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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) ( 26436 )  

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)    1982, 11 (S1): 4-5.   DOI: 10.3785/j.issn.1008-9292.1982.S1.006
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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) ( 2318 )  

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

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Study on the epidemic development of COVID-19 in Hubei province by a modified SEIR model
CAO Shengli,FENG Peihua,SHI Pengpeng
J Zhejiang Univ (Med Sci)    2020, 49 (2): 178-184.   DOI: 10.3785/j.issn.1008-9292.2020.02.05
Abstract   HTML PDF (3310KB) ( 996 )  

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) ( 1026 )  

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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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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Research progress on the role of TANK-binding kinase 1 in anti-virus innate immune response
WANG Xue, ZHANG Yuchuan, CHEN Wei
Journal of ZheJiang University(Medical Science)    2016, 45 (5): 550-557.   DOI: 10.3785/j.issn.1008-9292.2016.09.16
Abstract   PDF (1952KB) ( 224 )  

The innate immune response against viral infection is mainly relies on type I interferon, the production of which is mediated by TANK-binding kinase 1 (TBK1). It is revealed that the downstream TBK1 is activated by viral nucleic acid sensors RIG-I, cGAS and TLR3. The activity of TBK1 is complexly and precisely regulated by different type of protein modifications, including phosphorylation, ubiquitination and Sumolylation. This article focuses on the role of TBK1 in anti-viral innate immunity and the regulatory mechanism for the TBK1 activation.

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Comparison of seizure induced by different drugs in ICR Mice
HU Lin,ZHANG Huadan,CHEN Yatian,HUA Nan,ZENG Linghui
Journal of ZheJiang University(Medical Science)    2013, 42 (6): 609-614.   DOI: 10.3785/j.issn.1008-9292.2013.06.003
Abstract   PDF (1313KB) ( 397 )  
Objective: To compare seizure induced by different epileptic drugs in ICR mice.
Methods: Male adult ICR mice were injected with pilocarpine (Pilo),kainic acid (KA) and pentylenetetrazole (PTZ) to induce status epilepticus (SE).After 2 h of SE,seizures were terminated by injection of diazepam.Mice were sacrificed and sectioned for assessment of neuronal cell death by Fluro-Jade B staining after 7 d and mossy fiber sprouting by Timm staining after 28 d,respectively.Spontaneous seizures were detected by video for 28 d.
Results: Pilo and KA induced typical SE in ICR mice,which was identical to those observed in rats and C57/BL6 mice.Timm staining showed evident mossy fiber sprouting in both Pilo and KA treated mice.The incidences of spontaneous seizure were 57.1% and 35.7% in Pilo and KA treated mice,respectively.Mice treated with PTZ represented kindling model.No mossy fiber sprouting and spontaneous seizures were observed.No cell death was detected in all three groups.
Conclusions: Similar seizure pattern is observed in ICR mice as in rats and C57/BL6 mice.Both Pilo and KA model are the ideal models for chronic temporal lobe epilepsy.ICR mice can be widely used as a cheaper substitute in epilepsy research.
 
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Effects of FK866 on migration of A549 cells and related mechanism
XIE Xian,XU Xiaofang,WANG Qi,LU Yunbi,WU Ming,ZHANG Weiping
J Zhejiang Univ (Med Sci)    2018, 47 (1): 1-9.   DOI: 10.3785/j.issn.1008-9292.2018.02.01
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Objective: To investigate the effect of nicotinamide phosphoribosyltransferase (NAMPT) inhibitor FK866 on the migration of human non-small cell cancer A549 cells and related mechanism. Methods: The inhibition effect of FK866 on A549 cells was tested by MTT assay. A549 cells were treated with 1.0 and 10.0 nmol/L FK866, and the cell migration was evaluated by modified wound scratch assay. The mRNA expression of E-cadherin and vimentin was detected by real-time RT-PCR, and the expression of ERK1/2 and pERK1/2 was determined by Western blotting. Results: FK866 inhibited the proliferation of A549 cells in a time- and concentration-dependent manner; after treatment for 72 h, the IC50 of FK866 was 9.55 nmol/L. When 1.0 nmol/L or 10.0 nmol/L FK866 was continuously applied 48 h before and 48 h after a scratch was made in wound scratch assay, the migration of A549 cells was significantly inhibited. However, when the FK866 was applied only 48 h after the scratch, the migration of A549 cells was inhibited by 10.0 nmol/L but not by 1.0 nmol/L FK866. The mRNA expression of E-cadherin and vimentin, and the activated ERK1/2 were significantly increased after 1.0 nmol/L FK866 treatment for 72 h. The pretreatment with nicotinamide adenine dinucleotide (NAD) precursor nicotinamide mononucleotide(1.0 mmol/L) or ERK1/2 inhibitor U0126 (10.0 μmol/L) reversed the up-regulation of E-cadherin and vimentin expression induced by FK866. Conclusions: Low concentration of FK866 decreases the migration of A549 cells through the inhibition of NAD level, activation of ERK1/2 and up-regulation of E-cadherin expression. However, it also up-regulates the expression of vimentin, indicating that it may have dual effects on the migration of tumor cells.

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Progress on cancer associated fibroblasts in tumor immunoregulation
LI Gaopeng,HE Jia,WANG Qingqing
J Zhejiang Univ (Med Sci)    2018, 47 (5): 558-563.   DOI: 10.3785/j.issn.1008-9292.2018.10.17
Abstract   HTML PDF (477KB) ( 380 )  

Cancer associated fibroblasts (CAFs) are important components of the tumor microenvironment. Through secreting of multiple growth factors, cytokines and proteases, CAFs play a significant role in regulating the recruitment and function of various innate immune cells and adaptive immune cells in tumor microenvironment. In addition, extracellular matrix secreted by CAFs can also promote the formation of immunosuppression and hypoxia of tumor microenvironment. Here, we review the progress on CAFs in regulation of immune cells and tumor immunity.

