. The anxiety of patients was assessed by Hamilton Anxiety Scale, and the depression of patients was assessed by Hamilton Depression Scale. Multivariate Logistic regression analysis was performed to explore the risk factors of anxiety and depression in these patients. Results: Female patients are more likely to have anxiety (OR=3.206, 95%CI:1.073-9.583, P < 0.05) and depression (OR=9.111, 95%CI:2.143-38.729, P < 0.01) than male patients; patients with known contact history of epidemic area and personnel in epidemic area are more likely to have depression (OR=3.267, 95%CI:1.082-9.597, P < 0.05). Conclusion: During the isolation treatment of suspected COVID-19 patients, early psychological intervention should be carried out for the female patients with known contact history of epidemic area and personnel in epidemic area, and drug treatment should be given in advance if necessary.

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Pregnant women complicated with COVID-19: a clinical analysis of 3 cases
CHEN Xu,LI Yang,WANG Jinxi,CAI Hongliu,CAO Hongcui,SHENG Jifang
J Zhejiang Univ (Med Sci)    2020, 49 (2): 240-244.   DOI: 10.3785/j.issn.1008-9292.2020.03.08
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Objective: To analyze the clinical characteristics and pregnancy outcomes of pregnant women complicated with coronavirus disease 2019 (COVID-19). Methods: The clinical data of 3 pregnant women with COVID-19 admitted to the First Affiliated Hospital of Zhejiang University School of Medicine from January 19 to February 10, 2020 were retrospectively analyzed. Results: There was one case in the first-trimester pregnancy (case 1), one in the second-trimester pregnancy (case 2) and one in third-trimester pregnancy (case 3). Cough, fever, fatigue, lung imaging changes were the main manifestations. The white cell count, lymphocyte percentage had no significantly changes in case 1 and case 3, while the levels of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6 and IL-10 elevated. The lymphocyte count and lymphocyte percentage decreased and the inflammatory indicators significantly increased in case 2. All patients were treated with antiviral, antitussive, oxygen inhalation; case 3 received glucocorticoids, case 2 with severe illness received glucocorticoids and additionally gamma globulin. All three cases were cured and discharged. Case 1 with early pregnancy chose to terminate pregnancy after discharge; case 2 chose to continue pregnancy without obstetric complications; and case 3 had cesarean section delivery due to abnormal fetal heart monitoring. Conclusion: The report shows that COVID-19 in pregnancy women could be cured with active treatment, and the maternal and fetal outcomes can be satisfactory.

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Follow-up testing of viral nucleic acid in discharged patients with moderate type of COVID-19
LI Youjiang,HU Yingying,ZHANG Xiaodong,YU Yuanyuan,LI Bin,WU Jianguo,WU Yingping,XIA Xiaoping,XU Jian
J Zhejiang Univ (Med Sci)    2020, 49 (2): 270-274.   DOI: 10.3785/j.issn.1008-9292.2020.03.11
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Objective: To investigate the clinical outcome of patients with moderate type of coronavirus disease 2019 (COVID-19) after discharge by retesting viral nucleic acid. Methods: Seven patients with moderate COVID-19 met the discharge criteria enacted by National Health Commission were quarantined in hospital for 7 days, then continuously quarantined at home for 4 weeks after discharged. During the quarantined period, the symptoms and signs were documented, and sputum or nasal swab and feces samples were collected to test SARS-CoV-2 nucleic acid by RT-PCR method. Results: There was no symptoms and signs during the quarantine period in all 7 patients. However, respiratory swabs from 3 patients were confirmed positive of SARS-CoV-2 nucleic acid at 5 to 7 days after they met the discharge criteria. Conclusion: There is a relatively high incidence of positive viral nucleic acid in patients met the discharge criteria, and it is suggested that patients met the current discharge criteria should be quarantined in hospital for another 7 days and the follow-up viral testing is necessary.

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What is narrative medicine?
GUO Liping
J Zhejiang Univ (Med Sci)    2019, 48 (5): 467-473.   DOI: 10.3785/j.issn.1008-9292.2019.10.01
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Narrative medicine first entered China in 2011 and has developed rapidly since then. The patient-centered care, shared decision making and relational medicine in the medical sphere, together with patients narrating their illness and narratology contributed to the rise of narrative medicine. Through listening to patients' narratives, paying attention to their emotions, and representing their stories in various ways, clinicians can connect with patients and empathize with them. In this way, affiliation and mutual trust with patients can be established. Patients will feel good in the doctor-patient encounter because of such humane care, and clinicians may get satisfaction from their work. Narrative medicine courses characterized by close reading of literature and writing should be added to the curriculum of medical education as the major content of medical humanities, so as to train narrative competence for the future doctors.

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Advances in newborn screening and immune system reconstitution of severe combined immunodeficiency
HUANG Shumin,ZHAO Zhengyan
J Zhejiang Univ (Med Sci)    2019, 48 (4): 351-357.   DOI: 10.3785/j.issn.1008-9292.2019.08.01
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Severe combined immunodeficiency disease (SCID) is a group of rare congenital diseases characterized by severe deficiencies in T lymphocyte counts and/or function. The recurrent, persistent and severe infections are its clinical manifestations. Neonatal screening and immune system reconstruction would improve the prognosis of SCID children. Newborn screening programs based on T-cell receptor excision circles (TRECs) quantitative detection have been carried out in clinical practice, however, the methods still have some limitations. Other new methods such as mass spectrometry and T lymphocyte-specific biomarker assays are still under investigation. Hematopoietic stem cell transplantation and gene therapy are the two main methods for reconstructing immune function in SCID children. Through improving the success rate of transplantation and the long-term safety and stability of viral vectors, some achievements have been made by many centers already. However, large-scale prospective studies are needed for evaluation of the long-term efficacy. In this article, the recent progress in newborn screening and immune reconstitution of SCID is reviewed.

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Research progress on selective immunoproteasome inhibitors
KONG Limin,LU Jingyi,ZHU Huajian,ZHANG Jiankang
J Zhejiang Univ (Med Sci)    2019, 48 (6): 688-694.   DOI: 10.3785/j.issn.1008-9292.2019.12.15
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Immunoproteasome is associated with various diseases such as hematologic malignancies, inflammatory, autoimmune and central nervous system diseases, and over expression of immunoproteasome is observed in all of these diseases. Immunoproteasome inhibitors can reduce the expression of immunoproteasome by inhibiting the production of related cell-inducing factors and the activity of T lymphocyte for treating related diseases. In order to achieve good efficacy and reduce the toxic effects, key for development of selective immunoproteasome inhibitors is the high selectivity and potent activity of the three active subunits of the proteasome. This review summarizes the structure and functions of immunoproteasome and the associated diseases. Besides, structure, activity and status of selective immunoproteasome inhibitors are also been highlighted.

