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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
Abstract   HTML PDF (1044KB) ( 34954 )  

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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Journal of ZheJiang University(Medical Science)    0, (): 1-.  
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Establishment of chondrocyte degeneration model in vitro by rat serum
WANG Xiao-jun, ZHANG Hao, ZHAN Hong-sheng, DING Dao-fang
Journal of ZheJiang University(Medical Science)    2015, 44 (3): 308-314.   DOI: 10.3785/j.issn.1008-9292.2015.05.11
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Objective: To establish a model of chondrocyte degeneration in vitro. Methods: Chondrocytes were isolated from articular cartilages of newly born SD rats by digestion with typeⅡ collagenase. The chondrocytes were cultured with H-DMEM medium containing 10%FBS, 50 ng/mL IL-1β+10%FBS, 2.5% rat serum and 5% rat serum, respectively; and the chondrocytes at passage one were used in the experiments. The morphology changes were investigated under phase contrast microscope after chondrocytes were treated with rat serum and IL-1β. Proliferation of chondrocytes was detected by MTT method. The protein expression levels of PCNA, typeⅡ collagen and MMP-13 were examined by Western blotting. The levels of ADAMTS5, MMP-9, Aggrecan and SOX-9 mRNA were detected by real-time PCR. Results: The cell morphology was changed from polygon to spindle in both rat serum groups and IL-1β group, and the proliferation of chondrocytes in these groups was much higher than that in control group. The results showed that the expression levels of typeⅡ collagen, Aggrecan and SOX-9 decreased while the expression levels of MMP-13, MMP-9 and ADMATS5 were up-regulated in rat serum and IL-1β-treated groups compared with control group. Conclusion: The results indicate that rat serum can induce chondrocyte degeneration and may be used for osteoarthritis model in vitro.

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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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Sodium cromoglycate attenuates experimental endometriosis in rats by regulating mast cells
ZHU Li-bo, LIN Kai-qing, ZHANG Xin-mei, LIN Jun
Journal of ZheJiang University(Medical Science)    2015, 44 (3): 278-284.   DOI: 10.3785/j.issn.1008-9292.2015.05.07
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Objective: To investigate the effect of sodium cromoglycate on experimental endometriosis in rats. Methods: Endometriosis model was established in 36 unpregnant female SD rats by transplanting autologous fragments of endometrium to the inner surface of the abdominal wall. The endometriotic lesions were measured by a second laparotomy 2 weeks after surgery. Then the rats were randomly divided into four groups(n=8 in each group) to receive intraperitoneal injection of different doses of sodium cromoglycate for 2 weeks: high-dose group(20 mg·kg-1·d-1); low-dose group(10 mg·kg-1·d-1); the negative control group and the blank control group. The animals were sacrificed and the size of the lesions were measured. The endometriosis model of SD rats was identified by HE staining and immunohistochemical staining of keratin and vimentin. The total number of mast cells and their degranulation were measured by Toluidine blue staining; the concentrations of TNF-α in serum were measured by enzyme linked immunosorbent assay; the concentrations of estradiol in serum were measured by enzyme immunoassay; the expression of tryptase and nerve growth factor(NGF) were measured by immunohistochemical staining. Results: The number of activated mast cells(MC) by Toluidine blue staining in high-dose group was significantly lower than that in negative control group(P<0.05), and its ratio of degranulation/total number of MC was significantly lower than that in negative control group or blank control group(P<0.05). The serum TNF-α levels and tryptase expression in tissues in high-dose group were significantly lower than those in negative control group or blank control group(P<0.05). However, no significant difference in the size of endometriotic lesions and expression of NGF was found among groups(P>0.05). Conclusion: Sodium cromoglycate can stabilize mast cells from degranulation, which may relieve the clinical symptoms of endometriosis by reducing TNF-α and tryptase levels.

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Bioinformatic analysis of pygo1 gene in Homo sapiens
HAO Ai-ping
Journal of ZheJiang University(Medical Science)    2014, 43 (4): 453-457.   DOI: 10.3785/j.issn.1008-9292.2014.06.002
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Objective: To analyze the structure and function of PYGO1 protein with bioinformatics. Methods: The bioinformatic methods and tools were used to analyze the physical and chemical properties, transmembrane region, hydrophobicity and hyrdrophilicity, secondary structure and functional category of PYGO1 protein. Results: The bioinformatic analysis revealed that proline content was the highest of all amino acid residues in PYGO1 protein; the molecular formula was C1943H2937N577O635S18 with a relative molecular mass of 45; and the theoretical isoelectric point was 6.38. The analysis also demonstrated that PYGO1 was a hydrophilic and non-transmembrane protein; its main component was alpha-helix and random coil; it contained a plant homeodomain. Conclusion: Human pygo1 gene may act as a transcription regulation factor to regulate the heart development and the progress of heart diseases.
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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
Abstract   HTML PDF (2555KB) ( 1584 )  

