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.

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 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.

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.

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.

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.

Alzheimer's disease （AD） is a neurodegenerative disease with progressive losses of memory and cognitive function as the main clinical manifestations. It is difficult to be cured because of the complex pathogenesis. Histone acetylation regulates gene transcription and chromosome structure remodeling without changing the coding sequences of genes， participating in the pathological process of AD via modulating the amyloid beta-protein （Aβ） deposition， Tau phosphorylation， neuron growth， and synaptic plasticity. Traditional Chinese medicine can prevent and control AS via multiple targets and pathways from a holistic view. Animal and cell experiments have proven that traditional Chinese medicine can attenuate AD by regulating histone acetylation. Focusing on the key role of histone acetylation in AD， this study reviews the relevant studies in the last five years from the aspects of active ingredients of traditional Chinese medicine and traditional Chinese medicine compound prescriptions. The available studies suggest that the main mechanisms involve antagonizing apoptosis， inhibiting oxidative stress， ameliorating Tau and Aβ deposition， maintaining synaptic function， nourishing neurons， and repairing myelin sheath. The treatment methods include invigorating kidney and tranquilizing mind， tonifying spleen and harmonizing middle energizer， and opening orifices and resolving phlegm. The commonly used herbal medicines in compound prescriptions include Poria， Glycyrrhizae Radix et Rhizoma， Chuanxiong Rhizoma， Acori Tatarinowii Rhizoma， and Paeoniae Radix Alba. The findings indicate that traditional Chinese medicine demonstrates great potential in the prevention and treatment of AD， providing a theoretical basis for the clinical treatment and research of AD.