Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the most common chronic liver disease worldwide. Its pathological process is centered on the “two-hit” theory， with gut-liver axis dysregulation running through the entire disease course from steatosis to liver cirrhosis and even hepatocellular carcinoma， and it forms an extensive cross-system regulatory mechanism with the metabolic， cardiovascular， renal， and psychological and nervous systems through multi-dimensional pathways such as the “gut-liver-brain axis”， the “liver-kidney axis”， and the “liver-heart axis”. Disease progression is not limited to the liver itself， and it also involves functional imbalance of multiple organ systems throughout the body. This article systematically elaborates on the association mechanism of “liver pathological progression-multi-axis regulation-comorbidity occurrence” in MAFLD， proposes synergistic management strategies integrating early screening based on risk stratification， targeted intervention， and multidisciplinary diagnosis and treatment， and analyzes the limitations of current research and future development directions， in order to provide a theoretical basis and practical guidance for precise diagnosis and treatment and individualized management of MAFLD.

Objective:To establish the quality standard of Galla Turcica standard decoction; To provide a reference for the quality evaluation of its decoction granules.Methods:The moisture, total ash, acid-insoluble ash, and extract of Galla Turcica were assessed according to the guidelines specified in the Chinese Pharmacopoeia (Volume Ⅳ); high-performance liquid chromatography (HPLC) was employed to quantify the gallic acid content in sixteen batches of Galla Turcica and standard decoction, from which the transfer rate was calculated; the paste rate, moisture, and extract yield were quantitatively analyzed, establishing the comprehensive fingerprint of Galla Turcica standard decoction. The quantitative value transfer rules of common peaks from medicinal materials to standard decoction were studied through similarity evaluation and stoichiometric analysis. Results:The gallic acid content of the sixteen batches of Galla Turcica standard decoction ranged from 76.79 mg/g to 115.04 mg/g, the range of transfer rate was 24.02% to 47.82%, the extraction rate was 34.04% to 63.23%, the moisture was 1.11% to 2.06%, and the extract was 94.44% to 101.75%. A total of nine characteristic peaks were identified in the fingerprints of the sixteen batches of Galla Turcica and standard decoction, and four characteristic peaks were identified: gallic acid (GA), 1, 2, 3, 6 - tetragalloylglucose (TeGG), ellagic acid (EA) and 1, 2, 3, 4, 6, - pentagalloylglucose (PGG). Clustering analysis revealed that at a measurement distance of fifteen, the sixteen batches could be grouped into two categories. Principal component analysis (PCA) showed that three principal components were extracted with a cumulative variance contribution rate of 84.204%, which could represent most of the information of the samples.Conclusions:The standard decoction preparation process developed in this study adheres to the requirements of traditional decoction methods and has proven to be both effective and feasible. This method can be used for the research and quality evaluation of standard decoction of Galla Turcica, and provide a basis for subsequent formulation granules and related research.

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

Human carboxylesterase 2A (hCES2A) plays pivotal roles in prodrug activation and hydrolytic metabolism of ester-bearing chemicals. Targeted inhibition of intestinal hCES2A represents a feasible strategy to mitigate irinotecan-triggered gut toxicity (ITGT), but the orally active, selective, and efficacious hCES2A inhibitors are rarely reported. Here, a novel drug-like hCES2A inhibitor was developed via three rounds of structure-based drug design (SBDD) and structural optimization. Initially, donepezil was identified as a moderate hCES2A inhibitor from 2000 US Food and Drug Administration (FDA)-approved drugs. Following two rounds of SBDD and structural optimization, a donepezil derivative (B7) was identified as a strong reversible hCES2A inhibitor. Subsequently, nine B7 carbamates were rationally designed, synthesized and biologically assayed. Among all synthesized carbamates, C3 showed the most potent time-dependent inhibition on hCES2A (IC₅₀ = 0.56 nmol/L), excellent specificity and favorable drug-like properties. C3 could covalently modify the catalytic serine of hCES2A with high selectivity, while this agent also showed favorable safety profiles, high intestinal exposure, and impressive effects for ameliorating ITGT in both human intestinal organoids and tumor-bearing mice. Collectively, this study showcases a rational strategy for developing drug-like and serine-targeting covalent inhibitors against target serine hydrolase(s), while C3 emerges as a promising orally active drug candidate for ameliorating ITGT.

