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MPZL1 as an HGF/MET signaling amplifier promotes cell migration and invasion in glioblastoma

Genes & Diseases 2024年第5期11卷 70-73页

作者： Haimin song Bowen Ni Xuetao Peng Weijuan Xu shaochun Yang Runwei Yang Ziyu Wang Kaishu Li Rui Lin Yunxiao Zhang Jinglin Guo Kezhi Wu Guangwei shi Jichao sun Chunming He Yawei Liu Department of Neurosurgery The First Affiliated Hospital of Gannan Medical UniversityGanzhouJiangxi 341000China Department of Neurosurgery&Medical Research Center Shunde HospitalSouthern Medical University(The First People’s Hospital of Shunde Foshan)FoshanGuangdong 528300China Medical Research Center Shunde HospitalSouthern Medical University(The First People’s Hospital of Shunde Foshan)FoshanGuangdong 528300China Bidding and Procurement Office Shunde HospitalSouthern Medical University(The First People’s Hospital of Shunde Foshan)FoshanGuangdong 528300China Department of Neurosurgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Neurosurgery The Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuanGuangdong 511518China Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical CollegeShantouGuangdong 515041China Department of Geriatrics Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSouthern University of Science and Technology)ShenzhenGuangdong 518020China

The extremely poor prognosis of patients is largely due to hepatocyte growth factor(HGF)/MET signaling,which promotes migration and invasion of glioblastoma(IDH wildtype;GBM;WHO grade 4).1,2 Clinical trials targeting MET,the only receptor of HGF,have yielded unimpressive results in GBM.3,4 Here we found that HGF induced strong chemotaxis on GBM cells,but MET expression was extremely ***,therefore,used single-cell RNA sequencing(scRNA-seq)coupled with label-free proteome profiling to identify membrane proteins associated with HGF/MET signaling amplification in GBM and to provide a novel modulator,MPZL1,for HGF/MET-targeted therapy.

关键词： invasion prognosis Clinical

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Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy

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Chinese Chemical Letters 2024年第4期35卷 268-274页

作者： Xinyue Lan Junguang Liang Churan Wen Xiaolong Quan Huimin Lin Qinqin Xu Peixian Chen Guangyu Yao Dan Zhou Meng Yu Breast Center Department of General SurgeryNanfang HospitalSouthern Medical UniversityGuangzhou 510515China NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Breast surgery The First People's Hospital of FoshanFoshan 528100China Zhujiang hospital Southern Medical UniversityGuangzhou 510282China

Despite the synergy of immune checkpoint blockade(ICB) therapy and photodynamic therapy(PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6(Ce6) and programmed death-ligand 1 antibody(αPD-L1) for flexible local photoimmunotherapy with merely singledosed administration. The presence of polyunsaturated fatty acid(docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species(ROs)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. The immunogenic cell death(ICD) effect of PDT evoked “cold” breast tumor to “hot” one, and then assisted the cascade releasedαPD-L1 to synergistically boost the immunotherapy. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform,showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.

关键词： Photodynamic therapy Immunotherapy Responsive release Immunogenic cell death Liposomal hydrogel

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A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

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Neural Regeneration Research 2024年第2期19卷 324-330页

作者： Xi Chen Yuhu Zhang Department of Neurology Guangdong Neuroscience InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina shantou University Medical College ShantouGuangdong ProvinceChina

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially *** dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and *** contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial *** from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s *** research has reported evidence that the cerebellum receives both dopaminergic and cholinergic ***,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully ***,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains ***,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional *** findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

关键词： anterior brain system cerebellum cholinergic cognitive impairment dopaminergic dual syndrome hypothesis neuroimage neurotransmitter Parkinson’s disease posterior brain system therapeutic targets

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Prevalence of bacteria, fungi, and virus coinfections with sARs-CoV-2 Omicron variant among patients with severe COVID-19 in guangzhou, China, winter 2022

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Biosafety and Health 2024年第2期6卷 92-97页

作者： Qinghong Fan Mengling Jiang Jun Zhang Guofang Tang Ming Gao Yingfen Wen Xizi Deng Jun Dai Honghao Lai Peng Qian Yaqing Lin Ruiying He Liya Li Yueping Li Zhengtu Li Xuesong Liu Yimin Li Na Yu Yun Lan Fengyu Hu Feng Li Institute of Infectious Diseases Guangzhou Eighth People's HospitalGuangzhou Medical UniversityGuangzhou 510440China state Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of GuangzhouMedicalUniversityGuangzhou510120China guangzhou Laboratory Guangzhou 510700China

