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Integrated single-cell rna sequencing analysis reveals distinct cellular and transcriptional modules associated with survival in lung cancer

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Signal Transduction and Targeted Therapy 2022年第2期7卷 479-491页

作者： Li Zhang Yiming Zhang Chengdi Wang Ying Yang Yinyun Ni Zhoufeng Wang Tingting Song Menglin Yao Zhiqiang Liu Ningning Chao Yongfeng Yang Jun Shao Zhidan Li Ran Zhou Li Chen Dan Zhang Yuancun Zhao Wei Liu Yupeng Li Ping He Jing-wen Lin Yuan Wang Kang Zhang Lu Chen Weimin Li Department of Respiratory and Critical Care Medicine National Clinical Research Center for GeriatricsCenter of Precision MedicinePrecision Medicine Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalWest China School of MedicineSichuan UniversityChengduSichuan ProvinceChina Key Laboratory of Birth Defects and Related Diseases of Women and Children West China Second University HospitalState Key Laboratory of BiotherapySichuan UniversityChengduChina Department of Neurology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and Technology and University HospitalMacaoChina

Lung adenocarcinoma(LUAD)and squamous carcinoma(LUSC)are two major subtypes of non-small cell lung cancer with distinct pathologic features and treatment *** heterogeneity can be attributed to genetic,transcriptional,and epigenetic ***,we established a multi-omics atlas,integrating 52 single-cell rna sequencing and 2342 public bulk rna *** investigated their differences in genetic amplification,cellular compositions,and expression *** revealed that LUAD and LUSC contained amplifications occurring selectively in subclusters of AT2 and basal cells,and had distinct cellular composition modules associated with poor survival of lung *** and stage-specific gene analyses further uncovered critical transcription factors and genes in tumor ***,we identified subclusters with proliferating and differentiating properties in AT2 and basal *** assays of ten genes,including sub-cluster markers AQP5 and KPNA2,further indicated their functional roles,providing potential targets for early diagnosis and treatment in lung cancer.

关键词： lung cancer diagnosis

An inspiration to the studies on mechanisms of acupuncture and moxibustion action derived from 2021 Nobel Prize in Physiology or Medicine

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Acupuncture and Herbal Medicine 2022年第1期2卷 1-8页

作者： Yi Guo Yongming Li Tianle Xu Michael Xi Zhu Zhifang Xu Baomin Dou Yanwei Li Zhihan Chen research Center of Experimental Acupuncture Science Tianjin University of Traditional Chinese MedicineTianjinChina School of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina National Clinical research Center for Chinese Medicine Acupuncture and Moxibustion TianjinChina American Traditional Chinese Medicine Society New YorkNYUSA Collaborative Innovation Center for Brain Science Department of Anatomy and PhysiologyShanghai Jiao Tong University School of MedicineShanghaiChina Department of Integrative Biology and Pharmacology The University of Texas Health Science Center at HoustonHoustonTXUSA School of Acupuncture&Moxibustion and Tuina Tianjin University of Traditional Chinese MedicineTianjinChina

The editorial board of Acupuncture and Herbal Medicine recently convened an academic seminar with a focus on studies regarding the mechanisms mediating acupuncture efficacy and moxibustion action inspired by the 2021 Nobel Prize in Physiology or ***,Professor Bailong Xiao introduced the Nobel Prize for research on the mechanically activated Piezo ion channel,evaluating the structure of the Piezo channel and its physiological and pathological functions,and proposed a possible role for the Piezo channel in acupuncture mechanical *** Michael Xi Zhu introduced the discovery of the transient receptor potential(TRP)family,reporting that the therapeutic effects of Chinese medicine and acupuncture may be achieved via the TRP family,and that information regarding associations between the meridian and lymphatic systems may have important research and medical *** addition,Professor Tianle Xu reviewed the history of ion channel research,particularly the physiological and pharmacological effects of non-classical ion channels(eg,the acid sensing ion channel family)and pointed out that the characterization and neural circuits of acupuncture deqi manipulation are important for elucidating the mechanisms of acupuncture *** Yongming Li similarly proposed that the 2021 Nobel Prize may open the door to disclosing the histological basis of acupuncture and moxibustion and analyzing the main scientific concerns regarding the clinical translation of acupuncture and moxibustion from basic to translational ***,Professor Yi Guo summarized the study progress of the acupoint microenvironment induced by acupuncture over the course of nearly 30 years and put forward the hypothesis that acupuncture may initiate the physical-chemical coupling network by activating ion channel receptors in acupoints via physical and mechanical ***,we conclude that a primary achievement of the 2021 Nobel Prize in Physiology or Medic