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Prospects for research on small molecular targeted drugs in treatment of acute myeloid leukemia
Journal of ZheJiang University(Medical Science)    2012, 41 (5): 469-472.   DOI: 10.3785/j.issn.1008-9292.2012.05.001
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Video head impulse test for evaluation of vestibular function in patients with vestibular neuritis and benign paroxysmal positional vertigo
GUAN Qiongfeng,ZHANG Lisan,HONG Wenke,YANG Yi,CHEN Zhaoying,ZHANG Dan,HU Xingyue
J Zhejiang Univ (Med Sci)    2017, 46 (1): 52-58.   DOI: 10.3785/j.issn.1008-9292.2017.02.08
Abstract   HTML PDF (1199KB) ( 260 )  
Objective

To assess the clinical application of video head impulse test (vHIT) for vestibular function in vestibular neuritis (VN) and benign paroxysmal positional vertigo (BPPV) patients.

Methods

Thirty-three patients with VN and 43 patients with BPPV were enrolled from Sir Run Run Shaw Hospital and Ningbo Second Hospital from March 15 to September 10, 2015; and 50 healthy controls were also enrolled in the study. vHIT was used to quantitatively test the vestibulo-ocular reflex (VOR) gains of a pair of horizontal semicircular canals. VOR gains two pairs of vertical semicircular canals, and the corresponding asymmetrical value of three VOR gains. The saccades information was also recorded.

Results

Compared with the healthy control group and BPPV patients, the affected horizontal and vertical VOR gains were declined and the corresponding asymmetries were increased in VN patients (all P < 0.01). BPPV group also showed higher vertical VOR gain asymmetries compared with the healthy control group (all P < 0.01), but no significant difference was observed in VOR gains and horizontal VOR gain asymmetry (all P>0.05). The sensibility of vHIT in diagnosis of VN was 87.9%. Among 33 VN patients, 22 were diagnosed with superior vestibular nerve dysfunction, 7 were found with inferior vestibular nerve dysfunction and 3 were with both dysfunction; and 1 case was not distinguished.

Conclusion

Video head impulse test can quantitatively evaluate the vestibular dysfunction of VN and can help early diagnosis of VN, which may be widely used in clinic.

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Clinical investigation on transarterial chemoembolization with indigenous drug-eluting beads in treatment of unresectable hepatocellular carcinoma
CHEN Gang,ZHANG Ding,YING Yacao,WANG Zhifeng,TAO Wei,ZHU Hao,ZHANG Jingfeng,PENG Zhiyi
J Zhejiang Univ (Med Sci)    2017, 46 (1): 44-51.   DOI: 10.3785/j.issn.1008-9292.2017.02.07
Abstract   HTML PDF (1197KB) ( 295 )  
Objective

To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC).

Methods

The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres?) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy. The response to treatment, disease recurrence, complications and adverse effects were documented and compared between two groups.

Results

There were no significant differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and disease control rate (CR+PR+SD), disease recurrence, complications and adverse effects of interventional therapy between cTACE group and DEB-TACE group. Additionally, there were no significant differences about locoregional biliary injuries, intrahepatic biloma, and newly detected intra-or extrahepatic HCC on MRI between cTACE group and DEB-TACE group.

Conclusion

There were no statistically significant differences between cTACE group and DEB-TACE group with regard to the short-term response, disease recurrence, complications and side effects. Hepatic-locoregional complications may be more frequent in DEB-TACE group than those in cTACE group.

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From endoplasmic reticulum to Golgi apparatus:a secretory pathway controlled by signal molecules
WANG Jiasheng,LUO Jianhong,ZHANG Xiaomin
Journal of ZheJiang University(Medical Science)    2013, 42 (4): 472-.   DOI: 10.3785/j.issn.1008-9292.2013.04.017
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[Abstract]Protein transport from endoplasmic reticulum (ER) to Golgi apparatus has long been known to be a central process for protein quality control and sorting.Recent studies have revealed that a large number of signal molecules are involved in regulation of membrane trafficking through ER,ER-Golgi intermediate compartment and Golgi apparatus.These molecules can significantly change the transport rate of proteins by regulating vesicle budding and fusion.Protein transport from ER to Golgi apparatus is not only controlled by signal pathways triggered from outside the cell,it is also regulated by feedback signals from the transport pathway.

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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
Abstract   HTML PDF (1156KB) ( 370 )  

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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Journal of ZheJiang University(Medical Science)    1959, 2 (2): 121-125.   DOI: 10.3785/j.issn.1008-9292.1959.02.009
Abstract   PDF (1699KB) ( 103 )  
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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) ( 489 )  

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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Journal of ZheJiang University(Medical Science)    1959, 2 (4): 295-298.   DOI: 10.3785/j.issn.1008-9292.1959.04.002
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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) ( 193 )  

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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Journal of ZheJiang University(Medical Science)    1982, 11 (6): 311-313.   DOI: 10.3785/j.issn.1008-9292.1982.06.017
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TcpC induces apoptosis of human vascular endothelial cells and its mechanisms
ZHANG Chong, ZHOU Jia-Le, FANG Jie, ZHANG Da-Yong, WANG Bao-Ming, CHEN Rui-Ling, PAN Jian-Ping
Journal of ZheJiang University(Medical Science)    2013, 42 (5): 492-497.   DOI: 10.3785/j.issn.1008-9292.2013.05.003
Abstract   PDF (1689KB) ( 362 )  

Objective: To investigate the effects of TcpC on human umbilical vascular endothelial cells (HUVECs) and its mechanisms.
Methods: HUVECs were co-cultured with TcpC secreting wild-type E. coli strain CFT073 (TcpCwt) or tcpc gene-deleted CFT073 mutant strain (TcpCmut) in transwell system,respectively. Apoptosis of HUVECs was analyzed by Annexin-V/PI double staining. Mitochondrial membrane depolarization was detected by JC-1 staining. Expression of apoptosis-related proteins in HUVECs was determined by Western blot.
Results: HUVECs showed morphological changes after co-cultured with TcpCwt for 24 h:the cells became detached and cell debris increased,and cell number was also decreased when compared to HUVECs co-cultured with TcpCmut. The apoptosis of HUVEC cells co-cultured with TcpCwt for 24 h significantly increased,compared to that of control group and TcpCmut group (60.1% 9.7% vs 9.0% 1.3% and 16.9% 0.4%,respectively, P<0.05); meanwhile the mitochondrial depolarization of HUVECs co-cultured with TcpCwt was significantly increased,compared to that in control and TcpCmut groups (64.5% 0.9% vs 14.5% 2.1% and 15.6% 3.3%,respectively,P<0.05). Cleavage of PARP and inhibition of Mcl-1 and XIAP expression were seen in HUVECs co-cultured with TcpCwt,but not in groups of control and TcpCmut.
Conclusion: TcpC secreted from CFT073 can induce apoptosis of HUVECs through mitochondrial pathway,in which PARP is cleaved and Mcl-1 and XIAP expressions are inhibited.

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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
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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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Icaritin promotes maturation and mineralization of mouse osteoblast MC3T3-E1 cells through CXCR4/SDF-1 signal pathway
WEI Zhenlong,SHI Wengui,CHEN Keming,ZHOU Jian,WANG Minggang
J Zhejiang Univ (Med Sci)    2017, 46 (6): 571-577.   DOI: 10.3785/j.issn.1008-9292.2017.12.01
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Objective: To investigate the effect of icaritin on maturation and mineralization of mouse osteoblast MC3T3-E1 cells and its mechanism. Methods: The cultured MC3T3-E1 cells were divided into blank control group, CXC chemokine receptor type 4 (CXCR4) inhibitor (AMD3100) group, icaritin group, and icaritin plus AMD3100 group. The expression of CXCR4, stromal cell-derived factor 1 (SDF-1) and osteogenesis-related genes and proteins were detected by real-time RT-PCR and Western blotting after drug treatment for 24 h. The alkaline phosphatase (ALP) activity was determined with ALP kit on d3 and d6; calcium nodules were detected by alizarin red staining after drug treatment for 14 d. Results: Real time RT-PCR showed that compared with the blank control group, relative expressions of CXCR4, SDF-1 and osteogenesis-related genes in icaritin group were significantly increased (P<0.05 or P<0.01); After AMD3100 treatment, the relative expression of CXCR4 gene was decreased (P<0.05). Western blot showed that compared with the blank control group, relative expressions of CXCR4, SDF-1 and osteogenesis-related proteins in the icaritin group were significantly increased (all P<0.01), but were decreased after AMD3100 was added (all P<0.01). The ALP activity of icaritin group was significantly higher than that of blank control group (all P<0.01) on d3 and d6 after drug treatment, while the activity of ALP was significantly decreased after AMD3100 treatment (all P<0.01). At d14 after drug treatment, compared with the blank control group, the area of alizarin red staining was increased in the icaritin group, while it was significantly reduced after the addition of AMD3100. Conclusion: Icaritin may promote maturation and mineralization of mouse osteoblast MC3T3-E1 cells through CXCR4/SDF-1 signaling pathway.

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Diagnostic efficacy of three test kits for SARS-CoV-2 nucleic acid detection
SHEN Lihua,HUANG Fei,CHEN Xiang,XIONG Zuan,YANG Xiaoyu,LI Hui,CHENG Feng,GUO Jian,GONG Guofu
J Zhejiang Univ (Med Sci)    2020, 49 (2): 185-190.   DOI: 10.3785/j.issn.1008-9292.2020.03.09
Abstract   HTML PDF (1055KB) ( 173 )  

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

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Research progress on receptor interacting proteins in inflammation
DING Jingjing,LU Yunbi
J Zhejiang Univ (Med Sci)    2018, 47 (1): 89-96.   DOI: 10.3785/j.issn.1008-9292.2018.02.13
Abstract   HTML PDF (1149KB) ( 140 )  

Receptor interacting proteins (RIPs) are a group of threonine/serine protein kinases, which have relatively conserved kinase domains and different non-kinase domains, and are involved in physiological and pathological processes including innate immune response and inflammation. In recent years, many studies have shown that RIPs mediate cell necroptosis and triggers inflammatory responses by participating in the formation of necrotic complexes, and RIP1 and RIP3 are particularly closely related to cell necrosis. Cell necroptosis is a well-regulated way of cell death. The death signal that transmit through the TNF signaling pathway and the Toll-like receptor signaling pathway can recruit and phosphorylate mixed lineage kinase domain-like protein (MLKL), and eventually leading to disintegration and death of cells, and the release of cells intercellular material after cell disintegration can trigger an inflammatory reaction. This review mainly focuses on the major signaling pathways and molecular mechanisms that are involved in the mediation of necrosis and inflammation by RIPs. It also highlights the importance of RIPs in the development of inflammatory diseases and their potentials as therapeutic targets for inflammatory diseases.