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Dynamic inflammatory response in a critically ill COVID-19 patient treated with corticosteroids
ZHAGN Sheng,LI Danping,CHEN Huazhong,ZHENG Dan,ZHOU Yiping,CHEN Baoguo,SHI Weiwu,LIN Ronghai
J Zhejiang Univ (Med Sci)    2020, 49 (2): 220-226.   DOI: 10.3785/j.issn.1008-9292.2020.03.10
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Objective: To investigate the effect of corticosteroids therapy on the inflammatory response in a critically ill coronavirus disease 2019 (COVID-19) patient. Methods: A 55-year old female patient with critical ill COVID-19 was admitted in Taizhou Hospital on January 19, 2020. The patient was treated with methylprednisolone 80 mg on the 2nd day after admission. Thereafter, the dose was adjusted in a timely manner and the therapy lasted for 13 days. The peripheral lymphocyte subsets (CD3+T, CD4+ T, CD8+ T, NK cells, B cells), as well as serum levels of lymphocyte factors (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were dynamically monitored. Results: On D1 of admission, the numbers of peripheral blood CD3+ T, CD4+ T, CD8+ T, and NK cells were significantly lower than the normal range. With the improvement of the disease, the numbers of CD3+ T, CD8+ T and CD4 + T cells gradually recovered and showed a linear growth trend (linear fitting equation: Y=18.59X+109.4, P < 0.05). On D2 of admission, the patient's IL-6 and IL-10 levels were significantly higher than normal values, IFN-γ was at a normal high value, and then rapidly decreased; IL-2, IL-4, and TNF-α were all in the normal range. On the D6 and D7, the IL-6 and IL-10 decreased to the normal range for the first time. On the D18, the sputum virus nucleic acid test was negative for the first time, and the fecal virus nucleic acid test was still positive; on the D20 the sputum and fecal virus nucleic acid test were both negative. On D34, the patient recovered and was discharged. At the discharge the muscle strength score of the patient was 44 and the daily life ability evaluation was 90. Conclusion: In the absence of effective antiviral drugs, early use of appropriate doses of corticosteroids in critically ill patient with COVID-19 can quickly alleviate inflammatory response and improve clinical symptoms, however, it may reduce the number of T cells, and to adjust the dose in time is necessary.

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Management of a colon cancer patient complicated with COVID-19
YE Ziqi,HONG Yun,WU Xiuhua,HONG Dongsheng,ZHANG Yanfang,DONG Xihao,RAO Yuefeng,LU Xiaoyang
J Zhejiang Univ (Med Sci)    2020, 49 (2): 245-248.   DOI: 10.3785/j.issn.1008-9292.2020.03.12
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Objective: To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19). Methods: The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed. Results: The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice. Conclusion: The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.

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Establishment of a rapid identification of adverse drug reaction program in R language implementation based on monitoring data
HONG Dongsheng,NI Jian,SHAN Wenya,LI Lu,HU Xi,YANG Hongyu,ZHAO Qingwei,ZHANG Xingguo
J Zhejiang Univ (Med Sci)    2020, 49 (2): 253-259.   DOI: 10.3785/j.issn.1008-9292.2020.03.07
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Objective: To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use. Methods: Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r). Results: The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results. Conclusion: In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.

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Nucleus translocation of membrane/cytoplasm proteins in tumor cells
ZHU Ziling, TAN Jing, DENG Hong
J Zhejiang Univ (Med Sci)    2019, 48 (3): 318-325.   DOI: 10.3785/j.issn.1008-9292.2019.06.13
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Proteins are the physical basis of life and perform all kinds of life activities. Proteins have different orientations and function in different tissues. The same protein, located in different subcellular regions, can perform different and even opposite functions. Both functional and structural proteins are capable of undergoing re-localization which can directly or indirectly participate in signal transduction. Due to abnormal transduction of signals during carcinogenesis, the proteins originally expressed in the cytoplasm are translocated into the nucleus and lead to functional changes in the tumor tissue. The changes of protein localization are affected by many factors, including the interaction between proteins, expression level of proteins and the cleaved intracellular domain of transmembrane protein.

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Advances in surgical treatment of ischemic cerebrovascular disease
ZHANG Jianmin
J Zhejiang Univ (Med Sci)    2019, 48 (3): 233-240.   DOI: 10.3785/j.issn.1008-9292.2019.06.01
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Restoration of cerebral blood flow is particularly important for the treatment of ischemic cerebrovascular disease. It is notable that surgical approaches play a unique role in treating this devastating disease. Among them, mechanical thrombectomy facilitates rapid and effective recanalization of occluded intracranial large vessels causing ischemic stroke, which contributes to improvement of cerebral perfusion in the ischemic penumbra; decompressive craniectomy is an important therapeutic option for acute massive cerebral infarction, and the timing of surgery determines the final clinical outcomes; for carotid endarterectomy in carotid-artery stenosis, individualized surgical plan is important for the safety and effectiveness of the operation; in the surgical revascularization of Moyamoya disease, precise evaluation of clinical and radiological characteristics, optimal surgical strategies and accuracy of intraoperative judgment will yield maximal therapeutic effects; and hybrid surgery is feasible for the therapy of complex ischemic cerebrovascular diseases, such as extracranial/intracranial arteries tandem stenosis and symptomatic chronic total occlusion of carotid artery. This paper reviews recent technical and clinical advances in the surgical treatment of ischemic cerebrovascular disease.

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Identification of dynamic co-expression networks in peripheral blood of rats after middle cerebral artery occlusion
PAN Zongfu,HU Xiaoping,ZHANG Yiwen,LI Li,HUANG Ping
J Zhejiang Univ (Med Sci)    2019, 48 (6): 587-593.   DOI: 10.3785/j.issn.1008-9292.2019.12.01
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Objective: To identify the time dependent profiles of gene expression and featured co-expression network modules in peripheral blood of rats after middle cerebral artery occlusion (MCAO). Methods: Microarray GSE119121 from GEO database was analyzed by R language to identify the significantly changed genes in peripheral blood at different time points (0, 1, 2, 3, 6 and 24 h) after MCAO. Gene expression patterns at different time courses were screened by STEM tools. Then, function annotation and pathway enrichment of differentially expressed genes (DEGs) were performed using the Gene Ontology (GO) database and the Kyoto Gene and Genomic Encyclopedia (KEGG) database. Depending on CEMiTool package, gene expression profile matrix was inputted into R to construct the co-expression networks and to analyze modules, and enrichment analysis was conducted to evaluate the correlation between the modules and different time points. Results: Comparing with gene at 0 h, the numbers of DEGs in peripheral blood at different time points after MCAO were 163 (1 h), 502 (2 h), 527 (3 h), 550 (6 h), and 75 (24 h), respectively. Moreover, a total of 38 gene expression patterns were enriched, and pattern 65 and pattern 34 were specifically up-regulated or down-regulated at 2-6 h. Hp, Nos2, P2ry10, and Klf12 were representative genes of these two models. The co-expression network module analysis showed that the gene status in the early acute phase (1-6 h) was positively correlated with the Module 2. Module 3 and Module 4 was positively correlated with phase phase 1-3 h and 2-6 h, respectively. Noteworthy, Module 6 gradually changed from positive correlation (0-2 h) to negative correlation (3-24 h) with the MCAO time course, and Module 6 was mainly related to viral response and innate immune response. The hub genes of Module 6 included Mx1, Mx2, and Rtp4. Conclusion: Our study has identified the featured genes and dynamic co-expression network modules in peripheral blood after acute ischemic stroke, which provides a potential basis for judging the onset time of ischemic stroke.