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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Serum sCD44v6 and sE-cadherin levels in patients with esophageal squamous cell carcinoma
Journal of ZheJiang University(Medical Science)    2012, 41 (3): 305-309.   DOI: 10.3785/j.issn.1008-9292.2012.03.012
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Objective: To investigate the serum levels of sCD44v6 and sE-cadherin (sE-cad) in patients with esophageal squamous cell carcinoma.
Methods: The serum samples were collected from 65 cases of esophageal squamous cell carcinoma,32 cases of erosive esophagitis and 35 healthy subjects.Serum sCD44v6 and sE-cad levels were measured by enzyme linked immunosorbent assay (ELISA).
Results: The mean levels of serum sCD44v6 and sE-cad in esophageal squamous cell carcinoma patients were significantly higher than those of erosive esophagitis patients and normal controls (both P<0.05).There was no significant difference in serum sCD44v6 and sE-cad levels between erosive esophagitis patients normal controls (P=0.566 and P=0.708,respectively).Serum sCD44v6 and sE-cad levels of esophageal cancer patients were not correlated with their clinicopathological features.Serum sCD44v6 level is not correlated with sE-cad level in squamous cell carcinoma patients(P=0.651).
Conclusion: Serum sCD44v6 and sE-cad might be a potential marker for screening of esophageal squamous cell carcinoma.
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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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Current status and prospects of tumor immunotherapy
Journal of ZheJiang University(Medical Science)    2010, 39 (4): 339-344.   DOI: 10.3785/j.issn.1008-9292.2010.04.001
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Research progress in toxicology of molecular targeted anticancer drugs
LOU Xiao-e, CHEN Min, YANG Bo
Journal of ZheJiang University(Medical Science)    2015, 44 (5): 473-478.   DOI: 10.3785/j.issn.1008-9292.2015.09.01
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Objective:Drug therapy is essential for cancer treatment. The molecular targeted anticancer drugs develop rapidly in recent years, since the effectiveness of traditional chemotherapy is unsatisfactory and the adverse reactions are high. However, molecular targeted anticancer drugs would damage the function of heart, liver or lung, and may cause adverse effects such as hand-foot syndrome, which restrains their clinical application. Therefore, it is critical for pharmaceutical toxicology to study the toxicity, the related mechanisms and the preventive measures of molecular targeted anticancer drugs.

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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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The pathogenesis of Ebola virus disease
LI Lan-juan
Journal of ZheJiang University(Medical Science)    2015, 44 (1): 1-8.   DOI: 10.3785/j.issn.1008-9292.2015.01.001
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Echocardiographic diagnosis of partial anomalous pulmonary venous connection
Journal of ZheJiang University(Medical Science)    2012, 41 (4): 450-452.   DOI: 10.3785/j.issn.1008-9292.2012.04.016
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Objective: To investigate partial anomalous pulmonary venous connection (PAPVC) with echocardiography.
Methods: The right ventricular volume overload was detected by routine echocardiography in 37 child patients, who underwent further echocardiography to find the abnormal locations of pulmonary vein opening at superior, inferior vena cava and right atrium. The ultrasound results were compared with surgical findings.
Results: In 30 patients the ultrasound diagnosis was consistent with surgery results, 7 were misdiagnosed by ultrasound with a detective rate of 81.1%. All 37 PAPVC patients presented varying degrees of right heart enlargement; PAPVC combined with atrial septal defect (ASD) was found in 34 cases.
Conclusions: The possibility of PAPVC should be considered when unexplained right heart volume overload was detected by echocardiography. Superior, inferior vena cava and right atrium should be inspected when the pulmonary veins were not seen in echocardiography.
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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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Guidelines for diagnosis and management of aneurysmal subarachnoid hemorrhage: top issues and prospective
ZHANG Jian-min
Journal of ZheJiang University(Medical Science)    2015, 44 (4): 357-360.   DOI: 10.3785/j.issn.1008-9292.2015.07.01
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Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is a kind of hemorrhagic stroke with high mortality and morbidity. Although the preoperative diagnosis, surgical clipping, endovascular treatment, and intensive care have progressed in recent years, the overall prognosis of aSAH patients remains poor. In 2011, the Neurocritical Care Society organized an international, multidisciplinary consensus conference addressed the critical care management of SAH. In 2012, the American Stroke Association (AHA) updated the guidelines of diagnosis and treatment of aSAH published in 2009. In 2013, European Stroke Organization established the guideline for management of intracranial aneurysms and SAH. In 2014, the Korean Society of Interventional Neuroradiology (KSIN) published clinical practice guideline for the management of ruptured and unruptured aneurysms. The guideline for diagnosis and management of aSAH for Chinese patients has been drafted in this year. Thus, the diagnosis and management of aSAH is a hot topic in neurosurgery. This editorial summarizes the above mentioned guidelines and focuses on the progress and update of these guidelines. In this article we discuss the advantage and disadvantage of those imaging techniques, the pros and cons of surgical clipping and endovascular treatment.

