Hepatic fibrosis is a reversible pathological process in various chronic liver diseases and is closely associated with the development and progression of severe liver diseases such as liver cirrhosis and hepatocellular carcinoma， and it has emerged as a significant global health challenge. In recent years， studies have shown that histone lactylation， a newly discovered epigenetic modification， actively participates in regulating the progression of hepatic fibrosis. This article systematically reviews the core regulatory effect of histone lactylation modification in the interaction between inflammatory microenvironment and hepatic fibrosis， in order to clarify the cascade regulatory mechanism of “inflammation-hepatic fibrosis” and provide new insights for early diagnosis， targeted intervention， and prevention of malignant transformation in hepatic fibrosis.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Liver fibrosis is a critical pathological process in the progression of chronic liver diseases and is mainly driven by the activation of hepatic stellate cells， and it is characterized by excessive deposition of extracellular matrix. Programmed cell death is widely observed in liver fibrosis and plays diverse roles in different types of cells. It is not only a mechanism for maintaining cellular homeostasis through metabolism， but it can also regulate the development and progression of diseases. Ferroptosis has recently emerged as a research focus due to its close association with lipid metabolism. This article systematically reviews the related concepts of lipid metabolism， ferroptosis， and liver fibrosis， analyzes the bridging role and dual regulatory function of ferroptosis in lipid metabolism and liver fibrosis， and further highlights the clinical application value of targeting ferroptosis in hepatic stellate cells for the treatment of liver fibrosis， in order to provide new perspectives for the mechanistic studies on liver fibrosis and the optimization of related clinical intervention strategies.

ObjectiveThe frequency difference limen (FDL) serves as a fundamental metric utilized for effectively quantifying the precise perceptual capabilities of the central auditory system. However, traditional measurement methods rely heavily on the active behavioral responses of subjects and are consequently highly susceptible to the negative influence of confounding subjective factors. Furthermore, existing research paradigms frequently employ uniform stimulus configurations that overlook critical individual perceptual differences. Based on brain-computer interface (BCI) technology, this comprehensive study aims to establish an objective and quantitative evaluation method for auditory frequency discrimination by systematically analyzing and decoding the specific neural responses elicited at the exact threshold state. MethodsWe designed a personalized rapid serial auditory presentation (RSAP) paradigm customized based on each individual’s precise FDL. A cohort of eleven healthy participants was recruited to evaluate the paradigm using pure-tone sequences at a baseline frequency of 4 000 Hz. This experimental paradigm simulates a realistic auditory perception environment through the continuous presentation of acoustic stimuli, thereby allowing for an in-depth investigation into the specific neural representations evoked by weak frequency deviations at the threshold state. Given that auditory stimulus-evoked response features exhibit complex and differentiated spatiotemporal distribution patterns across multiple frequency domains, this study further deeply integrates the cross-scale feature interaction module with the dynamic spatiotemporal attention allocation strategy, innovatively proposing the Multi-Scale Spatial-Temporal Dual Attention Network (MS-STAMNet). Specifically, the network constructs parallel processing branches with multiple receptive fields and introduces a dynamic adaptive weighting strategy to precisely localize core neural activity signals, further deeply integrating multi-scale information through cross-branch feature information interaction to achieve robust single-trial decoding of weak auditory evoked responses. ResultsThe comprehensive electrophysiological data analysis demonstrated that subtle auditory frequency deviation stimuli presented at the threshold level successfully elicited pronounced N2 and P3 event-related potential features, reflecting pre-attentive mismatch detection and subsequent cognitive evaluation, which were prominently distributed over the frontal, central, and temporal regions of the scalp. In the complex time-frequency domain, the extracted neural response characteristics exhibited distinct, statistically significant event-related synchronization within both the low-frequency δ and θ frequency bands, which was simultaneously accompanied by a widespread, prominent event-related desynchronization within the higher α band. A comparative analysis of model performance demonstrated that MS-STAMNet achieved an average unweighted average recall (UAR) of (69.67±6.12)% and area under the curve (AUC) of 0.761 8±0.07, significantly outperforming the established baseline models such as EEGNet and PLNet. Furthermore, a distinct dissociation phenomenon was verified between neural decoding and behavioral performance through regression analysis (R²=0.016, P=0.709), indicating that this model can effectively capture the implicit features of subtle frequency deviations, even when they fail to trigger explicit conscious responses. Additionally, attention weight visualization analysis further reveals the highly accurate focus of the network on key features concentrated over the bilateral temporal and fronto-parietal regions. ConclusionThis study systematically and comprehensively uncovers the multi-dimensional spatiotemporal evolutionary patterns of complex neural responses processing subtle acoustic variations under long-sequence threshold auditory stimulation. Concurrently, it verifies the efficacy and robustness of the proposed MS-STAMNet architecture in accurately deciphering weak, single-trial electroencephalogram signals amidst complex background noise. Ultimately, these neurophysiological and algorithmic findings lay a solid theoretical and methodological foundation for the objective and quantitative evaluation of individual auditory cognitive capabilities in clinical applications, transcending the fundamental limitations of traditional behavioral paradigms and providing robust technical support for future auditory research and related clinical assessments.