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2(sARs-CoV-2)Omicron BA.5.2 or BF.7 in China in the winter of 2022,which is suspected to contribute substantially to the overloaded severe cases,needs to be *** analyzed the coinfection status of 385 severe patients infected with the Omicron variant in guangzhou using metagenomic *** found that 317(82.3%)patients were coinfected with at least one additional pathogen(s),including bacteria(58.7%),fungi(27.1%)and viruses(73.5%).Pseudomonas aeruginosa(***)(24.2%),staphylococcus aureus(***)(14.0%),andKlebsiella pneumoniae(***)(13.4%)ranked as the top three coinfected *** fumigatus(***)(39.5%),Pneumocystis jirovecii(***)(24.4%)andCanidia albicans(***)(22.1%)were the top three coinfected ***-Barr virus(EBV)(63.1%),Human herpesvirus 7(HHV-7)(34.8%),and Herpes simplex virus 1(HsV-1)(32.6%)were the top three coinfected *** note,the detection of multiple coinfections of potential pathogenic bacteria,fungi,and viruses,despite lacking consistent patterns,highlighted a complicated synergistic contribution to disease *** study presents the most comprehensive spectrum of bacterial,fungal,and viral coinfections in Omicron-associated severe coronavirus disease 2019(COVID-19),implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.

关键词： sARs-CoV-2 Omicron BA.5.2 Omicron BF.7 Coinfection severeinfection

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Two Monte Carlo-based simulators for imaging-system modeling and projection simulation of flat-panel X-ray source

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Nuclear science and Techniques 2024年第7期35卷 31-46页

作者： Meng-Ke Qi Ting He Yi-Wen Zhou Jing Kang Zeng-Xiang Pan song Kang Wang-Jiang Wu Jun Chen Ling-Hong Zhou Yuan Xu school of Biomedical Engineering Southern Medical UniversityGuangzhou510515China state Key Laboratory of Optoelectronic Materials and Technologies Guangdong Province Key Laboratory of Display Material and TechnologySchool of Electronics and Information TechnologySun Yat-sen UniversityGuangzhou510275China Department of Radiotherapy Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou510515China

The advantages of a flat-panel X-ray source(FPXs)make it a promising candidate for imaging *** imaging-system modeling and projection simulation are critical for analyzing imaging performance and resolving overlapping projection issues in *** conventional analytical ray-tracing approach is limited by the number of patterns and is not applicable to FPXs-projection ***,the computation time of Monte Carlo(MC)simulation is independent of the size of the patterned arrays in *** study proposes two high-efficiency MC projection simulators for FPXs:a graphics processing unit(GPU)-based phase-space sampling MC(gPsMC)simulator and GPU-based fluence sampling MC(gFsMC)*** two simulators comprise three components:imaging-system modeling,photon initialization,and physical-interaction simulations in the ***-system modeling was performed by modeling the FPXs,imaging geometry,and *** gPsMC simulator samples the initial photons from the phase space,whereas the gFsMC simulator performs photon initialization from the calculated energy spectrum and fluence *** entire process of photon interaction with the geometry and arrival at the detector was simulated in parallel using multiple GPU kernels,and projections based on the two simulators were *** accuracies of the two simulators were evaluated by comparing them with the conventional analytical ray-tracing approach and acquired projections,and the efficiencies were evaluated by comparing the computation *** results of simulated and realistic experiments illustrate the accuracy and efficiency of the proposed gPsMC and gFsMC simulators in the projection calculation of various phantoms.

关键词： Flat-panel X-ray source(FPXs) Imaging-system modeling Projection simulation Monte Carlo-based simulators

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Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis

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World Journal of Gastrointestinal surgery 2024年第3期16卷 700-709页

作者： Kai Liu Chun-Xiao Wu Hui Liang Tao Wang Ji-Yuan Zhang Xiao-Tao Wang Department of Radiation and Oncology Traditional Chinese Hospital of Lu’an affiliated to Anhui University of Traditional Chinese MedicineLu’an 237000Anhui ProvinceChina Department of Gastroenterology Ehu branch of Xishan People’s Hospital of Wuxi CityWuxi 214116Jiangsu ProvinceChina Department of Gastrointestinal surgery The First Affiliated Hospital of Guangzhou University of Traditional Chinese MedicineGuangzhou 510400Guangdong ProvinceChina Department of Gastrointestinal surgery Hunan Provincial People’s HospitalChangsha 410002Hunan ProvinceChina Department of Traditional Chinese medicine Ehu branch of Xishan People’s Hospital of Wuxi CityWuxi 214116Jiangsu ProvinceChina

BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all *** is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with *** To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced *** This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January *** baseline attributes were compared using either the Chi-square test or the Fisher exact probability *** chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver *** The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver *** objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),***,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),*** median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than *** median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than *** Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

关键词： Gastric cancer spread of cancer to the liver Treatment with immunotherapy Effectiveness of treatment

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Circular RNAs in breast cancer diagnosis,treatment and prognosis

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Oncology Research 2024年第2期32卷 241-249页

作者： XIAOJIA HUANG CAILU sONG JINHUI ZHANG LEWEI ZHU HAILIN TANG Department of Breast Oncology surgery Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhou510095China state Key Laboratory of Oncology in south China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China Department of Breast surgery The First People’s Hospital of FoshanFoshan528000China

Breast cancer has surpassed lung cancer to become the most common malignancy *** incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public *** RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and *** breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various ***,circRNAs may serve as promising targets of therapeutic strategies for breast cancer *** study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast *** the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.

