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Chinese medical sciences Journal 2024年第2期39卷 140-143页

作者： Pu-An Cui Zhe-Xi Gong Zhong He School of Humanities and Social sciences Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100730China

Since the early 20th century,China has gradually established a clinical,educational,and research system centered around modern scientific medicine,which has now become the dominant force in China's medical and health system and services,with the construction and development of the Chinese Academy of medical sciences and Peking Union medical College as the most prominent *** scientific medicine in the new era requires close cooperation across multiple disciplines and fields to build a high-quality and efficient medical and health service *** also involves combining the excellent traditional Chinese culture with Western medicine to explore a unique path of modern scientific medicine with Chinese characteristics.

关键词： modern scientific medicine cultural confidence multiple view

Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer’s Disease Mouse Model

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Research 2024年第1期2023卷 81-95页

作者： Fangxuan Chu Ruxin Tan Xin Wang Xiaoqing Zhou Ren Ma Xiaoxu Ma Ying Li Ruixu Liu Chunlan Zhang Xu Liu Tao Yin Zhipeng Liu Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China Tianjin Institutes of Health science Tianjin301600China Neuroscience Center Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing100730China

The neuropathological features of Alzheimer’s disease include amyloid *** emerging evidence suggests that Piezo1,a mechanosensitive cation channel,plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure,but the importance of Piezo1-mediated mechanotransduction in brain functions is less ***,apart from mechanical stimulation,Piezo1 channels are strongly modulated by *** assume that Piezo1 may play a role in converting mechanical and electrical signals,which could induce the phagocytosis and degradation of Aβ,and the combined effect of mechanical and electrical stimulation is superior to single mechanical ***,we design a transcranial magneto-acoustic stimulation(TMAS)system,based on transcranial ultrasound stimulation(TUS)within a magnetic field that combines a magnetoacoustic coupling effect electric field and the mechanical force of ultrasound,and applied it to test the above hypothesis in 5xFAD *** tests,in vivo electrophysiological recordings,Golgi–Cox staining,enzyme-linked immunosorbent assay,immunofluorescence,immunohistochemistry,real-time quantitative PCR,Western blotting,RNA sequencing,and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1.

关键词： stimulation Alzheimer Piezo1

Farnesyltransferase inhibitor lonafarnib suppresses respiratory syncytial virus infection by blocking conformational change of fusion glycoprotein

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2970-2983页

作者： Qi Yang Bao Xue Fengjiang Liu Yongzhi Lu Jielin Tang Mengrong Yan Qiong Wu Ruyi Chen Anqi Zhou Lijie Liu Junjun Liu Changbin Qu Qingxin Wu Muqing Fu Jiayi Zhong Jianwei Dong Sijie Chen Fan Wang Yuan Zhou Jie Zheng Wei Peng Jinsai Shang Xinwen Chen Guangzhou National Laboratory Guangzhou 510005China State Key Laboratory of Respiratory Disease Guangzhou Medical UniversityGuangzhou 511436China Wuhan Institute of Virology Chinese Academy of SciencesWuhan 430071China School of Basic medical sciences Guangzhou Medical UniversityGuangzhou 511436China GMUGIBH Joint School of Life sciences Guangzhou Medical UniversityGuangzhou 511436China Guangzhou Institutes of Biomedicine and Health Chinese Academy of SciencesGuangzhou 510530China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203China School of Pharmaceutical science and Technology Hangzhou lnstitute for Advanced StudyUCASHangzhou 310024China

Respiratory syncytial virus(RSV)is the major cause of bronchiolitis and pneumonia in young children and the *** are currently no approved RSV-specific therapeutic small molecules *** high-throughput antiviral screening,we identified an oral drug,the prenylation inhibitor lonafarnib,which showed potent inhibition of the RSV fusion *** exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells(HBEC).Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry,but has farnesyltransferase-independent antiviral ***-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion *** at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody ***,lonafarnib dose-dependently reduced the replication of RSV in BALB/c ***,lonafarnib could be a potential fusion inhibitor for RSV infection.

关键词： neutral metastable approved

Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon Kim Deok Ryong Kim Department of Biochemistry and Convergence medical sciences and Institute of medical science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea Department of Anatomy and Convergence medical sciences and Institute of medical science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

An inulin-type fructan CP-A from Codonopsis pilosula attenuates experimental colitis in mice by promoting autophagy-mediated inactivation of NLRP3 inflammasome

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Chinese Journal of Natural Medicines 2024年第3期22卷 249-264页

作者： ZHOU Jiangtao WANG Jun WANG Jiajing LI Deyun HOU Jing LI Jiankuan BAI Yun’e GAO Jianping School of Pharmaceutical science Shanxi Medical UniversityJinzhong 030600China

