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Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images

Chinese Journal of Integrative Medicine 2024年第3期30卷 203-212页

作者： WANG Rong-rui CHEN Jia-liang DUAN Shao-jie LU Ying-xi CHEN Ping ZHOU Yuan-chen YAO Shu-kun graduate school of Beijing university of Chinese Medicine Beijing100029China Department of Gastroenterology China-Japan Friendship HospitalBeijing100029China Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing100015China Nanjing Linkwah Micro-electronics Institute Beijing100191China Institute of Microelectronics Tsinghua UniversityBeijing100084China Peking university China-Japan Friendship school of Clinical Medicine Beijing100029China

Objective:To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease(NAFLD) based on features of tongue images.Methods:Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019,then the anthropometric indexes and sampled tongue images were measured.The tongue images were labeled by features,based on a brief protocol,without knowing any other clinical data,after a series of corrections and data cleaning.The algorithm was trained on images using labels and several anthropometric indexes for inputs,utilizing machine learning technology.Finally,a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.Results:A total of 720 subjects were enrolled in this study,including 432 patients with NAFLD and 288 healthy volunteers.Of them,482 were randomly allocated into the training set and 238 into the validation set.The diagnostic model based on logistic regression exhibited excellent performance:in validation set,it achieved an accuracy of 86.98%,sensitivity of 91.43%,and specificity of 80.61%;with an area under the curve(AUC) of 0.93 [95% confidence interval(CI) 0.68–0.98].The decision tree model achieved an accuracy of 81.09%,sensitivity of 91.43%,and specificity of 66.33%;with an AUC of 0.89(95% CI 0.66–0.92) in validation set.Conclusions:The features of tongue images were associated with NAFLD.Both the 2 diagnostic models,which would be convenient,noninvasive,lightweight,rapid,and inexpensive technical references for early screening,can accurately distinguish NAFLD and are worth further study.

关键词： nonalcoholic fatty liver disease noninvasive diagnosis tongue image tongue diagnosis Chinese medicine machine learning

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Chinese Medicine Combined with Adjuvant Chemotherapy for Improving Myelosuppression in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis

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Chinese Journal of Integrative Medicine 2024年第7期30卷 643-652页

作者： LI Rui ZHANG Tong YAN Shao-hua YAN Yun-zi DING Ya-cong WANG Yan-song YANG Yu-fei Department of Oncology China Academy of Chinese Medical Sciences Xiyuan Hospital Department of Oncology Dongfang Hospital Beijing University of Chinese Medicine graduate school Beijing University of Chinese Medicine

Objective: To assess the effectiveness of Chinese herbal medicine(CHM) combined with adjuvant chemotherapy on myelosuppression for colorectal cancer(CRC) patients using network meta-analysis(NMA). Methods: Literature searches in both international(PubMed, Embase, Web of Science, and Cochrane Library) and Chinese(China Science and Technology Journal Database, Wanfang Data, China National Knowledge Infrastructure) databases for relevant randomized controlled trials(RCTs) were conducted from inception until October 10, 2022. We included RCTs of patients who received CHM combined with chemotherapy, including FOLFOX, XELOX, FOLFIRI, and other relevant regimens in the CHM treatment group. The outcomes included the incidence of myelosuppression, leukopenia, hemoglobin reduction, and thrombocytopenia. Two reviewers independently screened the databases, extracted the data, and assessed the risk of bias and credibility of evidence. RevMan 5.4.1 software and STATA 14.0 were used to perform the NMA. Results: A total of 31 RCTs were included, published from 2008 to 2021 in Chinese. Among these, 2,314 participants comparing the following 9 CHMs were identified: Shengbai Recipe(SBR), Bazhen Decoction(BZD), Jianpi Jiedu Recipe(JJR), Jianpi Recipe(JR), Compound Cantharis Capsule(CCC), Zaofan Pill(ZFP), Guilu Erxian Gel(GL), Buzhong Tiaogan Decoction(BZ), and Qiamagu Capsule(QM). The results of NMA found an indirect comparison. Based on the surface under the cumulative ranking curve(SUCRA), the ZFP+ chemotherapy group had the lowest incidence of myelosuppression, with an odds ratio(OR) of 0.08 [95% confidence interval(CI): 0.01, 0.76], whereas the GL+ chemotherapy group had the lowest incidence of leukopenia, hemoglobin reduction, and thrombocytopenia, with an OR of 5.25(95% CI: 2.41, 11.43), 4.66(95% CI: 2.23, 9.72), and 0.27(95% CI: 0.13, 0.54), respectively. Moreover, BZD + chemotherapy could alleviate leukopenia, hemoglobin reduction, and thrombocytopenia(P<0.01). Pairwise comparison showed that there was no difference in the