Background and aims Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide, with no currently effective treatment. ALD is caused by excessive lipid buildup, which eventually triggers inflammation and fibrosis in the liver. Activation of hepatic Kupffer cells (KCs) and macrophages drives liver inflammation, which can worsen alcohol-induced liver injury. The autophagy-lysosome system is crucial for macrophages to support their innate immune functions. Transcription factor EB (TFEB) is a key regulator of autophagy and lysosomal biogenesis, but the role of macrophage TFEB in ALD development is unknown. The aim of this study was to evaluate the effects of Gao-binge alcohol consumption on myeloid cell TFEB and elucidate the role of myeloid TFEB in ALD. Methods Two-to-three-month-old male and female LysM Cre− (WT) and LysM Cre+ Tfeb Flox/Flox (f/f) (myeloid-Tfeb KO) mice were subjected to chronic alcohol feeding plus an acute binge following the Gao-binge model. Serum alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol content were determined using biochemical assays. Total hepatic protein content and messenger RNA (mRNA) levels of autophagy-related proteins and inflammatory markers were determined using immunoblotting, immunohistochemistry, and real-time quantitative polymerase chain reaction (RT-qPCR). Isolated hepatic infiltrating macrophages and KCs from mice given intragastric ethanol infusions were analyzed by Western blot for TFEB and autophagy-related protein content. Raw 264.7 macrophages were treated with ethanol, lipopolysaccharide (LPS), and LPS plus ethanol to examine nuclear TFEB translocation using immunofluorescence. Results We found that TFEB levels were higher in macrophage/KC cells than in hepatocytes and cholangiocytes. While ethanol feeding increased serum alanine aminotransferase and aspartate aminotransferase levels, as well as hepatic triglyceride levels, no significant differences were observed between WT and myeloid-Tfeb KO mice. The number of F4/80-positive KCs/macrophages was similar in all four experimental groups, but hepatic neutrophil infiltration increased in alcohol-fed myeloid-Tfeb KO mice. LPS or ethanol alone induced nuclear TFEB translocation only moderately in Raw 264.7 macrophages. Conclusions Our findings suggest that myeloid TFEB is dispensable for alcohol-induced liver injury in mice.

