ObjectiveTo investigate the association of comprehensive control of multiple metabolic risk factors with the risk of all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease （MASLD） and its quantitative effect. MethodsA retrospective cohort study was conducted based on the data from National Health and Nutrition Examination Survey （NHANES） in 2003—2018. A total of 29 458 participants were enrolled， including 12 528 patients with MASLD and 16 930 non-MASLD controls. The control status of nine risk factors was assessed， i.e.， hypertension， diabetes， liver fibrosis （assessed by fibrosis-4 index ［FIB-4］）， aspartate aminotransferase （AST）/alanine aminotransferase （ALT） ratio， serum albumin， renal function （assessed by serum creatinine）， systemic inflammation （assessed by neutrophil count）， smoking， and physical activity. According to the status of comprehensive risk factor control， the patients with MASLD were further divided into low-control group with 1 107 patients， moderate-control group with 7 042 patients， and high-control group with 4 379 patients. A total of 397 participants were enrolled in the external validation cohort， among whom there were 266 participants with MASLD and 131 participants without MASLD. The Kruskal-Wallis H test was used for comparison of continuous data between multiple groups， and the chi-square test was used for comparison of categorical data between groups. The Cox proportional hazards model incorporating complex sampling weights for NHANES data were used to investigate the association between the degree of risk factor control and all-cause mortality， and the Kaplan-Meier curve， the log-rank test， restricted mean survival time （RMST）， and population attributable fraction （PAF） were used for further assessment. The robustness of the findings was validated in an independent clinical cohort （n=397）. ResultsThe cohort study based on the NHANES database showed that during the median follow-up time of 6.7 years， 1 171 deaths occurred among the 12 528 patients with MASLD. There was a significant reduction in mortality risk with the increase in the number of risk factors controlled （trend test： χ²=65.06， P<0.001）. Compared with the low-control group， the mortality risk decreased successively in the moderate-control group （hazard ratio ［HR］=0.59， 95% confidence interval ［CI］： 0.51 — 0.69） and the high-control group （HR=0.36， 95%CI： 0.27 — 0.48）， and the mortality risk was reduced by 22% for each additional risk factor controlled （HR=0.78， 95%CI： 0.74 — 0.82）. The PAF analysis showed that AST/ALT ratio control （PAF=19.2%） and physical activity （PAF=18.9%） were the largest contributors. The survival analysis of the sub-cohort constructed based on nearest neighbor matching （with a maximum follow-up time of 13.3 years） showed that there was a significant difference in cumulative survival rate between the MASLD groups with different control levels and the non-MASLD group （P<0.001）. The RMST analysis further quantified the survival benefit of each group， and the high-control group had the longest 10-year RMST （9.88 years）， which was superior to that of the non-MASLD group （9.43 years）， the moderate-control group （9.33 years）， and the low-control group （7.96 years）. The multivariable-adjusted model analysis of the complete cohort showed that compared with the non-MASLD population， the MASLD patients in the low-control group had a significant increase in mortality risk， the moderate-control group had a comparable mortality risk， and the high-control group had a significantly lower mortality risk. The subgroup analysis showed a significant protective effect of comprehensive control in both male and female individuals （P<0.05）， and the interaction analysis suggested a potentially stronger protective effect in female individuals （P_{for interaction}=0.031）. The protective effect was statistically significant in patients aged ≥60 years （P<0.05）. There was a significant difference in protective effect across the groups stratified based on waist circumference （P<0.05）， but there was no significant interaction between groups （P_{for interaction}=0.821）. In the external validation cohort， among the 397 participants， there were 72 cases of all-cause mortality （18.1%）. The survival analysis showed a significant gradient increase in the survival rate of MASLD patients with the increase in the level of control （P=0.022）. The RMST analysis showed that the moderate- and high-control groups had a better RMST than the non-MASLD group at 5 years （4.47 years vs 4.56 years vs 4.40 years）， with a more significant survival advantage at 10 years （8.67 years vs 8.95 years vs 8.44 years）. The Cox regression analysis showed that， with the low-control MASLD group as the reference， there was a significant reduction in mortality risk in the moderate-control group （HR=0.41， 95%CI： 0.21 — 0.81） and the high-control group （HR=0.32， 95%CI： 0.14 — 0.71）； with the non-MASLD population as the reference， there was a significant increase in mortality risk in the low-control group （HR=2.02， 95%CI： 1.03 — 3.95）， with a comparable mortality risk in the moderate-control group （HR=0.83， 95%CI： 0.48 — 1.44） and the high-control group （HR=0.66， 95%CI： 0.30 — 1.38）， and the point estimates of the effects were highly consistent with the main study. ConclusionAmong MASLD patients， better control of metabolic risk factors is associated with a lower mortality risk. Achieving optimal control can eliminate the excess mortality risk associated with MASLD， thereby helping patients achieve a better survival prognosis than the general population.

