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Gorham-Stout syndrome in China's Mainland:a case series of 67 patients and review of the literature

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第8期14卷 729-735页

作者： Po hu Xiang-gui YUAN xin-yang hu Fa-rong SHEN Jian-an WANG Cardiovascular Key Lab of Zhejiang Province Department of Cardiology the Second Affiliated Hospital School of Medicine Zhejiang University Department of Cardiology Zhejiang Hospital Department of Internal Medicine Hangzhou Binjiang Hospital the Second Affiliated Hospital (Binjiang Branch) School of Medicine Zhejiang University

Objective:Gorham-Stout syndrome (GSS) is a rare disorder of uncertain etiology and unpredictable prognosis. This study aims to present a comprehensive understanding of this rare entity. Methods:A literature search in PubMed and three Chinese databases was performed to screen histologically proven GSS cases among Chinese residents in the mainland. We analyzed the patients' clinical characteristics, the value of different treatment modalities and their influence on the clinical outcome. Results:Sixty-seven cases were finally enrolled. There were 43 men (64.2%) and 24 women (35.8%). The mean age at diagnosis was 28 years (1.5-71 years). The most common clinical symptoms included pain (n=40, 59.7%), functional impairment (n=13, 19.4%), and swelling (n=12, 17.9%). The radiographic presentation of 37 cases (55.2%) was disappearance of a portion of the bone. The others presented as radiolucent foci in the intramedullary or subcortical regions. A total of 42 cases provided data on therapy, these included surgery (n=27, 40.3%), radiation therapy (n=6, 9.0%), surgery combined with radiation therapy (n=2, 3.0%), and medicine therapy (n=7, 10.4%). For 30 of these 42 cases, follow-up data were available:21 cases had the disorder locally controlled and 9 had a symptom progression. Fortunately, the disease is not fatal in the majority of cases. Conclusions:GSS has no specific symptoms and it should be taken into consideration when an unclear massive osteolysis occurs. The efficacies of different treatment modalities are still unpredictable and further research is required to assess the values of different treatments.

关键词： Gorham-Stout syndrome (GSS) Massive osteolysis Chinese

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Optimal time for mesenchymal stem cell transplantation in rats with myocardial infarction

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第8期9卷 630-637页

作者： Chen-yang JIANG Chun GUI Ai-na HE xin-yang hu Jie CHEN Yun JIANG Jian-an WANG Department of Cardiology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310016 China Department of Cardiology the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China Department of Cardiology the First Affiliated Hospital Zhejiang Chinese Medical University Hangzhou 310006 China

Background:Bone marrow mesenchymal stem cell (MSC) transplantation is a promising strategy in the treatment of myocardial infarction (MI). However, the time for transplanting cells remains controversial. The aim of this study was to find an optimal time point for cell transplantation. Methods: MSCs were isolated and cultured from Sprague-Dawley (SD) rats. MI model was set up in SD rats by permanent ligation of left anterior descending coronary artery. MSCs were directly injected into the infarct border zone at 1 h, 1 week and 2 weeks after MI, respectively. Sham-operated and MI control groups received equal volume of phosphate buffered saline (PBS). At 4 weeks after MI, cardiac function was assessed by echocardiography; vessel density was analyzed on hematoxylin-eosin stained slides by light microscopy; the apoptosis of cardiomyocytes was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay; the expressions of proteins were analyzed by Western blot. Results: MSC transplantation improved cardiac function, reduced the apoptosis of cardiomyocytes and increased vessel density. These benefits were more obvious in 1-week group than in 1-h and 2-week groups. There are more obvious in-creases in the ratio of bcl-2/bax and the expression of vascular endothelial growth factor (VEGF) and more obvious decreases in the expression of cleaved-caspase-3 in 1-week group than those in other two groups. Conclusion: MSC transplantation was beneficial for the recovery of cardiac function. MSC transplantation at 1 week post-MI exerted the best effects on increases of cardiac function, anti-apoptosis and angiogenesis.

关键词： Mesenchymal stem cells (MSCs) Transplantation Myocardial infarction (MI) Apoptosis

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Complex coronary lesions and rotational atherectomy:one hospital's experience

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第8期13卷 645-651页

作者： Jun JIANG Yong SUN Mei-xiang XIANG Liang DONG Xian-bao LIU xin-yang hu Yan FENG Jian-an WANG Department of Cardiology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Cardiovascular Key Lab of Zhejiang Province the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China

Objective:To evaluate the safety and effectiveness of rotational atherectomy followed by drug eluting stent (DES) implantation in patients with complex coronary lesions. Methods:From August 2006 to August 2012, 253 consecutive patients with 289 lesions and who underwent rotational atherectomy in our center were enrolled in this study. Results:The overall procedure success rate was 98% with the cost of two (0.8%) coronary perforations, three (1.2%) dissections, five (2.0%) slow flows or no flows, three (1.2%) peri-procedure myocardial infarctions, and two (0.8%) in hospital deaths. During follow-up (mean three years), one (0.4%) patient died, two (0.8%) patients had acute myocardial infarction, 14 (5.5%) had restenosis, and target lesion revascularization occurred in eight patients (3.2%). Conclusions:Rotational atherectomy followed by DES implantation is a safe and effective technique for patients with complex coronary lesions, especially calcified and non-dilatable lesions.