关键词： 2021 Nobel Prize in Physiology or Medicine Acupuncture Ion channel Moxibustion Piezo TRPV1

Circular rnas in early brain development and their influence and clinical significance in neuropsychiatric disorders

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Neural Regeneration research 2020年第5期15卷 817-823页

作者： Chuan-Jun Zhuo Wei-Hong Hou De-Guo Jiang Hong-Jun Tian Li-Na Wang Feng Jia Chun-Hua Zhou Jing-Jing Zhu Department of Psychiatry and Genetics School of Mental HealthJining Medical UniversityJiningShandong ProvinceChina Department of Psychiatry and Molecular Psychiatry Wenzhou Seventh People’s HospitalWenzhouZhejiang ProvinceChina Department of Psychiatry and Imaging-Genetics and Co-morbidity (PNGC-Lab) Tianjin Anding HospitalTianjin Mental Health CenterMental Health Teaching HospitalTianjin Medical UniversityDepartment of PsychiatrySchool of Basic Medical ResearchTianjin Medical UniversityTianjinChina Department of Biochemistry and Molecular Biology Medical College of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of Biology University of North Carolina at CharlotteCharlotteNCUSA Department of Pharmacy First Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina

Neuropsychiatric disorders represent a set of severe and complex mental illnesses,and the exact etiologies of which are *** has been well documented that impairments in the early development of the brain contribute to the pathogenesis of many neuropsychiatric ***,the diagnosis of neuropsychiatric disorders largely relies on subjective cognitive assessment,because there are no widely accepted biochemical or genetic biomarkers for diagnosing mental *** rnas (circrnas) are a novel class of endogenous non-coding rna (ncrna) with a closed-loop *** recent years,there have been tremendous advances in our understanding of the expression profiles and biological roles of *** the brain,circrnas are particularly enriched and are expressed more abundantly in contrast to linear counterpart *** are highly active at neuronal *** features make circrnas uniquely crucial for understanding brain health,disease,and neuropsychiatric *** review focuses on the role of circrnas in early brain development and other brain-related processes that have been associated with the development of neuropsychiatric *** addition,we discuss the potential for blood or cerebrospinal fluid circrnas to be used as novel biomarkers in the early diagnosis of neuropsychiatric *** findings reviewed here may provide new insight into the pathological mechanisms underlying the onset and progression of neuropsychiatric disorders.

关键词： autism spectrum disorders bipolar disorder brain exosomal circrnas micrornas nerve regeneration non-coding rnas obsessive-compulsive disorders schizophrenia

AFAP1-AS1: a rising star among oncogenic long non-coding rnas

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Science China(Life Sciences) 2021年第10期64卷 1602-1611页

作者： Fang Xiong Kunjie Zhu Su Deng Hongbin Huang Liting Yang Zhaojian Gong Lei Shi Yi He Yanyan Tang Qianjin Liao Jianjun Yu Xiaoling Li Yong Li Guiyuan Li Zhaoyang Zeng Wei Xiong Shanshan Zhang Can Guo Science and Technology on Information System Engineering Laboratory National University of Defense TechnologyChangsha 410000China Department of Periodontology Center of StomatologyXiangya HospitalCentral South UniversityChangsha 410078China NHC Key Laboratory of Carcinogenesis and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education of China Cancer Research InstituteCentral South UniversityChangsha 410078China Hunan Key Laboratory of Cancer Metabolism Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Department of Oral and Maxillofacial Surgery The Second Xiangya HospitalCentral South UniversityChangsha 410011China Department of Medicine Dan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTexasUSA

Long non-coding rnas(lncrnas)have become a hotspot in biomedical *** interest reflects their extensive involvement in the regulation of the expression of other genes,and their influence on the occurrence and development of a variety of human *** filament associated protein 1-Antisense rna 1(AFAP1-AS1)is a recently discovered oncogenic *** is highly expressed in a variety of solid tumors,and regulates the expression of downstream genes and signaling pathways through adsorption and competing micrornas,or by the direct binding to other ***,AFAP1-AS1 promotes proliferation,chemotherapy resistance,and resistance to apoptosis,maintains stemness,and enhances invasion and migration of tumor *** paper summarizes the research concerning AFAP1-AS1 in malignant tumors,including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant *** also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further ***1-AS1 is expected to provide an example for studies of other lncrna molecules.

