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Small-molecule anti-COVID-19 drugs and a focus on China's homegrown mindeudesivir(WV116)

Frontiers of Medicine 2023年第6期17卷 1068-1079页

作者： Qiuyu Cao Yi Ding Yu Xu Mian Li Ruizhi Zheng Zhujun Cao Weiqing Wang Yufang Bi Guang Ning Yiping Xu Ren Zhao Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai National clinical Research center for Metabolic Diseases State Key Laboratory of Medical GenomicsKey Laboratory for Endocrine and Metabolic Diseases of the National Health CommissionShanghai National Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Infectious Disease Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China clinical trials center Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

The coronavirus disease 2019(COVID-19)pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral *** far,a few small-molecule antiviral drugs,including nirmatrelvir-ritonavir(Paxlovid),remdesivir,and molnupiravir have been marketed for the treatment of ***-ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate ***,the existing treatment options have limitations,and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still *** date,four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in *** drugs include azvudine,simnotrelvir-ritonavir(Xiannuoxin),leritrelvir,and mindeudesivir(VV11).Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for *** this review,we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for *** findings will expand our understanding and highlight the potential widespread application of China's homegrown anti-COVID-19 drugs.

关键词： COVID-19 antiviral drugs mindeudesivir

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Reversibility of visual field defects through induction of brain plasticity: vision restoration, recovery and rehabilitation using alternating current stimulation

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Neural Regeneration Research 2020年第10期15卷 1799-1806页

作者： Bernhard A.Sabel Ying Gao Andrea Antal Institute of Medical Psychology Medical FacultyOtto-von-Guericke University of MagdeburgMagdeburgGermany center for Behavioral and Brain Sciences(CBBS) MagdeburgGermany Sabel Vision Restoration center MagdeburgGermany Department of clinical Neurophysiology University Medical Center GottingenGottingenGermany

For decades visual field defects were considered irreversible because it was thought that in the visual system the regeneration potential of the neuronal tissues is ***,there is always some potential for partial recovery of the visual field defect that can be achieved through induction of *** refers to the ability of the brain to change its own functional architecture by modulating synaptic *** is maintained throughout life and just as neurological rehabilitation can improve motor coordination,visual field defects in glaucoma,diabetic retinopathy or optic neuropathy can be improved by inducing *** ophthalmology many new treatment paradigms have been tested that can induce neuroplastic changes,including non-invasive alternating current *** with alternating current stimulation(e.g.,30 minutes,daily for 10 days using transorbital electrodes and^10 Hz)activates the entire retina and parts of the *** and functional magnetic resonance imaging studies revealed local activation of the visual cortex,global reorganization of functional brain networks,and enhanced blood flow,which together activate neurons and their *** future of low vision is optimistic because vision loss is indeed,partially reversible.

关键词： alternating current stimulation glaucoma low vision optic nerve rehabilitation recovery stress vision vision restoration therapy visual field

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消化性溃疡出血流行病学的时间趋势

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世界核心医学期刊文摘（胃肠病学分册） 2005年第12期1卷 58-59页

作者： Ohmann C. Imhof M. Ruppert C. 赵菊辉 coordination Centre for clinical trials Medical Faculty Heinrich- Heine University Moorenstraβe 5 DE- 40225 Dü sseldorf Germany

