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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) ( 28893 )  

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

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

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

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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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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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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) ( 1170 )  

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) ( 1071 )  

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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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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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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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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Guidelines for diagnosis and management of aneurysmal subarachnoid hemorrhage: top issues and prospective
ZHANG Jian-min
Journal of ZheJiang University(Medical Science)    2015, 44 (4): 357-360.   DOI: 10.3785/j.issn.1008-9292.2015.07.01
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Objective: Aneurysmal subarachnoid hemorrhage (aSAH) is a kind of hemorrhagic stroke with high mortality and morbidity. Although the preoperative diagnosis, surgical clipping, endovascular treatment, and intensive care have progressed in recent years, the overall prognosis of aSAH patients remains poor. In 2011, the Neurocritical Care Society organized an international, multidisciplinary consensus conference addressed the critical care management of SAH. In 2012, the American Stroke Association (AHA) updated the guidelines of diagnosis and treatment of aSAH published in 2009. In 2013, European Stroke Organization established the guideline for management of intracranial aneurysms and SAH. In 2014, the Korean Society of Interventional Neuroradiology (KSIN) published clinical practice guideline for the management of ruptured and unruptured aneurysms. The guideline for diagnosis and management of aSAH for Chinese patients has been drafted in this year. Thus, the diagnosis and management of aSAH is a hot topic in neurosurgery. This editorial summarizes the above mentioned guidelines and focuses on the progress and update of these guidelines. In this article we discuss the advantage and disadvantage of those imaging techniques, the pros and cons of surgical clipping and endovascular treatment.

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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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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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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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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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Delayed lower extremity deep venous thrombosis after operation for osteofibrous dysplasia of the left femur: report of one case
HUANG Kai, XU Wei-xing, ZHANG Chun
Journal of ZheJiang University(Medical Science)    2014, 43 (3): 379-380.   DOI: 10.3785/j.issn.1008-9292.2014.04.002
Abstract   PDF (445KB) ( 601 )  

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

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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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Fourier transform infrared spectroscopy in detection of breast cancer
CHEN Su-han,et al
Journal of ZheJiang University(Medical Science)    2014, 43 (4): 494-500.   DOI: 10.3785/j.issn.1008-9292.2014.07.010
Abstract   PDF (1052KB) ( 583 )  
Breast cancer is the most common cancer in women. Later diagnosis of the disease is the leading cause of poor prognosis. Fourier-transform infrared (FTIR) spectroscopy is a novel approach to provide information about the molecular components and metabolic conditions of human tissue; therefore it can detect the early changes caused by cancer cells prior to histological manifestation. FTIR-based diagnosis is rapid, simple and label free, which meets the requirements of an automated and patient-friendly technique. The current article gives an overview of the experimental techniques, data analysis methods and spectral signatures of breast cancer in FTIR-based diagnosis, summarizes the present challenges by focusing on the history of FTIR spectroscopy in breast cancer since 1990s, and highlights some investigations that give a perspective of FTIR-based diagnosis.
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Effect of mTOR signaling pathway in epileptogenesis
Zeng Linghui,DING Meiping
Journal of ZheJiang University(Medical Science)    2013, 42 (6): 597-601.   DOI: 10.3785/j.issn.1008-9292.2013.06.001
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Progress in the effects of BRAP gene on cardiovascular diseases
LV Duo, ZHU Yi-min
J Zhejiang Univ (Med Sci)    2014, 43 (5): 602-.   DOI: 10.3785/j.issn.1008-9292.2014.09.019
Abstract   PDF (646KB) ( 543 )  

