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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military Medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li yun-Dan Liao zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue Institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical Medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina Henan Key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

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Persistence of charge density wave against variation of band structures in V_(x)Ti_(1−x)Se_(2)(x=0–0.1)

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Nano Research 2024年第3期17卷 2129-2135页

作者： Zhanfeng Liu Tongrui Li Wen Zhu Hongwei Shou Mukhtar Lawan Adam Qilong Cui Yuliang Li Sheng Wang yunbo Wu Hongen Zhu Yi Liu Shuangming Chen Xiaojun Wu Shengtao Cui Li Song zhe sun National Synchrotron Radiation Laboratory CAS Center for Excellence in NanoscienceUniversity of Science and Technology of ChinaHefei 230029China CAS Key Laboratory of Strongly-coupled Quantum Matter Physics University of Science and Technology of ChinaHefei 230026China Collaborative Innovation Center of Advanced Microstructures Nanjing 210093China State Key Laboratory of Inorganic Synthesis and Preparative Chemistry College of ChemistryJilin UniversityChangchun 130012China School of Chemistry and Materials Sciences CAS Key Laboratory of Materials for Energy Conversionand CAS Center for Excellence in NanoscienceUniversity of Science and Technology of ChinaHefei 230026China School zhejiang Institute of Photonelectronics Jinhua 321004China

Charge density wave(CDW)is a phenomenon that occurs in materials,accompanied by changes in their intrinsic electronic *** study of CDW and its modulation in materials holds tremendous significance in materials research,as it provides a unique approach to controlling the electronic properties of ***_(2) is a typical layered material with a CDW phase at low *** V substitution for Ti in TiSe_(2),we tuned the carrier concentration in V_(x)Ti_(1-x)Se_(2) to study how its electronic structures ***-resolved photoemission spectroscopy(ARPES)shows that the band-folding effect is sustained with the doping level up to 10%,indicating the persistence of the CDW phase,even though the band structure is strikingly different from that of the parent compound TiSe_(2).Though CDW can induce the band fold effect with a driving force from the perspective of electronic systems,our studies suggest that this behavior could be maintained by lattice distortion of the CDW phase,even if band structures deviate from the electron-driven CDW *** work provides a constraint for understanding the CDW mechanism in TiSe_(2),and highlights the role of lattice distortion in the band-folding effect.

关键词： charge density wave band structure lattice distortion

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Neddylation is a novel therapeutic target for lupus by regulating double negative T cell homeostasis

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Signal Transduction and Targeted Therapy 2024年第2期9卷 738-750页

作者： yun Zhang Lijun Du Chenxi Wang Zhangsheng Jiang Qingchi Duan Yiping Li Zhijun Xie Zhixing He Yi sun Lin Huang Liwei Lu Chengping Wen Key Laboratory of Chinese medicine rheumatology of zhejiang Province Research Institute of Chinese Medical Clinical Foundation and ImmunologyCollege of Basic Medical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of General Surgery Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of zhejiang University Hangzhou 310029China Department of Pathology and Shenzhen Institute of Research and Innovation The University of Hong KongHong KongChina Chongqing International Institute for Immunology Chongqing 400038China

Systemic lupus erythematosus(SLE),a severe autoimmune disorder,is characterized by systemic inflammatory response,autoantibody accumulation and damage to *** dysregulation of double-negative(DN)T cells is considered as a crucial commander during ***,a significant type of protein post-translational modification(PTM),has been well-proved to regulate T cell-mediated immune ***,the function of neddylation in SLE is still ***,we reported that neddylation inactivation with MLN4924,a specific inhibitor of NEDD8-activating enzyme E1(NAE1),or genetic abrogation of Ube2m in T cells decreased DN T cell accumulation and attenuated murine lupus *** investigations revealed that inactivation of neddylation blocked Bim ubiquitination degradation and maintained Bim level in DN T cells,contributing to the apoptosis of the accumulated DN T cells in lupus *** double knockout(KO)lupus-prone mice(Ube2m-/-Bim-/-lpr)were generated and results showed that loss of Bim reduced Ube2m deficiency-induced apoptosis in DN T cells and reversed the alleviated lupus *** findings identified that neddylation inactivation promoted Bim-mediated DN T cell apoptosis and attenuated lupus ***,we also found that in SLE patients,the proportion of DN T cells was raised and their apoptosis was ***,compared to healthy groups,SLE patients exhibited decreased Bim levels and elevated Cullin1 neddylation ***,the inhibition of neddylation induced Bim-dependent apoptosis of DN T cells isolated from SLE ***,our findings provide the direct evidence about the function of neddylation during lupus,suggesting a promising therapeutic approach for this disease.