Objective. Despite the introduction of effective medical treatment of peptic ulcer disease, bleeding is still a frequent complication. The aim of this study was to investigate whether the incidence and the risk profile of peptic ulcer haemorrhage have changed within a 10- year period. Material and methods. In a prospective epidemiological and observational study the incidence and risk profile of peptic ulcer haemorrhage in Dü sseldorf, Germany were compared between two time periods (period A: 1.3.89- 28.2.90 and period B: 1.4.99- 31.3.2000), involving nine hospitals with both surgical and medical departments. Patients with proven peptic ulcer haemorrhage at endoscopy or operation were included in the study; those with bleeding under defined severe stress conditions were excluded. Results. No differences in bleeding ulcer incidence were observed between periods A and B (51.4 per 100,000 person- years versus 48.7), or for duodenal ulcer (24.9 versus 25.7) or for gastric ulcer bleeding (26.5 versus 23.0). A marked increase in incidence rates was observed with increasing age. In period B, patients with bleeding ulcers were older (56% versus 41% 70 years or older), were usually taking non- steroidal anti- inflammatory drugs (NSAIDs) (45% versus 27% ) and were less likely to have a history of ulcer (25% versus 59% ) compared with patients in period A. Conclusions. The persisting high incidence of peptic ulcer disease is a superimposing of two trends: a higher incidence in the growing population of elderly patient with a higher intake of NSAIDs and a lower incidence among younger patients due to a decrease in incidence and improved medical treatment.

关键词：消化性溃疡出血时间趋势溃疡发病率风险预测应激性出血医院内科日至

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Role of Helicobacter pylori in gastric mucosa-associated lymphoid tissue lymphomas

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World Journal of Gastroenterology 2014年第3期20卷 684-698页

作者： Marta-Isabel Pereira José Augusto Medeiros clinical Hematology Department Coimbra University Hospital center Institute of Physiology Faculty of MedicineUniversity of CoimbraAzinhaga de Santa Comba

Mucosa-associated lymphoid tissue (MALT) lymphoma is an indolent extranodal marginal zone B-cell lymphoma, originating in acquired MALT that is induced in mucosal barriers as part of a normal adaptive immune response to a chronic immunoinflammatory stimulus, most notably chronic infection by Helicobacter pylori (H. pylori). This antigenic stimulation initially leads to lymphoid hyperplasia; the acquisition of additional genetic aberrations culminates in the activation of intracellular survival pathways, with disease progression due to proliferation and resistance to apoptosis, and the emergence of a malignant clone. There are descriptions of MALT lymphomas affecting practically every organ and system, with a marked geographic variability partially attributable to the epidemiology of the underlying risk factors; nevertheless, the digestive system (and predominantly the stomach) is the most frequently involved location, reflecting the gastrointestinal tract’s unique characteristics of contact with foreign antigens, high mucosal permeability, large extension and intrinsic lymphoid system. While early-stage gastric MALT lymphoma can frequently regress after the therapeutic reversal of the chronic immune stimulus through antibiotic eradication of H. pylori infection, the presence of immortalizing genetic abnormalities, of advanced disease or of eradication-refractoriness requires a more aggressive approach which is, presently, not consensual. The fact that MALT lymphomas are rare neoplasms, with a worldwide incidence of 1-1.5 cases per 105 population, per year, limits the ease of accrual of representative series of patients for robust clinical trials that could sustain informed evidence-based therapeutic decisions to optimize the quality of patient care.

关键词： Mucosa-associated lymphoid tissue lymphoma Marginal zone lymphoma Helicobacter pylori Gastric lymphoma Eradication therapy Nuclear factor-kappa B pathway

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Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2318-2334页

作者： Ya-Kun Jiang Wei Li Ying-Yang Qiu Meng Yue Department of Gastroenterology Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina Health Management center Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina Yong Loo Lin School of Medicine National University of SingaporeSingapore 119077Singapore

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy *** epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric *** combined with chemotherapy has been used as the first-line treatment for advanced gastric *** safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been ***,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric ***-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the ***-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as ***,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

关键词： Human epidermal growth factor receptor 2 Gastric cancer Targeted therapy Review

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Dual versus single antiplatelet therapy for patients with long-term oral anticoagulation undergoing coronary intervention： a systematic review and meta-analysis

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Journal of Geriatric Cardiology 2017年第12期14卷 725-736页

作者： Jing-Jing WU Chan ZOU Wen-Yu LIU Guo-Ping YANG center of clinical Pharmacology the Third Xiangya Hospital Central South University Changsha Hunan China College of Pharmacy Central South University Changsha Hunan China