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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Protective effect of grape seed proanthocyanidin on cultured RGC-5 cells against CoCl2-induced hypoxic injury
LIN Ka-na, LIN Mei-li, WEI Er-qing
Journal of ZheJiang University(Medical Science)    2015, 44 (1): 24-29.   DOI: 10.3785/j.issn.1008-9292.2015.01.004
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Objective: To investigate the protective effects of grape seed proanthocyanidin extracts (GSPE) against CoCl2-induced hypoxic injury in cultured RGC-5 cells. Methods: CoCl2 (400 μmol/L) was used to induce hypoxic injury in cultured RGC-5 cells; the cells were pretreated with 0, 100, 200, 400 and 800μmol/L GSPE for 24h. The cell viability was assayed by MTT; the apoptosis was detected by Hoechst 33342 staining; the intracellular reactive oxygen species (ROS) was measured by H2DCFDA oxidative reaction. The mRNA expression of Bcl-2, caspase 9 and caspase 3 was determined by real-time PCR. Results: Compared to hypoxic control group, pretreatment with GSPE significantly increased viability of RGC-5 cells (P <0.001), reduced cell apoptosis (P <0.001) and intracellular ROS (P <0.001). In addition, GSPE significantly increased the mRNA expression of Bcl-2 (P <0.001) and decreased mRNA expression of caspase 9 (P <0.001) and caspase 3 (P <0.001) compared to hypoxic control group. Conclusion: GSPE may have a protective effect against CoCl2-induced hypoxic injury in cultured RGC-5 cells. The decrease of intercellular ROS, up-regulation of Bcl-2 and down-regulation of caspase 9 and caspase 3 may be involved in the mechanism of the protective effect of GSPE.

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Highlights of the third edition of Chinese guidelines for AIDS diagnosis and treatment(2015)
SUN Jian-jun, LU Hong-zhou
Journal of ZheJiang University(Medical Science)    2015, 44 (6): 597-602.   DOI: 10.3785/j.issn.1008-9292.2015.11.01
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The third edition of Chinese guidelines for AIDS diagnosis and treatment was launched in 2015 by AIDS Professional Group, Society of Infectious Diseases, Chinese Medical Association. New edition emphasizes the importance of timely initiation of anti-retroviral therapy(ART). Like other guidelines, this edition recommends that once the HIV infection is confirmed, the ART should be initiated timely. For patients with HIV and opportunistic infections, once the infections are under control, the ART should be initiated without delay. For AIDS patients complicated with tuberculosis whose CD4 cell counts are less than 200/μL, the ART should start within 2 weeks after the initiation of anti-tuberculosis treatment. In this guideline, the drugs with severe toxicities and poor tolerance are excluded, and new drugs are added such as rilpivrine (RPV) and atazanavir (ATV) because of less toxicity and higher HIV depression effect; and 3TC+TDF+EFV is recommended as the first line regimen. As for children with HIV infection, especially for those less than 5 years, once the infection is confirmed the ART should be initiated immediately. For the prevention of HIV mother to children transmission, new edition recommends that HIV-infected pregnant women start ART early and keep on ART all their lives.