关键词： AFAP1-AS1 metastasis proliferation anti-cancer drug PD-1 immunotherapy

Target genes discovery through copy number alteration analysis in human hepatocellular carcinoma

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World Journal of Gastroenterology 2013年第47期19卷 8873-8879页

作者： De-Leung Gu Yen-Hsieh Chen Jou-Ho Shih Chi-Hung Lin Yuh-Shan Jou Chian-Feng Chen Institute of Biomedical Sciences Academia Sinica Institute of Microbiology and Immunology School of Life ScienceNational Yang-Ming University Bioinformatics Program Taiwan International Graduate ProgramAcademia Sinica Genome and Systems Biology Degree Program National Taiwan University VYM Genome research Center National Yang-Ming University

High-throughput short-read sequencing of exomes and whole cancer genomes in multiple human hepatocellular carcinoma(HCC)cohorts confirmed previously identified frequently mutated somatic genes,such as TP53,CTNNB1 and AXIN1,and identified several novel genes with moderate mutation frequencies,including ARID1A,ARID2,MLL,MLL2,MLL3,MLL4,IRF2,ATM,CDKN2A,FGF19,PIK3CA,RPS6KA3,JAK1,KEAP1,NFE2L2,C16orf62,LEPR,RAC2,and *** classification of these mutated genes suggested that alterations in pathways participating in chromatin remodeling,Wnt/β-catenin signaling,JAK/STAT signaling,and oxidative stress play critical roles in HCC ***,because there are few druggable genes used in HCC therapy,the identification of new therapeutic targets through integrated genomic approaches remains an important *** a large amount of HCC genomic data genotyped by high density single nucleotide polymorphism arrays is deposited in the public domain,copy number alteration(CNA)analyses of these arrays is a cost-effective way to reveal target genes through profiling of recurrent and overlapping amplicons,homozygous deletions and potentially unbalanced chromosomal translocations accumulated during HCC ***,integration of CNAs with other high-throughput genomic data,such as aberrantly coding transcriptomes and non-coding gene expression in human HCC tissues and rodent HCC models,provides lines of evidence that can be used to facilitate the identification of novel HCC target genes with the potential of improving the survival of HCC patients.

关键词： Copy number alteration High-density single nucleotide polymorphism arrays Driver genes Hepatocellular carcinoma

Liver Stiffness Measurement Can Reflect the Active Liver Necroinflammation in Population with Chronic Liver Disease:A Real-world Evidence Study

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Journal of Clinical and translational Hepatology 2019年第4期7卷 313-321页

作者： Leijie Wang Mingyu Zhu Lihua Cao Mingjie Yao Yiwei Lu Xiajie Wen Ying Zhang Jing Ning Huiling Long Yueyong Zhu Guoxin Hu Shuangsuo Dang Qingchun Fu Liang Chen Xinxin Zhang Jingmin Zhao Zhiliang Gao Yuemin Nan Fengmin Lu Department of Microbiology&Infectious Disease Center School of Basic Medical SciencesPeking University Health Science CenterBeijingChina Department of Infectious Diseases Rui Jin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Liver Disease Center Qinhuangdao Third HospitalQinhuangdaoHebeiChina Department of Anatomy and Embryology School of Basic Medical SciencesPeking University Health Science CenterBeijingChina Eshelman School of Pharmacy University of North CarolinaChapel HillNCUSA Department of Traditional and Western Medical Hepatology The Third Hospital of Hebei Medical UniversityShijiazhuangHebeiChina Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdongChina Liver research Center First Affiliated Hospital of Fujian Medical UniversityFuzhouFujianChina Department of Infectious Diseases Peking University Shenzhen HospitalShenzhenGuangdongChina Department of Infectious Diseases Second Affiliated Hospital of Medical College of Xi'an Jiaotong UniversityXi'anShaanxiChina Shanghai Liver Diseases research Center 85th HospitalNanjing Military CommandShanghaiChina Department of Liver Disease Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Pathology and Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Intervention and Cell Therapy Center Peking University Shenzhen HospitalShenzhenGuangdongChina

