Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Alzheimer disease(AD)is a progressive neurodegenerative disorder characterized by cognitive dysfunction and declining learning and memory abilities,significantly impacting daily lives and behavioral capacities of the patients.The mitogen-activated protein kinase(MAPK)signaling pathway,primarily composed of extracellular signal-regulated kinase,p38 MAPK,and c-Jun N-terminal kinase.Mounting evidence suggests that the MAPK signaling path-way is intimately linked to the pathogenesis of AD,providing crucial insights into the disease's progression.In recent years,traditional Chinese medicine(TCM)has demonstrated promising potential in treating AD,with its advantages of personalized therapy and multi-target regulation garnering increasing research attention.This study aims to review the ex-perimental research landscape of TCM interventions targeting the MAPK signaling pathway for the prevention and treat-ment of AD over the past five years.The findings reveal that effective compounds and herbal formulas in TCM,such as isorhamnetin,nobiletin,parthenolide,Glehnia littoralis,Ishige okamurae,shikonin,artemisinin,kaempferol,myrice-tin,and Tripterygium glycosides,can alleviate AD symptoms by modulating the MAPK signaling pathway.These interven-tions mitigate Aβ-induced neuronal damage,reduce Tau protein hyperphosphorylation,and suppress neuroinflammatory responses.The objective of this review is to provide a scientific and theoretical reference for the clinical prevention and treatment of AD and to inform the development of novel therapeutic agents.

Alzheimer disease(AD)is a neurodegenerative disorder characterized by the abnormal deposition of amyloid β-protein(Aβ).Inflammation plays a significant role in promoting this abnormal deposition.Toll-like receptor 4(TLR4)is recognized as a"primary regulator"of the inflammatory response,facilitating the activation of microglia and interacting with various pathways,including nuclear factor-κB and nucleotide-binding oligomerization domain-like recep-tor protein 3.This interaction can lead to an inflammatory cascade that accelerates the progression of AD.Numerous pro-spective studies have demonstrated that traditional Chinese medicine can modulate the TLR4 signaling pathway,effective-ly addressing both the onset and progression of AD.However,a comprehensive review of how Chinese medicine regulates this pathway in the treatment of AD is currently lacking.Therefore,this paper aims to detail the latest findings related to TLR4 in the prevention and treatment of AD,drawing from recent literature.It will explore the mediation of traditional Chinese medicine,preserving its essence,and provide references and a basis for clinical practices aimed at preventing and treating AD.

Alzheimer disease(AD)is a neurodegenerative disorder characterized by the abnormal deposition of amyloid β-protein(Aβ).Inflammation plays a significant role in promoting this abnormal deposition.Toll-like receptor 4(TLR4)is recognized as a"primary regulator"of the inflammatory response,facilitating the activation of microglia and interacting with various pathways,including nuclear factor-κB and nucleotide-binding oligomerization domain-like recep-tor protein 3.This interaction can lead to an inflammatory cascade that accelerates the progression of AD.Numerous pro-spective studies have demonstrated that traditional Chinese medicine can modulate the TLR4 signaling pathway,effective-ly addressing both the onset and progression of AD.However,a comprehensive review of how Chinese medicine regulates this pathway in the treatment of AD is currently lacking.Therefore,this paper aims to detail the latest findings related to TLR4 in the prevention and treatment of AD,drawing from recent literature.It will explore the mediation of traditional Chinese medicine,preserving its essence,and provide references and a basis for clinical practices aimed at preventing and treating AD.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Alzheimer disease(AD)is a progressive neurodegenerative disorder characterized by cognitive dysfunction and declining learning and memory abilities,significantly impacting daily lives and behavioral capacities of the patients.The mitogen-activated protein kinase(MAPK)signaling pathway,primarily composed of extracellular signal-regulated kinase,p38 MAPK,and c-Jun N-terminal kinase.Mounting evidence suggests that the MAPK signaling path-way is intimately linked to the pathogenesis of AD,providing crucial insights into the disease's progression.In recent years,traditional Chinese medicine(TCM)has demonstrated promising potential in treating AD,with its advantages of personalized therapy and multi-target regulation garnering increasing research attention.This study aims to review the ex-perimental research landscape of TCM interventions targeting the MAPK signaling pathway for the prevention and treat-ment of AD over the past five years.The findings reveal that effective compounds and herbal formulas in TCM,such as isorhamnetin,nobiletin,parthenolide,Glehnia littoralis,Ishige okamurae,shikonin,artemisinin,kaempferol,myrice-tin,and Tripterygium glycosides,can alleviate AD symptoms by modulating the MAPK signaling pathway.These interven-tions mitigate Aβ-induced neuronal damage,reduce Tau protein hyperphosphorylation,and suppress neuroinflammatory responses.The objective of this review is to provide a scientific and theoretical reference for the clinical prevention and treatment of AD and to inform the development of novel therapeutic agents.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.