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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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Advances of chemokines in pathogenesis of psoriasis
Journal of ZheJiang University(Medical Science)    2002, 31 (6): 483-487.   DOI: 10.3785/j.issn.1008-9292.2002.06.023
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Genetic imprinting and embryonic development
Journal of ZheJiang University(Medical Science)    2007, 36 (5): 509-514.   DOI: 10.3785/j.issn.1008-9292.2007.05.018
Abstract   PDF (272KB) ( 517 )  
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Age variations of head-face morphological traits of Hakka in Guangdong province
Journal of ZheJiang University(Medical Science)    2012, 41 (3): 250-258.   DOI: 10.3785/j.issn.1008-9292.2012.03.005
Abstract   PDF (1060KB) ( 516 )  
Objective: To investigate the age variations of head-face morphological traits of Hakka in Guangdong Province.
Methods: Thirty-eight physical indices of head and face of 671 Hakka adults (151 urban males,181 urban females,162 rural males and 177 rural females) from Meizhou city of Guangdong were investigated.Twelve physical indices of head and face were calculated and counted its indices distributions.The age changes of morphological traits of head and face were analyzed.
Results: With the age growing,the rate of eyefold of the upper eyelid was increased,and the Mongoloid fold decreased,the direction of eyeslits tended to level,nasal root height dropped,the zygomatic projection was more projected,the eye color turned to lighter,the upper red lips became thinner; medium-sized facial height,nasal height,upper lip skin height,physiognomic ear length,physiognomic ear breadth and breadth of alae nasi were decreased.The index of mouth breadth,morphological facia skin fold were positively correlated with the age.The index of minimum frontal breadth,face breadth,bigonial diameter,interocular breadth,external biocular breadth,lip height,thickness of lips and horizontal head circumference were negatively correlated with the age.With the age growing,morphological facial index and vertical cephalo-facial index was ascending.Moreover,length-height index of head,transverse frontoparietal index,zygomatico-frontal index and lip index were declining.
Conclusion: With the age growing,the head and face measurements,physical indices and the proportion of observed indices have changed in Hakka in Guangdong province.
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Impact of cerebral microbleeds on outcomes of acute ischemic stroke treated with intravenous thrombolysis
YAN Shen-qiang, WAN Jin-ping, GUO Yang, LOU Min
Journal of ZheJiang University(Medical Science)    2014, 43 (1): 20-27.   DOI: 10.3785/j.issn.1008-9292.2014.01.019
Abstract   PDF (789KB) ( 509 )  

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

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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) ( 508 )  

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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Somatic mutation and novel strategies for personalized targeting therapy
Journal of ZheJiang University(Medical Science)    2013, 42 (1): 1-.   DOI: 10.3785/j.issn.1008-9292.2013.01.001
Abstract   PDF (762KB) ( 501 )  
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Meta-analysis study on risk factors of colorectal cancer
Journal of ZheJiang University(Medical Science)    2002, 31 (4): 254-258.   DOI: 10.3785/j.issn.1008-9292.2002.04.007
Abstract   PDF (229KB) ( 492 )  
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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
Abstract   PDF (1110KB) ( 489 )  
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How to improve the diagnosis rate of early gastric cancer in China
ZOU Wen-bin, YANG Fan, LI Zhao-shen
Journal of ZheJiang University(Medical Science)    2015, 44 (1): 9-14,53.   DOI: 10.3785/j.issn.1008-9292.2015.01.002
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China has great burden of gastric cancer, and the diagnosis rate of early gastric cancer is relatively low (<10%). To perform screening, early endoscopic diagnosis and treatment of gastric cancer in high-risk population is a feasible and efficient way to change the current status. Therefore, the Chinese Society of Digestive Endoscopy recently issued Consensus on screening, "Endoscopic diagnosis and treatment of early gastric cancer screening in China". The consensus suggests a feasible and efficient strategy for early detection of gastric cancer: screening with non-invasive procedures, followed by intensive endoscopic examination for screened high-risk population. In this article, we also describe the current status, the causes, high-risk population and early diagnosis of gastric cancer in China; and review the new development of serology and endoscopic techniques for early diagnosis.

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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) ( 486 )  

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

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

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

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The role of central cholinergic system in epilepsy
J Zhejiang Univ (Med Sci)    2017, 46 (1): 15-21.   DOI: 10.3785/j.issn.1008-9292.2017.02.03
Abstract   HTML PDF (1058KB) ( 480 )  