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Construction of pBIFC-VN173-CXCR4 and pBIFC-VC155-NT21MP eukaryotic expression plasmids and their interaction in living cells
Journal of ZheJiang University(Medical Science)    2012, 41 (5): 519-526.   DOI: 10.3785/j.issn.1008-9292.2012.05.009
Abstract   PDF (2923KB) ( 446 )  
Objective: To construct pBIFC-VN173-CXCR4 and pBIFC-VC155-NT21MP eukaryotic expression plasmids and to investigate the interaction of chemokine receptor 4 (CXCR4) and viral macrophage inflammatory protein-Ⅱ(vMIP-Ⅱ) N terminal 21 peptides (NT21MP) in living cells.
Methods: DNA fragment encoding NT21MP was chemically synthesized and inserted into BiFC eukaryotic expression vector pBIFC-VC155.The full length of CXCR4 DNA fragment was amplified by RT-PCR from SKBR3 cells and inserted into BiFC eukaryotic expression plasmid pBIFC-VN173.Two recombinant vectors were identified by restriction enzyme digestion and DNA sequencing.The recombinant vectors were cotransfected into Africa green monkey kidney fibroblast COS-7 cells by using Lipofectamine 2000.The interaction of NT21MP and CXCR4 was detected by bimolecular fluorescence complementation (BiFC) assay.
Results: The restriction enzyme digestion and DNA sequences and open read frames of two vectors were consistent with experiment design.The BiFC plasmids were successfully cotransfected into the target cells and expressed.The strong BiFC signals were detected in pBIFC-VN173-CXCR4 and pBIFC-VC155-NT21MP cotransfected cells and the fluorescence signal was located in the cytoplasm.
Conclusions: The eukaryotic expression plasmids for BiFC assay are successfully constructed.The interaction of NT21MP and CXCR4 in living cells can be detected by using this technology.  
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Diagnosis value of serum NKX2-1 for primary lung cancer
Journal of ZheJiang University(Medical Science)    2012, 41 (5): 535-539.   DOI: 10.3785/j.issn.1008-9292.2012.05.011
Abstract   PDF (639KB) ( 300 )  
Objective: To evaluate serum Nkx2-1 (NKX homeobox-1) levels in diagnosis of primary lung cancer.
Methods: The serum NKX2-1 and CEA (carcinoma embryonic antigen) levels were measured in 61 patients with primary lung cancer admitted from May 2009 to December 2010 and 49 healthy individuals served as controls.The receiver operating characteristic curve (ROC) of NKX2-1 in diagnosis for primary lung cancer was analyzed.The value of serum NKX2-1 in diagnosing primary lung cancer was compared with that of CEA by χ2 test and Kappa test.
Results: The serum Nkx2-1 levels in lung cancer were significantly higher than those in controls [(1.4206±0.1257)ng/ml vs (0.7646±0.0734)ng/ml,P<0.01].ROC analysis showed the area under the curve of serum NKX2-1 was 0.859.The Kappa value of NKX2-1 was higher than that of CEA (0.586 vs 0.396,P<0.05).Combination of serum NKX2-1 with CEA improved the Kappa value to 0.704,and also had high sensitivity (83.6%) and specificity (87.0%) for diagnosis of primary lung cancer.
Conclusions: Serum NKX2-1 protein can be used as a marker for diagnosis of lung cancer,the combination of NKX2-1 with CEA may further improve the diagnostic value.
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TcpC induces apoptosis of macrophages through promoting ROS production
ZHANG Da-Yong, LIN Yi-Qian, HE Fei, FANG Jie, ZHANG Chong, WANG Bao-Ming, PAN Jian-Ping
Journal of ZheJiang University(Medical Science)    2013, 42 (5): 486-491.   DOI: 10.3785/j.issn.1008-9292.2013.05.002
Abstract   PDF (2580KB) ( 359 )  
Objective: To investigate the effects of Toll/interleukin 1 receptor domain-containing protein(TcpC)on macrophages and its mechanisms.
Methods: Murine macrophage J774A cells were co-cultured with TcpC producing wild type E. coli strain CFT073 (TcpCwt) or tcpc gene-deleted CFT073 mutant (TcpCmut) in Transwell system,respectively. Apoptosis of J774A cells co-cultured with TcpCwt or TcpCmut was analyzed by Annexin/PI double staining. The levels of reactive oxygen species (ROS) in J774A cells were determined by DCFH-DA staining after treatment with TcpCwt or TcpCmut at 6 h,12 h,24 h or 36 h. After the ROS was scavenged by N-acetylcysteine (NAC),the changes of J774A cell apoptosis were also examined. The expression of caspase-3 in J774A cells co-cultured with TcpCwt or TcpCmut in the presence or absence of 0.1 mmol NAC was detected by Western blot.
Results: J774A cells co-cultured with TcpCwt for 24 h or 36 h showed significantly increased apoptosis (27.39%±4.05% and 28.45%±4.55%,respectively) when compared to control group (7.96%±1.63% and 10.55%±1.44%,P<0.01) or TcpCmut group (11.45%±2.77% and 19.26%±2.89%,P<0.01). Levels of ROS in J774A cells treated with TcpCwt for 24 h (108.8±9.73) or 36 h (100.3±10.11) were significantly higher than those in control group (56.8±4.11 and 52.8±4.42,P<0.01) or TcpCmut (69.7±5.66 and 62.6±4.56,P<0.01). The pro-apoptotic effects of TcpCwt on J774A cells were reversed by 0.1 or 1 mMol NAC treatment. Expression of caspase-3 in J774A cells co-cultured with TcpCwt (0.43±0.04) decreased significantly when compared to control group (0.75±0.08,P<0.05) or TcpCmut group (0.80±0.12,P<0.05). However,total caspase-3 expression was restored in J774A cells co-cultured with TcpCwt in the presence of 0.1 mmol NAC (0.80±0.09).
Conclusion: TcpC can promote ROS production in macrophages,hereby inducing macrophage apoptosis.
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Maximal infarct volume to benefit from intravenous thrombolysis and its relation with onset to treatment time
ZHANG Meixia, ZHOU Ying, ZHANG Ruiting, ZHANG Sheng, LOU Min
Journal of ZheJiang University(Medical Science)    2017, 46 (4): 384-389.   DOI: 10.3785/j.issn.1008-9292.2017.08.07
Abstract   PDF (1015KB) ( 55 )  

