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Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis:A multicenter,randomized,double-blind,placebo-controlled phase 2b trial

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Chinese Medical Journal 2024年第2期137卷 200-208页

作者： Yan Zhao Jianzhong Zhang Bin Yang Jingyi Li Yangfeng Ding Liming Wu Litao Zhang Jinyan Wang Xiaohong Zhu Furen Zhang Xiaohua Tao Yumei Li Chunlei Zhang Linfeng Li Jianyun Lu Qingchun Diao Qianjin Lu Xiaoyong Man Fuqiu Li Xiujuan Xia Hao Cheng Yingmin Jia Guoqing Zhao Jinchun Yan Bo Chen Department of Dermatology Peking University People’s HospitalBeijing 100044China Department of Dermatology Dermatology HospitalSouthern Medical UniversityGuangzhouGuangdong 510091China Department of Dermatology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Dermatology Shanghai Skin Disease HospitalInstitute of PsoriasisTongji University School of MedicineShanghai 200443China Department of Dermatology Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China Department of Dermatology Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalTianjin 300120China Department of Dermatology Ningbo No.2 HospitalNingboZhejiang 315010China Department of Dermatology The Wuxi Second Affiliated Hospital of Nanjing Medical UniversityWuxiJiangsu 214002China Shandong Provincial Hospital for Skin Diseases&Shandong Provincial institute of Dermatology and Veneorology Shandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250022China Center for Plastic&Reconstructive Surgery Department of DermatologyZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)HangzhouZhejiang 310014China Department of Dermatology Affiliated Hospital of Jiangsu UniversityZhenjiangJiangsu 212001China Department of Dermatology Peking University Third HospitalBeijing 100191China Department of Dermatology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Dermatology The Third Xiangya Hospital of Central South UniversityChangshaHunan 410013China Department of Dermatology Chongqing Traditional Chinese Medicine HospitalChongqing 400011China Hunan Key Laboratory of Medical Epigenomics Department of DermatologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Department of Dermatology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Departme

Background:Atopic dermatitis(AD)affects approximately 10%of adults ***310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 *** trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe ***:This multicenter,randomized,double-blind,placebo-controlled,phase 2b trial was conducted in 21 medical institutions in China from February to November *** 120 eligible patients were enrolled and randomized(1:1:1)to receive subcutaneous injections of 300 mg CM310,150 mg CM310,or placebo every 2 weeks for 16 weeks,followed by an 8-week follow-up *** primary endpoint was the proportion of patients achieving≥75%improvement in the Eczema Area and Severity Index(EASI-75)score from baseline at week *** and pharmacodynamics were also ***:At week 16,the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups(70%[28/40]for high-dose and 65%[26/40]for low-dose)than that in the placebo group(20%[8/40]).The differences in EASI-75 response rate were 50%(high ***,95%CI 31%-69%)and 45%(low ***,95%CI 26%-64%),with both P values<***310 at both doses also significantly improved the EASI score,Investigator’s Global Assessment score,daily peak pruritus Numerical Rating Scale,AD-affected body surface area,and Dermatology Life Quality Index compared with ***310 treatment reduced levels of thymus and activation-regulated chemokine,total immunoglobulin E,lactate dehydrogenase,and blood *** incidence of treatment-emergent adverse events(TEAEs)was similar among all three groups,with the most common TEAEs reported being upper respiratory tract infection,atopic dermatitis,hyperlipidemia,and *** severe adverse events were deemed to be attributed to ***:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tol

关键词： CM310 Moderate-to-severe atopic dermatitis Interleukin-4 receptor alpha Adults

Glytan decreases portal pressure via mesentery vasoconstriction in portal hypertensive rats

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World Journal of Gastroenterology 2014年第44期20卷 16674-16682页

作者： Qing-Hong Du Lin Han Jun-Jie Jiang Ya Xu Wei-Hong Li Peng-Tao Li Xin-Yue Wang Xu Jia School of Fundamental medicine Beijing University of Chinese Medicine institute of Basic Research in Clinical medicine China Academy of Chinese Medical Sciences Dongzhimen Hospital Affiliated to Beijing University of Chinese medicine

AIM: To investigate the effects of Glytan on splanchnic hemodynamics and its reduction of portal pressure in portal hypertensive rats.

关键词： Glytan Portal hypertension Hemodynamics Mesentery Endothelin-1 Receptor Sensitivity

Is hepatic steatosis associated with left ventricular mass index increase in the general population?