Objective:To evaluate the impact of Diagnosis-Intervention Packet(DIP)payment reform on medical service costs and efficiency for inpatients in public hospitals,and to compare differences between surgical and medical groups.Methods:A quasi-experimental design was employed,using 605 636 discharged patients from a tertiary hospital in Hebei Province between January 2020 and March 2025 as the sample.The difference-in-differences(DID)model was used to analyze the changes in key indicators between the DIP settlement group(intervention group)and the non-DIP settlement group(control group).Results:Total hospitalization costs,out-of-pocket expenses,and medication costs were significantly reduced in the DIP settlement group(P<0.05),while costs for examinations,nursing,laboratory tests,and treatments increased significantly(P<0.05).Material costs increased by 30.7%in the surgical group(P<0.1)and decreased by 19.8%in the medical group(P<0.01).In terms of efficiency,the average length of stay,time,and cost consumption index all decreased(P<0.01),while the proportion of medical services increased(P<0.01).The case mix index(CMI)showed no significant changes.Conclusion:The DIP reform effectively controlled costs and improved efficiency,but it also resulted in cost shifting and departmental disparities.Therefore,it is necessary to optimize cost control and departmental management policies.

Yanchi Tan sheep,a specialty of Ningxia,China,is famous for its excellent meat quality,but the detailed mechanisms of its muscle development and meat quality formation are still unclear.In or-der to preliminarily investigate the unique molecular mechanisms in the muscle development of the sheep,the present study was carried out to collect the longest dorsal muscle(LDM)samples from 6-month-old and 12-month-old female Tan sheep,and we screened the genes and long non-coding RNA(lncRNAs)that may play important roles in regulating the muscle development and meat quality formation through transcriptome sequencing(RNA-seq).The results showed that a total of 504 mRNAs and 1,483 lncRNAs were detected between the two groups of LDMs,with significant differences(P＜0.05).And we also pre-dicted 103 potential lncRNA-mRNA cis-regulatory relationship pairs with significant differences(P＜0.05).Skeletal muscle development-related genes such as MSTN,CDKN1A,FHL1 and skeletal muscle metabolism-related genes such as LPL and SCD were subsequently screened based on the functional anal-ysis of differentially expressed mRNA.Based on the functional analysis of differentially expressed lncRNA target genes,13 lncRNAs potentially related to muscle development(LNC.17926.1,LNC.981.1,LNC.16284.1,etc.)and 8 lncRNAs potentially related to skeletal muscle metabolism(LNC.15496.1,LNC.18149.1,etc.)were identified.5 lncRNAs and 4 mRNAs expressed in both groups were randomly selected for qPCR validation experiments,and their results were consistent with RNA-seq,which corrob-orated with the reliability of the sequencing results.This study lays a solid foundation for future investiga-tions of muscle development,meat quality formation mechanism and molecular breeding in Tan sheep,and provides a scientific basis for improving the meat production performance of other domestic sheep breeds.