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HIF-1 signal pathway in cellular response to hypoxia
Journal of ZheJiang University(Medical Science)    2011, 40 (5): 559-566.   DOI: 10.3785/j.issn.1008-9292.2011.05.017
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HIF-1 is composed of HIF-1α and HIF-1β subunits. It promotes target genes transcription under hypoxia and plays essential roles in cell development, physiological adaptations, and pathological processes. In the past 10 years, the research on signaling pathways of HIF-1 in response to cell hypoxia stress, especially on HIF-1α-mediated gene transcription has made great progress.
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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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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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Radiological study on rat lumbar vertebral semidislocation model
CHEN Bo, LIN Xun, ZHANG Min, ZHAN Hong-sheng, SHI Yin-yu
Journal of ZheJiang University(Medical Science)    2015, 44 (2): 117-123.   DOI: 10.3785/j.issn.1008-9292.2015.03.001
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Objective: To investigate the impact of fixation in part lumbar segment on rat model with radiography. Methods: One hundred and twenty SPF male SD rats (350~450g) were randomly divided into simple fixation group (SF group), rotary fixation group (RF group) and sham-operation group (Sham group). The external link fixation system was implanted into the L4-L6 of SF group and RF group rats. In RF group, L5 spinous process of rats was rotated to the right side, making the L4, L6 and L5 spinous process not in a straight line. In SF group, the external link fixation system was implanted simply and not rotated. The anterior and posterior diameter in the intervertebral space and the distance between spinous processes were examined 1, 4, 8 and 12 weeks after fixation.Results: The anterior diameter in the intervertebral space between L3-L4, L4-L5, L5-L6, and L6-S1 of SF groups 4 weeks after fixation were 28.11±3.94, 25.73±4.70, 29.51±6.34 and 34.97±4.65 pixels; the posterior diameter were 7.39±1.63, 6.65±1.76, 7.02±1.52 and 9.62±2.50 pixels; the distance between spinous process were 39.33±11.74, 14.11±5.75, 21.32±6.84 and 77.43±13.69 pixels, the values were less than those in Sham groups (P<0.05). The anterior and posterior diameter in the intervertebral space and the distance between spinous process of SF groups 8 and 12 weeks after fixation continuously decreased compared with Sham group rats (P<0.05). The results of RF groups were consistent with the measurement of SF groups, the anterior and posterior diameter in the intervertebral space and the distance between spinous process of RF group rats were less than those in Sham groups 4, 8 and 12 weeks after fixation (P<0.05). Osteophyte formation was observed in SF and RF groups 8 weeks after fixation. Conclusion: The fixation in part lumbar segment can result in the decrease of intervertebral space and the formation of osteophytes.

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Prevention of urethral stricture after transurethral vaporesection of prostate by adjustable urethral tractor
Journal of ZheJiang University(Medical Science)    2006, 35 (5): 564-567.   DOI: 10.3785/j.issn.1008-9292.2006.05.019
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Expression and distribution of cysteinyl leukotriene receptors CysLT1R and CysLT2R,and GPR17 in brain of Parkinson disease model mice
Journal of ZheJiang University(Medical Science)    2013, 42 (1): 52-.   DOI: 10.3785/j.issn.1008-9292.2013.01.009
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Objective: To examine the spatiotemporal profiles and localization of CysLT1R,CysLT2R and GPR17 in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson disease (PD).
Methods: PD model was induced by subcutaneous injection of MPTP (25 mg/kg) for 5 d in adult male C57BL/6 mice.At d10 after MPTP injection,the expression and cellular localization of CysLT1R,CysLT2R and GPR17 in the substantia nigra were detected by immunohistochemistry and immunofluorescence.
Results: CysLT1R,CysLT2R and GPR17 were normally localized in TH-positive dopaminergic neurons and microglia,while CysLT2R was also expressed in astrocytes.In dopaminergic neurons,approximately 91% co-expressed GPR17,77% co-expressed CysLT1R and 52% co-expressed CysLT2R.Compared with the control group,TH-positive cells in the substantia nigra were significantly reduced in PD mice.CysLT1R,CysLT2R and GPR17-positive cells were significantly reduced; and CysLT1R,CysLT2R,GPR17-positive dopaminergic neurons were also significantly reduced in the PD group.In the striatum,both CysLT1R and GPR17 were normally expressed in neurons; whereas CysLT2R was expressed in astrocytes.In PD striatum,CysLT1R and GPR17-positive cells were decreased,but CysLT2R expression was significantly increased which mainly expressed in the proliferating astrocytes.
Conclusion: CysLT1R,CysLT2R and GPR17 may be involved in the MPTP-induced PD damage in mice.
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Optimization of genomic DNA extraction with magnetic bead- based semi-automatic system
Journal of ZheJiang University(Medical Science)    2012, 41 (3): 320-326.   DOI: 10.3785/j.issn.1008-9292.2012.03.015
Abstract   PDF (1082KB) ( 616 )  
Objective: To develop a rapid and effective method for genomic DNA extraction with magnetic bead-based semi-automatic system.
Methods: DNA was extracted from whole blood samples semi-automatically with nucleic acid automatic extraction system.The concentration and purity of samples was determined by UV-spectrophotometer.Orthogonal design was used to analyze the main effect of lysis time,blood volume,magnetic bead quantity and ethanol concentration on the DNA yield; also the 2-way interaction of these factors.
Results: Lysis time,blood volume,magnetic bead quantity and ethanol concentration were associated with DNA yield (P<0.05),but no interaction existed.DNA yield was higher under the condition with 15 min of lysis time,100 μl of blood volume,80 μl of magnetic beads and 80% of ethanol.A significant association was found between the magnetic bead quantity and DNA purity OD260/OD280 (P=0.008).Interaction of blood volume and lysis time also existed (P=0.013).DNA purity was better when the extracting condition was 40 μl of magnetic beads,15 min of lysis time and 100 μl of blood volume.Magnetic beads and ethanol concentration were associated with DNA purity OD260/OD230(P=0.017 and P<0.05),the result was better when magnetic beads was 40 μl and ethanol concentration was 80%.
Conclusion: The results indicate that the optimized conditions with 40 μl magnetic beads will generate higher quality of genomic DNA from the whole blood samples.
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Delayed lower extremity deep venous thrombosis after operation for osteofibrous dysplasia of the left femur: report of one case
HUANG Kai, XU Wei-xing, ZHANG Chun
Journal of ZheJiang University(Medical Science)    2014, 43 (3): 379-380.   DOI: 10.3785/j.issn.1008-9292.2014.04.002
Abstract   PDF (445KB) ( 601 )  