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World Journal of Hepatology 2017年第19期9卷 857-866页

作者： Katharina Piontek Carsten O Schmidt Sebastian E Baumeister Markus M Lerch Julia Mayerle Marcus Dorr Stephan B Felix Henry Volzke institute for Medical Psychology University Medicine Greifswald institute for Community medicine University Medicine Greifswald Department of medicine A University Medicine Greifswald Department of Cardiology University Medicine Greifswald German Centre for Cardiovascular Research Partner site Greifswald

AIM To investigate the association between hepatic steatosis and change in left ventricular mass index(LVMI) over five years, and examine whether systolic and diastolic blood pressures are mediators of the association between hepatic steatosis and LVMI using a general population *** We analyzed data from the Study of Health in Pomerania. The study population comprised 1298individuals aged 45 to 81 years. Hepatic steatosis was defined as the presence of a hyperechogenic pattern of the liver together with elevated serum alanine transferase levels. Left ventricular mass was determined echocardiographically and indexed to height2.7. Path analyses were conducted to differentiate direct and indirect paths from hepatic steatosis to LVMI encompassing systolic and diastolic blood pressure as potential mediating *** Hepatic steatosis was a significant predictor for all measured echocardiographic characteristics at baseline. Path analyses revealed that the association of hepatic steatosis with LVMI change after five years was negligibly small(β =-0.12, s.e. = 0.21, P = 0.55). Systolic blood pressure at baseline was inversely associated with LVMI change(β =-0.09, s.e. = 0.03, P < 0.01), while no association between diastolic blood pressure at baseline and LVMI change was evident(β = 0.03, s.e. = 0.05, P = 0.56). The effect of the indirect path from hepatic steatosis to LVMI via systolic baseline blood pressure was small(β =-0.20, s.e. = 0.10, P = 0.07). No indirect effect was observed for the path via diastolic baseline blood pressure(β = 0.03, s.e. = 0.06, P = 0.60). Similar associations were observed in the subgroup of individuals not receiving beta-blockers, calcium channel blockers, or drugs acting on the reninangiotensin *** Baseline associations between hepatic steatosis and LVMI do not extend to associations with LVMI change after five years. More studies are needed to study the longitudinal effects of hepatic steatosis on LVMI.

关键词： Hepatic steatosis Left ventricular mass index Blood pressure General Population Study of Health in Pomerania

Tumor suppressor p53 cross-talks with TRIM family proteins

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Genes & Diseases 2021年第4期8卷 463-474页

作者： Juan Liu Cen Zhang Xue Wang Wenwei Hu Zhaohui Feng Department of radiation Oncology Rutgers Cancer Institute of New JerseyRutgers-State University of New Jersey195 Little Albany StreetNew BrunswickNJ 08903USA

p53 is a key tumor *** a transcription factor,p53 accumulates in cells in response to various stress signals and selectively transcribes its target genes to regulate a wide variety of cellular stress responses to exert its function in tumor *** addition to tumor suppression,p53 is also involved in many other physiological and pathological processes,***-infection,immune response,development,reproduction,neurodegeneration and *** maintain its proper function,p53 is under tight and delicate regulation through different mechanisms,particularly the posttranslational *** tripartite motif(TRIM)family proteins are a large group of proteins characterized by the RING,B-Box and coiled-coil(RBCC)domains at the *** proteins play important roles in regulation of many fundamental biological processes,including cell proliferation and death,DNA repair,transcription,and immune *** of TRIM proteins have been linked to many diseases including cancer,infectious diseases,developmental disorders,and ***,recent studies have revealed that many TRIM proteins are involved in the regulation of p53,and at the same time,many TRIM proteins are also regulated by ***,we review the cross-talk between p53 and TRIM proteins,and its impact upon cellular biological processes as well as cancer and other diseases.

关键词： Cancer p53 Posttranslational modification TRIM proteins Tumor suppressor Ubiquitination

Self-assembly of differentiated dental pulp stem cells facilitates spheroid human dental organoid formation and prevascularization

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World Journal of Stem Cells 2024年第3期16卷 287-304页

作者： Fei Liu Jing Xiao Lei-Hui Chen Yu-Yue Pan Jun-Zhang Tian Zhi-Ren Zhang Xiao-Chun Bai School of Basic Medical Sciences Southern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Health Management Guangdong Second Provincial General HospitalGuangzhou 510317Guangdong ProvinceChina Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment Zhuhai People’s Hospital Affiliated with Jinan UniversityZhuhai 519000Guangdong ProvinceChina Centre of Reproduction Development and AgingFaculty of Health SciencesUniversity of MacaoMacao 999078China Department of Stomatology Guangdong Second Provincial General HospitalGuangzhou 510317Guangdong ProvinceChina Zhuhai institute of Translational medicine Zhuhai Hospital Affiliated with Jinan UniversityZhuhai 519000Guangdong ProvinceChina Department of Cell Biology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina