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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Measurement of facial bone wall thickness of maxillary anterior teeth and premolars on cone beam computed tomography images
Journal of ZheJiang University(Medical Science)    2012, 41 (3): 234-238.   DOI: 10.3785/j.issn.1008-9292.2012.03.002
Abstract   PDF (1079KB) ( 456 )  
Objective: To measure the thickness of facial bone wall of maxillary anterior teeth and premolars based on cone beam computed tomography (CBCT) images.
Methods: CBCT images from 118 patients were collected from the Affiliated Stomatology Hospital of Zhejiang University.The thickness perpendicular to the long axis of facial bone wall was measured at two locations: 4 mm apical to the cementoenamel junction (point 1) and the middle of the root (point 2).
Results: The thickness of the facial bone walls of central incisors,lateral incisors and canines ranged from 0.5 to 1.5 mm.A thin facial bone wall (﹤1.0 mm) was quite frequent in central incisors (44.1% at point 1,56.8% at point 2),lateral incisors (65.2% at point 1,89.8% at point 2) and canines (45.8% at point 1,61.0% at point 2).In contrast,the majority of examined first premolars (77.1% at point 1,68.7% at point 2) and second premolars (94.1% at point 1,94.1% at point 2) exhibited a thick facial bone wall (≥1.0 mm).
Conclusions: A thin facial bone wall of teeth in the anterior maxilla is common.Radiographic analysis of facial bone wall using CBCT is recommended for selection of appropriate treatment approach.
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Thresholds of CT perfusion in predicting ischemic penumbra and infarct core in patients with acute ischemic stroke
YU Yan-nan, DING Xin-fa, ZHANG Sheng, LOU Min
Journal of ZheJiang University(Medical Science)    2014, 43 (1): 7-13.   DOI: 10.3785/j.issn.1008-9292.2014.01.022
Abstract   PDF (1708KB) ( 453 )  

Objective: To determine the optimal parameters and their thresholds on CT perfusion (CTP) to predict the penumbra and core in patients with acute ischemic stroke.
Methods: The data of 39 thrombolytic candidates with acute cerebral anterior-circulation ischemic stroke admitted in the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to October 2013 were retrospectively reviewed. Patients all underwent CTP at admission and CTP or magnetic resonance perfusion (MRP) 24 h after thrombolysis. Patients were classified as non-reperfusion group (to define the threshold of penumbra, n=10) and reperfusion group (to define the threshold of infarct core, n=21) by reperfusion status. According to the baseline CTP and 24 h imaging, the volumes of threshold-based hypoperfusion lesions and final infarction were calculated. Paired t test, correlation analysis and Bland-Altman plot were performed to assess the optimal thresholds for predicting the penumbra and infarct core.
Results: In non-reperfusion group, the best agreement was found between final infarct volume and delay time>3 s (bias 3.3 ml, 95% limits of agreement: -41.7 to 48.3 ml, r=0.933, P<0.001), while in reperfusion group, the best agreement was noted between final infarct volume and rCBF<30% (bias -2.2 ml, 95% limits of agreement: -25.6 to 21.2 ml; r=0.923, P<0.001).
Conclusion: Delay time>3 s and rCBF<30% are the optimal thresholds for predicting the penumbra and infarct core on CTP, respectively. These thresholds may be of help to estimate the mismatch status and select eligible patients for thrombolysis.

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Kyoto global consensus report for treatment of Helicobacter pylori and its implications for China
XIE Chuan, LYU Nonghua
Journal of ZheJiang University(Medical Science)    2016, 45 (1): 1-4.   DOI: 10.3785/j.issn.1008-9292.2016.01.01
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Kyoto global consensus report on Helicobacter pylori gastritis (Gut, July 2015) is another important international consensus since the European Maastricht Ⅳ consensus was published. Kyoto consensus will improve the etiology-based classification, the diagnostic assessment of gastritis, and the treatment of H. pylori-associated dyspepsia and H. pylori gastritis. However, because of high rate of H. pylori infection and antibiotic resistance as well as limited health resources in China, we need to develop our own strategies of H. pylori infection control with the reference of the Kyoto global consensus.