Pain modulation encompasses a complex neurobiological process, in which the lateral habenula (LHb) plays a crucial role in integrating, regulating and modulating pain signals. It is also involved in pain-related memory functions associated with perception, transmission and regulation of pain. Furthermore, the LHb collaborates with structures such as the spinal dorsal horn, forebrain, and amygdala to form an essential neural circuit that contributes to sensitization, development of tolerance, and adaptation processes related to pain. However, there remains limited understanding regarding the specific roles and interactions among different neuron subtypes within the LHb concerning pain regulation. Additionally, further investigation is warranted to explore functional changes and plasticity within both the LHb and its associated neural circuits in chronic pain models. Future research endeavors should utilize advanced neuroimaging techniques alongside optogenetics and gene editing technologies to elucidate intricate neural circuits, cellular architecture, and molecular mechanisms governing LHb function in pain regulation. In conclusion, this paper aims to comprehensively review existing literature on the involvement of the LHb and its neural circuits in modulating pain, thereby enhancing our understanding of their neurobiological mechanisms while providing novel targets for precise therapeutic strategies aimed at alleviating pain.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Pain modulation encompasses a complex neurobiological process, in which the lateral habenula (LHb) plays a crucial role in integrating, regulating and modulating pain signals. It is also involved in pain-related memory functions associated with perception, transmission and regulation of pain. Furthermore, the LHb collaborates with structures such as the spinal dorsal horn, forebrain, and amygdala to form an essential neural circuit that contributes to sensitization, development of tolerance, and adaptation processes related to pain. However, there remains limited understanding regarding the specific roles and interactions among different neuron subtypes within the LHb concerning pain regulation. Additionally, further investigation is warranted to explore functional changes and plasticity within both the LHb and its associated neural circuits in chronic pain models. Future research endeavors should utilize advanced neuroimaging techniques alongside optogenetics and gene editing technologies to elucidate intricate neural circuits, cellular architecture, and molecular mechanisms governing LHb function in pain regulation. In conclusion, this paper aims to comprehensively review existing literature on the involvement of the LHb and its neural circuits in modulating pain, thereby enhancing our understanding of their neurobiological mechanisms while providing novel targets for precise therapeutic strategies aimed at alleviating pain.

Objective To analyze the the differences in the use of medical consumables of single diseases,so as to provide ideas for the supervision of the rational use of medical consumables.Methods The case information of the patients discharged from some hospital in Hunan Province who underwent artificial femoral head replacement for femoral neck fracture,transurethral plasma electrosurgery for prostatic hyperplasia and percutaneous nephrolithotripsy for renal calculi from January 1,2022 to December 31,2023 were selected.Based on the results of the normality test,difference analyses were carried out over the consumption ratios of inpatients undergoing different procedures at different time periods and the consumption ratios treated by different physicians,and the percentile method was used to determine the recommended range for the consumption ratio based on the difference analysis results.SPSS 26.0 software was used for statistical analysis.Results The inpatients undergoing artificial femoral head replacement for femoral neck fracture at different periods had no significant difference in the consumption ratio(P>0.05);the inpatients going through transurethral plasma electrosurgery for prostatic hyperplasia had the consumption ratio in 2023 decreased by 5.22%when compared with that in 2022,with the difference being statistically significant(P<0.05);the inpatients undergoing percutaneous nephrolithotripsy for renal calculi had the consumption ratio at 2023 increased by 6.49%when compared with that at 2022,with the difference being statistically significant(P<0.05).There were no strong correlations between physician and inpatient consumption ratios for the three single-diseases(P<0.05),while the consumption ratios by different physicians for each single disease had differences.There were respectively 50%,40%and 50%of the physicians implementing artificial femoral head replacement for femoral neck fracture,transurethral plasma electrosurgery for prostatic hyperplasia and percutaneous nephrolithotripsy for renal calculi had the average consumption ratios higher than the average annual consumption ratios for the single diseases.The recommended ranges of the consumption ratio was[51.16%,63.89%]for artificial femoral head replacement for femoral neck fracture,[8.76%,10.77%]for transurethral plasma electrosurgery for prostatic hyperplasia and[26.40%,32.80%]for percutaneous nephrolithotripsy for renal calculi.Conclusion Under the premise of ensuring the quality of medical care,medical consumables can be scientifically and rationally supervised by setting a reasonable range,seizing the"vital few"and implementing joint management and control to reduce the consumption ratio.[Chinese Medical Equipment Journal,2025,46(7):87-91]