Background and Aims: non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical *** diagnostic accuracy of transient elastography-based liver stiffness measurement(LSM)for liver fibrosis could be affected by liver necroinflam-mation,the latter of which could intensify stiffness of the *** results have prompted us to explore the diagnosis potential of LSM for liver ***: Three cross-sectional cohorts of liver biopsy-proven chronic liver dis-ease patients were enrolled,including 1417 chronic hepatitis B(CHB)patients from 10 different medical centers,106 non-al-coholic steatohepatitis patients,and 143 patients with auto-immune-related liver *** longitudinal cohort of 14 entecavir treatment patients was also *** re-ceiver operating characteristic(ROC)curve was employed to explore the diagnostic value of ***: In CHB patients,LSM value ascended with the increased severity of liver nec-roinflammation in patients with the same fibrosis *** positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoim-mune-related liver diseases ***,the ROC curve exhibited that LSM could identify moderate and se-vere inflammation in CHB patients(area under the ROC curve as 0.779 and 0.838)and in non-alcoholic steatohepatitis pa-tients(area under the ROC curve as 0.826 and 0.871),*** moderate diagnostic value was also found in autoimmune-related liver diseases *** addition,in the longitudinal entecavir treated CHB cohort,a decline of LSM values was observed in parallel with the control of inflam-matory activity in ***: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.

关键词： Liver stiffness measurement Liver necroinflammatory grade Alanine aminotransferase Chronic liver disease

Individualized red-cell transfusion strategy for non-cardiac surgery in adults:a randomized controlled trial

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Chinese Medical Journal 2023年第23期136卷 2857-2866页

作者： Ren Liao Jin Liu Wei Zhang Hong Zheng Zhaoqiong Zhu Haorui Sun Zhangsheng Yu Huiqun Jia Yanyuan Sun Li Qin Wenli Yu Zhen Luo Yanqing Chen Kexian Zhang Lulu Ma Hui Yang Hong Wu Limin Liu Fang Yuan Hongwei Xu Jianwen Zhang Lei Zhang Dexing Liu Han Huang Department of Anesthesiology Research Unit for Perioperative Stress Assessment and Clinical DecisionChinese Academy of Medical Sciences(2018RU012)West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Anesthesiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China Department of Anesthesiology The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiang 830054China Department of Anesthesiology The Affiliated Hospital of Zunyi Medical CollegeZunyiGuizhou 563003China Department of Anesthesiology Beijing Friendship Hospital of Capital Medical UniversityBeijing 100069China Department of Bioinformatics and Biostatistics School of Life Science and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Department of Anesthesiology The Fourth Hospital of Hebei Medical UniversityShijiangzhuangHebei 050019China Department of Anesthesiology Xijing Hospital of the Fourth Military Medical UniversityXi’anShaanxi 710032China Department of Transfusion West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Anesthesiology Tianjin First Center HospitalTianjin 300192China Department of Anesthesiology Fujian Provincial HospitalFuzhouFujian 350001China Department of Anesthesiology Sichuan Cancer Hospital&InstituteChengduSichuan 610041China Department of Anesthesiology Peking Union Medical College HospitalBeijing 100032China Department of Anesthesiology Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Department of Hepato-Bilio-Pancreatic Surgery West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Orthopedic Surgery West China Hospital of Sichuan UniversityChengduSichuan 610041China Department of Anesthesiology General Hospital Affiliated to Tianjin Medical UniversityTianjin 300052China Department of Anesthesiology and translational Neuroscience Center West China Second University Hospital of S

Background:Red-cell transfusion is critical for surgery during the peri-operative period;however,the transfusion threshold remains controversial mainly owing to the diversity among *** patient’s medical status should be evaluated before making a transfusion ***,we developed an individualized transfusion strategy using the West-China-Liu’s Score based on the physiology of oxygen delivery/consumption balance and designed an open-label,multicenter,randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively,providing valid evidence for peri-operative ***:Patients aged>14 years undergoing elective non-cardiac surgery with estimated blood loss>1000 mL or 20%blood volume and hemoglobin concentrationnon-inferiority test).Results:We enrolled 1182 patients:379,419,and 384 received individualized,restrictive,and liberal strategies,*** 30.6%(116/379)of patients in the individualized strategy received a red-cell transfusion,less than 62.5%(262/419)in the restrictive strategy(absolute risk difference,31.92%;97.5%confidence interval[CI]:24.42-39.42%;odds ratio,3.78%;97.5%CI:2.70-5.30%;P<0.001),and 89.8%(345/384)in the liberal strategy(absolute risk difference,59.24%;97.5%CI:52.91-65.57%;odds ratio,20.06;97.5%CI:12.74-31.57;P<0.001).No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three ***:The individualized red-cell transfusion stra

关键词： Individualized transfusion strategy West-China-Liu’s Score Red cells Blood volume Hemoglobins Postoperative care

Histone crotonylation in neurobiology:to be or not to be?