Lower extremity deep venous thrombosis (LDVT) is one of the most common complications in orthopedic surgery, and it often occurs in the first 24 h after operation. We report a case of delayed LDVT, which occurred on d 16 after operation for osteofibrous dysplasia on the left femur. Upon the diagnosis confirmed, thrombolysis and anticoagulation therapy was conducted. The symptoms disappeared 3 weeks later and lower limb vascular ultrasound examination showed no remnant thrombosis.

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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
Abstract   HTML PDF (1055KB) ( 584 )  

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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Fourier transform infrared spectroscopy in detection of breast cancer
CHEN Su-han,et al
Journal of ZheJiang University(Medical Science)    2014, 43 (4): 494-500.   DOI: 10.3785/j.issn.1008-9292.2014.07.010
Abstract   PDF (1052KB) ( 583 )  
Breast cancer is the most common cancer in women. Later diagnosis of the disease is the leading cause of poor prognosis. Fourier-transform infrared (FTIR) spectroscopy is a novel approach to provide information about the molecular components and metabolic conditions of human tissue; therefore it can detect the early changes caused by cancer cells prior to histological manifestation. FTIR-based diagnosis is rapid, simple and label free, which meets the requirements of an automated and patient-friendly technique. The current article gives an overview of the experimental techniques, data analysis methods and spectral signatures of breast cancer in FTIR-based diagnosis, summarizes the present challenges by focusing on the history of FTIR spectroscopy in breast cancer since 1990s, and highlights some investigations that give a perspective of FTIR-based diagnosis.
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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
Abstract   HTML PDF (2811KB) ( 577 )  

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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Progress in the effects of BRAP gene on cardiovascular diseases
LV Duo, ZHU Yi-min
J Zhejiang Univ (Med Sci)    2014, 43 (5): 602-.   DOI: 10.3785/j.issn.1008-9292.2014.09.019
Abstract   PDF (646KB) ( 558 )  

BRAP (BRCA1 associated protein) is one of BRCA1 (Breast cancer suppressor protein) associated cytoplasmic proteins. BRAP gene has been found to be associated with the risk of some cancers, and the associations between BRAP and cardiovascular diseases and metabolic syndrome is gradually attracting much attention. However, the explicit mechanisms involved remain to be fully elucidated. We reviewed the association between BRAP gene and cardiovascular diseases and metabolic syndromes and the biologic mechanisms in the regulation of metabolism, hoping to provide clues on our future researches.