Objective To investigate the correlation between different diabetes mellitus(DM)subtypes and the inci-dence of glaucoma through bidirectional Mendelian randomization(MR)analysis.Methods Based on a bidirectional MR analysis framework,the highly correlated single nucleotide polymorphism(SNP)was selected from the genome-wide asso-ciation study(GWAS)data as the instrumental variable(Ⅳ)for three DM subtypes[including type 1 diabetes mellitus(T1DM),type 2 diabetes mellitus(T2DM),and gestational diabetes mellitus(GDM)]and glaucoma to analyze the bidi-rectional causal relationship between different DM subtypes and glaucoma.Besides,the MR-Egger method,weighted medi-an method,inverse-variance weighted method,simple random model,and weighted mode method were adopted to conduct a comprehensive analysis,and the obtained results were subjected to sensitivity analyses.Results The bidirectional MR analysis results revealed no causal association between T1DM and glaucoma.The forward MR analysis results indicated that T2DM may promote the development of glaucoma(IVW:OR=1.09,95％CI:1.05～1.14),while the development of glau-coma did not increase the risk of T2DM.Meanwhile,the multivariable MR analysis results showed that T2DM might be a potential risk factor for the development of glaucoma.The forward MR analysis results demonstrated that GDM did not in-crease the incidence of glaucoma;whereas the reverse MR analysis results suggested that glaucoma might increase the sus-ceptibility to GDM(IVW:OR=1.11,95％CI:1.02～1.21).The sensitivity analysis results confirmed the stability and relia-bility of these findings.Conclusion T2DM may contribute to the development of glaucoma,and patients with glaucoma may exhibit heightened susceptibility to GDM during pregnancy.

Objective:To investigate the effect of mild moxibustion on transient receptor potential vanilloid type 1(TRPV1)channel expression in primary dysmenorrhea(PD)rats and explore its mechanism in alleviating central pain sensitization.Methods:Thirty-two female non-pregnant Wistar rats were randomized into a blank group,a model group,a mild moxibustion group,and a capsazepine group,with 8 rats in each group.Except for the blank group,the other three groups used estradiol benzoate,ice-water bath,and oxytocin to establish the rat PD model of cold-dampness stagnation pattern.The interventions began on day 1 of modeling,once a day,and lasted 10 d.The mild moxibustion group received mild moxibustion at Shenque(CV8)and Guanyuan(CV4),20 min/time;in the capsazepine group,capsazepine was injected at a dose of 2 mg/(kg·bw).The abdominal pain threshold was measured 10-30 min after oxytocin injection on day 11;enzyme-linked immunosorbent assay was used to detect serum prostaglandin F2α(PGF2α)level;the expression of TRPV1,cluster of differentiation 11B(CD11B),and proto-oncogene c-Fos in the spinal dorsal horn and hypothalamus was detected by immunofluorescence and Western blotting.Results:Compared to the blank group,the model group showed a decreased pain threshold(P<0.05)and an increased serum PGF2α level with elevated TRPV1,CD11B,and c-Fos protein expression in the spinal dorsal horn and hypothalamus(P<0.05).Compared to the model group,both the mild moxibustion group and capsazepine group showed significantly increased pain thresholds(P<0.05),along with decreased serum PGF2α levels and reduced protein expression levels of TRPV1,CD11B,and c-Fos in the spinal dorsal horn and hypothalamus(P<0.05).Rat pain threshold in the capsazepine group was higher than that in the mild moxibustion group(P<0.05).Serum PGF2α level,the expression levels of CD11B and c-Fos proteins in the spinal dorsal horn,as well as TRPV1,CD11B,and c-Fos proteins in the hypothalamus of the capsazepine group were lower than those in the mild moxibustion group(P<0.05).Conclusion:Mild moxibustion at Shenque(CV8)and Guanyuan(CV4)may alleviate the central pain sensitization in PD rats by down-regulating TRPV1 channel expression in the spinal dorsal horn and hypothalamus,thus playing an analgesic effect.