关键词： Chinese herbal medicine colorectal cancer network meta-analysis systematic review myelosuppression chemotherapy

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Chinese herbal medicine Ginkgo biloba L.preparations for ischemic stroke:An overview of systematic reviews and meta-analyses

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Journal of Integrative Medicine 2024年第2期22卷 163-179页

作者： Tian-tian Meng Ya-ping You Min Li Jian-bo Guo Xin-bin Song Jing-yi Ding Xiao-long Xie An-qi Li Shang-jin Li Xiang-jun Yin Peng Wang Zhe Wang Bao-liang Wang Qing-yong He Department of Cardiology Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100032China Department of Rehabilitation Dongfang HospitalBeijing University of Chinese MedicineBeijing 100071China school of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China school of Chinese Medicine the University of Hong KongHong KongChina graduate school Henan University of Chinese MedicineZhengzhou 450008Henan ProvinceChina Department of Acupuncture and Moxibustion Dongzhimen HospitalBeijing University of Chinese MedicineBeijing 100010China Department of Cardiology Guang’anmen HospitalChina Academy of Chinese Medical SciencesZhengzhou 450008Henan ProvinceChina school of Integrated Traditional Chinese and Western Medicine Southwest Medical UniversityHangzhou 310053Zhejiang ProvinceChina school of Basic Medical Sciences Zhejiang Chinese Medical UniversityHangzhu 310053Zhejang ProvinceChina Department of Neurology the First Affiliated Hospital of Henan University of Chinese MedicineZhengzhou 450003Henan ProvinceChina

Background:Ginkgo biloba L.preparations(GBLPs)are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke(IS).Recently,several systematic reviews(SRs)and meta-analyses(MAs)of GBLPs for IS have been published.Objective:This overview aims to assess the quality of related SRs and MAs.Search strategy:Pub Med,Embase,Cochrane Library,Web of Science,Chinese Biological Medicine,China National Knowledge Infrastructure,Wanfang,and Chinese Science and Technology Journals databases were searched from their inception to December 31,2022.Inclusion criteria:SRs and MAs of randomized controlled trials(RCTs)that explored the efficacy of GBLPs for patients with IS were included.Data extraction and analysis:Two independent reviewers extracted data and assessed the methodological quality,risk of bias(ROB),reporting quality,and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2),Risk of Bias in Systematic Reviews(ROBIS),the Preferred Reporting Items for Systematic Reviews and Meta-analyses(PRISMA),and the Grading of Recommendations Assessment,Development and Evaluation(GRADE),respectively.Additionally,descriptive analysis and data synthesis were conducted.Results:Twenty-nine SRs/MAs involving 119 outcomes were included in this review.The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2,and 28 had a high ROB based on the ROBIS.According to the PRISMA statement,the reporting items of the included SRs/MAs are relatively complete.The results based on GRADE showed that of the 119 outcomes,8 were rated as moderate quality,24 as low quality,and 87 as very low quality.Based on the data synthesis,GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores.Conclusion:GBLPs can be considered a beneficial supplemental therapy for IS.However,because of the low quality of the existing evidence,high-quality RCTs and SRs/MAs are warranted t

关键词： statement synthesis alone

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Grouping-Based Optimal Design of Collector System Topology for a Large-Scale Offshore Wind Farm by Improved Simulated Annealing

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Protection and Control of Modern Power Systems 2024年第1期9卷 94-111页

作者： Ruilin Chen Zeyu Zhang Junxuan Hu Lei Zhao Chuangzhi Li Xiaoshun Zhang Shantou university ShantouChina ZHONGNAN ENGINEERING CORPORATION LIMITED North China Electric Power university Department of Electronic and Information Engineering College of EngineeringShantouUniversityShantouChina Sichuan university ChengduChina Foshan graduate school Northeastern UniversityFoshan 528311China College of Information Science and Engineering Northeastern UniversityShenyang 110819China