Objective:To investigate the relationship between maximal infarct volume to benefit from intravenous thrombolysis (IVT) and onset to needle time (ONT). Methods:The clinical and image data of acute ischemic stroke patients who received IVT in the second Affiliated Hospital, Zhejiang University School of Medicine during May 2009 to June 2016 were retrospectively reviewed. Patients were classified into within-time-window group (ONT ≤ 4.5 h) and beyond-time-window group (ONT>4.5 h). Good and poor outcome were defined as modified Rankin scale (mRS) ≤ 2 or >2 at 3 months, respectively. The maximal infarct volume was analyzed by receiver operating characteristic (ROC) curve. Results:Among 587 patients (465 cases were within-time-window, 122 cases were beyond-time-window), baseline core volume was 15(2-46)mL,and 324 (55.2%) patients achieved good outcome. Compared with the good-outcome group, the baseline core volume was larger in the poor-outcome group (32 mL vs 5 mL,Z=-9.766,P<0.01). After adjusting age, ONT, baseline National Institutes of Health Stroke Scale (NIHSS) and atrial fibrillation, baseline infarct core volume independently predicted poor outcome (OR=1.014, 95% CI:1.008-1.020, P<0.01). The ROC curve analysis showed that the maximal infarct core volume for achieving good outcome in the within-time-window group and beyond-time-window group were 152 mL and 71mL, respectively. The maximal infarct volume to benefit from IVT diminished with the increasing delayed ONT of every 30 min (ρ=-0.691, P<0.05). Conclusion:The maximal infarct volume to benefit from thrombolysis is larger in patients treated within time window than those beyond the time window, and that volume diminishes with ONT delay.

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Application of rehabilitation medicine in enhanced recovery after surgery
LI Haijun,CHEN Zuobing
J Zhejiang Univ (Med Sci)    2017, 46 (6): 675-678.   DOI: 10.3785/j.issn.1008-9292.2017.12.16
Abstract   HTML PDF (944KB) ( 162 )  

Enhanced recovery after surgery (ERAS) has been widely used in perioperative optimization. As an important component of ERAS, rehabilitation medicine mainly focuses on perioperative physical fitness management, respiratory training, exercise training to reduce the incidence of postoperative pulmonary infection, improve gastrointestinal and cardiopulmonary function. This paper explains rehabilitation medicine for respiratory, musculoskeletal, cardiovascular and digestive systems during the perioperative period.

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Expression of g6pd gene in wild type zebrafish embryos of early development
XIA Haixiong,LI Li,ZHOU Yanhua,REN Pingping,HE Zhixu,SHU Liping
J Zhejiang Univ (Med Sci)    2018, 47 (1): 57-63.   DOI: 10.3785/j.issn.1008-9292.2018.02.08
Abstract   HTML PDF (1153KB) ( 94 )  

Objective: To observe the expression of g6pd gene in the early development stage of wild zebrafish embryos. Methods: The collinearity of g6pd gene and the sequence similarity of G6pd protein were analyzed with gene database and BLAST software, respectively. Expression of g6pd gene in different development stages of zebrafish embryos was detected by in situ hybridization. The g6pd-EGFP-pCS2+ recombinant plasmids were microinjected into zebrafish embryos, and fluorescence was observed under a fluorescence microscope. The expression of G6pd protein at 24, 48 and 72 hour post fertilization (hpf) zebrafish embryos was detected by Western blotting; the enzyme activity of G6pd at 24, 48 and 72 hpf zebrafish embryos was detected by modified G6pd quantitative ratio method. Results: The G6pd protein similarity of zebrafish and human was 88%, and that of zebrafish and mouse was 87%. The results of in situ hybridization showed that the g6pd gene was mainly expressed in the hematopoietic tissues of zebrafish; the results observed after microinjection of g6pd-EGFP-pCS2+ recombinant plasmid were consistent with the results of in situ hybridization. At 24, 48 and 72 hpf, the relative expression levels of G6pd protein in zebrafish embryos were 1.44±0.03, 1.47±0.05, and 1.54±0.02, respectively(P > 0.05); the G6pd enzyme activity levels were 1.74±0.17, 1.75±0.12, 1.71±0.22, respectively (P > 0.05). Conclusion: The study has observed the expression of g6pd gene and G6pd protein, and G6pd enzyme activity in zebrafish embryos at different development phases, which provides a reference for the establishment of a zebrafish G6PD deficiency model.

