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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) ( 38491 )  

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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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
Abstract   HTML PDF (1114KB) ( 6681 )  

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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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
Abstract   HTML PDF (4462KB) ( 2251 )  

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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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) ( 1984 )  

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
Abstract   HTML PDF (1074KB) ( 1648 )  

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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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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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
Abstract   HTML PDF (1025KB) ( 1242 )  

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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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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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) ( 1012 )  

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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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
Abstract   HTML PDF (12251KB) ( 968 )  

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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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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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) ( 905 )  

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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Progress on structural biology of voltage-gated ion channels
SONG Fangjun,GUO Hongtao
J Zhejiang Univ (Med Sci)    2019, 48 (1): 25-33.   DOI: 10.3785/j.issn.1008-9292.2019.02.05
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Ion channels mediate ion transport across membranes, and play vital roles in processes of matter exchange, energy transfer and signal transduction in living organisms. Recently, structural studies of ion channels have greatly advanced our understanding of their ion selectivity and gating mechanisms. Structural studies of voltage-gated potassium channels elucidate the structural basis for potassium selectivity and voltage-gating mechanism; structural studies of voltage-gated sodium channels reveal their slow and fast inactivation mechanisms; and structural studies of transient receptor potential (TRP) channels provide complex and diverse structures of TRP channels, and their ligand gating mechanisms. In the article we summarize recent progress on ion channel structural biology, and outlook the prospect of ion channel structural biology in the future.

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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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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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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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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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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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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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Effects of different cell lysis buffers on protein quantification
Journal of ZheJiang University(Medical Science)    2008, 37 (1): 45-50.   DOI: 10.3785/j.issn.1008-9292.2008.01.009
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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
Abstract   PDF (663KB) ( 713 )  

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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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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STUDY ON STRUCTURE OF POLYSTYRENE
Zheng Hao
Journal of ZheJiang University(Medical Science)    1996, 25 (4): 149-150.   DOI: 10.3785/j.issn.1008-9292.1996.04.002
Abstract   PDF (145KB) ( 681 )  

Polystyrene extracted from rare-earth coordination catalyst yields a white or yellow powder with the variation of polymerization conditions. The author studied the structure of polystyrene by IR、13C-NMR、1H-NMR. The white or yellow powder showed irregular structrue.-C-C(CH3C6H5)-C(CH3C6H5)-was found in the macromolecule chain of the yellow polystyrene.

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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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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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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
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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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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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Analysis of GFM1 gene mutations in a family with combined oxidative phosphorylation deficiency 1
SHEN Yaping,YAN Kai,DONG Minyue,YANG Rulai,HUANG Xinwen
J Zhejiang Univ (Med Sci)    2020, 49 (5): 574-580.   DOI: 10.3785/j.issn.1008-9292.2020.10.04
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Objective: To analyze the clinical phenotype and genetic characteristics of a family with combined oxidative phosphorylation deficiency 1 (COXPD-1). Methods: The whole exome sequencing was performed in parents of the proband; and the genetic defects were verified by Sanger sequencing technology in the dried blood spot of the proband, the amniotic fluid sample of the little brother of proband, and the peripheral blood of the parents. Results: Whole exome sequencing and Sanger validation showed compound heterozygous mutations of GFM1 gene c.688G>A(p.G230S) and c.1576C>T (p.R526X) in both the proband and her little brother, and the c.1576C>T of GFM1 variant was first reported. The two patients were died in early infancy, and presented with metabolic acidosis, high lactic acid, abnormal liver function, feeding difficulties, microcephaly, development retardation and epilepsy. Conclusion: GFM1 gene c.688G>A and c.1576C>T compound heterozygous mutations are the cause of this family of COXPD-1.