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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) ( 448 )  
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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Research frontiers and trends of the analytical technology for Chinese medicine
Journal of ZheJiang University(Medical Science)    2012, 41 (1): 1-5.   DOI: 10.3785/j.issn.1008-9292.2012.01.001
Abstract   PDF (1159KB) ( 446 )  
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Nicotinamide phosphoribosyltransferase and its roles in cancer
XU Xiao-fang,WU Ming
Journal of ZheJiang University(Medical Science)    2014, 43 (1): 109-114.   DOI: 10.3785/j.issn.1008-9292.2014.01.004
Abstract   PDF (600KB) ( 443 )  

Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme for synthesis of nicotinamide adenine dinucleotide in mammalian cells.Recent studies show that Nampt also works as a cytokine that exerts insulin-mimetic effects by binding to the insulin receptor,induces B-cell differentiation,inhibits neutrophil apoptosis,and affects immune and inflammatory functions.This review is focused on current knowledge regarding the structure and function of Nampt and its roles in carcinogenesis.

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Prospect and guideline update of sentinel lymph node biopsy for patients with early-stage breast carcinoma
ZHOU Mei-qi,et al
Journal of ZheJiang University(Medical Science)    2014, 43 (4): 381-387.   DOI: 10.3785/j.issn.1008-9292.2014.07.001
Abstract   PDF (1131KB) ( 443 )  

Axillary lymph nodes are the most common and initial site of metastasis of breast carcinoma. Precise axillary staging of breast carcinoma before initial treatment is crucial as it allows efficient identification for local and systemic treatment options, and provides prognostic information. Sentinel lymph node biopsy (SLNB) is an accurate minimally invasive technology for axillary staging. Although top evidence of high-quality clinical trials showed that SLNB could safely and effectively replace axillary lymph node dissection (ALND) for axillary negative patients with decrease in complications and improvement in quality of life, there are specific indications and contraindications for SLNB. Clinicians should balance the compliance of guideline and native clinical practice, especially for the circumstance of multifocal/multicentric lesion, breast biopsy history, and neoadjuvant chemotherapy. With the accumulation of clinical practice and new results of clinical trials, axillary therapy has changed from unique surgery to patient-tailored multi-disciplinary intervention, although ALND should be recommended traditionally if SLNB is positive. Intensive and accurate preoperative axillary staging is gradually valued by clinicians. Development of imaging modality especially ultrasonography and ultrasound-guided biopsy can identify some extra lymph node positive patients directly to ALND with avoidance of unnecessary SLNB. Thus, the positive rate of SLNB will decline significantly. It seems possible that axillary management will step into a noninvasive era abandoning SLNB in some patients with small breast cancer. In this article we review the prospect and guideline update of SLNB for patients with early-stage breast cancer.

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Expert consensus on induction of human embryonic stem cells into tenocytes
CHEN Xiao, ZOU Xiaohui, YU Guangyan, FU Xin, CAO Tong, XIAO Yin, OUYANG Hongwei
Journal of ZheJiang University(Medical Science)    2016, 45 (2): 105-111.   DOI: 10.3785/j.issn.1008-9292.2016.03.01
Abstract   PDF (1336KB) ( 442 )  

Embryonic stem cells have unlimited proliferative capacity, which may provide a source of tendon stem/progenitor cells for tissue engineering. Experts of International Science and Technology Collaborative Program of Ministry of Science and Technology have developed a protocol consensus on differentiation of human embryonic stem cells into the tendon cells. The consensus recommends a protocol of two-step generation of human embryonic stem cells into tendon cells: the human embryonic stem cells are first differentiated into mesenchymal stem cells on different material surfaces; then with the scaffold-free tissue engineering tendon formed by high-density planting, the mesenchymal stem cells are induced into tendon cells under static or dynamic mechanical stimulation in vivo and in vitro. Tissue engineering tendon established in vitro by the protocol can be used as a model in toxicological analysis and safety evaluation of tendon-relevant small molecule compounds, medical materials and drugs.