Inulin-type fructan CP-A,a predominant polysaccharide in Codonopsis pilosula,demonstrates regulatory effects on immune activity and *** efficacy of CP-A in treating ulcerative colitis(UC)is,however,not *** study employed an in vitro lipopolysaccharide(LPS)-induced colonic epithelial cell model(NCM460)and an in vivo dextran sulfate sodium(DSS)-induced colitis mouse model to explore CP-A’s protective effects against experimental colitis and its underlying *** monitored the clinical symptoms in mice using various parameters:body weight,disease activity index(DAI),colon length,spleen weight,and histopathological ***,molecular markers were assessed through enzyme-linked immunosorbent assay(ELISA),quantitative real-time polymerase chain reaction(qRT-PCR),immunofluorescence(IF),immunohistochemistry(IHC),and Western blotting *** showed that CP-A significantly reduced reactive oxygen species(ROS),tumor necrosis factor-alpha(TNF-α),and interleukins(IL-6,IL-1β,IL-18)in LPS-induced cells while increasing IL-4 and IL-10 levels and enhancing the expression of Claudin-1,ZO-1,and occludin proteins in NCM460 ***,in vivo findings revealed that CPA administration markedly improved DAI,reduced colon shortening,and decreased the production of myeloperoxidase(MPO),malondialdehyde(MDA),ROS,IL-1β,IL-18,and NOD-like receptor protein 3(NLRP3)inflammasome-associated genes/proteins in UC ***-A treatment also elevated glutathione(GSH)and superoxide dismutase(SOD)levels,stimulated autophagy(LC3B,P62,Beclin-1,and ATG5),and reinforced Claudin-1 and ZO-1 expression,thereby aiding in intestinal epithelial barrier repair in colitis ***,the inhibition of autophagy via chloroquine(CQ)diminished CP-A’s protective impact against colitis in *** findings elucidate that CP-A’s therapeutic effect on experimental colitis possibly involves mitigating intestinal inflammation through autophagymediated N

关键词： Inulin-type fructan CP-A Codonopsis pilosula Ulcerative colitis NLRP3 inflammasome Autophagy

Enzymatic self-assembly/disassembly turns “ON”/“OFF” the mimetic hydrolytic activity of histidine nanofibers

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science China Chemistry 2024年第2期67卷 517-522页

作者： Xianbao Sun Manli Wang Xiaoyang Liu Wenjun Zhan Guangqiong Xu Qiaochu Jiang Hai-Dong Xu Fuqiang Wang Gaolin Liang State Key Laboratory of Digital medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Analysis Center Nanjing Medical UniversityNanjing210029China

Mimetic enzymes are devised as alternates or supplements of natural enzymes in broad fields but regulating their activities in a switchable manner remains ***,we proposed an enzymatic self-assembly/disassembly strategy to address this issue.A peptide molecule Nap FFEYIH(YH) was rationally designed which,after self-assembling into nanofibers,lined up the histidine moieties to form active hydrolysis centers for mimicking hydrolase *** dephosphorylation of Nap FFEYp IH(Yp H) by alkaline phosphatase to yield YH also turned “ON” the hydrolase *** turn,phosphorylation of YH by phosphokinase epidermal growth factor receptor to yield Yp H disassembled the nanofibers and thus turned the activity “OFF”.As such,the “ON”/“OFF” of the mimetic hydrolase activities could be regulated under physiological conditions through ALP/EGFR-mediated self-assembly/disassembly of histidine *** work provides a feasible strategy for the on-demand fabrication of artificial enzymes with controllable and superior activities.

关键词： disassembly hydrolytic activity mimetic enzyme phosphorylation self-assembly

Impact of next-generation sequencing on antimicrobial treatment in immunocompromised adults with suspected infections

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World Journal of Emergency Medicine 2024年第2期15卷 105-110页

作者： Jia Li Jiazhen Luo Tao Hu Ling Cheng Weiwei Shang Li Yan Department of Intensive Care Unit Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Emergency Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Tongji medical College Huazhong University of Science and TechnologyWuhan 430030China Department of Geriatrics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

BACKGROUND:Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial *** objective of the study was to assess the diagnostic value of next-generation sequencing(NGS)for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected ***:This was a retrospective *** January and August 2020,47 adult immunocompromised patients underwent NGS testing under the following clinical conditions:1)prolonged fever and negative conventional cultures;2)new-onset fever despite empiric antimicrobial treatment;and 3)afebrile with suspected infections on *** data,including conventional microbial test results and antimicrobial treatment before and after NGS,were *** were analyzed according to documented changes in antimicrobial treatment(escalated,no change,or deescalated)after the NGS ***:The median time from hospitalization to NGS sampling was 19 *** relevant pathogens were detected via NGS in 61.7% of patients(29/47),more than half of whom suffered from fungemia(n=17),resulting in an antimicrobial escalation in 53.2% of patients(25/47)and antimicrobial de-escalation in 0.2% of patients(1/47).Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella,Pneumocystis jirovecii,and *** the remaining three cases,NGS detected clinically relevant pathogens also detected by conventional cultures a few days *** antimicrobial treatment was subsequently adjusted according to the susceptibility test ***,NGS changed antimicrobial management in 55.3%(26/47)of patients,and conventional culture detected clinically relevant pathogens in 14.9% of the patients(7/47).CONCLUSION:With its rapid identification and high sensitivity,NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients w