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Effects of emergency medical service on prognosis of ischemic stroke patients treated with intravenous thrombolysis
ZHONG Wansi, CHEN Zhicai, CHEN Hongfang, XU Dongjuan, WANG Zhimin, HU Haifang, WU Chenglong, ZHANG Xiaoling, MA Xiaodong, WANG Yaxian, HU Haitao, LOU Min, Improving In-hospital Stroke Service Utilisation (MISSION) in Zhejiang Province
J Zhejiang Univ (Med Sci)    2019, 48 (3): 241-246.   DOI: 10.3785/j.issn.1008-9292.2019.06.02
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Objective: To investigate the effect of emergency medical service (EMS) on the prognosis of ischemic stroke patients treated with intravenous thrombolysis. Methods: Clinical data of 2123 ischemic stroke patients treated with intravenous thrombolysis in 70 hospitals in Zhejiang province were retrospectively analyzed. There were 808 patients sent to the hospital by ambulance (EMS group) and 1315 patients by other transportations (non-EMS group). Good outcome was defined as modified Rankin Scale (mRS) ≤ 2 at 3-month. The onset to needle time (ONT), onset to door time (ODT), door to needle time (DNT) and outcome were compared between EMS group and non-EMS group. Binary logistic regression was used to explore the influencing factors for the outcome at 3-month. Results: Compared with the non-EMS group, patients in the EMS group were older, with higher baseline National Institute of Health Sroke Scale (NIHSS) score, and had a higher proportion of atrial fibrillation (all P < 0.05), but there were no significant differences in ONT, ODT and DNT between two groups (all P>0.05). Binary logistic regression showed that EMS was not independently associated with good outcome (OR=0.856, 95%CI:0.664-1.103, P>0.05). Conclusion: EMS had not improve the outcome of patients receiving intravenous thrombolysis in Zhejiang province.

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The roles of habenula and related neural circuits in neuropsychiatric diseases
WU Yuxing, ZHANG Shihong, CHEN Zhong
J Zhejiang Univ (Med Sci)    2019, 48 (3): 310-317.   DOI: 10.3785/j.issn.1008-9292.2019.06.12
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The habenula is a small and bilateral nucleus above dorsal thalamus, which contains several different types of neurons. The habenula has extensive connections with the forebrain, septum and monoaminergic nuclei in the midbrain and brainstem. Habenula is known as an 'anti-reward' nucleus, which can be activated by aversive stimulus and negative reward prediction errors. Accumulating researchs have implicated that the habenula is involved in several behaviors crucial to survival. Meanwhile, the roles of the habenula in neuropsychiatric diseases have received increasing attention. This review summaries the studies regarding the roles of habenula and the related circuits in neuropathic pain, depression, drug addiction and schizophrenia, and discusses the possibility to use the habenula as a treatment target.

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Advanced treatment time improves outcomes of patients with ischemic stroke undergoing reperfusion therapy
CHEN Hongfang, GONG Xiaoxian, XU Dongjuan, WANG Zhimin, HU Haifang, WU Chenglong, ZHANG Xiaoling, MA Xiaodong, WANG Yaxian, HU Haitao, LOU Min, CHEN Zhicai, Improving In-hospital Stroke Service Utilisation (MISSION) in Zhejiang Province
J Zhejiang Univ (Med Sci)    2019, 48 (3): 247-253.   DOI: 10.3785/j.issn.1008-9292.2019.06.03
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Objective: To investigate the effect of treatment time on the outcome of patients with ischemic stroke undergoing reperfusion therapy. Methods: The clinical data of 3229 ischemic stroke patients who received intravenous thrombolysis with or without arterial thrombolysis from 71 hospitals in Zhejiang province from June 2017 to September 2018 were retrospectively reviewed. The good outcome was defined as modified Rankin Scale (mRS) ≤ 2. Binary logistic regression analysis was used to investigate the association of door to needle time (DNT), or door to reperfusion time (DRT) with the outcomes in patients treated by intravenous thrombolysis or bridging arterial thrombolysis, respectively. Results: Binary logistic regression showed that DNT (OR=0.994, 95%CI:0.991-0.997, P < 0.01) or DRT (OR=0.989, 95%CI:0.983-0.995, P < 0.01) were independently associated with good outcomes, respectively. Every hour decreases in DNT resulted in a 4.7%increased probability of functional independence (mRS 0-2) in patients treated by intravenous thrombolysis; Every hour decreases in DRT was associated with a 11.4%increased probability of functional independence in patients treated by intravenous thrombolysis with arterial thrombolysis. Conclusion: Good outcomes are associated with lower DNT in ischemic stroke patients treated by intravenous thrombolysis or lower DRT in patients treated by intravenous thrombolysis bridging arterial thrombolysis.

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Research frontier of inflammatory bowel disease
FAN Yihong, LYU Bin
J Zhejiang Univ (Med Sci)    2019, 48 (3): 334-341.   DOI: 10.3785/j.issn.1008-9292.2019.06.15
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Development and prospects of fecal microbiota transplantation
HU Yue, LYU Bin
J Zhejiang Univ (Med Sci)    2019, 48 (3): 342-346.   DOI: 10.3785/j.issn.1008-9292.2019.06.16
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Replication and transmission mechanisms of highly pathogenic human coronaviruses
HE Yeyan,ZHENG Chanying
J Zhejiang Univ (Med Sci)    2020, 49 (1): 0-0.   DOI: 10.3785/j.issn.1008-9292.2020.03.16
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The three known human highly pathogenic coronaviruses are severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human highly pathogenic coronaviruses are composed of non-structural proteins, structural proteins and accessory proteins. Viral particles recognize host receptors via spike glycoprotein (S protein), enter host cells by membrane fusion, replicate in host cells through large replication-transcription complexes, and promote proliferation by interfering with and suppressing the host's immune response. Human highly pathogenic coronaviruses are hosted by humans and vertebrates. Viral particles are transmitted through droplets, contact and aerosols or likely through digestive tract, urine, eyes and other routes. This review discusses the mechanisms of proliferation and transmission of highly pathogenic human coronaviruses based on the results of existing research, providing basis for future study on interrupting the transmission and pathogenicity of human highly pathogenic coronaviruses.

