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Efficacy and safety of clarithromycin for patients with sepsis or septic shock:a systematic review and meta-analysis

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Emergency and Critical Care Medicine 2024年第2期4卷 90-96页

作者： Pengyue Zhao Renqi Yao Jiaqi Yang Wei Wen Yongming Yao Xiaohui Du Department of General Surgery First Medical Center of the Chinese PLA General HospitalBeijingChina translational Medicine research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General HospitalBeijingChina Department of Burn Surgery the First Affiliated Hospital of Naval Medical UniversityShanghaiChina Department of General Surgery Hainan Hospital of Chinese PLA General HospitalSanyaHainanChina

Background:Clarithromycin exerts an immunomodulatory role in several human ***,whether this effect improves the prognosis in patients with sepsis remains controversial,and higher levels of clinical evidence are urgently *** the best of our knowledge,no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in ***:A comprehensive literature search of PubMed,EMBASE,and the Cochrane Library was conducted up to December 31,*** randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were *** were pooled by applying a fixed-effects model and a relative risk(RR)estimate with 95%confidence intervals(CIs)using Review Manager(version 5.3;Cochrane Collaboration,Copenhagen,Denmark).Results:Three randomized controlled trials involving a total of 910 patients were *** pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome(RR:1.51;95%CI:1.02-2.25;P=0.04;I^(2)=0%),28-day mortality(RR:1.09;95%CI:0.87-1.36;P=0.46;I^(2)=0%),and 90-day mortality(RR:0.86;95%CI:0.71-1.03;P=0.10;I^(2)=81%)in patients with sepsis or septic ***,there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group(RR:1.02;95%CI:0.87-1.19;P=0.83;I^(2)=18%).Conclusion:Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with ***,administration of clarithromycin did not increase the risk of adverse events.

关键词： Clarithromycin Meta-analysis Outcomes Sepsis Septic shock

Gene expression profiles and treatments for metastatic renal cell carcinoma:What does still need to be defined?

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Asian Journal of Urology 2022年第3期9卷 206-207页

作者： Emilio F.Giunta Pasquale Rescigno Roberto Pili interdisciplinary group for translational research and clinical trials Urological Cancers(GIRT-Uro)Candiolo Cancer InstituteFPO-IRCCSCandioloTurinItaly Division of Hematology and Oncology Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloBuffaloNYUSA

Approximately one third of renal cell carcinoma(RCC)patients have metastasis at the time of diagnosis,while one third of localized patients inevitably develop disease recurrence[1,2].To date,there are four drug combinations with immunotherapies which have been approved by the US Food and Drug Administration as first-line therapy in metastatic RCC(mRCC):pembrolizumab(anti-programmed cell death protein 1[anti-PD-1]antibody)plus axitinib(vascular endothelial growth factor receptor[VEGF-R]tyrosine kinase inhibitor[TKI]),avelumab(anti-PD-L1 antibody)plus axitinib,nivolumab(anti-PD-1 antibody)plus cabozantinib(multi-target TKI),and nivolumab plus ipilimumab(anticytotoxic T lymphocyte antigen 4 antibody),replacing monotherapies with TKIs targeting the VEGF-R pathway[1].

关键词： diagnosis metastasis death

中国非儿童癌症患者脓毒血症流行情况及地域分布:一项全国横断面研究

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Science Bulletin 2024年第11期69卷 1637-1641页

作者：陆斌胥洋李娜周月阳马旭东陈燕董润周翔代敏陈宏达翁利杜斌中国国家重症医学质控中心和中国重症医学临床试验组 Center for Prevention and Early Intervention National Infrastructures for Translational MedicineInstitute of Clinical MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Pharmacy Administration and clinical Pharmacy School of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China Department of Medical Epidemiology and Biostatistics Karolinska InstitutetStockholm 17177Sweden Department of Medical Administration National Health Commission of the People’s Republic of ChinaBeijing 100044China Medical Intensive Care Unit State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Intensive Care Unit State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China 不详

Cancer poses a major public health burden worldwide,with approximately 18,094,716 newly diagnosed cases and 9,894,402 cancer-related deaths in 2020[1].Infections such as sepsis are among the leading causes of death in... 详细信息

关键词：脓毒血症横断面研究 death 地域分布

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Consensus on the clinical diagnosis and treatment of grade 3 pancreatic neuroendocrine tumors

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胰腺病学杂志(英文) 2024年第2期07卷 97-105页