关键词： inactivation double finding

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Bioinformatics comprehensive analysis confirmed the potential involvement of SLC22A1 in lower-grade glioma progression and prognosis

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BIOCELL 2024年第5期48卷 803-815页

作者： JING HUI NANA sun YONG LIU CHUNBO YU YONG KE YONG CAO ANXIAO YU QINGHONG KONG yun LIU Guizhou Provincial College-Based Key Lab for Tumor Prevention and Treatment with DistinctiveMedicines Zunyi Medical UniversityZunyi563000China College of Basic Medicine Zunyi Medical UniversityZunyi563000China Department of Dermatology Guizhou Province Cosmetic Plastic Surgery HospitalAffiliated Hospital of Zunyi Medical UniversityZunyi563000China School of Forensic Medicine Zunyi Medical UniversityZunyi563000China

Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its impact on cancer prognosis remains ***:We conducted a comprehensive analysis utilizing data from The Cancer Genome Atlas(TCGA)and other databases to assess the prognostic value and functional implications across various *** of SLC22A1 RNA in glioma U251 cells was performed to access the impact of SLC22A1 on lowergrade glioma(LGG)***:Our findings demonstrated a significant correlation between SLC22A1 expression and the survival time of patients with various cancers(p0.8).Cell proliferation and clone formation experiment proved that decreased expression of SLC22A1 in glioma U251 cells inhibited glioma cell ***:Our findings suggest SLC22A1 has huge prospects as a promising biomarker and therapeutic target for LGG ***22A1 has only been proved to support cellular function *** findings demonstrated a robust connection between the tumor microenvironment and functional proteins that maintain basal cell metabolism,which gifts unique tumor immune characteristics of ***,we provide a highly practical prediction model for estimating the survival rate of LGG patients.

关键词： SLC22A1 LGG prognosis immune nomogram

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SARS-CoV-2 envelope protein impairs airway epithelial barrier function and exacerbates airway inflammation via increased intracellular Cl^(-)concentration

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1745-1759页

作者： Jian-Bang Xu Wei-Jie Guan Yi-Lin Zhang Zhuo-Er Qiu Lei Chen Xiao-Chun Hou Junqing Yue Yu-yun Zhou Jie Sheng Lei Zhao yun-Xin Zhu Jing sun Jincun Zhao Wen-Liang Zhou Nan-Shan Zhong State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseNational Center for Respiratory MedicineDepartment of Respiratory and Critical Care MedicineGuangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Department of Thoracic Surgery Guangzhou Institute for Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouP.R.China Guangzhou National Laboratory GuangzhouP.R.China School of Life Sciences Sun Yat-sen UniversityGuangzhouP.R.China Guangdong Provincial Key Laboratory of Pharmaceutical Functional Genes School of Life SciencesSun Yat-sen UniversityGuangzhouP.R.China Department of Physiology School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouP.R.China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection disrupts the epithelial barrier and triggers airway *** envelope(E)protein,a core virulence structural component of coronaviruses,may play a role in this *** could interfere with transepithelial Cl^(-)transport via impairment of the cystic fibrosis transmembrane conductance regulator(CFTR),which modulates nuclear factor kB(NF-kB)***,the pathological effects of SARS-CoV-2 E protein on airway epithelial barrier function,Cl^(-)transport and the robust inflammatory response remain to be ***,we have demonstrated that E protein down-regulated the expression of tight junctional proteins,leading to the disruption of the airway epithelial *** addition,E protein triggered the activation of Toll-like receptor(TLR)2/4 and downstream c-Jun N-terminal kinase(JNK)signaling,resulting in an increased intracellular Cl^(-)concentration([Cl^(-)]_(i))via up-regulating phosphodiesterase 4D(PDE4D)expression in airway epithelial *** elevated[Cl^(-)]_(i);contributed to the heightened airway inflammation through promoting the phosphorylation of serum/glucocorticoid regulated kinase 1(SGK1).Moreover,blockade of SGK1 or PDE4 alleviated the robust inflammatory response induced by E ***,these findings provide novel insights into the pathogenic role of SARS-CoV-2 E protein in airway epithelial damage and the ongoing airway inflammation during SARS-CoV-2 infection.

关键词： airway inflammation elevated

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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Research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun yun Hyeon-Ju Jeong Eun-Ju Jin yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network Research Center Sungkyunkwan University School of MedicineSuwonKorea Research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information Research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

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Neural Regeneration Research 2024年第2期19卷 458-464页

作者： Lin Feng Da Li Yao Tian Chengshun Zhao yun sun Xiaolong Kou Jun Wu Liu Wang Qi Gu Wei Li Jie Hao Baoyang Hu Yukai Wang State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Institute for Stem Cell and Regenerative Medicine Chinese Academy of SciencesBeijingChina National Stem Cell Resource Center Chinese Academy of SciencesBeijingChina Savaid Medical School University of Chinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s *** of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s ***,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation ***,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor *** beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in ***,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell ***,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