During the construction of an offshore wind farm(OWF),the capital cost of the collector cable system accounts for a large proportion of the total cost.Consequently,the optimal design of the collector system topology(CST)is one of the most crucial tasks in OWF planning.However,for a large-scale OWF,the optimal design of CST is a complex integer programming problem with high-dimension variables and various constraints.Therefore,it is difficult to acquire a high-quality optimal design scheme.To address this issue,this paper proposes a new grouping-based optimal design of CST for a large-scale OWF.First,all the wind turbines are divided into multiple groups according to their geographical locations and the maximum allowed connected wind turbines by each cable.This not only reduces the optimization dimension and difficulty,but also effectively satisfies the‘no cross’constraint by putting the geographically closed wind turbines into the same group.Secondly,the electrical topology among different wind turbines in each group is initially generated by an improved dynamic minimum spanning tree(DMST).The division groups of the OWF are then adjusted to further reduce the capital cost by improved simulated annealing.To verify the proposed technique,comparison case studies are carried out with five algorithms on two different OWF.

关键词： dimension Optimal initially

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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen Xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its function.However,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain elusive.In this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent y-secretase.We identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in mice.Finaly,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout mice.This data demonstrates that the a-secretase is essential for CNTNAP2 processing and its function.Our study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

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Chinese Journal of Cancer Research 2024年第1期36卷 25-35页

作者： Zhuanzhuan Mu Xin Zhang Dongquan Liang Jugao Fang Ge Chen Wenting Guo Di Sun Yuqing Sun Zhentian Kai Lisha Huang Jun Liang Yansong Lin Department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine Beijing 100730China Pepperdine university graduate school of Education and Psychology Los Angeles 90045USA Department of Head and Neck Surgery Affiliated Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of General Surgery State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Central Laboratory State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College(PUMC)HospitalChinese Academy of Medical Sciences&PUMCBeijing 100730China Department of Bioinformatics Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Medicine Zhejiang Shaoxing Topgen Biomedical Technology Co.LtdShanghai 201321China Department of Oncology Peking University International HospitalBeijing 102206China

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

关键词： Differentiated thyroid cancer distant metastases genetic alterations RAI refractoriness molecular risk stratification

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Atherogenic index of plasma combined with waist circumference and body mass index to predict metabolic-associated fatty liver disease

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World Journal of Gastroenterology 2022年第36期28卷 5364-5379页

作者： Shao-Jie Duan Zhi-Ying Ren Tao Zheng Hong-Ye Peng Zuo-Hu Niu Hui Xia Jia-Liang Chen Yuan-Chen Zhou Rong-Rui Wang Shu-Kun Yao graduate school Beijing University of Chinese MedicineBeijing 100029China Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China graduate school Peking University China-Japan Friendship School of Clinical MedicineBeijing 100029China Department of Gastroenterology China-Japan Friendship HospitalBeijing 100029China

BACKGROUND Early identification of metabolic-associated fatty liver disease(MAFLD)is urgent.Atherogenic index of plasma(AIP)is a reference predictor of obesity-related diseases,but its predictive value for MAFLD remains unclear.No studies have reported whether its combination with waist circumference(WC)and body mass index(BMI)can improve the predictive performance for MAFLD.AIM To systematically explore the relationship between AIP and MAFLD and evaluate its predictive value for MAFLD and to pioneer a novel noninvasive predictive model combining AIP,WC,and BMI while validating its predictive performance for MAFLD.METHODS This cross-sectional study consecutively enrolled 864 participants.Multivariate logistic regression analysis and receiver operating characteristic curve were used to evaluate the relationship between AIP and MAFLD and its predictive power for MAFLD.The novel prediction model A-W-B combining AIP,WC,and BMI to predict MAFLD was established,and internal verification was completed by magnetic resonance imaging diagnosis.RESULTS Subjects with higher AIP exhibited a significantly increased risk of MAFLD,with an odds ratio of 12.420(6.008-25.675)for AIP after adjusting for various confounding factors.The area under receiver operating characteristic curve of the A-W-B model was 0.833(0.807-0.858),which was significantly higher than that of AIP,WC,and BMI(all P<0.05).Subgroup analysis illustrated that the A-W-B model had significantly higher area under receiver operating characteristic curves in female,young and nonobese subgroups(all P<0.05).The best cutoff values for the A-W-B model to predict MAFLD in males and females were 0.5932 and 0.4105,respectively.Additionally,in the validation set,the area under receiver operating characteristic curve of the A-W-B model to predict MAFLD was 0.862(0.791-0.916).The A-W-B level was strongly and positively associated with the liver proton density fat fraction(r=0.630,P<0.001)and significantly increased with the severity of MAFLD(P<0.05).CONCLUSION AIP was strongly