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Effect of mTOR signaling pathway in epileptogenesis
Zeng Linghui,DING Meiping
Journal of ZheJiang University(Medical Science)    2013, 42 (6): 597-601.   DOI: 10.3785/j.issn.1008-9292.2013.06.001
Abstract   PDF (806KB) ( 555 )  
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Research on pediatric endocrine and inherited metabolic disorders in China
LIANG Li, XU Yanping
Journal of ZheJiang University(Medical Science)    2013, 42 (4): 369-.   DOI: 10.3785/j.issn.1008-9292.2013.04.001
Abstract   PDF (820KB) ( 551 )  
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Advances of chemokines in pathogenesis of psoriasis
Journal of ZheJiang University(Medical Science)    2002, 31 (6): 483-487.   DOI: 10.3785/j.issn.1008-9292.2002.06.023
Abstract   PDF (153KB) ( 542 )  
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The role of central cholinergic system in epilepsy
J Zhejiang Univ (Med Sci)    2017, 46 (1): 15-21.   DOI: 10.3785/j.issn.1008-9292.2017.02.03
Abstract   HTML PDF (1058KB) ( 542 )  

Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy. In the network level, cholinergic projection neurons as well as their interaction with other neurons may regulate the development of epilepsy, especially the cholinergic circuit from basal forebrain to hippocampus, while cholinergic local interneurons have not been reported to be associated with epilepsy. With the development of optogenetics and other techniques, dissect and regulate cholinergic related epilepsy circuit has become a hotspot of epilepsy research.

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Protective effect of grape seed proanthocyanidin on cultured RGC-5 cells against CoCl2-induced hypoxic injury
LIN Ka-na, LIN Mei-li, WEI Er-qing
Journal of ZheJiang University(Medical Science)    2015, 44 (1): 24-29.   DOI: 10.3785/j.issn.1008-9292.2015.01.004
Abstract   PDF (1827KB) ( 541 )  

Objective: To investigate the protective effects of grape seed proanthocyanidin extracts (GSPE) against CoCl2-induced hypoxic injury in cultured RGC-5 cells. Methods: CoCl2 (400 μmol/L) was used to induce hypoxic injury in cultured RGC-5 cells; the cells were pretreated with 0, 100, 200, 400 and 800μmol/L GSPE for 24h. The cell viability was assayed by MTT; the apoptosis was detected by Hoechst 33342 staining; the intracellular reactive oxygen species (ROS) was measured by H2DCFDA oxidative reaction. The mRNA expression of Bcl-2, caspase 9 and caspase 3 was determined by real-time PCR. Results: Compared to hypoxic control group, pretreatment with GSPE significantly increased viability of RGC-5 cells (P <0.001), reduced cell apoptosis (P <0.001) and intracellular ROS (P <0.001). In addition, GSPE significantly increased the mRNA expression of Bcl-2 (P <0.001) and decreased mRNA expression of caspase 9 (P <0.001) and caspase 3 (P <0.001) compared to hypoxic control group. Conclusion: GSPE may have a protective effect against CoCl2-induced hypoxic injury in cultured RGC-5 cells. The decrease of intercellular ROS, up-regulation of Bcl-2 and down-regulation of caspase 9 and caspase 3 may be involved in the mechanism of the protective effect of GSPE.

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Highlights of the third edition of Chinese guidelines for AIDS diagnosis and treatment(2015)
SUN Jian-jun, LU Hong-zhou
Journal of ZheJiang University(Medical Science)    2015, 44 (6): 597-602.   DOI: 10.3785/j.issn.1008-9292.2015.11.01
Abstract   PDF (900KB) ( 538 )  

The third edition of Chinese guidelines for AIDS diagnosis and treatment was launched in 2015 by AIDS Professional Group, Society of Infectious Diseases, Chinese Medical Association. New edition emphasizes the importance of timely initiation of anti-retroviral therapy(ART). Like other guidelines, this edition recommends that once the HIV infection is confirmed, the ART should be initiated timely. For patients with HIV and opportunistic infections, once the infections are under control, the ART should be initiated without delay. For AIDS patients complicated with tuberculosis whose CD4 cell counts are less than 200/μL, the ART should start within 2 weeks after the initiation of anti-tuberculosis treatment. In this guideline, the drugs with severe toxicities and poor tolerance are excluded, and new drugs are added such as rilpivrine (RPV) and atazanavir (ATV) because of less toxicity and higher HIV depression effect; and 3TC+TDF+EFV is recommended as the first line regimen. As for children with HIV infection, especially for those less than 5 years, once the infection is confirmed the ART should be initiated immediately. For the prevention of HIV mother to children transmission, new edition recommends that HIV-infected pregnant women start ART early and keep on ART all their lives.

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Meta-analysis study on risk factors of colorectal cancer
Journal of ZheJiang University(Medical Science)    2002, 31 (4): 254-258.   DOI: 10.3785/j.issn.1008-9292.2002.04.007
Abstract   PDF (229KB) ( 536 )  
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Clinical experience of high-flow nasal cannula oxygen therapy in severe COVID-19 patients
HE Guojun,HAN Yijiao,FANG Qiang,ZHOU Jianying,SHEN Jifang,LI Tong,PU Qibin,CHEN Aijun,QI Zhiyang,SUN Lijun,CAI Hongliu
J Zhejiang Univ (Med Sci)    2020, 49 (2): 232-239.   DOI: 10.3785/j.issn.1008-9292.2020.03.13
Abstract   HTML PDF (1077KB) ( 533 )  

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial flow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO2) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.