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Ultrasound diagnosis of left inferior vena cava and double inferior vena cava in fetus
ZHANG Ziwei,WANG Junmei
J Zhejiang Univ (Med Sci)    2019, 48 (4): 446-452.   DOI: 10.3785/j.issn.1008-9292.2019.08.16
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Objective: To evaluate the application of ultrasonography in prenatal diagnosis of left inferior vena cava and double inferior vena cava in fetus. Methods: The clinical data and ultrasonographic findings of the fetuses with left inferior vena cava (18 cases) or double inferior vena cava (16 cases) were retrospectively analyzed. Results: The ultrasonographic images of left inferior vena cava showed that in the transverse view of the fetal upper abdomen the inferior vena cava and abdominal aorta were in the normal position; below the level of the hilum, the inferior vena cava was located behind the left side of the abdominal aorta; at the level of the hilum, it crossed the front of the abdominal aorta and run diagonally to the upper right, forming the right inferior vena cava and finally entered into the right atrium. The ultrasonographic images of double inferior vena cava showed that in the transverse view of the fetal lower abdomen, in front of spine there were three transections of blood vessels; in coronal plane of abdomen, the veins run on both sides of the abdominal aorta and entered to the iliac vein of the same side. In 34 cases of abnormal inferior vena cava, there were 17 cases complicated with other system abnormalities, including 13 cases of cardiac anomalies. Conclusions: The left inferior vena cava and double inferior vena cava have characteristic imaging findings, and prenatal diagnosis can be made with ultrasonography. This type of congenital deformity is frequently complicated with other system abnormalities, which should be excluded in fetus, especially for heart system.

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Advances in serum biomarkers for early diagnosis of gastric cancer
ZHANG Yunzhu, ZHU Chunpeng, LU Xinliang
J Zhejiang Univ (Med Sci)    2019, 48 (3): 326-333.   DOI: 10.3785/j.issn.1008-9292.2019.06.14
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Early diagnosis is the key to improve the prognosis of gastric cancer. How to screen out high-risk subjects of gastric cancer in population is a hot spot. Serum-based early detection of gastric cancer is suitable for high-risk population screening, which is more convenient and safer. This article reviews the diagnostic value of serum biomarkers for gastric cancer, including serum DNA methylation, various RNAs, pepsinogen, gastrin, osteopontin, MG7-Ag and CA724. Until now, there is still lack of ideal biomarkers for gastric cancer, and searching for specific RNAs may be promising for early diagnosis and screening of gastric cancer.

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Correlation of phosphorylated S6 protein expression in blood and brain tissue in mice and rats with kainic acid-induced seizure
FAN Miao, DONG Shuminin, ZOU Xinyi, ZHENG Boyuan, HUANG Yurun, WANG Jianda, ZENG Linghui
J Zhejiang Univ (Med Sci)    2019, 48 (3): 303-309.   DOI: 10.3785/j.issn.1008-9292.2019.06.11
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Objective: To determine the correlation of phosphorylated ribosomal S6 protein (P-S6) content in blood and brain tissue in mice and rats with seizure. Methods: Seizure models were induced by intraperitoric injection of kainic acid (KA) in C57BL/mice and SD rats. Flow cytometry was used to detect the content of P-S6 in blood; Western blot was used to detect the expression of P-S6 in brain tissues. The correlation between P-S6 expression in blood and in brain tissue was examine by Pearson analysis, and the correlation between P-S6 expression in blood and the severity of seizure was also observed. Results: Western blotting analysis showed that the expression of P-S6 was significantly increased in peripheral blood and brain tissue in mice 1 h after KA-induced seizure, and the expression levels increased to (1.49±0.45) times (P < 0.05) and (2.55±0.66) times (P < 0.01) of the control group, respectively. Flow cytometry showed that the positive percentage and average fluorescence intensity of P-S6 in the blood of mice increased significantly 1 h after KA-induced seizures (P < 0.01), which was consistent with the expression of P-S6 in brain tissue (r=0.8474, P < 0.01). Flow cytometry showed that the average fluorescence intensity of P-S6 in blood increased from 14.89±9.75 to 52.35±21.72 (P < 0.01) in rats with seizure, which was consistent with the change of P-S6 in brain tissue (r=0.9385, P < 0.01). Rats with higher levels of seizure were of higher levels of P-S6 in peripheral blood. Conclusion: Consistent correlation of P-S6 expression is demonstrated in peripheral blood and in brain tissue after KA-induced seizure, suggesting that the expression of P-S6 in blood can accurately reflect the changes of mTOR signaling pathway in brain tissue.

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Progress on evaluation, diagnosis and management of disorders of sex development
CHEN Guangjie,WANG Xiaohao,TANG Daxing
J Zhejiang Univ (Med Sci)    2019, 48 (4): 358-366.   DOI: 10.3785/j.issn.1008-9292.2019.08.02
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Disorders of sex development (DSD) refer to a group of diseases characterized by abnormal congenital development of chromosomes, gonad or genitals with different pathophysiological changes and clinical manifestations. DSD is more common in neonates and adolescents, and neonates often show genital abnormalities while adolescents show abnormal sexual development during puberty. It is the international consensus that the scope of DSD should include basic clinical evaluation (internal and external genitalia and endocrine hormones), diagnostic confirmation (chromosome, genetic diagnosis), psychological assessment for children and family, treatment (sex assignment, hormone replacement and surgical intervention), potential fertility protection and long-term follow-up, which require the expertise of pediatric endocrinology, pediatric urology, clinical psychology, genetic disciplines, medical images and other related disciplines; that is, individualized management of children with DSD requires an experienced multidisciplinary team (MDT). This article reviews the recent progress on the evaluation, diagnosis and management of disorders of sex development.

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Restless legs syndrome in ischemic stroke patients: clinical features and significance
ZHANG Lisan, SUN Yi, WANG Tiantian, PAN Yu, YAO Ying, PAN Liuqing, XU Qinglin, ZHANG Wenying, XU Jiahui, HU Xingyue
J Zhejiang Univ (Med Sci)    2019, 48 (3): 275-281.   DOI: 10.3785/j.issn.1008-9292.2019.06.07
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Objective: To investigate the clinical features and implication of restless legs syndrome (RLS) in ischemic stroke patients. Methods: A total of 199 ischemic stroke patients were enrolled and assessed by polysomnography (PSG). RLS was identified according to criteria of International Restless Legs Syndrome Study Group. Epworth Sleepiness Scale (ESS), Mini-mental State Examination (MMSE) and Patient Health Questionnaire (PHQ-9) were used to evaluate the sleep quality, cognitive function and post-stroke depression, respectively. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the neurological function 3 months after stroke onset. Gender-and age-matched non-ischemic stroke patients with RLS (primary PLS) were selected as controls. Results: Twenty-two cases of RLS were identified among 199 ischemic stroke patients (11.1%). Generalized linear model and logistic regression showed that low serum ferritin level (β=-133.3 mg/L, 95%CI:-200.4--0.1, P < 0.01), subcortical infarction (OR=4.05, 95%CI:1.15-14.18, P < 0.05) and female (OR=2.54, 95%CI:1.04-6.23, P < 0.05) were identified as the risk factors of RLS in ischemic stroke patients. Compared with ischemic stroke patients without RLS, ESS increased by 4.37 (95%CI:2.33-6.41, P < 0.01), PHQ-9 increased by 2.17 (95%CI:0.39--3.94, P < 0.05), and reduced NIHSS from the baseline deceased by 0.97 (95%CI:-1.79--0.15, P < 0.05) in ischemic stroke patients with RLS. In addition, the incidence of moderate-severe depression increased (OR=4.27, 95%CI:1.40-13.10, P < 0.05) in ischemic stroke patients with RLS. The index of periodic leg movements of sleep (PLMS) with arousal in ischemic stroke patients with RLS was significantly higher than that in patients with primary RLS (β=12.85, 95%CI:2.04-23.67, P < 0.05). Conclusion: RLS is common in ischemic stroke patients and has adverse influences on patients.