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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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ecent advances in metabolism-based drug-drug interactions
Journal of ZheJiang University(Medical Science)    2009, 38 (2): 215-224.   DOI: 10.3785/j.issn.1008-9292.2009.02.017
Abstract   PDF (468KB) ( 614 )  
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Effect of morphine chloride on contractility of small intestinal muscle in vitro or in vivo and its mechanisms
Journal of ZheJiang University(Medical Science)    2008, 37 (3): 271-275.   DOI: 10.3785/j.issn.1008-9292.2008.03.010
Abstract   PDF (288KB) ( 612 )  
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Efficacy of bismuth-based quadruple therapy as first-line treatment for helicobacter pylori infection
Journal of ZheJiang University(Medical Science)    2011, 40 (3): 327-331.   DOI: 10.3785/j.issn.1008-9292.2011.03.017
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Objective: To evaluate the efficacy of bismuth-based quadruple therapy as the first-line treatment for H.pylori infection.
Methods: A total of 136 patients with H.pylori related peptic ulcer or chronic gastritis were randomized into two groups: 67 patients in bismuth-based quadruple group received esomeprazole 20 mg,clarithromycin 0.5 g,amoxicillin 1.0 g,and bismuth potassium citrate 220 mg for 7 d; 69 patients in standard triple group received esomeprazole 20 mg,clarithromycin 0.5 g and amoxicillin 1.0 g for 7 d. Outcome of eradication therapy was assessed by 14C-UBT.On ITT and PP analysis,calculating the cost-effectiveness ratio (C/E) and the incremental cost-effectiveness ratio(△C/△E).
Results: On ITT and PP analysis,the eradication rates of the quadruple therapy group were 82.09% and 88.71%,and those of the triple therapy group were 66.67% and 73.02% (P<0.05).The cost-effectiveness ratio of two groups was 4.15 and 4.82; The incremental cost-effectiveness ratio of quadruple therapy group was 1.02 as against triple therapy group.
Conclusion: Compared to the standard triple therapy regimen,the bismuth-containing quadruple therapy regimen has higher eradication rate and cost-effectiveness,which can be recommended as the fist-line treatment for H.pylori infection.
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The role of central cholinergic system in epilepsy
WANG Ying,WANG Yi,CHEN Zhong
J Zhejiang Univ (Med Sci)    2017, 46 (1): 15-21.   DOI: 10.3785/j.issn.1008-9292.2017.02.03
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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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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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Progress on epigenetic regulation of iron homeostasis
DUAN Lingyan,YIN Xiangju,MENG Hong'en,FANG Xuexian,MIN Junxia,WANG Fudi
J Zhejiang Univ (Med Sci)    2020, 49 (1): 58-70.   DOI: 10.3785/j.issn.1008-9292.2020.02.25
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Iron homeostasis plays an important role for the maintenance of human health. It is known that iron metabolism is tightly regulated by several key genes, including divalent metal transport-1(DMT1), transferrin receptor 1(TFR1), transferrin receptor 2(TFR2), ferroportin(FPN), hepcidin(HAMP), hemojuvelin(HJV) and Ferritin H. Recently, it is reported that DNA methylation, histone acetylation, and microRNA (miRNA) epigenetically regulated iron homeostasis. Among these epigenetic regulators, DNA hypermethylation of the promoter region of FPN, TFR2, HAMP, HJV and bone morphogenetic protein 6 (BMP6) genes result in inhibitory effect on the expression of these iron-related gene. In addition, histone deacetylase (HADC) suppresses HAMP gene expression. On the contrary, HADC inhibitor upregulates HAMP gene expression. Additional reports showed that miRNA can also modulate iron absorption, transport, storage and utilization via downregulation of DMT1, FPN, TFR1, TFR2, Ferritin H and other genes. It is noteworthy that some key epigenetic regulatory enzymes, such as DNA demethylase TET2 and histone lysine demethylase JmjC KDMs, require iron for the enzymatic activities. In this review, we summarize the recent progress of DNA methylation, histone acetylation and miRNA in regulating iron metabolism and also discuss the future research directions.

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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
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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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Advances on Golgi glycoprotein 73 and its association with diseases
Journal of ZheJiang University(Medical Science)    2012, 41 (2): 215-221.   DOI: 10.3785/j.issn.1008-9292.2012.02.017
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Golgi glycoprotein 73(GP73) is a transmembrane glycoprotein residing in the cis-Golgi complex,which is strongly expressed in hepatocellular carcinoma (HCC) and secreted into the blood.It has been regarded as a promising serum tumor marker for the detection of HCC with higher sensitivity and specificity than AFP.GP73 is also significantly elevated in kidney cancer,prostate cancer,lung adenocarcinoma,esophageal cancer and seminomas; therefore,it would be helpful for the diagnosis of these diseases.However,the function of GP73 and the regulatory mechanism for its expression are unclear.In this article,the physical-chemical properties,the regulation of its expression,the relation with various cancers and the clinical applications of GP73 are reviewed.
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Trend of natural drug development
Journal of ZheJiang University(Medical Science)    2002, 31 (6): 479-482.   DOI: 10.3785/j.issn.1008-9292.2002.06.022
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Value of ~(18)F-FDG-PET/CT in diagnosis of classic fever of unknown origin
Journal of ZheJiang University(Medical Science)    2010, 39 (2): 174-180.   DOI: 10.3785/j.issn.1008-9292.2010.02.011
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Objective: To evaluate the application of ~(18)F-FDG PET/CT in diagnosis of classic fever of unknown origin. Methods: A total of 27 consecutive patients with classic fever of unknown origin (FUO) (19 men,8 women; aged 24-82 y) underwent ~(18)F-FDG PET/CT scans.The images were interpreted by visual inspection and semiquantitative analysis (standardized uptake value,SUV).Final diagnosis was based on histopathology or clinical follow-up. Results: The cause of FUO was confirmed by followed investigations in 21 of 27 cases after PET/CT scan,including 10 cases of infection,4 of noninfectious inflammation,4 of malignancies and 3 of miscellaneous disorders; and remaining 6 cases were still confirmed FUO.The sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 100.0;,83.3;,83.3;,100.0; and 96.3;,respectively. Conclusion: For patients with fever of unknown origin,~(18)F-FDG-PET/CT can be a sensitive,reliable imaging modality.It is suggested that ~(18)F-FDG-PET/CT should be considered earlier in detecting the causes of FUO,which is difficultly diagnosed by conventional modalities.

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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
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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
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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
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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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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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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
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Research advances on regulation of Pseudomonas aeruginosa biofilm formation and its therapeutic strategies
Journal of ZheJiang University(Medical Science)    2010, 39 (1): 103-108.   DOI: 10.3785/j.issn.1008-9292.2010.01.018
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Pseudomonas aeruginosa is an important pathogenic bacterium of nosocomial infections.The microbe easily produce biofilm which brings us much difficulties in clinical treatment.The formation processes of biofilm,including the stages of early bacteria planting,mushroom-like structure forming and extracellular matrix producing,are regulated by a series of molecules and genes.And quorum sensing system of the microbe is responsible for regulation of the whole process of biofilm formation.According to the process of biofilm formation and the mimitat associated regulation mechanism,several anti-biofilm therapeutic strategies have been applied in clinical medicine,and some novel drugs and methods are developed.

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Effect of salpingectomy on ovarian function
Journal of ZheJiang University(Medical Science)    2006, 35 (5): 555-559.   DOI: 10.3785/j.issn.1008-9292.2006.05.017
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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
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