作者： Chen Jie Wu Wenming Bai Chunmei Chi Yihebali Huo Li Jiang Liming Ji Yuan Luo Jie Li Jie Li Jingnan Lou Wenhui Shao Chenghao Shen Lin Wang Feng Wang Yu Xue Ling Xu Jin Yuan Chunhui Yu Xianjun Yin Xiaoyu Zhao Hong Zhu Xiongzeng Zhao Yupei Centre for Neuroendocrine Tumors Fudan University Shanghai Cancer Center Shanghai China Department of General Surgery State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China Department of Medical Oncology Peking Union Medical College Hospital Chinese Academy of Medical Science &amp Peking Union Medical College Beijing China Department of Medical Oncology National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare Diseases Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing China Department of Diagnostic Radiology National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Pathology Zhongshan Hospital Fudan University Shanghai China Department of Pathology China-Japan Friendship Hospital Beijing China Department of Gastroenterological Oncology Beijing Cancer Hospital Peking University Cancer Hospital &amp Institute Beijing China Department of Gastroenterology Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing China Department of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai China Department of Pancreatic-Biliary Surgery Second Affiliated Hospital of Naval Medical University Shanghai China Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital &amp Department of Nuclear Medicine Nanjing First Hospital Nanjing Medical University Nanjing China Depar

The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

关键词： clinical diagnosis Grade 3 Pancreatic neuroendocrine tumors Treatment

Early assessment of the safety and immunogenicity of a third dose(booster)of COVID-19 immunization in Chinese adults

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Frontiers of Medicine 2022年第1期16卷 93-101页

作者： Yuntao Zhang Yunkai Yang Niu Qiao Xuewei Wang Ling Ding Xiujuan Zhu Yu Liang Zibo Han Feng Liu Xinxin Zhang Xiaoming Yang China National Biotec group Company Limited Beijing 100024China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Beijing Institute of Biological Products China National Biotec Group Company LimitedBeijing 100176China National Vaccine and Serum Institute China National Biotec Group Company LimitedBeijing 101111China Department of Infectious Diseases Research Laboratory of Clinical VirologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Inducing durable and effective immunity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)via vaccination is essential to combat the current pandemic of coronavirus disease 2019(COVID-19).It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time,which calls for an additional vaccination regime,as known as booster immunization,to restore immunity among previously vaccinated *** we report a pilot open-label trial of a third dose of BBIBP-CorV,an inactivated SARS-CoV-2 vaccine(Vero cell),on 136 participants aged between 18 to 63 *** and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day *** systemic reactogenicity was either absent or mild,SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks,surpassing the peak antibody titers elicited by the initial two-dose immunization *** increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third ***,in an exploratory study,a newly developed recombinant protein vaccine,NVSI-06-08(CHO Cells),was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed ***,these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity,providing support for further trials of booster vaccination in larger populations.

关键词： COVID-19 SARS-CoV-2 vaccine immunization booster immunization

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Long-term functional outcomes improved with deep brain stimulation in patients with disorders of consciousness

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Stroke & Vascular Neurology 2023年第5期8卷 368-378页

作者： Yi Yang Qiheng He Yuanyuan Dang Xiaoyu Xia Xin Xu Xueling Chen Jizong Zhao Jianghong He Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina translational Medicine Center Chinese Institute for Brain ResearchBeijingChina Beijing Institute of Brain Disorders Capital Medical UniversityBeijingChina Department of Neurosurgery PLA General HospitalBeijingChina Academician Office China National Clinical Research Center for Neurological DiseasesBeijingChina

Background Deep brain stimulation(DBS)has been preliminarily applied to treat patients with disorders of consciousness(DoCs).The study aimed to determine whether DBS was effective for treating patients with DoC and identify factors related to patients’*** Data from 365 patients with DoCs who were consecutively admitted from 15 July 2011 to 31 December 2021 were retrospectively *** regression and subgroup analysis were performed to adjust for potential *** primary outcome was improvement in consciousness at 1 *** An overall improvement in consciousness at 1 year was achieved in 32.4%(12/37)of the DBS group compared with 4.3%(14/328)of the conservative *** full adjustment,DBS significantly improved consciousness at 1 year(adjusted OR 11.90,95%CI 3.65-38.46,ptrials are still needed.

关键词： stimulation patients admitted

clinical safety and efficacy of allogenic human adipose mesenchymal stromal cells-derived exosomes in patients with mild to moderate Alzheimer’s disease:a phaseⅠ/Ⅱclinical trial

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General Psychiatry 2023年第5期36卷 350-360页

作者： Xinyi Xie Qingxiang Song Chengxiang Dai Shishuang Cui Ran Tang Suke Li Jing Chang Ping Li Jintao Wang Jianping Li Chao Gao Hongzhuan Chen Shengdi Chen Rujing Ren Xiaoling Gao Gang Wang Department of Neurology and Institute of Neurology Shanghai Jiao Tong University Medical School Affiliated Ruijin HospitalShanghaiChina Department of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related GenesShanghai Universities Collaborative Innovation Center for Translational MedicineShanghai Jiao Tong University School of MedicineShanghaiChina Department of Regenerative Medicine Business Cellular Biomedicine GroupShanghaiChina Daxing research Institute University of Science and TechnologyBeijingChina Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghaiChina

Background There have been no effective treatments for slowing or reversing Alzheimer’s disease(AD)until *** preclinical evidence,including this study,suggests that mesenchymal stem cells-secreted exosomes(MSCs-Exos)have the potential to cure *** The first three-arm,drug-intervention,phase I/II clinical trial was conducted to explore the safety and efficacy of allogenic human adipose MSCs-Exos(ahaMSCs-Exos)in patients with mild to moderate *** The eligible subjects were assigned to one of three dosage groups,intranasally administrated with ahaMSCs-Exos two times per week for 12 weeks,and underwent follow-up visits at weeks 16,24,36 and *** No adverse events were *** the medium-dose arm,Alzheimer’s Disease Assessment Scale–Cognitive section(ADAS-cog)scores decreased by 2.33(1.19)and the basic version of Montreal Cognitive Assessment scores increased by 2.38(0.58)at week 12 compared with baseline levels,indicating improved cognitive ***,the ADAS-cog scores in the medium-dose arm decreased continuously by 3.98 points until week *** were no significant differences in altered amyloid or tau deposition among the three arms,but hippocampal volume shrank less in the medium-dose arm to some *** Intranasal administration of ahaMSCs-Exos was safe and well tolerated,and a dose of at least 4×10^(8)particles could be selected for further clinical trials.

关键词： clinical Alzheimer dosage

Immunotherapy for Alzheimer’s disease:targetingβ-amyloid and beyond

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translational Neurodegeneration 2022年第1期11卷 690-706页

作者： Chenghuan Song Jiyun Shi Pingao Zhang Yongfang Zhang Jianrong Xu Lanxue Zhao Rui Zhang Hao Wang Hongzhuan Chen Department of Pharmacology and Chemical Biology Shanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Universities Collaborative Innovation Center for translational Medicine Shanghai Jiao Tong University School of MedicineShanghai 200025China Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education Shanghai Jiao Tong University School of MedicineShanghai 200025China Academy of Integrative Medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of clinical Pharmacy Institute of Interdisciplinary Integrative Medicine ResearchShuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China.

Alzheimer’s disease(AD)is the most common neurodegenerative disease in the elderly ***,the complexity of AD pathogenesis leads to discrepancies in the understanding of this disease,and may be the main reason for the failure of AD drug ***,many ongoing preclinical and clinical studies will continually open up avenues to unravel disease mechanisms and guide strategies for AD diagnosis and drug *** example,immunotherapeutic strategies targeting amyloid-β(Aβ)and tau proteins were once deemed almost certainly effective in clinical treatment due to the excellent preclinical ***,the repeated failures of clinical trials on vaccines and humanized anti-Aβand anti-tau monoclonal antibodies have resulted in doubts on this ***,a new anti-Aβmonoclonal antibody(Aducanumab)has been approved by the US Food and Drug Administration,which brings us back to the realization that immunotherapy strategies targeting Aβmay be still ***,immunotherapies based on other targets such as tau,microglia and gut-brain axis are also under *** research is still needed to clarify the forms and epitopes of targeted proteins to improve the accuracy and effectiveness of immunotherapeutic *** this review,we focus on the immunotherapies based on Aβ,tau and microglia and their mechanisms of action in *** addition,we present up-to-date advances and future perspectives on immunotherapeutic strategies for AD.

关键词： Alzheimer’s disease Immunotherapy Vaccine Antibody Drug development

Drug discovery of sclerostin inhibitors

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Acta Pharmaceutica Sinica B 2022年第5期12卷 2150-2170页

作者： Sifan Yu Dijie Li Ning Zhang Shuaijian Ni Meiheng Sun Luyao Wang Huan Xiao Dingdong Liu Jin Liu Yuanyuan Yu Zongkang Zhang Samuel Tin Yui Yeung Shu Zhang Aiping Lu Zhenlin Zhang Baoting Zhang Ge Zhang Law Sau Fai Institute for Advancing translational Medicine in Bone and Joint Diseases School of Chinese MedicineHong Kong Baptist UniversityKowloon TsaiHong Kong 999077China Institute of Integrated Bioinfomedicine and translational Science School of Chinese MedicineHong Kong Baptist UniversityKowloon TsaiHong Kong 999077China Institute of Precision Medicine and Innovative Drug Discovery HKBU Institute for Research and Continuing EducationShenzhen 518000China School of Chinese Medicine Faculty of Medicinethe Chinese University of Hong KongHong Kong 999077China The Key Laboratory of Aerospace Medicine Ministry of EducationAir Force Medical UniversityXi’an 710000China Shanghai clinical research Center of Bone Disease Department of Osteoporosis and Bone DiseasesShanghai Jiao Tong University Afﬁliated Sixth People’s HospitalShanghai 200000China

Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA,the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis;however, it conferred high cardiovascular risk in clinical trials. Furthermore,romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.

关键词： Sclerostin WNT signalling pathway Sclerostin inhibitors Antibody Bone diseases Aptamer Small molecule inhibitors Artificial intelligence

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