关键词： Immunocompromised patients Next-generation sequencing Antimicrobial management

Ethylene thiourea exposure induces neurobehavioral toxicity in zebrafish by disrupting axon growth and neuromuscular junctions

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Journal of Environmental sciences 2024年第3期137卷 108-119页

作者： Jingming Wang Zhiquan Yu Yongfeng Wang Yuanyao Chen Lin Xiao Yanjun Zong Qiyuan Feng Lianqi Peng Huiping Zhang Chunyan Liu Institute of Reproductive Health Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Ethylene thiourea(ETU)converted from ethylene bisdithiocarbamate(EBDC)fungicides has aroused great concern because of its prevalence and harmful *** ETU-induced neurotoxicity has been reported,the potential mechanisms remain *** study provided insights into its neurotoxic effects at environmentally relevant concentrations in *** findings showed that embryonic exposure to ETU decreased the hatch rate and delayed somite ***,ETU treatment significantly reduced the dark velocity in the locomotion *** upregulated tendency of the mitogen-activated protein kinases(MAPK)pathway(mknk1,atf4,mapkapk3)screened by transcriptome analysis implied motor neuron degeneration,which was validated by subsequent morphological observation,as axon length and branches were truncated in the 62.5μg/L ETU ***,although the rescue experiment with a p38 MAPK inhibitor(SB203580)successfully ameliorated axon degeneration,it failed to reverse the locomotion *** exploration of transcriptome data revealed the varied expression of presynaptic scaffold protein-related genes(pcloa,pclob,bsna),whose downregulation might impair the neuromuscular junction(NMJ).Therefore,we reasonably suspected that ETU-induced neurobehavioral deficits might result from the combined effects of the MAPK pathway and presynaptic *** this,we highlighted the necessity to take precautions and early interventions for susceptible ETU-exposed populations.

关键词： Ethylene thiourea(ETU) Behavior Neuromuscular junction MAPK signaling pathway Piccolo and bassoon Danio rerio

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma

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Current medical science 2024年第2期44卷 399-405页

作者： Xu CHEN Ya-ni PENG Fang-ling CHENG Dan CAO An-yu TAO Jian CHEN Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of medical Ultrasound Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Complete resection of malignant gliomas is often *** previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain *** study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant ***:A total of 64 patients diagnosed with malignant glioma(WHO grade HI and IV)who underwent surgery between 2012 and 2018 were *** them,29 patients received *** effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding ***:The ICEUS group showed better survival rates both in OS and PFS than the control *** univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for *** multivariate analysis,age and ICEUS were significant prognostic factors for both OS and *** quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding ***:ICEUS facilitates the identification of residual *** and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.

关键词： intraoperative contrast-enhanced ultrasound malignant glioma extent of resection survival prognosis

Efficacy of tadalafil on improvement of men with erectile dysfunction caused by COVID-19:A randomized placebo-controlled trial

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Asian Journal of Urology 2024年第1期11卷 128-133页

作者： Iman Shamohammadi Seyedmohammad Kazemeyni Mohammadali Sadighi Tara Hasanzadeh Alireza Dizavi Department of Urology Nemazee HospitalShiraz University of Medical ScienceShirazIran Department of Urology Shariati HospitalTehran University of Medical ScienceTehranIran

Objective: According to the high prevalence of COVID-19 and the subsequent risk of men's sexual health, we decided to investigate the efficacy of tadalafil on improvement of men with erectile dysfunction caused by ***: In this study, 70 outpatients who were recovered from COVID-19 without acute respiratory distress syndrome with negative polymerase chain reaction test and a complaint of erectile dysfunction were divided into two groups: 35 patients who received tadalafil 5 mg daily and 35 who received placebo. For each patient, basic assessment of sexual function was performed using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Then, treatment was started from 2 months after complete recovery of COVID-19 with negative polymerase chain reaction test for 3 months. At the end of the treatments, the patients were re-evaluated for sexual function using the complete version of IIEF questionnaire. Finally, the results before and after treatment in the intervention group were compared with those of the control ***: Treatment with both tadalafil and placebo improved the patients' sexual function criteria compared to the baseline. However, this improvement was significantly higher in the intervention group with tadalafil than the control group with placebo (p<0.05).Conclusion: Daily administration of tadalafil 5 mg seems to be effective and safe for improvement of erectile dysfunction caused by COVID-19.

关键词： Tadalafil Erectile dysfunction COVID-19 Sexual function