关键词： Complex coronary lesions Calcified coronary lesions Rotational atherectomy Drug eluting stents

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Tongxinluo promotes mesenchymal stem cell tube formation in vitro

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第8期12卷 644-651页

作者： xin-yang hu Wen-xia WANG Min-jia YU Xian-bao LIU Rong-rong WU Feng GAO xin huANG Jiang CAO Xiao-jie XIE Jian-an WANG Cardiovascular Key Lab of Zhejiang Province the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China Department of Cardiology the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Objective： To study whether Tongxinluo （TXL） can induce angiogenesis in bone marrow mesenchymal stem cells （MSCs）, and to investigate the underlying mechanism. Methods： Bone marrow MSCs were obtained from male Sprague-Dawley rats. We established an angiogenesis model in vitro via matrigel experiment. MSCs were seeded on matrigel coated 24-well plates, and treated by TXL 50 and 100 mg/L. After 24 h, we observed the tube formations of MSCs in the matrigel. Cell migration ability was examined by wound scratch test and transwell assay. Expressions of vascular endothelial growth factor （VEGF）, fetal liver kinase-1 （FIk-1）, matrix metalloproteinase-2 （MMP-2）, MMP-9, and tissue inhibitor of metalloproteinase-2 （TIMP-2） were analyzed at the protein level by Western blot. Gelatin zymography assay was applied to investigating the MSC paracrine abilities of pro-MMP-2 and activated MMP-2. Results： TXL promoted MSC tube formation in matrigel. The ratio of TXL 100 mg/L treated-MSC tubular length was increased 3.04-fold compared to the control group （P〈0.05）. Scratch test and transwell assay showed that TXL could improve the cell migration ability of MSCs. Western blot experiments showed that TXL promoted MSC synthesis of MMP-2, but it had no influence on the expressions of MMP-9 and TIMP-2. This effect was confirmed by gelatin zymography assay, which showed that TXL increased MSC secretion of pro-MMP-2 and activated MMP-2. VEGF expression of TXL treated-MSCs was increased compared to the control group. The expression of FIk-1 was not different among the groups. Conclusions： This study demonstrates that TXL can promote the tube formation of MSCs, and the underlying mechanisms are associated with increased migration ability of MSCs and the up-regulation of MMP-2 and VEGF expressions.

关键词： Bone marrow mesenchymal stem cells Tongxinluo Angiogenesis Migration Tube formation

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Heat shock protein 90 protects rat mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis via the PI3K/Akt and ERK1/2 pathways

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第8期11卷 608-617页

作者： Feng GAO xin-yang hu Xiao-jie XIE Qi-yuan XU Ya-ping WANG Xian-bao LIU Mei-xiang XIANG Yong SUN Jian-an WANG Department of Cardiology Hangzhou 310009 China Cardiovascular Key Lab of Zhejiang Province the Second~ffiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Mesenchymal stem cell （MSC） transplantation has shown a therapeutic potential to repair the ischemic and infracted myocardium, but the effects are limited by the apoptosis and loss of donor cells in host cardiac microenvironment. The aim of this study is to explore the cytoprotection of heat shock protein 90 （Hsp90） against hypoxia and serum deprivation-induced apoptosis and the possible mechanisms in rat MSCs. Cell viability was determined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） assay. Apoptosis was assessed by Hoechst 33258 nuclear staining and flow cytometric analysis with annexin V/PI staining. The gene expression of Toll-like receptor-4 （TLR-4） and V-erb-b2 erythroblastic leukemia viral oncogene homolog 2 （ErbB2） was detected by real-time poly- merase chain reaction （PCR）. The protein levels of cleaved caspase-3, Bcl-2, Bcl-xL, Bax, totaI-ERK, phospho-ERK, totaI-Akt, phospho-Akt, and Hsp90 were detected by Western blot. The production of nitric oxide was measured by spectrophotometric assay. Hsp90 improves MSC viability and protects MSCs against apoptosis induced by serum deprivation and hypoxia. The protective role of Hsp90 not only elevates Bcl-2/Bax and Bcl-xL/Bax expression and attenuates cleaved caspase-3 expression via down-regulating membrane TLR-4 and ErbB2 receptors and then ac- tivating their downstream PI3K/Akt and ERK1/2 pathways, but also enhances the paracrine effect of MSCs. These findings demonstrated a novel and effective treatment strategy against MSC apoptosis in cell transplantation.