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Genetic analysis and prenatal diagnosis of a sporadic family with neurofibromatosis type 1
LIU Bei,YANG Yanmei,YAN Kai,CHEN Min,WANG Liya,HUANG Yingzhi,QIAN Yeqing,DONG Minyue
J Zhejiang Univ (Med Sci)    2019, 48 (4): 367-372.   DOI: 10.3785/j.issn.1008-9292.2019.08.03
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Objective: To identify pathogenic mutation for a family with neurofibromatosis type 1(NF1) and provide prenatal diagnosis for them. Methods: Mutation analysis of the sporadic family with NF1 was performed with target captured next generation sequencing and Sanger sequencing. RNA samples were extracted from the lymphocytes of NF1 patient and her parents. RT-PCR and Sanger sequencing were performed to analyze the relative mRNA expression in the samples. Prenatal diagnosis of the pathogenic mutation was offered to the fetus. Results: A novel splicing mutation c.1260+4A>T in the NF1 gene was found in the proband of the family, but was not found in her parents.cDNA sequencing showed that 13 bases inserted into the 3' end of exon 11 in the NF1 gene lead to a frameshift mutation. Prenatal diagnosis suggested that the fetus did not carried the mutant. Conclusion: The NF1: c.1260+4A>T mutation found in the NF1 patient is considered to be pathogenic, which provides information for family genetic counseling and prenatal diagnosis.

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Genetic analysis of newborns with abnormal metabolism of 3-hydroxyisovalerylcarnitine
WU Dingwen,LU Bin,YANG Jianbin,YANG Rulai,HUANG Xinwen,TONG Fan,ZHENG Jing,ZHAO Zhengyan
J Zhejiang Univ (Med Sci)    2019, 48 (4): 390-396.   DOI: 10.3785/j.issn.1008-9292.2019.08.07
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Objective: To investigate the genetic characterization of 3-hydroxyisovalerylcarnitine (C5-OH) metabolic abnormality in neonates. Methods: Fifty two newborns with increased C5-OH, C5-OH/C3 and C5-OH/C8 detected by tandem mass spectrometry during neonatal screening were enrolled in the study. Genomic DNA was extracted from the whole blood samples of 52 cases and their parents. Seventy-nine genes associated with genetic and metabolic diseases including MCCC1, MCCC2 were targeted by liquid capture technique. Variation information of these genes was examined by high-throughput sequencing and bioinformatic analysis, and then was classified based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. The genetic types were classified as wild-type, MCCC1-maternal-mutation, MCCC1-paternal-mutation and MCCC2-mutation. Wilcoxon rank-sum test was performed for the increased multiples of C5-OH calculated in neonatal screening. Results: Twenty one MCCC1 variants (14 novel) were identified in 37 cases, 6 MCCC2 variants (5 novel) in 4 cases. The increased multiple of C5-OH calculated in MCCC1-maternal-mutation and MCCC2-mutation groups were significantly higher than that in wild-type group (all P < 0.05), while there was no significant difference between MCCC1-paternal-mutation group and wild-type group (P>0.05). Conclusion: Mutations on MCCC1 and MCCC2 genes are the major genetic causes for the increased C5-OH in neonates, and maternal single heterozygous mutation can contribute to the moderately to severely increased C5-OH.

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High dose vitamin C inhibits proliferation of breast cancer cells through reducing glycolysis and protein synthesis
WANG Qingmei, XU Qianzi, WEI Anyi, CHEN Shishuo, ZHANG Chong, ZENG Linghui
J Zhejiang Univ (Med Sci)    2019, 48 (3): 296-302.   DOI: 10.3785/j.issn.1008-9292.2019.06.10
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Objective: To investigate the effects of high dose vitamin C (VC) on proliferation of breast cancer cells and to explore its mechanisms. Methods: Human breast cancer cells Bcap37 and MDA-MB-453 were treated with VC at low dose (0.01 mmol/L), medium dose (0.10 mmol/L) and high dose (2.00 mmol/L). Cell proliferation was determined with CCK-8 assay, protein expression was evaluated by Western blot, and the secretion of lactic acid in tumor cells was detected by colorimetric method. Bcap37 cells were inoculated in nude mice, and tumor baring nude mice were intraperitoneally injected with high VC(4 g/kg, VC group, n=5)or normal saline (control group, n=5) for 24 d. Tumor weight and body weight were calculated. Results: In vitro experiments demonstrated that high dose VC significantly inhibited cell proliferation in Bcap37 and MDA-MB-453 cells (all P < 0.01); the expressions of Glut1 and mTOR signaling pathway-related proteins were decreased (all P < 0.05); and the secretion of lactic acid was also markedly reduced (all P < 0.05). In vivo experiment showed that the tumor weight was decreased in mice treated with high-dose VC as compared with control group (P < 0.05), but no difference in body weights between two groups was observed. Conclusion: High dose VC may inhibit proliferation of breast cancer cells both in vitro and in vivo through reducing glycolysis and protein synthesis.