关键词： Atherogenic index of plasma Metabolic-associated fatty liver disease Receiver operating characteristic curve Predictor

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Efficacy and Safety of Guihuang Formula in Treating Type Ⅲ Prostatitis Patients with Dampness-Heat and Blood Stasis Syndrome: A Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2022年第10期28卷 879-884页

作者： LIU Sheng-jing DENG Ying-jun ZENG Yin ZHAO Ming GUO Jun GAO Qing-he Department of Andrology Xiyuan Hospital of China Academy of Chinese Medical SciencesBeijing(100091)China graduate school of China Academy of Chinese Medical Sciences Beijing(100700)China Department of Andrology Beijing Chinese Medicine Hospital Afﬁliated to Capital Medical UniversityBeijing(100010)China graduate school Beijing University of Chinese MedicineBeijing(100029)China

Objective: To observe the efficacy and safety of Guihuang Formula(GHF) in treating patients with type Ⅲ prostatitis and Chinese medicine syndrome of dampness-heat and blood stasis. Methods: Sixty-six type Ⅲ prostatitis patients with dampness-heat and blood stasis syndrome were randomly divided into the treatment group(GHF) and the control group(tamsulosin) using a random number table, with 33 cases each group. The treatment group received GHF twice a day, and the control group received tamsulosin 0.2 mg once daily before bedtime. Patients in both groups received treatment for 6 weeks and was followed up for 2 weeks. The outcomes included the National Institute of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score, Chinese Medicine Symptoms Score(CMSS), expressed prostatic secretions(EPS) and adverse events(AEs). Results: After treatment, the NIH-CPSI total score and domain scores of pain discomfort, urination and quality of life decreased significantly from the baseline in both groups(P0.05). In addition, no serious AEs were observed. Conclusion: GHF is effective in treating type Ⅲ prostatitis patients with dampness-heat and blood stasis syndrome without serious AEs.(Registration No. ChiCTR1900026966)

关键词： typeⅢprostatitis dampness-heat and blood stasis syndrome Guihuang Formula Chinese medicine randomized controlled trial

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Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China:A national multicenter survey of 35,566 individuals

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 113-120页

作者： Meng-Fan Liu Rui-Xia Ma Xian-Bao Cao Hua Zhang Shui-Hong Zhou Wei-Hong Jiang Yan Jiang Jing-Wu Sun Qin-Tai Yang Xue-Zhong Li Ya-Nan Sun Li Shi Min Wang Xi-Cheng Song Fu-Quan Chen Xiao-Shu Zhang Hong-Quan Wei Shao-Qing Yu Dong-Dong Zhu Luo Ba Zhi-Wei Cao Xu-Ping Xiao Xin Wei Zhi-Hong Lin Feng-Hong Chen Chun-Guang Shan Guang-Ke Wang Jing Ye Shen-Hong Qu Chang-Qing Zhao Zhen-Lin Wang Hua-Bin Li Feng Liu Xiao-Bo Cui Sheng-Nan Ye Zheng Liu Yu Xu Xiao Cai Wei Huang Ru-Xin Zhang Yu-Lin Zhao Guo-Dong Yu Guang-Gang Shi Mei-Ping Lu Yang Shen Yu-Tong Zhao Jia-Hong Pei Shao-Bing Xie Long-Gang Yu Ye-Hai Liu Shao-Wei Gu Yu-Cheng Yang Lei Cheng Jian-Feng liu graduate school of Beijing university of Chinese Medicine BeijingChina Department of Otorhinolaryngology Head and Neck Surgery China-Japan Friendship HospitalBeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First People's Hospital of YinchuanYinchuanChina Department of Otorhinolaryngology The First People's Hospital of Yunnan ProvinceKunmingChina Department of Otorhinolaryngology The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina Department of Otorhinolaryngology Head and Neck Surgery Xiangya Hospital Central South UniversityChangshaChina Department of Otorhinolaryngology Head and Neck Surgery The Affiliated Hospital of Qingdao UniversityQingdaoChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of USTCHefeiChina Department of Otorhinolaryngology Head and Neck Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina Department of Otorhinolaryngology Head and Neck Surgery Qilu Hospital of Shandong UniversityJinanChina Department of Otorhinolaryngology Head and Neck Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbinChina Department of Otolaryngology The Second Hospital of Shandong UniversityShandong UniversityJinanChina Department of Otorhinolaryngology Head and Neck Surgery Peking University People's HospitalBeijingChina Department of Otorhinolaryngology Head and Neck Surgery Yantai Yuhuangding HospitalQingdao UniversityYantaiChina Department of Otorhinolaryngology Head and Neck Surgery Xijing HospitalThe Fourth Military Medical UniversityXi'anChina Gansu Provincial Center for Disease Control and Prevention LanzhouChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of China Medical UniversityShenyangChina Department of Otorhinolaryngology Head and Neck Surgery Tongji Hospit