Objective The main aim of this meta-analysis is to compare the efficacy and safety of dual versus single antiplatelet therapy for pa- tients taking oral anticoagulation （OAC） after coronary intervention. Background The optimal regimen remains controversial for patients taking OAC after coronary intervention. Methods PubMed, Embase and Cochrane Central Register of Controlled trials were searched for eligible studies including data of triple therapy （TT） versus OAC plus single antiplatelet therapy for patients requiring OAC after coronary intervention. The primary outcome was major adverse cardiac and cerebrovascular event （MACCE）. The safety outcome was major bleeding. Results Fourteen studies with 32,825 patients were included. Among prospective studies, patients with TT had a trend toward a higher risk of major bleeding [odds ratios （OR）： 1.56, 95% confidence interval （CI）： 0.98-2.49, P = 0.06] and a markedly higher risk of all-cause death （OR; 2.11, 95% CI： 1.10-4.06 P = 0.02） compared with OAC plus clopidogrel. Meanwhile, TT was associated with decreased risks of MACCE （OR： 0.63, 95% CI： 051-0.77 P 〈 0.0001）, all-cause death （OR： 0.45, 95% CI： 0.20-0.97, P = 0.04）, and stroke/transient ischemic attack （TIA）/peripheral embolism （PE）（OR= 0.29, 95% CI： 0.09~3.96, P = 0.04） compared with OAC plus aspirin. Conclusions For pa- tients requiring OAC after coronary intervention, OAC plus clopidogrel may bring more clinical net benefit than TT, whereas OAC plus aspirin should be the last choice. More large-size randomized control trials are needed to confirm these findings.

关键词： Coronary intervention Dual therapy Efficacy Oral anticoagulation Safety Triple therapy

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Pouch size influences clinical outcome of pouch construction after total gastrectomy:A meta-analysis

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World Journal of Gastroenterology 2014年第29期20卷 10166-10173页

作者： Heng-Lei Dong Yu-Bei Huang Xue-Wei Ding Feng-Ju Song Ke-Xin Chen Xi-Shan Hao Department of Epidemiology and Biostatistics Tianjin Medical University Cancer Hospital and InstituteNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy Department of Gastric Cancer Surgery Tianjin Medical University Cancer Hospital and InstituteNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy

AIM: To assess the clinical significance of pouch size in total gastrectomy for gastric malignancies.

关键词： Total gastrectomy Gastric cancer Pouch size Systematic review

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Exploring the transformative impact of traditional Chinese medicine on depression:Insights from animal models

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World Journal of Psychiatry 2024年第5期14卷 607-623页

作者： Yan Yang Yan-Kun Chen Meng-Zhou Xie School of Nursing Hunan University of Chinese MedicineChangsha 410200Hunan ProvinceChina Precision Medicine R&D center Zhuhai Institute of Advanced TechnologyChinese Academy of SciencesZhuhai 519000Guangdong ProvinceChina School of Chinese Medicine Hunan University of Chinese MedicineChangsha 410200Hunan ProvinceChina Hunan Engineering Technology Research center for Medicinal and Functional Food Hunan University of Chinese MedicineChangsha 410200Hunan ProvinceChina Key Laboratory of TCM Heart and Lung Syndrome Differentiation and Medicated Diet and Dietotherapy Hunan University of Chinese MedicineChangsha 410200Hunan ProvinceChina

Depression,a prevalent and complex mental health condition,presents a significant global health *** is one of the most frequent mental disorders;deaths from it account for 14.3%of people *** recent years,the integration of complementary and alternative medicine,including traditional Chinese medicine(TCM),has gained attention as a potential avenue for addressing *** comprehensive review critically assesses the efficacy of TCM interventions in alleviating depressive *** in-depth look at different research studies,clinical trials,and meta-analyses is used in this review to look into how TCM practices like herbal formulations,acupuncture,and mindbody practices *** review looks at the quality of the evidence,the rigor of the methods,and any possible flaws in the current *** gives us an idea of where TCM stands right now in terms of treating *** comprehensive review aims to assess the efficacy of TCM interventions in alleviating depressive *** order to learn more about their possible healing effects,the study also looks into how different types of TCM work,such as herbal formulas,acupuncture,and mind-body practices.