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Genetic imprinting and embryonic development
Journal of ZheJiang University(Medical Science)    2007, 36 (5): 509-514.   DOI: 10.3785/j.issn.1008-9292.2007.05.018
Abstract   PDF (272KB) ( 528 )  
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Epidemiologic study on current pubertal development in Chinese school-aged children
ZHU Mingqiang,FU Junfen,LIANG Li,GONG Cunxiu,XIONG Feng,LIU Geli,LUO Fei
Journal of ZheJiang University(Medical Science)    2013, 42 (4): 396-.   DOI: 10.3785/j.issn.1008-9292.2013.04.005
Abstract   PDF (993KB) ( 526 )  

Abstract]Objective: To survey the current status of pubertal development of Chinese children and to compare the precocious puberty prevalence of different regions. Methods: A cross-sectional epidemiological study was conducted on 18 707 children and adolescents aged 6~18 y with male/female ratio of 9 812/8 895 from 6 representative geographical areas in China,including Beijing,Tianjin,Hangzhou,Shanghai,Chongqing and Nanning.The height,weight,waist circumference (WC),hip circumference(HC) and sexual maturation states (Tanner stages:breast stages for girls and testicular volume for boys) of children and adolescents were measured.Probit analysis was used to calculate the median age and 95%confidence interval (CI) for onset of breast and testicular development.The prevalence of precocious puberty of different regions and BMI,waist circumference of different groups were compared. Results: Breast development before 8 y was observed in 2.91%of girls,and testicular volume 4 ml or more before 9 y was observed in 1.74% of boys.The median age of onset of Tanner stages 2 for breast development in girls was 9.69 y (95%CI:9.63~9.75); the median age of onset of puberty as indicated by Tanner stages 2 for testicular development in boys was 11.25 y (95%CI:11.19~11.30).The prevalence of precocious puberty (43 girls and 37 boys) was 0.43% (80/18 707).The prevalence of precocious puberty in northern region was higher than that in southwest region(0.736% vs 0.282%,P<0.05).There was no difference in onset age of precocious puberty in girls among three regions; but the onset age of precocious puberty in boys was earlier in east China [(7.4±0.28)y].The SD values of BMI and waist-to-hip ratio (W/H) in precocious puberty children were higher than those in the peer normal children.There was no difference in BMI,waist circumference and waist-to-hip ratio in the precocious puberty children among different regions. Conclusions: The current diagnostic criteria of precocious puberty are suitable for the children in the survey areas.The prevalence and the onset age of precocious puberty are various in different regions.A positive association between obesity and precocious puberty is found both in boys and girls.

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Research frontiers and trends of the analytical technology for Chinese medicine
Journal of ZheJiang University(Medical Science)    2012, 41 (1): 1-5.   DOI: 10.3785/j.issn.1008-9292.2012.01.001
Abstract   PDF (1159KB) ( 524 )  
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Age variations of head-face morphological traits of Hakka in Guangdong province
Journal of ZheJiang University(Medical Science)    2012, 41 (3): 250-258.   DOI: 10.3785/j.issn.1008-9292.2012.03.005
Abstract   PDF (1060KB) ( 522 )  
Objective: To investigate the age variations of head-face morphological traits of Hakka in Guangdong Province.
Methods: Thirty-eight physical indices of head and face of 671 Hakka adults (151 urban males,181 urban females,162 rural males and 177 rural females) from Meizhou city of Guangdong were investigated.Twelve physical indices of head and face were calculated and counted its indices distributions.The age changes of morphological traits of head and face were analyzed.
Results: With the age growing,the rate of eyefold of the upper eyelid was increased,and the Mongoloid fold decreased,the direction of eyeslits tended to level,nasal root height dropped,the zygomatic projection was more projected,the eye color turned to lighter,the upper red lips became thinner; medium-sized facial height,nasal height,upper lip skin height,physiognomic ear length,physiognomic ear breadth and breadth of alae nasi were decreased.The index of mouth breadth,morphological facia skin fold were positively correlated with the age.The index of minimum frontal breadth,face breadth,bigonial diameter,interocular breadth,external biocular breadth,lip height,thickness of lips and horizontal head circumference were negatively correlated with the age.With the age growing,morphological facial index and vertical cephalo-facial index was ascending.Moreover,length-height index of head,transverse frontoparietal index,zygomatico-frontal index and lip index were declining.
Conclusion: With the age growing,the head and face measurements,physical indices and the proportion of observed indices have changed in Hakka in Guangdong province.
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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
Abstract   HTML PDF (1758KB) ( 521 )  

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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Recent advances on dental implant system
Journal of ZheJiang University(Medical Science)    2012, 41 (3): 229-233.   DOI: 10.3785/j.issn.1008-9292.2012.03.001
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Impact of cerebral microbleeds on outcomes of acute ischemic stroke treated with intravenous thrombolysis
YAN Shen-qiang, WAN Jin-ping, GUO Yang, LOU Min
Journal of ZheJiang University(Medical Science)    2014, 43 (1): 20-27.   DOI: 10.3785/j.issn.1008-9292.2014.01.019
Abstract   PDF (789KB) ( 509 )  