关键词： Heat shock protein Apoptosis Stem cell Hypoxia Phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) Extracellular-signal-regulate kinase (ERK)

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Adjunctive aripiprazole for antipsychotic-related hyperprolactinaemia in patients with first-episode schizophrenia:a metaanalysis

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General Psychiatry 2019年第5期32卷 249-256页

作者： Wei Zheng Dong-Bin Cai xin-hu yang Wei Zheng Gabor S Ungvari Chee H Ng Zhan-Ming Shi Mei-Ling hu Yu-Ping Ning Yu-Tao Xiang The Affiliated Brain Hospital of Guangzhou Medical University Guangzhou Huiai HospitalGuangzhouChina Shenzhen Traditional Chinese Medicine ShenzhenChina School of Medicine Xiamen UniversityXiamenChina University of Notre Dame Australia FremantleWestern AustraliaAustralia Division of Psychiatry School of MedicineUniversity of Western AustraliaPerthWestern AustraliaAustralia Department of Psychiatry University of MelbourneMelbourneVictoriaAustralia Chongqing Jiangbei Mental Health Center ChongqingChina Shangrao Fifth People's Hospital ShangraoChina Unit of Psychiatry Faculty of Health SciencesUniversity of MacaoMacao SARChina Center for Cognition and Brain Sciences University of MacaoMacao SARChina

Background Hyperprolactinaemia is a common antipsychotic(AP)-induced adverse effect,particularly in female *** This meta-analysis examined the efficacy and safety of adjunctive aripiprazole in preventing AP-related hyperprolactinaemia in patients with first-episode *** PubMed,PsycINFO,EMBASE,Cochrane Library,WanFang and China Journal Net databases were searched to identify eligible randomised controlled trials(RCTs).Primary outcomes were the reductions of serum prolactin level and prolactin-related *** were independently extracted by two reviewers and analysed using RevMan(V.5.3).Weighted/standardised mean differences(WMDs/SMDs)±95%Cis were *** In the five RCTs(n=400),the adjunctive aripiprazole(n=197)and the control groups(n=203)with a mean of 11.2 weeks of treatment duration were *** aripiprazole group had a significantly lower endpoint serum prolactin level in all patients(five RCTs,n=385;WMD:-50.43 ng/mL(95%Cl:-75.05 to-25.81),p<0.00001;l2=99%),female patients(two RCTs,n=186;WMD:-22.58 ng/mL(95%Cl:-25.67 to-19.49),p<0.00001;l2=0%)and male patients(two RCTs,n=127;WMD:-68.80 ng/mL(95%Cl:-100.11 to-37.49),p<0.0001).In the sensitivity analysis for the endpoint serum prolactin level in all patients,the findings remained significant(p<0.00001;l2=96%).The aripiprazole group was s叩erior to the control group in improving negative symptoms as assessed by the Positive and Negative Syndrome Scale(three RCTs,n=213;SMD:-0.51(95%Cl:-0.79 to-0.24),p=0.0002;l2=0%).Adverse effects and discontinuation rates were similar between the two *** Adjunctive aripiprazole appears to be associated with reduced AP-induced hyperprolactinaemia and improved prolactin-related symptoms in first-episode *** studies with large sample sizes are needed to confirm these findings.

关键词： patients schizophrenia prolactin

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Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2006年第8期7卷 641-647页

作者： WANG Jian-an LUO Rong-hua ZHANG xing XIE Xiao-jie hu xin-yang HE Ai-na CHEN Jie LI Jia-hui Department of Cardiology the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China Center of Lab Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310016 China

Objective: This study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction. Methods: Forty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson’s trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis. Results: The fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group, ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4 groups. Conclusion: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

关键词： Remodelling Acute myocardial infarction Perindopril Bone marrow mesenchymal stem cell

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Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第8期13卷 616-623页

作者： Xian-bao LIU Han CHEN hui-qiang CHEN Mei-fei Zhu xin-yang hu Ya-ping WANG Zhi JIANG Yin-chuan XU Mei-xiang XIANG Jian-an WANG Cardiovascular Key Lab of Zhejiang Province the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Cardiology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Intensive Care Unit Zhejiang Provincial Hospital of Traditional Chinese MedicineHangzhou 310006China

Objective： Mesenchymal stem cell （MSC） transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 （Angl） preconditioning on MSC survival and sub- sequent heart function improvement after transplantation. Methods： MSCs were cultured with or without 50 ng/ml Angl in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-（4,5- Dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （MTT） and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl trans- ferase biotin-dUPT nick end labeling （TUNEL） assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson＇s trichrome staining, respectively. Results： Angl preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Angl-preconditioned cell survival was significantly in- creased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Angl preconditioning. After transplantation, the Angl-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group. Conclusions： Angl preconditioning enhances MSC survival, contributing to further improvement of heart function.