关键词： Traditional Chinese medicine Depression Efficacy Treatment Holistic approach

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Expert consensus on the clinical application of PI3K/AKT/mTOR inhibitors in the treatment of advanced breast cancer

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Cancer Innovation 2022年第1期1卷 25-54页

作者： The Society of clinical Research of Oncology Medications of China Anticancer Association Breast Cancer Expert Committee of National Cancer Quality Control center Boao Cancer Innovation Institute Fei Ma Binghe Xu 不详 Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/CancerHospitalChinese Academy of MedicalSciences and Peking Union MedicalCollegeBejing 100021China Department of Medical Oncology and clinical Trial center National Cancer Center/National ClinicalResearch Center for Cancer/CancerHospitalChinese Academy of MedicalSciences and Peking Union MedicalCollegeBeijing 100021China

Phosphoinositide 3‐kinase(PI3K)/protein kinase B(PKB or AKT)/mammalian target of rapamycin(mTOR)signaling pathway(PAM pathway)plays an important role in the development of breast cancer and are closely associated with the resistance to endocrine therapy in advanced breast ***,anticancer treatment targeting key molecules in this signaling pathway has become a research hotspot in recent *** clinical trials have demonstrated that PI3K/AKT/mTOR inhibitors bring significant clinical benefit to patients with advanced breast cancer,especially to those with hormone receptor(HR)‐positive,human epidermal growth factor receptor(HER)2‐negative advanced breast ***,a PI3K inhibitor,and everolimus,an mTOR inhibitor,have been approved by *** on their high efficacy and relatively good safety profile,an expanded indication of everolimus in breast cancer has been approved by National Medical Products Administration(NMPA).Alpelisib is expected to be approved in China in the near *** members of the consensus expert panel reached this consensus to comprehensively define the role of PI3K/AKT/mTOR signaling pathway in breast cancer,efficacy and clinical applications of PI3K/AKT/mTOR inhibitors,management of adverse reactions,and PIK3CA mutation detection,to promote the understanding of PI3K/AKT/mTOR inhibitors for Chinese oncologists,improve clinical decision‐making,and prolong the survival of target patient population.

关键词： breast cancer PI3K/AKT/mTOR inhibitors

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Detection of an 8p23.1 Inversion Using High-Resolution Optical Genome Mapping

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Maternal-Fetal Medicine 2024年第3期6卷 173-177页

作者： Chunxiang Zhou Huijun Li Yiyan Shi Linlin He Honglei Duan Jie Li Obstetrics and Gynecology Medical center Nanjing Drum Tower HospitalAffiliated Hospital of Nanjing Medical UniversityNanjing 210008China

Objective:To evaluate the performance of optical genomemapping(OGM)in identifying an inversion located in the short armof chromosome 8(8p,8p23.1),flanked by regions of complex segmental duplication(SD),using the GRCh38 and telomere-to-telomere(T2T)genome ***:We investigated a couple suspected of carrying the 8p23.1 inversion due to a terminal deletion combined with an interstitial duplication of 8p found in their *** was performed on both *** data were mapped to the current GRCh38 and the updated T2T genome references,***:The 8p23.1 inversion was observed in the female when mapping OGM data to the T2T *** contrast,under the GRCh38 reference,the orientation between the suspected breakpoints within the SD regions could not be *** variants of uncertain significance were also identified in both ***:Our findings highlight the superiority of the T2T reference in recognizing structural variations involving SD *** enhanced SV detection using the T2T reference may contribute to a better understanding of genome instability and human diseases.

关键词： Genome mapping Telomere-to-Telomere reference Segmental duplication 8p23.1 inversion

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