关键词： axonal integrity cell cryopreservation cellular environment cellular niche cell replacement therapy dopaminergic progenitors human pluripotent stem cell mechanical damage neuronal cell delivery Parkinson’s disease small-aperture gelatin microcarriers

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Rare primary colonic T cell lymphoma with curative resection by endoscopic submucosal dissection:A case report

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World Journal of Clinical Cases 2024年第22期12卷 5229-5235页

作者： Yu-Hui sun Shuang-Shuang Lu Ying Fang zhe Xiong Qiu-Yue sun Jin Huang Nanjing Medical University The Affiliated Changzhou Second People's Hospital of Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina Gastroenterology Center The Affiliated Changzhou Second People's Hospital of Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina Dalian Medical University The Affiliated Changzhou Second People's Hospital of Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina

BACKGROUND The gastrointestinal tract is a well-known extranodal site of lymphoma.B-cell lymph-oma is the most common type,while T-cell lymphoma is *** gastrointestinal lymphoma mainly occurs in the stomach and small intestine,and the colon is less frequently involved,especially in *** SUMMARY A 45-year-old woman was admitted to our hospital for physical *** revealed a visible pedunculated polyp in the transverse colon,for which endoscopic submucosal dissection(ESD)was *** suggested highly active proliferation of T lymphocytes with atypical *** A middle-aged female patient was found to have colonic T-cell lymphoma by *** lesion was successfully removed by ESD,and the surgical margin was *** is essential to raise awareness of colonic T-cell lymphoma and choose the appropriate treatment.

关键词： Primary colorectal lymphoma T-cell lymphoma Endoscopic submucosal dissection Pedunculated polyp Case report

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主动脉瓣修复术的历史、现状和未来

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中华外科杂志 2024年第5期62卷 364-369页

作者：孙境郑哲中国医学科学院、北京协和医学院、国家心血管病中心、阜外医院心血管外科北京100037

主动脉瓣修复术是一种古老的手术方式,它与主动脉瓣置换术同时起步,但由于效果不佳逐渐被舍弃。目前主动脉瓣置换术已成为主动脉瓣功能障碍伴或不伴主动脉根部病变患者的首选治疗方法。由于人工瓣膜面临衰败和抗凝相关并发症,主动脉瓣... 详细信息

主动脉瓣修复术是一种古老的手术方式,它与主动脉瓣置换术同时起步,但由于效果不佳逐渐被舍弃。目前主动脉瓣置换术已成为主动脉瓣功能障碍伴或不伴主动脉根部病变患者的首选治疗方法。由于人工瓣膜面临衰败和抗凝相关并发症,主动脉瓣修复术再次成为一种治疗选择,它避免了人工瓣膜相关的长期风险,但存在主动脉瓣关闭不全复发的风险。主动脉根部重塑术和再植术两种划时代手术的出现,降低了关闭不全复发的风险。主动脉根部功能解剖概念与主动脉瓣关闭不全机制的提出与确立奠定了现代主动脉瓣修复的理论基础。主动脉瓣修复成为一种涉及瓣环、窦部、窦管交界、瓣叶等的综合修复策略,患者术后远期生存率接近健康人群,瓣膜相关再干预率与瓣膜置换术相似,逐渐成为主动脉瓣关闭不全伴或不伴主动脉根部病变患者的一种替代治疗方式。

关键词：主动脉瓣关闭不全心血管外科手术主动脉瓣修复术主动脉瓣置换术再手术

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“双减”政策助推学校体育教学高质量发展的多维逻辑、时代价值与实践向度

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教育科学 2024年第1期40卷 57-63页

作者：孙哲王松东北大学体育部辽宁沈阳110819 清华大学体育部北京100084

“双减”政策作为一项学校体育教育改革,其根本之策在于全面提高学校体育教学质量。“双减”政策助推学校体育教学高质量发展呈现多维逻辑:一是政治逻辑,“减负”政策引发学校体育教学变革的方向;二是理论逻辑,马克思主义哲学“人的全... 详细信息

“双减”政策作为一项学校体育教育改革,其根本之策在于全面提高学校体育教学质量。“双减”政策助推学校体育教学高质量发展呈现多维逻辑:一是政治逻辑,“减负”政策引发学校体育教学变革的方向;二是理论逻辑,马克思主义哲学“人的全面发展”的传承与创新;三是行动逻辑,实现从“有学上”到“上好学”的内涵式转变。面对新时代新征程,“双减”政策在助推学校体育教学高质量发展方面具有以“健康第一”教育理念促进人全面发展、以课后延时体育服务效能反哺学校体育教学质量、以教育督导全面深化改革完善学校体育教学评价体系的时代价值,这决定了“双减”政策的实践向度:统筹社会力量,筑牢“健康第一”教育理念;优化基本要素,提升学校体育课堂教学质量;强化治理能力,增进课后延时体育服务水平;聚焦中高考体育,完善学校体育教学评价机制。

关键词： “双减”政策学校体育教学高质量发展学校体育教育

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