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Analysis of intravenous thrombolysis time and prognosis in patients with in-hospital stroke
ZHANG Congcong, LOU Min, CHEN Zhicai, CHEN Hongfang, XU Dongjuan, WANG Zhimin, HU Haifang, WU Chenglong, ZHANG Xiaoling, MA Xiaodong, WANG Yaxian, HU Haitao, Improving In-hospital Stroke Service Utilisation (MISSION) in Zhejiang Province
J Zhejiang Univ (Med Sci)    2019, 48 (3): 260-266.   DOI: 10.3785/j.issn.1008-9292.2019.06.05
Abstract   HTML PDF (0KB) ( 22 )  

Objective: To compare the time delay between in-hospital stroke and out-of-hospital stroke patients, and to explore the influence factors for the prognosis of in-hospital stroke patients treated by intravenous thrombolysis. Methods: Clinical data of 3050 patients with ischemic stroke who received intravenous thrombolysis in 71 hospitals in Zhejiang province from June 2017 to September 2018 were analyzed. Differences of time delay including door to imaging time (DIT), imaging to needle time (INT) and door to needle time (DNT) between in-hospital stroke (n=101) and out-of-hospital stroke (n=2949) were observed. The influencing factors for the outcome at 3 month after intravenous thrombolysis in patients with in-hospital stroke were analyzed using binary logistic regression analysis. Results: Patients with in-hospital stroke had longer DIT[53.5 (32.0-79.8) min vs. 20.0 (14.0-28.0) min, P < 0.01], longer IDT[47.5(27.3-64.0)min vs. 36.0(24.0-53.0)min, P < 0.01], and longer DNT[99.0 (70.5-140.5) min vs. 55.0 (41.0-74.0) min, P < 0.01], compared with patients with out-of-hospital stroke; patients in comprehensive stroke center had longer DIT[59.5(44.5-83.3) min vs. 37.5(16.5-63.5) min, P < 0.01], longer DNT[110.0(77.0-145.0) min vs. 88.0 (53.8-124.3) min, P < 0.05], but shorter INT[36.5(23.8-60.3)min vs. 53.5 (34.3-64.8) min, P < 0.05], compared with patients in primary stroke center. Age (OR=0.934, 95%CI: 0.882-0.989, P < 0.05) and baseline National Institute of Health Stroke Scale score (OR=0.912, 95%CI: 0.855-0.973, P < 0.01) were independent risk factors for prognosis of in-hospital stroke patients. Conclusion: In-hospital stroke had longer DIT and DNT than out-of-hospital stroke, which suggests that a more smooth thrombolysis process of in-hospital stroke should be established.

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Research progress on mechanism in adaptation of hemoglobin to plateau hypoxia
LI Xue,LI Wenbin,FENG Shilan,WANG Rong
J Zhejiang Univ (Med Sci)    2019, 48 (6): 674-681.   DOI: 10.3785/j.issn.1008-9292.2019.12.13
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Low oxygen partial pressure is the main cause of acute mountain sickness.Hemoglobin plays a crucial physiological role in the binding, utilization, transportation and release of oxygen in the body. To increase the capacity of oxygen binding of hemoglobin or the capacity of oxygen supply in tissues can help alleviate altitude sickness. However, increasing hemoglobin content has certain limitations. Using techniques from molecular biology, researchers are looking for endogenous or exogenous substances that can regulate the conformation of hemoglobin to increase oxygen uptake in the alveoli, or the availability of alveolar oxygen in the tissues. At present, the research on allosteric modulators to improve the affinity of hemoglobin has made some progress, and research on applying this mechanism to plateau hypoxia is also underway. This article reviews the relationship between hemoglobin and hypoxia, the structure of hemoglobin and the role of various allosteric modulators in hypoxia, which would provide information for finding new substances regulating the conformation of hemoglobin.

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Application of enhanced recovery after surgery in the treatment of children with congenital choledochal cyst
ZHAO Hangyan,CAI Duote,GAO Zhigang,CHEN Qingjiang,ZHU Jihua,HUANG Jinjin
J Zhejiang Univ (Med Sci)    2019, 48 (5): 474-480.   DOI: 10.3785/j.issn.1008-9292.2019.10.02
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Objective: To explore the feasibility of enhanced recovery after surgery (ERAS) in treatment of children with congenital choledochal cyst. Methods: One hundred and thirty children with congenital choledochal cysts admitted in the Children's Hospital of Zhejiang University from June 2017 to June 2019 were divided into ERAS group (n=65) and control group (n=65) according to admission order. The intestinal tract condition during operation, time of operation, surgical results, time for eating after operation, abdominal drainage after operation, length of hospital stay after operation, total hospital expenses and complications were compared between two groups. Results: Compared with the control group, the satisfaction of intestinal operation field, recovery of gastrointestinal function after operation, time required for the volume of peritoneal drainage fluid to be less than 50 mL, time of abdominal drainage tube removal, and length of hospital stay were all improved in ERAS group (P < 0.05 or P < 0.01).ERAS group had more peritoneal effusion after removal of abdominal drainage tube (P < 0.01), but the incidence of edema after operation was lower (P < 0.05). The satisfaction of parents in the two groups was similar, but the cooperation of parents in the ERAS group was improved (P < 0.05) and the total cost of hospitalization was reduced (P < 0.01). Conclusion: ERAS has advantages over the traditional scheme and can be used in the clinical treatment of children with congenital choledochal cyst.

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Genetic study of a family of neuronal ceroid lipofuscinosis caused by a heterozygous mutation of CLN6 gene
LOU Tie,HUANG Yingzhi,DONG Minyue
J Zhejiang Univ (Med Sci)    2019, 48 (4): 373-377.   DOI: 10.3785/j.issn.1008-9292.2019.08.04
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Objective: To analyze the genetic cause of a family with autosomal recessive neuronal ceroid lipofuscinoses (NCL). Methods: The proband was screened for mutations within the coding region of the candidate genes through high-throughput targeted sequencing. Potential causative mutations were verified by PCR and Sanger sequencing in the proband and his parents. RT-PCR and TA clone sequencing were performed to investigate whether the mRNAs were abnormally spliced. Results: The sequencing results revealed compound heterozygous mutations of CLN6:c.486+2T>C and c.486+4A>T, which were respectively inherited from his parents. RT-PCR and TA cloning sequencing suggested that the mRNAs were abnormally spliced in two forms due to both mutations. Conclusions: The compound heterozygous mutations of CLN6:c.486+2T>C and c.486+4A>T are possibly the genetic causes of the NCL family. Detection of the novel mutation has extended mutation spectrum of CLN6.

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Application of Logistic regression and decision tree analysis in prediction of acute myocardial infarction events
ZHANG Sheng,HU Zhenjie,YE Lu,ZHENG Yaru
J Zhejiang Univ (Med Sci)    2019, 48 (6): 594-602.   DOI: 10.3785/j.issn.1008-9292.2019.12.02
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Objective: To evaluate the application of decision tree method and Logistic regression in the prediction of acute myocardial infarction (AMI) events. Methods: The clinical data of 295 patients, who underwent coronary angiography due to angina or chest pain with unidentified causes in Zhejiang provincial People's Hospital during October 2018 and April 2019, were retrospectively analyzed. Fifty five patients were identified as AMI. Logistic regression and decision tree methods were performed to establish predictive models for the occurrence of AMI, respectively; and the models created by decision tree analysis were divided into Logistic regression-independent model (Tree 1) and Logistic regression-dependent model (Tree 2). The performance of Logistic regression and decision tree models were compared using the area under the receiver operating characteristic (ROC) curve. Results: Logistic regression analysis showed that history of coronary artery disease, multi-vessel coronary artery disease, statin use and apolipoprotein (ApoA1) level were independent influencing factors of AMI events (all P < 0.05). Logistic regression-independent decision tree model (Tree 1) showed that multi-vessel coronary artery disease was the root node, and history of coronary artery disease, ApoA1 level (the cutoff value:1.314 g/L) and anti-platelet drug use were descendant nodes. In Logistic regression-dependent decision tree model (Tree 2), multi-vessel coronary artery disease was still the root node, but only followed by two descendant nodes including history of coronary artery disease and ApoA1 level. The area under the curve (AUC) of ROC of Logistic regression model was 0.826, and AUCs of decision tree models were 0.765 and 0.726, respectively. AUC of Logistic regression model was significantly higher than that of Tree 2 (95% CI=0.041-0.145, Z=3.534, P < 0.001), but was not higher than that of Tree 1 (95% CI=-0.014-0.121, Z=-1.173, P>0.05). Conclusion: The predictive value for AMI event was comparable between Logistic regression-independent decision tree model and Logistic regression model, implying the data mining methods are feasible and effective in AMI prevention and control.