关键词： Mesenchymal stem cells Angiopoietin-1 Preconditioning Survival Myocardial infarction

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Meta-analysis of C242T polymorphism in CYBA genes: risk of acute coronary syndrome is lower in Asians but not in Caucasians

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2015年第5期16卷 370-379页

作者： Po hu Ming-yuan huANG xin-yang hu Xiao-jie XIE Mei-xiang XIANG Xian-bao LIU Jian-an WANG Key Laboratory for Diagnosis and Treatment of Cardiovascular Disease of Zhejiang Province the Second Affiliated HospitalSchool of Medicine Zhejiang University Department of Cardiology the Second Affiliated Hospital School of Medicine Zhejiang University

Background：A lot of studies have demonstrated that C242T polymorphism in CYBA genes may play an important role in the pathological process of acute coronary syndrome （ACS）. However, the results are not consistent. To further evaluate this debate, we performed a meta-analysis to determine the relationship between C242T poly-morphism and ACS. Methods and results：We screened PubMed/MEDLINE, EBSCIO, and EMBASE research reports until Mar. 2014 and extracted data from 10 studies involving 6102 ACS patients and 8669 controls. Subgroup analysis by ethnicity documented a significant decreased risk of ACS for C242T polymorphism in the Asian population under al elic comparison （odd ratio （OR） 0.73;95%confidence intervals （CI） 0.64–0.83）, dominant model （OR 0.71;95%CI 0.62–0.82）, and homozygote comparison （OR 0.57;95%CI 0.35–0.92）. However, in the overal population and es-pecial y with Caucasians, no significant association was uncovered. Further meta-regression analysis revealed that the heterogeneity among studies was largely attributed to ethnicity. No publication bias was detected through a funnel plot and an Egger’s linear regression test. Conclusions： Taken together, our results suggest that the C242T poly-morphism might be a protective factor against developing ACS in the Asian population. Further researches wil be needed to identify the confounding factors which modified the protective effect of T al ele among Caucasians.

关键词： CYBA C242T polymorphism Acute coronary syndrome

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Fractional Flow Reserve Guided Percutaneous Coronary ntervention Improves Clinical Outcome with Reduced Cost in Contemporary Clinical Practice

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Chinese Medical Journal 2015年第15期128卷 2000-2005页

作者： Po hu Meng-Yao Tang Wen-Chao Song Jun Jiang Yong Sun Xian-Bao Liu Chang-Ling Li xin-yang hu Jian-An Wang Department of Cardiology Second Affiliated Hospital College of Medicine Zhejiang University Hangzhou Zhejiang 310009 China Key Laboratory for Diagnosis and Treatment of Cardiovascular Disease of Zhejiang Province Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou Zhejiang 310009 China

Background：Fractional flow reserve （FFR） is currently considered as the gold standard for evaluating the functional significance of coronary ***,its potential benefits in real-world practice remain unknown in *** study aimed to test the hypothesis that the use of FFR is associated with improved outcome and reduced cost in Chinese real-world clinical ***：A retrospective cohort study was carried out using the database of Second Affiliated Hospital of Zhejiang University,a tertiary and high-volume center in *** events were compared using the Cox proportional hazards model during a median follow-up of 13 ***：The study cohort consisted of 366 consecutive patients referred for coronary revascularization with adjunct FFR and 366 matched controls,from 2010 to *** adverse cardiac events （MACEs）（death,myocardial infarction,repeated revascularization,or hospitalization for angina） at 4 years were found in 12.0% ofangiography-guided patients and 4.9% in the FFR-guided group （P 〈 0.001）.The mean number of implanted stents was significantly lower in FFR treated subjects （0.52 ± 0.82 stents） compared with the angiography-guided group （0.93 ± 0.96 stents）（P 〈 0.001）.No difference in overall costs at initial hospitalization was observed between angiography-guided percutaneous coronary intervention （PCI） compared with FFR-guided PCI （RMB 33,000 Yuan,range：RMB 7393-44,700 Yuan） versus RMB 21,200 Yuan （RMB 19,100-47,100 Yuan）（P =0.54）.However,costs for MACEs during follow-up were significantly reduced in the FFR-guided arm （P 〈 0.001）.Conclusions：In the contemporary clinical practice,FFR-guided PCI is associated with decreased use of stents,improved clinical outcome,and reduced costs,compared with angiography-guided PCI.

关键词： Costs and Cost Analysis Fractional Flow Reserve Myocardial Percutaneous Coronary Intervention Prognosis

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