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Chinese Medical Journal 2022年第9期135卷 1036-1038页

作者： Cechuan Deng Jia-Hua Qu InKyeom Kim Xiaoqiang Tang Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Medical Genetics Prenatal Diagnostic CenterWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Laboratory of Cardiovascular Science Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMaryland 21224USA Department of Pharmacology School of MedicineKyungpook National UniversityDaeguRepublic of Korea Cardiovascular research Institute School of MedicineKyungpook National UniversityDaeguRepublic of Korea Department of Biomedical Science BK21 Plus KNU Biomedical Convergence ProgramSchool of MedicineKyungpook National UniversityDaeguRepublic of Korea

Epigenetic regulation is a pivotal mechanism that controls gene transcription and cell *** the past decades,it has been observed that histone,DNA,and rna modifications participate in determining the fate of neural stem cells(NSCs).These modifications include histone acetylation and methylation,as well as DNA and rna *** note,non-coding rnas also participate in neural differentiation.[1]In addition to acetylation,many other types of acylations to histone lysines,including crotonylation,propionylation,succinylation,and malonylation,have been identified.[2]The roles of these histone acylations in neuroscience remain elusive.

关键词： neural differentiation. modification

The Pivotal Role of TNF -α in Rheumatoid Arthritis

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中医药学刊 2004年第10期22卷 1847-1849,1865页

作者： Kodar Lee Shanghai University of TCM 200032Shanghais a main pro - inflammatory factor the up - regulation of TNF -αin RA patients plays a pivotal role in RA pathogenesis. The process of TNF production starts with the binding of a ligand( which is commonly a microbial product)to a cell surface Toll receptor which stimulates a signal transduction pathway that activates NF - KB transcription factors. Activated NF - KB enters nuclei and induces the transcription of genes associated with inflammation including those coding for TNF. The production of TNF and other inflammatory cytokines serves to recruit other inflammatory cells which in turn release cytokines and subsequently amplify the immune response. TNF exerts its effect via binding of TNFR1and TNFR2 receptors. Many experimental and clinical study have proved the effectiveness of TNF - αa ctivity blockade. Recent therapeutic interventions including TNF - αand IL - 1 inhibitors strongly support the importance of cytokines in RA. The mechanism of anti - TNF - αaction in vivo is complex and probably includes suppression of other pro - inflammatory cytokines decreased synovial cellular infiltration interference with osteoclast activation and decreased angiogenisis. Studies using anti -TNF agents clearly show that they can slow or prevent the progression of bone and cartilage damage in RA. This activity probably involves suppression of osteoclasts in joint lesions. Etanercept Infiiximab and adalimumab are the three main biologic agents that were focused on clinically at present.

As a main pro-inflammatory factor, the up-regulation of TNF-α in RA patients plays a pivotal role in RA pathogenesis. The process of TNF production starts with the binding of a ligand( which is commonly a microbial product) to a cell surface Toll receptor, which stimulates a signal transduction pathway that activates NF - κB transcription factors. Activated NF - κB enters nuclei and induces the transcription of genes associated with inflammation, including those coding for TNF. The production of TNF and other inflammatory cytokines serves to recruit other inflammatory cells, which in turn release cytokines and subsequently amplify the immune response. TNF exerts its effect via binding of TNFRland TNFR2 receptors. Many experimental and clinical study have proved the effectiveness of TNF - αa ctivity blockade. Recent therapeutic interventions, including TNF - α and IL - 1 inhibitors, strongly support the importance of cytokines in RA. The mechanism of anti - TNF - α action in vivo is complex and probably includes suppression of other pro - inflammatory cytokines, decreased synovial cellular infiltration, interference with osteoclast activation, and decreased angiogenisis. Studies using anti -TNF agents clearly show that they can slow or prevent the progression of bone and cartilage damage in RA. This activity probably involves suppression of osteoclasts in joint lesions. Etanereept, Infliximab and adalimumab are the three main biologic agents that were fo-cused on clinically at present.

关键词： TNF-α RA TNFR