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Rapamycin improves learning and memory ability in ICR mice with pilocarpine-induced temporal lobe epilepsy
ZHANG Huadan,XIE Yacong,WENG Ling,ZHANG Yuchen,SHI Qiongyao,CHEN Tao,ZENG Linghui
Journal of ZheJiang University(Medical Science)    DOI: 10.3785/j.issn.1008-9292.2013.06.002
Endoscopic trans-fistula drainage for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy
ZHU Ziyi,LI Zhijun,HE Zhengfu,WANG Yunzhen
J Zhejiang Univ (Med Sci)    2017, 46 (6): 637-642.   DOI: 10.3785/j.issn.1008-9292.2017.12.10
Abstract   HTML PDF (1052KB) ( 126 )  

Objective: To evaluate the efficiency and safety of endoscopic trans-fistula drainage (ETFD) for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy. Methods: Among 456 esophageal cancer patients receiving esophagectomy between February 2012 and February 2017 in Sir Run Run Shaw Hospital, 15 cases were diagnosed as gastroesophageal anastomotic fistula with para-fistula abscess after surgery. Seven cases received ETFD treatment (ETFD group), and 8 cases received conventional treatment (control group). Recovery of inflammatory markers and fistula, length of hospital stay after esophagectomy and total medical expenses were compared between ETFD group and control group. Results: All patients recovered in ETFD group. Time of white cell count returning to normal and decline of C-reactive protein, time of fistula healing and length of hospital stay after esophagectomy in ETFD group were significantly shorter than those of control group (all P < 0.05). And medical expenses in ETFD group was also lower (P < 0.05). Conclusion: ETFD is effective and safe for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy.

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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) ( 483 )  

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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Journal of ZheJiang University(Medical Science)    1995, 24 (5): 229-231.   DOI: 10.3785/j.issn.1008-9292.1995.05.017
Abstract   PDF (242KB) ( 112 )  
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Journal of ZheJiang University(Medical Science)    1964, 5 (4): 1-8.   DOI: 10.3785/j.issn.1008-9292.1964.04.001
Abstract   PDF (702KB) ( 116 )  
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Early management of intracranial ruptured vertebral dissecting aneurysms
Journal of ZheJiang University(Medical Science)    2012, 41 (1): 93-98.   DOI: 10.3785/j.issn.1008-9292.2012.01.016
Abstract   PDF (2110KB) ( 330 )  
Objective: To evaluate the early management of intracranial ruptured vertebral dissecting aneurysms.
Methods: Twenty-two patients with ruptured vertebral dissecting aneurysms were managed by various treatment modalities according to their conditions.One aneurysm was treated by proximal vertebral artery coiling,15 aneurysms by aneurysm and parent artery coiling,and 5 aneurysms by stent-assisted coiling(4 of 5 by stent-within-a-stent technique),one by single double-stent.Bloody cerebrospinal fluid was drained by postoperative lumbar subarachnoid drainage in order to prevent cerebral vasospasm.
Results: All 22 cases were successful without bleeding complication during the operation.There was 1 case of early postoperative non-aneurysmal hemorrhage,2 cases of posterial group cranial nerves palsies,1 case harbored Hunt & Hess IV who gave up treatment.After follow-up for 3-18 months,there was no rebleeding and infarction.Twenty patients recovered well,except 1 having posterial group cranial nerves palsies.Fourteen cases were followed up by angiography.In 3 patients treated by stent-assisted coiling,DSA showed that aneurysms disappeared and loading vessel passed freely.DSA of 11 cases with aneurysm and parent artery coiling demonstrated complete obliteration of the dissection without aneurysm imaging.
Conclusions: Early endovascular treatment of ruptured vertebral dissecting aneurysms is essential.The selective method of endovascular management according to the characteristics of aneurysm is safe and effective.Double stent-assisted coiling should be the first choice.
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Effects of snakegourd root polysaccharide on apoptosis of MCF-7 cells
Journal of ZheJiang University(Medical Science)    2012, 41 (5): 527-534.   DOI: 10.3785/j.issn.1008-9292.2012.05.010
Abstract   PDF (2507KB) ( 255 )  
Objective: To investigate the effects of snakegourd root polysaccharide on apoptosis of human breast cancer cells (MCF-7 cells).
Methods: Colorimetric MTT assay was used to measure the inhibition of snakegourd root polysaccharide on MCF-7 cells.The morphological changes of MCF-7 cells were observed by fluorescence microscope after DAPI staining and transmission electron microscope.The apoptosis of MCF-7 cells was examined by DNA agarose gel electrophoresis analysis of DNA fragmentation amd flow cytometry.The activity of Caspase-3 and Caspase-8 was detected by colorimetric assay.
Results: Polysaccharide of snakegourd root significantly inhibited MCF-7 cells in a dose- and time-dependent manner.The nuclear condensation and marginalization were observed by DAPI staining and transmission electron microscope.The characteristic ladder of apoptosis in DNA electrophoresis was detected in MCF-7 cells treated with 10.0 μmol/L polysaccharide of snakegourd root at d 2.The activities of Caspase-3 and Caspase-8 were increased in a time-dependent manner.The rates of apoptosis in MCF-7 cells were(5.2±1.3)%,(13.1±4.7)% ,(27.6±6.8)% and(43.8±9.8)% treated with 1.0,5.0,10.0 and 20.0 μmol/L snakegourd root polysaccharide at d 2,respectively.The maximal activities of intracellular Caspase-3 and Caspase-8 were(2.32±0.12)U/μg and(1.92±0.11)U/μg at d 2 and d 1,respectively when MCF-7 cells were treated with 10.0 μmol/L.
Conclusion: The polysaccharide of snakegourd root can induce the apoptosis of MCF-7 cells,which is associated with the activation of intracellular Caspase-3 and Caspase-8.
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Expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer
Journal of ZheJiang University(Medical Science)    2012, 41 (5): 540-546.   DOI: 10.3785/j.issn.1008-9292.2012.05.012
Abstract   PDF (1451KB) ( 437 )  
Objective: To investigate the expression of RRM1 and ERCC1 genes in tumor tissues and peripheral blood lymphocytes of advanced non-small cell lung cancer (NSCLC).
Methods: Tissue and peripheral blood samples were collected from 49 advanced NSCLC patients treated with gemcitabine plus carboplatin.The expressions of RRM1 and ERCC1 mRNA in tumor tissue and peripheral lymphocytes were detected by real-time fluorescent quantitative PCR.The relationship of gene expression with clinical characteristics,chemotherapy response and prognosis was analyzed.
Results: The RRM1 expression in tumor tissues was positively correlated with that in peripheral blood lymphocytes,while no significant correlation was observed between ERCC1 expression in tumor tissues and that in peripheral blood (rs=0.332 and 0.258;P=0.020 and 0.073,respectively).The expression of RRM1 and ERCC1 in tumor tissues peripheral lymphocytes was synchronous(rs=0.634 and 0.351;P<0.001 and 0.013,respectively).There was no significant correlation of gene expression with gender,age,smoking status,performance status,clinical stages and histological types of patients (P>0.05).Significant difference was found in response rate to chemotherapy(P<0.05,P<0.01,P<0.05),median survival time(P<0.05,P<0.01,P<0.05) and 1-year survival rate (P<0.01,<0.05,P<0.05) between patients with low RRM1 and ERCC1 expression levels in tumor tissues or low RRM1 expression levels in peripheral blood and those with high RRM1 and ERCC1 expression levels.The patients with low ERCC1 expression levels in tumor tissues gained higher 2-year survival rate(P<0.05).There was no correlation of the expression of ERCC1 in peripheral blood with the response to chemotherapy and prognosis(P>0.05).
Conclusion: The expression of RRMI and ERCC1 genes in tumor tissues and RRM1 in peripheral blood lymphocytes is closely correlated with the response to chemotherapy and prognosis of patients with advanced NSCLC treated with gemcitabine plus carboplatin.
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Principles and suggestions on biosafety protection of biological specimen preservation during prevalence of COVID-19
ZHANG Xiaoyan, SUN Wei, SHANG Shiqiang, MAO Jianhua, FU Junfen, SHU Qiang, JIANG Kewen
J Zhejiang Univ (Med Sci)    2020, 49 (2): 170-177.   DOI: 10.3785/j.issn.1008-9292.2020.02.04
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Coronavirus disease 2019 (COVID-19) is a grade B infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In pace with the spreading of the disease, biosafety risk of the biological specimen preservation in biobanks has been significantly increased and biosafety protection during biological specimen preservation become increasingly important. According to the related national rules and the corresponding guidelines of Chinese Medical Association, this paper introduced the etiology about SARS-CoV-2, epidemiology about COVID-19, and the biosafety protection principles of individuals and biological specimen storage places in the process of personal protection, protection of collection, transport, handling, preservation, detection, post-detection disposal and emergencies of biological specimen. Emphasized to carry out a strict biosafety-risk assessment on biological specimen basing on virus load information, infectivity, and sample type (possible contact transmission, aerosol transmission, and fecal oral transmission).