Objective: To assess the impact of cerebral microbleeds (CMBs) on clinical outcomes in patients with acute ischemic stroke treated by intravenous thrombolysis.
Methods: The clinical data of 225 patients with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator therapy in the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to May 2013 were reviewed. The severity of CMBs and hemorrhagic transformation (HT) after thrombolytic therapy and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months were evaluated. Favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. Multivariate logistic-regression analysis and binary logistic-regression were used to determine independent risk factors of HT and favorable outcome.
Results: The mean age of 225 patients was (66.29±13.01) y, 73 (32.4%) patients were women, mean pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 11.40±5.89, and onset-to-needle time was (238.40±89.16) min. Totally, 522 CMBs were detected in 91 patients (36.1%). Postlytic radiological HT was found in 64 patients (28.4%), among which 43 (19.1%) were hemorrhagic infarction and 21 (9.3%) were parenchymal hematoma. Univariate analysis showed that patients with HT had higher NIHSS score and more incidence of atrial fibrillation and that patients with unfavorable outcome were older and had higher NIHSS score and more CMBs. Multivariate logistic regression analysis showed that multiple CMBs (≥3) was independently associated with parenchymal hematoma (OR=4.957, 95%CI 1.306-18.811, P=0.019), but not with hemorrhagic infarction (OR=1.204, 95%CI 0.386-3.754, P=0.749). Binary logistic regression analysis showed that multiple CMBs (≥3) was independently associated with unfavorable outcome (OR=3.496, 95%CI 1.381-8.849, P=0.008).
Conclusion: Multiple CMBs are correlated with parenchymal hematoma and unfavorable neurological outcome after thrombolytic therapy in patients with acute ischemic stroke.

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Somatic mutation and novel strategies for personalized targeting therapy
Journal of ZheJiang University(Medical Science)    2013, 42 (1): 1-.   DOI: 10.3785/j.issn.1008-9292.2013.01.001
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Bayesian statistics in spatial epidemiology
Journal of ZheJiang University(Medical Science)    2008, 37 (6): 642-647.   DOI: 10.3785/j.issn.1008-9292.2008.06.017
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Factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer in women with secondary infertility
LIU Yi-feng, YE Xiao-qun, ZHU Lin-ling, HUANG Yun, WU Yi-qing, XU Peng, KONG Yu-jia, LIU Feng, SUN Sai-jun, ZHANG Dan
Journal of ZheJiang University(Medical Science)    2015, 44 (3): 237-246.   DOI: 10.3785/j.issn.1008-9292.2015.05.01
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Objective: To investigate the factors related to clinical pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)in women with secondary infertility. Methods: The clinical, laboratory and follow-up data of 1129 cycles in 1099 patients with secondary infertility undergoing IVF-ET in Women's Hospital, Zhejiang University School of Medicine between July 2012 to July 2014 were retrospectively reviewed. The factors related to pregnancy outcomes were analyzed by univariate and logistic regression methods. The clinical pregnancy rates in women with different age and different number of embryos transferred were compared. The clinical outcomes of stimulation with gonadotropin releasing hormone(GnRH)agonist long protocol,GnRH agonist short protocol and GnH antagonist protocol were evaluated in secondary infertile patients aged≥40 years. Results: Among 1129 cycles, 376 cases(33.30%) had clinical pregnancy and 753 cases(66.70%)had no clinical pregnancy. There were significant differences in age, body mass index, basal follicle-stimulating hormone level, antral follicle number,paternal age and number of embryos transferred between pregnancy and no pregnancy groups(P<0.05); while only maternal age(OR=0.900,95%CI:0.873~0.928,P<0.001)and the number of embryos transferred(OR=2.248,95%CI:1.906~2.652,P<0.001)were the independent factors affecting the clinical pregnancy outcome of IVF-ET. There was no significant difference in clinical pregnancy rate between women aged 30~40 years with two embryos transferred and those aged<30 years with two or three embryos transferred(P>0.05). There were no significances in clinical pregnancy rate among women aged≥40 years using GnRH agonist long protocol,GnRH agonist short protocol and GnRH antagonist protocol for stimulation(P>0.05). Conclusion: Maternal age and number of embryos transferred have independent effect on IVF-ET clinical pregnancy outcome of secondary infertile women. We suggest that no more than two embryos should be transferred for women in their thirties to minimize the risk of multiple pregnancy while still having an acceptable pregnancy rate. The pregnancy rate of patients over 40 years decreases significantly, and there is no difference in pregnancy rate by using GnRH agonist long protocol,GnRH agonist short protocol or GnRH antagonist protocol.