Objective:This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China.Methods:This study was conducted by 45 tertiary Grade-A hospitals in China.Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28,2022,and February 21,2023.The collected information included basic demographics,medical history,smoking and drinking history,vaccination history,changes in olfactory and gustatory functions before and after infection,and other postinfection symptoms,as well as the duration and improvement status of olfactory and gustatory disorders.Results:Complete questionnaires were obtained from 35,566 subjects.The overall incidence of olfactory and taste dysfunction was 67.75%.Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction.Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction.Before infection,the average olfactory and taste VAS scores were 8.41 and 8.51,respectively;after infection,they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey.The median duration of dysosmia and dysgeusia was 15 and 12 days,respectively,with 0.5%of patients having symptoms lasting for more than 28 days.The overall self-reported improvement rate was 59.16%.Recovery was higher in males,never smokers,those who received two or three vaccine doses,and those that had never experienced dental health issues,or chronic accompanying symptoms.Conclusions:The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China.Incidence and prognosis are influenced by several factors,including sex,SARS-CoV-2 vaccination,history of head-facial trauma,nasal and oral health status,smoking and drinking history,and the persistence of accompanying symptoms.

关键词： epidemiologic studies incidence olfactory disorders prognosis SARS-CoV-2 taste disorders

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Dihydroergotamine ameliorates liver fibrosis by targeting transforming growth factor β type Ⅱ receptor

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World Journal of Gastroenterology 2023年第20期29卷 3103-3118页

作者： Ke-Xin Zheng Shou-Li Yuan Meng Dong Han-Lin Zhang Xiao-Xiao Jiang Chun-Long Yan Rong-Cai Ye Hui-Qiao Zhou Li Chen Rui Jiang Zi-Yu Cheng Zhi Zhang Qi Wang Wan-Zhu Jin Wen Xie Center of Liver Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China graduate school University of the Chinese Academy of SciencesBeijing 100049China graduate school Agriculture College of Yanbian UniversityYanji 133002Jilin ProvinceChina

BACKGROUND The transforming growth factor β(TGFβ) signaling pathway plays a crucial role in the development of liver fibrosis by activating TGFβ type Ⅱ receptor(TGFβR2), followed by the recruitment of TGFβR1 finally triggering downstream signaling pathway.AIM To find drugs targeting TGFβR2 that inhibit TGFβR1/TGFβR2 complex formation, theoretically inhibit TGFβ signaling pathway, and thereby ameliorate liver fibrosis.METHODS Food and Drug Administration-approved drugs were screened for binding affinity with TGFβR2 by virtual molecular docking. We identified 6 candidates and further explored their potential by Cell Counting Kit-8(CCK-8) cell cytotoxic experiment to validate toxicity and titrated the best cellular working concentrations. Next, we further demonstrated the detailed molecular working mechanisms using mutagenesis analysis. Finally, we used a mouse model to investigate its potential anti-liver fibrosis effect.RESULTS We identified 6 drug candidates. Among these 6 drugs, dihydroergotamine(DHE) shows great ability in reducing fibrotic gene expressions such as collagen, p-SMAD3, and α-SMA in TGFβ induced cellular model of liver fibrosis in LX-2 cells. Furthermore, we demonstrated that DHE binds to TGFβR2. Moreover, mutation of Leu27, Phe30, Thr51, Ser52, Ile53, and Glu55 of TGFβR2 disrupted the binding of TGFβR2 with DHE. In addition, DHE significantly improved liver fibrosis, as evidenced by Masson’s trichrome staining of liver sections. This is further supported by the width and the velocity of the portal vein, and serum markers of liver function. In line with those observations, DHE also decreased macrophages infiltration and extracellular matrix deposition in the liver.CONCLUSION DHE alleviates liver fibrosis by binding to TGFβR2 thereby suppressing TGFβ signaling pathway. We show here that as far as drug repurposing, DHE has great potential to treat liver fibrosis.

关键词： Liver fibrosis Transforming growth factorβ(TGFβ)signaling pathway TGFβtype II receptor(TGFβR2) Virtual screening Drug-repurposing Dihydroergotamine

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