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Anesthesia management in cesarean section for patient with COVID-19: a case report
KANG Xianhui,ZHANG Rong,HE Huiliang,YAO Yongxing,ZHENG Yueying,WEN Xiaohong,ZHU Shengmei
J Zhejiang Univ (Med Sci)    2020, 49 (2): 249-252.   DOI: 10.3785/j.issn.1008-9292.2020.03.04
Abstract   HTML PDF (1025KB) ( 387 )  

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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Simplified gonadorelin stimulation test in diagnosis of precocious puberty
Journal of ZheJiang University(Medical Science)    2004, 33 (5): 452-455.   DOI: 10.3785/j.issn.1008-9292.2004.05.017
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Monitoring time of interictal epileptiform discharges by long-term video EEG in patients with epilepsy
WU Han,WANG Zhongjin,MING Wenjie,WANG Shuang,DING Meiping
J Zhejiang Univ (Med Sci)    2017, 46 (1): 30-35.   DOI: 10.3785/j.issn.1008-9292.2017.02.05
Abstract   HTML PDF (1067KB) ( 289 )  
Objective

To optimize the monitoring time of interictal epileptiform discharges (IED) in patients with epilepsy by long-term video electroencephalogram (VEEG).

Methods

The cumulative percentages of IED detected by VEEG in 346 epilepsy patients (349 times) with different purposes, different waking sleep states and different MRI findings were retrospectively analyzed. According to the purposes, there were 164 patients (165 times) for clarifying diagnosis, 124 patients (124 times) for preoperative evaluation and 58 patients (60 times) for adjustment of medications. According to MRI results, there were responsible lesions in 98 patients (98 times) and no responsible lesions in 173 patients (174 times).

Results

Among 346 patients (349 times), IED was detected within 24 h in 231 patients (times). The percentage of detection in patients with purpose of preoperative evaluation was higher than those with purpose of diagnosis and medication adjustment. The detection of LED was gradually increased in first 8 h with 59.0%, then stably in 24 h. 46.8% IED was recorded during sleep time, particularly in the second stage of sleep. The cumulative percentage of IED in patients with abnormal MRI findings was higher in all periods. It reached 83.7% within 8 h, and then tended to be stable.

Conclusion

The study shows that LED should be monitored by VEEG at least 8 hours and should include the second stage of sleep in patients with epilepsy. Patients with refractory epilepsy and with abnormal lesions on MRI should record IED more frequently.