BACKGROUND The self-assembly of solid organs from stem cells has the potential to greatly expand the applicability of regenerative *** cells can self-organise into microsized organ units,partially modelling tissue function and *** pulp organoids have been used to recapitulate the processes of tooth development and related ***,the lack of vasculature limits the utility of dental pulp *** To improve survival and aid in recovery after stem cell transplantation,we demonstrated the three-dimensional(3D)self-assembly of adult stem cell-human dental pulp stem cells(hDPSCs)and endothelial cells(ECs)into a novel type of spheroid-shaped dental pulp organoid in vitro under hypoxia and conditioned medium(CM).METHODS During culture,primary hDPSCs were induced to differentiate into ECs by exposing them to a hypoxic environment and *** hypoxic pretreated hDPSCs were then mixed with ECs at specific ratios and conditioned in a 3D environment to produce prevascularized dental pulp *** biological characteristics of the organoids were analysed,and the regulatory pathways associated with angiogenesis were *** The combination of these two agents resulted in prevascularized human dental pulp organoids(Vorganoids)that more closely resembled dental pulp tissue in terms of morphology and ***-cell RNA sequencing of dental pulp tissue and RNA sequencing of Vorganoids were integrated to analyse key regulatory pathways associated with *** biomarkers forkhead box protein O1 and fibroblast growth factor 2 were identified to be involved in the regulation of *** In this innovative study,we effectively established an in vitro model of Vorganoids and used it to elucidate new mechanisms of angiogenesis during regeneration,facilitating the development of clinical treatment strategies.

关键词： Human dental pulp stem cells Prevascularized organoids Integrated analyses Angiogenesis Forkhead box protein O1

Nineteen Clinical Features of Fever in Chinese medicine

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Journal of Traditional Chinese medicine 2010年第4期30卷 302-304页

作者：于明珠王义国 Michele Ball 张启明田欣 Shandong University of Chinese medicine institute of Basic Research in Clinical medicine China Academy of Chinese Medical Sciences Beijing University of Chinese medicine

Objective:Based on the 4,067 descriptions about fever in the medical records of the well-known Chinese medicine physicians throughout the ages, 19 different clinical features of fever are summarized as follows: chilly fever, high fever, low fever, dull fever, bones fever, alternating chills and fever, tidal fever, head fever, face fever, chest fever, back fever, abdomen fever, waist fever, palms and soles fever, lower extremity fever, afternoon fever, evening fever, postpartum fever, and menstrual fever. Although, some of these fever features have not be paid close attention to in Western medicine, stage-division and classification about fever in Western medicine deserve to be used by Chinese medicine for reference.

关键词： fever Clinical feature diagnostics of Chinese medicine

Diagnostic use of superb microvascular imaging in evaluating septic arthritis of the manubriosternal joint:A case report

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World Journal of Clinical Cases 2023年第18期11卷 4397-4405页

作者： Goda Seskute Dominyka Kausaite Ana Chalkovskaja Egle Bulotaite Irena Butrimiene Clinic of Rheumatology Orthopaedics Traumatologyand Reconstructive SurgeryCentre of RheumatologyInstitute of Clinical MedicineFaculty of MedicineVilnius UniversityVilnius 01513Lithuania Clinic of Internal Diseases Family Medicine and OncologyInstitute of Clinical MedicineFaculty of MedicineVilnius UniversityVilnius 01513Lithuania Department of Radiology Nuclear Medicine and Medical PhysicsInstitute of Biomedical SciencesFaculty of MedicineVilnius UniversityVilnius 01513Lithuania

BACKGROUND Septic arthritis of the manubriosternal joint is a diagnostic challenge due to its rarity and anatomical *** ultrasound,plain radiographs,and computed tomography are not able to confirm or even suspect arthritis *** microvascular imaging is a new advanced Doppler technique in evaluating low-flow microvascular *** higher sensitivity for increased perisynovial vascularity helps to suspect septic arthritis and forms a methodical approach to using magnetic resonance imaging(MRI).CASE SUMMARY A 34-year-old immunocompetent woman presented with a fever and a dull ache in the chest radiating to the right *** injury and the most common respiratory and cardiac disorders were ruled *** cultures came back positive for Staphylococcus aureus,and sepsis was confirmed.A small lump was noted on the chest during the first week of *** microvascular imaging was performed and septic arthritis of the manubriosternal joint was *** confirmed the diagnosis and showed septic arthritis of the manubriosternal joint with several localized abscesses behind the *** patient was treated for three weeks with intravenous antibiotics and the outcome was favorable:Inflammatory markers became normal,and the lump *** months later,the patient was examined for a new episode of mild pain in the sternum and was diagnosed with persistent perichondritis by ultrasound in comparison with *** Superb microvascular imaging is a useful tool for the early diagnosis of septic arthritis of the manubriosternal joint and following-up.