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Effects of resveratrol on aging of mesenchymal stem cells and its mechanism
ZHANG Dayong,LIN Jiuzhou,WANG Yayan,XU Shan,LUO Chengzhuan,CAI Jiaye,JIANG Xuefan,PAN Jianping
J Zhejiang Univ (Med Sci)    2019, 48 (6): 617-624.   DOI: 10.3785/j.issn.1008-9292.2019.12.05
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Objective: To investigate the effects of resveratrol (Res) on aging of marrow mesenchymal stem cells (MSCs), and to explore its mechanism. Methods: MSCs were isolated from young SD rats and cultured in vitro. The optimal D-gal concentration for induction of MSCs senescence was determined. Then MSCs were randomly divided into four groups, namely the control group, 10μmol/L, 50μmol/L and 100μmol/L Res groups. After the cells were treated with different concentration of Res for 48 h, the senescence-associated changes were examined with senescence-associated-β-galactosidase (SA-β-gal) staining; the expression of p53, p16 and γ-H2AX was evaluated by Western blot. The total active oxygen species (ROS) level was determined by flow cytometry with DCFH-DA staining. In order to assess the effect of Res on the mitochondrial function, MitoSox Red staining was used to detect mitochondrial ROS levels in each group, mitochondrial membrane potential was detected by JC-1 assay, mPTP method was used to detect mitochondrial membrane channel opening level, and Western blot was used to detect the expression level of cytoplasmic cytochrome C (Cyt-C). Results: D-gal 10 and 50 g/L significantly increased the number of SA-β-gal positive cells and the level of mitochondrial ROS (all P < 0.01). Therefore, 10 g/L D-gal was used to induce the senescence of MSCs in subsequent experiment. Compared with the control group, the number of SA-β-gal positive cells in Res groups significantly decreased (all P < 0.01), the expression of p53, p16 and γ-H2AX decreased, and the total and mitochondrial ROS level also decreased (all P < 0.01). Moreover, mitochondrial membrane potential, open level of mitochondrial membrane channels and the levels of cytoplasm Cyt-C in the Res treatment groups decreased compared with the control group (P < 0.05 or P < 0.01). Conclusion: Resveratrol can protect the mitochondrial function of MSCs, and effectively delay the MSC senescence.

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Glucosides of chaenomeles speciosa attenuate ischemia/reperfusion-induced brain injury by regulating NF-κB P65/TNF-α in mouse model
MA Jing, HE Wenlong, GAO Chongyang, YU Ruiyun, XUE Peng, NIU Yongchao
J Zhejiang Univ (Med Sci)    2019, 48 (3): 289-295.   DOI: 10.3785/j.issn.1008-9292.2019.06.09
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Objective: To investigate the effect and mechanism of glucosides of chaenomeles speciosa (GCS) on ischemia/reperfusion-induced brain injury in mouse model. Methods: Fifty 8-week C57BL/C mice were randomly divided into five groups with 10 in each group:sham group, model group, GCS 30 mg/kg group, GCS 60 mg/kg group and GCS 90 mg/kg group, and the GCS was administrated by gavage (once a day) for 14 d. HE staining was performed to investigate the cell morphology; the Zea-Longa scores were measured for neurological activity; TUNEL staining was performed to investigate the cell apoptosis; ELISA was used to detected the oxidative stress and inflammation; Western Blot was performed to investigate the key pathway and neurological functional molecules. Results: Compared with the sham group, the brain tissues in model group were seriously damaged, presenting severe cell apoptosis, oxidative stress and inflammation, associated with increased NF-κB P65 and TNF-α levels as well as decreased myelin associate glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp)levels (all P<0.01). Compared with the model group, the brain tissues in GCS groups were ameliorated, and cell apoptosis, oxidative stress and inflammation were inhibited, associated with decreased NF-κB P65 and TNF-α levels as well as increased MAG and OMgp levels (all P<0.01), which were more markedly in GCS 60 mg/kg group. Conclusion: GCS can inhibit the NF-κB P65 and TNF-α, reduce the oxidative stress and inflammation, decrease the cell apoptosis in mouse ischemia/reperfusion-induced brain injury model, and 60 mg/kg GCS may be the optimal dose.

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Effect of trimetazidine on cardiac function and exercise tolerance in hypertension patients with diabetic
YE Pingxian, YE Pingzhen, HE Jinping
J Zhejiang Univ (Med Sci)    2019, 48 (3): 282-288.   DOI: 10.3785/j.issn.1008-9292.2019.06.08
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Objective: To determine the effect of trimetazidine on cardiac function and exercise tolerance in primary hypertension patients with type 2 diabetic. Methods: In this randomized, double-blind, placebo-controlled prospective study, 60 primary hypertensive patients with diabetic were equally assigned into two groups, patients received trimetazidine (20 mg, 3 times a day) or placebo for 1 year. Echocardiography, cardiopulmonary exercise testing were performed; and the plasma N terminal pro B type natriuretic peptide (NT-ProBNP), hr-CRP, TNF-α, angiotensin Ⅱ and endothelin concentration were determined before and after treatment. Results: In trimetazidine group, the left ventricular mass index, the mitral flow velocity E wave to A wave ratio (E/A), the peak early diastolic velocity (VE) to late diastolic velocity (VA) ratio (VE/VA) and the peak systolic velocity (Vs) were significantly improved, the plasma NT-ProBNP level was significantly decreased, and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were significantly increased (all P < 0.05); plasma concentration of hr-CRP, TNF-α, angiotensin Ⅱ and endothelin were significantly reduced after trimetazidine treatment, compared with baseline (all P < 0.05) and with placebo (all P < 0.05). There were no significant differences in any of above parameters after treatment in placebo group (all P>0.05). No severe adverse reaction was observed in both groups. Conclusion: For patients with both hypertension and diabetes, trimetazidine can improve cardiac function and increase exercise tolerance.