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Research progress on mechanism of Nix-mediated mitophagy
ZHENG Yanrong,ZHANG Xiangnan,CHEN Zhong
J Zhejiang Univ (Med Sci)    2017, 46 (1): 92-96.   DOI: 10.3785/j.issn.1008-9292.2017.02.14
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Autophagy is fundamental to maintain cellular homeostasis. As one kind of the most well-studied selective autophagy, autophagy of mitochondria (mitophagy) is crucial for the clearance of damaged mitochondria. Mitophagy dysfunction has been proved to be closely associated with many human diseases. Nix is a key protein for mitophagy during the maturation of reticulocytes. However, the detailed molecular mechanisms underlying Nix-mediated mitophagy are not fully understood. This article summarizes three possible working models of Nix in mitophagy induction. Firstly, Nix can interplay with Parkin, another important protein for mitophagy, to initiate mitophagy. Secondly, Nix can serve as a receptor for autophagy machinery by interacting with Atg8 family through its LIR motif. Finally, as a BH3-only protein, Nix can compete with Beclin-1 to bind other members of Bcl-2 family resulting in increased free Beclin-1 in cytosol, which further promotes autophagy flux.

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A case of neuromyelitis optica spectrum disorders complicated with systemic lupus erythematosus and thymoma
ZHOU Haijin,XIA Ping,HU Xingyue
J Zhejiang Univ (Med Sci)    2018, 47 (1): 71-74.   DOI: 10.3785/j.issn.1008-9292.2018.02.10
Abstract   HTML PDF (1006KB) ( 104 )  

A 53-year-old male patient presented with hypopsia of his right eye for 2 months and lower extremities weakness for 8 days. Thoracic MRI demonstrated a lesion at T3 level appearing as hyperintense on T2-weighted images with non-enhancement by contrast medium and demyelinating lesion was considered. Aquaporin-4-Ab was positive and the antibody titer was 1:320 in serum. The diagnosis of neuromyelitis optica spectrum disorders was made. In addition, systemic lupus erythematosus and thymoma coexisted in this patient. After methylprednisolone impact treatment, plasma exchange and immunosuppressive therapy, the right vision and lower extremities weakness of the patient were improved.

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Research progress of protein tyrosine phosphatase SHP-2
Journal of ZheJiang University(Medical Science)    2012, 41 (5): 581-585.   DOI: 10.3785/j.issn.1008-9292.2012.05.019
Abstract   PDF (543KB) ( 332 )  
The Src homology-2 domain-containing phosphatase SHP-2 encoded by PTPN11 is an essential component in several signaling pathways.Different types of mutation in SHP-2 have been confirmed in several types of leukemia and solid tumors.Elucidation of the events underlying Shp2-evoked transformation may provide new insights into the novel targets for anti-cancer therapy.
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Cytotoxicity of homoharringtonine on leukemic stem-like cells in AML cell line KG-1
Journal of ZheJiang University(Medical Science)    2012, 41 (5): 485-490.   DOI: 10.3785/j.issn.1008-9292.2012.05.004
Abstract   PDF (2387KB) ( 315 )  
Objective: To investigate the effect of homoharringtonine (HHT) on leukemic stem-like cells (LSC) in human acute myeloid leukemia (AML) cell lines.
Methods: The phenotypes of AML cell lines U937,Kasumi-1,and KG-1 cells were analyzed by flow cytometry (FACS).The effect of HHT on leukemia stem-like cells with immunophenotype of CD34+CD38-CD96+ was detected with FACS.Cell growth was measured by MTT assay.Activation of Caspase pathway and expression of apoptotsis-related regulator proteins were examined by Western blotting.
Results: FACS demonstrated that the 69% of KG-1 cells expressed LSC phenotype CD34+CD38-CD96+,while 26.7% on Kasumi-1 cells expressed this marker.In contrast,U937 cells showed CD96 negative.HHT significantly inhibited cell growth of KG-1 cells with an IC50 of 16.9 ng/ml at 48 h.The ratio of CD34+CD38-CD96+ cells decreased from 63.6% to 17.1% after HHT treatment.Enhanced apoptosis was demonstrated in HHT group evidenced by strong activation of Caspase-9,Caspase-3 and PARP.HHT treatment resulted in down-regulation of expression of anti-apoptotic protein BCL-2 and phosphated-Akt.
Conclusion: HHT can effectively kill the leukemic stem-like cells in human AML cell line KG1 by inhibiting cell growth and inducing apoptosis which is associated with activation of Caspase pathway and down-regulation of anti-apoptotic proteins and phosphated-Akt.
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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
Abstract   HTML PDF (1042KB) ( 340 )  

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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Killing effect of aurora kinase inhibitor ENMD-2076 on acute myelogenous leukemia cells
Journal of ZheJiang University(Medical Science)    2012, 41 (5): 479-484.   DOI: 10.3785/j.issn.1008-9292.2012.05.003
Abstract   PDF (1663KB) ( 288 )  
Objective: To investigate the effect of aurora kinase inhibitor ENMD-2076 on human acute myelogenous leukemia (AML) cell lines.
Methods: AML THP-1 and Kasumi-1 cells were treated with ENMD-2076 for 24 h and 48 h,respectively.Cell growth was measured by MTT assay.Apoptosis was determined using Hoechst staining apoptosis detection kit.Activation of Caspase pathway and expression of apoptosis regulator proteins were detected by Western blot.
Results: ENMD-2076 significantly induced growth arrest and apoptosis in THP-1 and Kasumi-1 cells.Enhanced apoptosis was observed in ENMD-2076 group evidenced by strong activation of Caspase-9,Caspase-3 and PARP.Furthermore,the ENMD-2076 treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression.Also,up-regulated expression of pro-apoptotic protein Bak,Bad and Bax was detected after ENMD-2076 treatment.
Conclusion: ENMD-2076 can kill effectively AML cells by inhibiting cell growth and inducing apoptosis,which is associated with activation of Caspase pathway and regulation of pro-apoptotic and anti-apoptotic proteins.
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Journal of ZheJiang University(Medical Science)    1992, 21 (3): 138-141,143.   DOI: 10.3785/j.issn.1008-9292.1992.03.015
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