关键词： Power Doppler Superb microvascular imaging Ultrasound Septic arthritis Manubriosternal joint Case report

Anti-oxidant and anti-inflammatory effects of hydrogenrich water alleviate ethanol-induced fatty liver in mice

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World Journal of Gastroenterology 2017年第27期23卷 4920-4934页

作者： Ching-Pin Lin Wen-Chen Chuang Fung-Jou Lu Chih-Yen Chen institute of Biochemistry Microbiology and ImmunologyChung Shan Medical University Division of Gastroenterology Department of Internal MedicineChung Shan Medical University Hospital institute of medicine Chung Shan Medical University Division of Gastroenterology and Hepatology Department of MedicineTaipei Veterans General Hospital Faculty of medicine National Yang-Ming University School of Medicine

AIM To investigate the effects of hydrogen-rich water(HRW) treatment on prevention of ethanol(Et OH)-induced early fatty liver in *** In vitro reduction of hydrogen peroxide by HRW was determined with a chemiluminescence system. Female mice were randomly divided into five groups: control,Et OH,Et OH + silymarin,Et OH + HRW and Et OH + silymarin + HRW. Each group was fed a Lieber-De Carli liquid diet containing Et OH or isocaloric maltose dextrin(control diet). Silymarin was used as a positive control to compare HRW efficacy against chronic Et OH-induced hepatotoxicity. HRW was freshly prepared and given at a dosage of 1.2 m L/mouse trice daily. Blood and liver tissue were collected after chronic-binge liquid-diet feeding for 12 *** The in vitro study showed that HRW directly scavenged hydrogen peroxide. The in vivo study showed that HRW increased expression of acyl ghrelin,which was correlated with food intake. HRW treatment significantly reduced Et OH-induced increases in serum alanine aminotransferase,aspartate aminotransferase,triglycerol and total cholesterol levels,hepatic lipid accumulation and inflammatory cytokines,including tumor necrosis factor-alpha(TNF-α) and interleukin(IL)-6. HRW attenuated malondialdehyde level,restored glutathione depletion and increased superoxide dismutase,glutathione peroxidase and catalase activities in the liver. Moreover,HRW reduced TNF-α and IL-6 levels but increased IL-10 and IL-22 *** HRW protects against chronic Et OH-induced liver injury,possibly by inducing acyl ghrelin to suppress the pro-inflammatory cytokines TNF-α and IL-6 and induce IL-10 and IL-22,thus activating antioxidant enzymes against oxidative stress.

关键词： Hydrogen Chronic plus binge Et OH feeding Antioxidant Protective cytokine Acyl ghrelin Female mice

Spermatozoa protein alterations in infertile men with bilateral varicocele

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Asian Journal of Andrology 2016年第1期18卷 43-53页

作者： Ashok Agarwal Rakesh Sharma Damayanthi Durairajanayagam Zhihong Cui Ahmet Ayaz Sajal Gupta Belinda Willard Banu Gopalan Edmund Sabanegh Center for Reproductive medicine Glickman Urological and Kidney Institute Cleveland Clinic Cleveland OH USA Faculty of medicine MARA University of Technology Selanger Malaysia Lerner Research institute Cleveland Clinic Cleveland OH USA

Among infertile men, a diagnosis of unilateral varicocele is made in 90% of varicocele cases and bilateral in the remaining varicocele cases. However, there are reports of under-diagnosis of bilateral varicocele among infertile men and that its prevalence is greater than 10%. In this prospective study, we aimed to examine the differentially expressed proteins （DEP） extracted from spermatozoa cells of patients with bilateral varicocele and fertile donors. Subjects consisted of 17 men diagnosed with bilateral varicocele and 10 proven fertile men as healthy controls. Using the LTQ-orbitrap elite hybrid mass spectrometry system, proteomic analysis was done on pooled samples from 3 patients with bilateral varicocele and 5 fertile men. From these samples, 73 DEP were identified of which 58 proteins were differentially expressed, with 7 proteins unique to the bilateral varicocele group and 8 proteins to the fertile control group. Majority of the DEPs were observed to be associated with metabolic processes, stress responses, oxidoreductase activity, enzyme regulation, and immune system processes. Seven DEP were involved in sperm function such as capacitation, motility, and sperm-zona binding. Proteins TEKT3 and TCP11 were validated by Western blot analysis and may serve as potential biomarkers for bilateral varicocele. In this study, we have demonstrated for the first time the presence of DEP and identified proteins with distinct reproductive functions which are altered in infertile men with bilateral varicocele. Functional proteomic profiling provides insight into the mechanistic implications of bilateral varicocele-associated male infertility.

关键词： bilateral varicocele bioinformatics male infertility proteomics spermatozoa proteins varicocele