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Outcome of re-pregnancy in women with uterine artery embolization for postpartum hemorrhage
LIN Xiaoxiao,SUN Daifei,FU Jun,ZHONG Huizhen
J Zhejiang Univ (Med Sci)    2019, 48 (5): 540-545.   DOI: 10.3785/j.issn.1008-9292.2019.10.12
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Objective: To evaluate the outcome of re-pregnancy in women with uterine artery embolization(UAE)for postpartum hemorrhage(PPH). Methods: Clinical data of 117 pregnant women with previous PPH admitted in Ningbo Women and Children's Hospital from January 2010 to January 2016 were retrospectively analyzed. Among them 40 cases were treated with UAE (UAE group) and 77 cases were not treated with UAE (control group). The outcomes of re-pregnancy were followed up and compared between two groups. Results: There were significant differences in the incidence of induced abortion in early pregnancy and cesarean scars pregnancy (CSP) between the two groups (P < 0.05 or P < 0.01). In the UAE group, the incidence of PPH, placental accretion and hysterectomy rate was significantly higher than that of control group (P < 0.05 or P < 0.01). Multivariate analysis showed that UAE was independent risk factor for CSP, placenta accretion, PPH and hystere-ctomy (P < 0.05 or P < 0.01). Conclusions: The overall fertility and re-pregnant outcomes in women with previous UAE for PPH are favorable. However, the risk of CSP, placenta accretion and associated recurrence of PPH and hysterectomy is higher in women receiving UAE during subsequent pregnancy.

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Analysis of medication characteristics of traditional Chinese medicine in treating COVID-19 based on data mining
FAN Tiantian,CHEN Yongcan,BAI Yu,MA Fengqi,WANG Hengcang,YANG Yiping,CHEN Jinxu,LIN Yuqi
J Zhejiang Univ (Med Sci)    2020, 49 (2): 260-269.   DOI: 10.3785/j.issn.1008-9292.2020.03.14
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Objective: To analysis the medication characteristics of the prescriptions issued via open channel by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine in treating coronavirus disease 2019 (COVID-19). Methods: We collected the data of traditional Chinese medicine related to treatment plans published by the National and Provincial Health Committee and the State Administration of Traditional Chinese Medicine from the start of COVID-19 outbreak to February 19, 2020. The frequency analysis, cluster analysis and association analysis were performed. Results: The study collected 4 national and 34 regional prevention and treatment plans, 578 items, 84 traditional Chinese formulations, 60 Chinese patent medicines, and 230 Chinese herbs. The high frequently used herbs were Liquorice, Scutellariabaicalensis, Semen armeniacaeamarae, and Gypsum. The commonly used traditional formulations included Maxing Shigan decoction, Yin Qiao powder, and Xuanbai Chengqi decoction. The Chinese patent drugs included Angong Niuhuang pill, Xuebijing injection, and Lianhua Qingwen capsule. The most common paired medications were Ephedra and Semen armeniacaeamarae, Fructusforsythiae and Liquorice. Two core combinations and one novel formula were discovered in the study. Conclusions: Yin Qiao powder and Huopo Xialing decoction are the basic formulations for Weifen syndrome of COVID-19. In addition, Maxing Shigan decoction, Liang Ge powder, Qingwen Baidu decoction and Da Yuan decoction are the basic formulations for Qifen syndrome of COVID-19. The main medication characteristics are clearing heat, entilating lung, removing toxicity and removing turbidity. It shows that removing toxicity and eliminating evil are the prescription thought in treating epidemic disease of traditional Chinese medicine.

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Association of maternal age with fetal sex chromosome aneuploidies
LEI Yu,DONG Minyue
J Zhejiang Univ (Med Sci)    2019, 48 (4): 409-413.   DOI: 10.3785/j.issn.1008-9292.2019.08.10
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Objective: To analyze the impact of maternal age on sex chromosome aneuploidies (SCA). Methods: Pregnant women who had karyotype analysis of amniotic fluid in Women's Hospital, Zhejiang University School of Medicine from January 2014 to July 2018 were recruited. The association of the maternal age with fetal SCAs was analyzed. Results: The incidence of 45, X in age group >34- < 38 was lower than that of ≤ 28 age group (P < 0.05). For the incidences of total sex chromosome trisomy and 47, XXY in age groups 34- < 38 and ≥38 were higher than age groups ≤28 and >28-34 (P < 0.05 or P < 0.01). The incidence of 47, XXX in age group ≥ 38 was higher than that in age group>28-34 (P < 0.05). However, the incidence of 47, XYY had no differences among the four groups (P>0.05). After excluding the high risk of sex chromosome abnormalities by non-invasive prenatal testing (NIPT), we found that for 45, X, the incidences of two groups with advanced age were lower than that of ≤ 28 year-old group of age group (P < 0.05 or P < 0.01), and incidence in age group >34- < 38 was also lower than that in age group >28-34 (P < 0.05). The other results were consistent with those without excluding the high risk of sex chromosome abnormalities by NIPT. Conclusion: Advanced age decreases the incidence of 45, X, but increases the risk of sex chromosome trisomy, especially 47, XXX and 47, XXY.

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Noninvasive prenatal screening for twin pregnancy: an analysis of 2057 cases
YIN Yixuan,ZHU Hui,QIAN Yeqing,JIN Jinglei,MEI Jin,DONG Minyue
J Zhejiang Univ (Med Sci)    2019, 48 (4): 403-408.   DOI: 10.3785/j.issn.1008-9292.2019.08.09
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Objective: To analyze the results of noninvasive prenatal screening (NIPS) for fetal chromosome aneuploidy in twin pregnancy. Methods: A total of 2057 women with twin-pregnancy between 12-26+6 weeks were recruited from Women's Hospital, Zhejiang University School of Medicine, Hangzhou Municipal Women's Hospital and Jiaxing Maternal and Child Health Hospital during February 2015 to August 2018. The cell-free DNA was extracted from the peripheral blood sample for DNA library, and non-invasive prenatal testing (NIPT) was performed by high-throughput sequencing technique. The fetal karyotype analysis or neonatal karyotype analysis was performed in pregnant women with fetal chromosome aneuploidy, and all subjects were followed up. The efficiency of NIPS testing for twin aneuploidy was calculated. Results: NIPS revealed chromosome abnormalities in 11 out of 2057 twin pregnant women, 9 cases were confirmed chromosome abnormalities, 2 cases were normal and no false negative cases. In this screening, the detection rate, sensitivity, specificity, positive predictive value, false positive rate of NIPS were 100.00%, 100.00%, 99.90%, 81.82%, 0.10%. Those were 100.00%, 100.00%, 99.95%, 87.50% and 0.05% for trisomy 21, 100.00%, 100.00%, 100.00%, 100.00%, 0.00% for trisomy18, and the specificity and false positive rate for trisomy13 were 99.95% and 0.05%, respectively. Conclusion: NIPS can detect fetal chromosomal aneuploidy rapidly and accurately in twin pregnancies, and it is of value in clinical application.

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