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The role of ferroptosis in chronic diseases
CHEN Junyi,YANG Xiang,FANG Xuexian,WANG Fudi,MIN Junxia
J Zhejiang Univ (Med Sci)    2020, 49 (1): 44-57.   DOI: 10.3785/j.issn.1008-9292.2020.02.24
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Recently, ferroptosis, an iron-dependent novel type of cell death, has been characterized as an excessive accumulation of lipid peroxides and reactive oxygen species. Emerging studies demonstrate that ferroptosis not only plays an important role in the pathogenesis and progression of chronic diseases, but also functions differently in the different disease context. Notably, it is shown that activation of ferroptosis could potently inhibit tumor growth and increase sensitivity to chemotherapy and immunotherapy in various cancer settings. As a result, the development of more efficacious ferroptosis agonists remains the mainstay of ferroptosis-targeting strategy for cancer therapeutics. By contrast, in non-cancerous chronic diseases, including cardiovascular & cerebrovascular diseases and neurodegenerative diseases, ferroptosis functions as a risk factor to promote these diseases progression through triggering or accelerating tissue injury. As a matter of fact, blocking ferroptosis has been demonstrated to effectively prevent ischemia-reperfusion heart disease in preclinical animal models. Therefore, it is a promising field to develope potent ferroptosis inhibitors for preventing and treating cardiovascular & cerebrovascular diseases and neurodegenerative diseases. In this article, we summarize the most recent progress on ferroptosis in chronic diseases, and draw attention to the possible clinical impact of this recently emerged ferroptosis modalities.

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How to improve the diagnosis rate of early gastric cancer in China
ZOU Wen-bin, YANG Fan, LI Zhao-shen
Journal of ZheJiang University(Medical Science)    2015, 44 (1): 9-14,53.   DOI: 10.3785/j.issn.1008-9292.2015.01.002
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China has great burden of gastric cancer, and the diagnosis rate of early gastric cancer is relatively low (<10%). To perform screening, early endoscopic diagnosis and treatment of gastric cancer in high-risk population is a feasible and efficient way to change the current status. Therefore, the Chinese Society of Digestive Endoscopy recently issued Consensus on screening, "Endoscopic diagnosis and treatment of early gastric cancer screening in China". The consensus suggests a feasible and efficient strategy for early detection of gastric cancer: screening with non-invasive procedures, followed by intensive endoscopic examination for screened high-risk population. In this article, we also describe the current status, the causes, high-risk population and early diagnosis of gastric cancer in China; and review the new development of serology and endoscopic techniques for early diagnosis.

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Nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients
HONG Qing, ZHANG Li-san, CHEN Yin, HE Xu-dong, HU Xing-yue
Journal of ZheJiang University(Medical Science)    2015, 44 (1): 61-66.   DOI: 10.3785/j.issn.1008-9292.2015.01.010
Abstract   PDF (1120KB) ( 484 )  

Objective: To investigate the nutritional status in acute stage ischemic stroke and its relation to disease severity and prognosis of patients. Methods: Fifty patients with ischemic stroke were admitted in hospital within 48 h after onset. National Institute of Health stroke scale (NIHSS) was used to assess the severity of stroke. Physical index and laboratory index were measured on d1, d7 and d14 after admission. Physical index included body weight, body mass index, triceps skin folds, upper arm circumference and arm muscle circumference. Laboratory index included prealbumin, high sensitivity C-reactive protein (hs-CRP), complement C3 and cortisol. The severity of metabolic disturbance was expressed as the difference of biochemical indexes between the d7 and d1. All cases were followed up for 6 months. The prognosis of stroke was evaluated with modified Rankin (mRankin) scores. Results: No significant changes of physical indexes were found between d7 and d1. The levels of prealbumin and complement C3 on d7 after admission were significantly decreased compared to d1 (198.8 mg/L±20.3 mg/L vs 286.7 mg/L±23.8 mg/L and 0.6 g/L±0.1 g/L vs 1.0 g/L±0.1 g/L, respectively, both P <0.05). The levels of hs-CRP and cortisol at d7 were significantly increased compared to d1 (495.2 nmol/L±39.5 nmol/L vs 24.1 mg/L±5.2 mg/L and 396.4 nmol/L±41.3 nmol/L vs 5.1 mg/L±1.2 mg/L, respectively, both P <0.05). On d14 after admission hs-CRP(13.2 mg/L±4.5 mg/L) and cortisol levels (463.4 nmol/L±32.1 nmol/L) were still significantly higher than d1 (both P <0.05). However, there were no difference in prealbumin (259.2 mg/L±22.8 mg/L) and complement C3 (0.8 g/L±0.2 g/L) levels between d1 and d14 after admission. Correlation analysis revealed that the NIHSS scores and mRankin scores were correlated with nutrition metabolism disturbances (P <0.05). Conclusion: Nutrition metabolism disturbances in patients with acute ischemic stroke are related to the disease duration, the severity and prognosis of stroke.

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