关键词： CircRNA Breast cancer Diagnosis Treatment Biomarker

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Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients:A meta-analysis

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Cancer Innovation 2024年第3期3卷 49-64页

作者： Huiyi Liu Lu Fu shuyu Jin Xingdong Ye Yanlin Chen sijia Pu Yumei Xue Department of Cardiology Guangdong Cardiovascular InstituteGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina The second school of Clinical Medicine Southern Medical UniversityGuangzhouGuangdongChina school of Medicine South China University of TechnologyGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of Clinical Pharmacology Research Center of Medical SciencesGuangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina

Background:With the emergence of cytotoxic T lymphocyte-associated protein-4(CTLA-4)inhibitors,the outcomes of patients with malignant tumors have improved ***,the incidence of cardiovascular adverse events has also increased,which can affect tumor *** this study,we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor ***:Randomized clinical trials published in English from January 1,2013,to November 30,2022,were searched using the Cochrane Library and PubMed *** included trials examined all grade and grades 3–5 cardiac and vascular adverse *** involved comparisons of CTLA-4 inhibitors to placebo,CTLA-4 inhibitors plus chemotherapy to chemotherapy alone,CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone,and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target *** odds ratio(OR)and corresponding 95%confidence intervals(CIs)were calculated using the Mantel-Haenszel ***:Overall,20 trials were ***-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity(OR=1.33,95%CI:1.00–1.75,p=0.05).The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors(OR=1.73,95%CI:1.13–2.65,p=0.01),as well as the incidence rate of grades 3–5 cardiovascular adverse events(OR=2.00,95%CI:1.08–3.70,p=0.03).Compared with the non-CTLA-4 inhibitor group,CTLA-4 inhibitors plus chemotherapy,PD-1/PD-L1 inhibitors,or target agent did not significantly affect the incidence of cardiac and vascular *** incidence of grades 3–5 cardiac failure,hypertension,pericardial effusion,myocarditis,and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor,but the data were not statistically ***:Our findings suggest that the

关键词： cardiovascular toxicity CTLA-4 inhibitors malignancies

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Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

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Infectious Diseases & Immunity 2024年第1期4卷 10-24页

作者： Cong Peng Fan Jiang Yinping Liu Yong Xue Peng Cheng Jie Wang Liang Wang Wenping Gong Hebei North University Zhangjiakou 075000Hebei ProvinceChina Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment Senior Department of TuberculosisEighth Medical Center of PLA General HospitalBeijing 100091China Department of Geriatrics Eighth Medical Center of PLA General HospitalBeijing 100091China section of Health No.94804 Unit of the Chinese People's Liberation ArmyShanghai 200434China

Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and ***,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection ***,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic ***:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and *** responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead *** study was conducted from April 2022 to December 2022 in the seniorDepartment of Tuberculosis at the 8thMedical Center of PLA General hospital,*** samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic ***:A novel MEBDB,designated as CP19128P,was ***19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell *** silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune ***19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(Pspecific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and *** IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from

关键词： Tuberculosis Latent tuberculosis infection Active tuberculosis Multiepitope-based diagnostic biomarker Bioinformatics:Immunoinformatics

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Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

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World Journal of Psychiatry 2024年第1期14卷 88-101页

作者： Zhong-Yu Huang Zi-Pan Lyu Hong-Gui Li Hua-Zhi You Xiang-Na Yang Cai-Hui Cha Center for Medical Research on Innovation and Translation Institute of Clinical MedicineGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510000Guangdong ProvinceChina school of Biological sciences Nanyang Technological UniversityNanyang Ave 639798Singapore Department of Pediatrics First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Nutrition First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510405Guangdong ProvinceChina Department of Pediatric Traditional Chinese Medicine Clinic Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina Department of Psychology Guangzhou Women and Children's Medical CenterGuangzhou 510632Guangdong ProvinceChina

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(AsD).However,the etiology of AsD is not completely *** presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for *** To estimate and interpret the causal relationship between AsD and metabolite profile,taking into consideration both genetic and environmental *** A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAs)including a metabolite GWAs dataset covering 453 metabolites from 7824 European and an AsD GWAs dataset comprising 18381 AsD cases and 27969 healthy *** in plasma were set as exposures with AsD as the main *** causal relationships were estimated using the inverse variant weight(IVW)*** also performed leave-one-out sensitivity tests to validate the robustness of the *** on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,swissTargetPrediction,sTRING,and *** Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of AsD(β=0.262,sE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and *** Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and *** findings offer perspectives for the discovery of diagnos

关键词： Des-Arg(9)bradykinin Autism spectrum disorder Mendelian randomization Metabolite Enrichment analysis

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