Objective To analyze the drug resistance and genomic characteristics of clinically isolated hypermuco-viscous Klebsiella pneumoniae(hmKp).Methods Klebsiella pneumoniae isolated from clinical specimens from the sentinel hospitals of National Pathogen Identification Network in Huai'an City from 2019 to 2023 were collected,strains were identified by VITEK 2 Compact,mucus phenotype was determined by string test,resistance of hmKp was determined by microbroth dilution method.Molecular typing was conducted by whole-genome sequencing tech-nology,annotation of virulence and resistance genes carried by strains was performed.Results A total of 60 strains of hmKp were collected,mainly isolated from sputum specimens(33.33％)and blood specimens(28.33％).The average genome size of 60 strains was 5.6 Mb,with an average GC content of 57.09％.Multilocus sequence typing(MLST)showed that there were 28 ST types,with the dominant ST types being ST1 1(11.67％),ST15(11.67％),and ST412(10.00％).Core genome MLST(cgMLST)analysis revealed that some strains were highly homologous,and no outbreak strains were found.Multidrug-resistant strains accounted for 60.00％,while imipe-nem-resistant strains accounted for 28.33％.64 types of resistance genes were carried,84.38％of which were loca-ted on mobile element.The carriage rates of fosfomycin-related resistance genes and extended-spectrum β-lactam an-tibiotic-related resistance genes were relatively high in the strains,at 100％and 98.33％,respectively.Among car-bapenem-resistance gene blaKPC-2,21.67％was carried by ST11,ST1,and ST15 strains,among bla NDM-5 gene,3.33％was carried by ST76 strain.A total of 101 virulence genes were carried,most were Colibactin and type Ⅵsecretion system-related virulence genes.All strains carried capsule synthesis regulation-related genes(rcsA,rcsB),efflux pump-related genes(acrA,acrB),and enterobacterin-related genes(entABCEF,fepABCDFG,fes).Conclusion Clinically isolated hmKp in Huai'an exhibits multidrug resistance,with dominant ST types ST11,ST15,and ST412,carrying multiple horizontally transferable resistance and virulence genes,prevention and control measures should be strengthened.

Objective:To analyze the effect of migration experiences during working age on the status of chronic disease development among rural older adults.Methods:Based on data from the China Health and Retirement Longitudinal Study(CHARLS),this study applied regression model and group-based trajectory model to examines the impact of migration experience on the status and growth trajectories of chronic diseases among rural older adults.Results:(1)Rural older adults with migration experience are more likely to develop chronic diseases and have a greater number of chronic disease in later life.(2)Rural older adults with migration experiences have a higher starting point and a faster rate of growth trajectory of chronic disease.Suggestions:It is necessary to strengthen occupational protection and health education for the rural-urban migrant population,reinforce the intervention and management of chronic diseases for the returning population,and improve the whole life-cycle medical insurance system,to break the disadvantageous cumulative effect of migration experience on health.

OBJECTIVE: To assess health equity in the Yangtze River region to improve understanding of the correlation between hand, foot, and mouth disease (HFMD) and socioeconomic factors. METHODS: From 2014-2016, data on HFMD incidence, population statistics, economic indicators, and meteorology from 26 cities along the Yangtze River were analyzed. A multi-city random-effects meta-analysis was performed to study the relationship between temperature and HFMD transmission, and health equity was assessed with respect to socio-economic impact. RESULTS: Over the study period, 919,458 HFMD cases were reported, with Shanghai (162,303) having the highest incidence and Tongling (5,513) having the lowest. Males were more commonly affected (male-to-female ratio, 1.49:1). The exposure-response relationship had an M-shaped curve, with two HFMD peaks occurring at 4 °C and 26 °C. The relative risk had two peaks at 1.30 °C (1.834, 95% CI: 1.204-2.794) and 31.4 °C (1.143, 95% CI: 0.901-1.451), forming an M shape, with the first peak higher than the second. The most significant impact of temperature on HFMD was observed between -2 °C and 18.1 °C. The concentration index (0.2463) indicated moderate concentration differences, whereas the Theil index (0.0418) showed low inequality in distribution. CONCLUSION The incidence of HFMD varied across cities, particularly with changes in temperature. Economically prosperous areas showed higher risks, indicating disparities. Targeted interventions in these areas are crucial for mitigating the risk of HFMD.
Female ; Humans ; Male ; China/epidemiology* ; Cities/epidemiology* ; Hand, Foot and Mouth Disease/transmission* ; Incidence ; Risk Factors ; Temperature