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Progression in metastasis of colorectal carcinoma
ZHAO Liang,et al
Journal of ZheJiang University(Medical Science)    2014, 43 (4): 486-493.   DOI: 10.3785/j.issn.1008-9292.2014.07.009
Abstract   PDF (1063KB) ( 440 )  
Globally, the incidence of colorectal carcinoma (CRC) ranks the third among all cancers. The incidence of CRC is continually increasing in China. Invasion and metastasis are the major causes of death. Metastasis is a complex multistep malignant process, including the detachment of tumor cells from the primary site, interaction of tumor cells with the surrounding extracellular matrix, entering into the circulation or lymph system, adhesion to the endothelial cells of vascular wall, migration of tumor cells into secondary sites, angiogenesis and formation of new metastases. This article reviews the recent research progress in aspects of the metastasis related genes, microRNAs, epithelial mesenchymal transition, tumor stem cells, and micro environment of colorectal cancer.
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The relationship between hypoxia-inducible factor-1α expression and apoptosis in early brain injury after subarachnoid hemorrhage
HU Qiang,WU Cheng,CHEN Jing-yin,YAN Feng,LI Jian-ru,CHEN Gao
Journal of ZheJiang University(Medical Science)    2014, 43 (1): 58-65.   DOI: 10.3785/j.issn.1008-9292.2014.01.009
Abstract   PDF (3208KB) ( 438 )  

Objective: To investigate the association of hypoxia-inducible factor-1α (HIF-1α) expression and apoptosis in the cerebral cortex following subarachnoid hemorrhage (SAH).
Methods: Subarachnoid hemorrhage was induced by modified monofilament puncture method in rats.Thirty-five adult male Sprague-Dawley rats were randomly assigned to five groups: sham-operated group,SAH 6 h,SAH 12 h,SAH 24 h and SAH 72 h groups.HIF-1α expression was assessed by immunofluorescence staining.TdT-mediated dUTP-biotin nick end-labeling (TUNEL) technique was adopted to detect apoptotic cells.Double immunolabeling was used to identify cell types with positive HIF-1α expression.
Results: The expression of HIF-1α was increased at 6 h (4.65%±1.01%),peaked at 24 h (18.55%±4.23%),and decreased at 72 h (6.31%±1.15%) after SAH (P<0.05).TUNEL-positive cells were up-regulated in the brain at 6 h (7.09%±2.34%),peaked at 24 h (25.54%±7.36%),and down-regulated at 72 h (14.11%±3.03%) after SAH (P<0.05).A significant positive correlation was noted between HIF-1α positive rates and TUNEL positive rates following SAH (r=0.738,P<0.05).Double immunolabeling indicated that HIF-1α was expressed predominantly in neurons and some nuclei with positive HIF-1α were co-stained with TUNEL.
Conclusion: The data indicate that HIF-1α might participate in the pathological progression of early brain injury after SAH.

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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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Update of pathological diagnosis of pulmonary neuroendocrine tumor
TENG Xiaodong, ZHAO Ming, LAI Maode
Journal of ZheJiang University(Medical Science)    2016, 45 (1): 36-44.   DOI: 10.3785/j.issn.1008-9292.2016.01.06
Abstract   PDF (1224KB) ( 436 )  

Pulmonary neuroendocrine tumors are common in pathological practice and its pathological classification and histological grading are not exactly the same as that of those in the digestive tract and pancreas. In 2015 edition of World Health Organization classification, pulmonary neuroendocrine tumors are classified as carcinoid tumors (including typical carcinoid and atypical carcinoid), small cell lung carcinoma, large cell neuroendocrine carcinoma, and precursor lesion diffuse idiopathic neuroendocrine cell hyperplasia; each category has distinctive morphological and immunohistochemical features. The morphologic features including growth patterns and cytological appearances are keys for the diagnosis of neuroendocrine tumor, and immunohistochemical findings are also critical for its diagnosis. Furthermore, the diagnostic criteria vary for different types of specimen. In this article, we present a concise review and summary of the update of clinicopathological characterizations of pulmonary neuroendocrine tumor, with an emphasis on its diagnostic criteria and differential diagnosis.

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