Objective To explore the current situation and experience of the development of multi-hospital areas in foreign medical institutions,and to analyze its enlightenment to the construction of"one hospital with multiple campuses"in public hospitals in China.Methods Through the combing of relevant literature,it systematically analyzes the development status of multi-hospital construction of medical institutions in typical countries such as the United States,the United Kingdom,and Germany,summarizes the relevant experience of different countries,and analyzes the current situation of the construction of"one hospital with multiple campuses"in China's public hospitals.Results At present,the orderly development of multiple hospitals of foreign medical institutions mainly depends on the homogenization of medical care,the scientific management of human resources and the improvement of information construction.China can learn from its experience and technical means to build a development pattern of"one hospital with multiple campuses"suitable for China's national conditions.Conclusion In the future,the construction of"one hospital with multiple campuses"in China's public hospitals should focus on"rationalization of human resource allocation,homogenization of medical service quality,and intelligent information system construction",improve"human resource allocation",establish and improve"information sharing mechanism",differentiate the layout of"hospital functions",and strengthen"quality supervision and patient feedback",aiming to improve the construction effect of"one hospital with multiple campuses"in China's public hospitals.

Objective:To investigate the key genetic mutations during the progressive disease (PD) /leukemic transformation (LT) course in MDS by analyzing the dynamic changes of genetic mutations in patients with myelodysplastic neoplasms (MDS) with or without PD/LT.Methods:This study enrolled 84 patients with sequential MDS from May 2019 to August 2023 at ZhongDa Hospital Southeast University and used the next generation sequencing to detect gene mutations. The dynamic changes of genetic mutations in patients with MDS with or without PD/LT were retrospectively analyzed.Results:①This study analyzed data from 84 patients diagnosed with MDS with a median age of 63 (range: 31-95) years and consisting of 51 males and 33 females. Participants were distributed to the PD cohort ( n=20), LT cohort ( n=13), and non-PD/LT cohort ( n=51). Patients from the PD/LT cohorts demonstrated a higher proportion of bone marrow blasts than the non-PD/LT cohort at the first sequencing (1.6% vs. 0.4%, P=0.013). ②The most frequently mutated genes that were detected at first sequencing were ASXL1 ( n=21, 25.0%), TP53 ( n=17, 20.2%), TET2 ( n=12, 14.3%), DNMT3A ( n=11, 13.1%), and U2AF1 ( n=11, 13.1%). Further, patients from the PD/LT cohorts exhibited a higher median number of mutated genes than the non-PD/LT cohort (2 vs.1, P=0.014) at first sequencing. TET2 (27.3% vs. 5.9%, P=0.010), SETBP1 (15.2% vs.2.0%, P=0.033), and RUNX1 (18.2% vs. 2.0%, P=0.013) mutations were enriched in the PD/LT cohorts than in the non-PD/LT cohort. ③The most frequently detected acquired mutations (Ⅰ mutations) and clonally expanded mutations (Ⅱ mutations) were TP53 ( n=9, 10.7%), TET2 ( n=7, 8.3%), ASXL1 ( n=7, 8.3%), and RAS pathway ( n=7, 8.3%). Furthermore, patients from the PD/LT cohorts showed a higher median number of Ⅰ/Ⅱ genes than the non-PD/LT cohort (2 vs. 0, P<0.001), and Ⅰ/Ⅱ RAS pathway (21.2% vs. 0, P=0.001), TP53 (27.3% vs. 0, P<0.001), and TET2 (18.2% vs. 2.0%, P=0.013) mutations were enriched in PD/LT cohorts than in the non-PD/LT cohorts. ④Most of the TP53 mutations (9/12, 75.0%) in PD/LT cohorts were Ⅰ/Ⅱ mutations, whereas all of the TP53 mutations in non-PD/LT cohort were clone-decrease mutations (Ⅲ mutations) (5/8, 62.5%) or clone-stable mutations (Ⅳ mutations) (3/8, 37.5%). Most of the RAS pathway mutations (7/8,87.5%) in the PD/LT cohorts were Ⅰ/Ⅱ mutations, whereas only one patient in the non-PD/LT cohort demonstrated RAS pathway mutations, which belonged to Ⅳ mutations. Conclusion:Patients from the PD/LT cohorts demonstrated a higher proportion of bone marrow blasts and a higher median number of mutations than the non-PD/LT cohort at first sequencing; TET2, SETBP1, and RUNX1 mutations were enriched in the PD/LT cohorts than in the non-PD/LT cohort at first sequencing. Patients from the PD/LT cohorts exhibited a higher number of Ⅰ/Ⅱ mutations than the non-PD/LT cohort. Further, Ⅰ/Ⅱ TP53, RAS pathway, and TET2 mutations were enriched in the PD/LT cohorts, and Ⅰ/Ⅱ TP53 and RAS pathway mutations may contribute to the PD/LT.

Good endometrial receptivity is an essential factor for embryo implantation,and gene expression in endometrial tissue during the window of implantation(WOI)is closely related to receptivity.Transcriptome sequencing technology enables the identification of gene expression profiles of endometrium during different menstrual phases,as well as microRNAs and long-chain non-coding RNA sequences involved in regulating gene expression.Combining this technology with bioinformatics analysis provides a better understanding of specific gene expression during the receptive period and offers technical support for studying its regulatory mechanism.Moreover,gene expression profiles of the endometrium during different menstrual phases hold significant clinical application value for accurately assessing endometrium receptivity in infertility patients and those with repeated implantation failure,thereby guiding individualized embryo transfer strategies.This review summarizes the progress of transcriptome sequencing in evaluating human endometrial receptivity and discusses future research directions.This review aims to understand the complex molecular mechanisms of endometrial receptivity formation and regulation from the transcriptional level,in order to improve the implantation rate of embryos in assisted reproductive technology and reduce the abortion rate.

Objective To analyze the clinical characteristics,laboratory test,imaging examination,and treatment outcome of invasive Klebsiella pneumoniae liver abscess syndrome(IKPLAS)in the elderly,and improve clinicians' understanding on this disease.Methods Clinical data of 7 elderly patients who were diagnosed with IKPLAS in a hospital from January 2020 to February 2024 were analyzed retrospectively.Results Among the 7 elderly patients with IKPLAS,there were 3 males and 4 females,ranging in age from 60 to 78 years old.All 7 patients were with community-acquired infection.The main clinical symptoms were fever(n=7),chills(n=6),upper abdominal pain(n=4),fatigue and poor appetite(n=3),cough and expectoration(n=5),vomiting(n=3),vision decrease(n=2),and disturbance of consciousness(n=1).All 7 patients had pathogenic evidence of Klebsiella pneumoniae(KP),including 4 cases with KP isolated from liver puncture pus,3 from blood culture,and 1 from both liver puncture pus and intraocular pus.Among the 7 patients,there were 5,2,1,3,1,1 cases combined with pulmonary abscess,endophthalmitis,brain abscess,bloodstream infection,urinary system infection,and pelvic infection,re-spectively.Conclusion Elderly patients with IKPLAS have a variety of underlying diseases and diverse clinical symptoms,showing no specificity.Once IKPLAS was suspected,timely testing for pathogen and screening for other metastatic infection sites outside the liver should be performed.Timely drainage of liver abscess and selection of ap-propriate antimicrobial agents for treatment based on antimicrobial susceptibility testing result can improve patients' survival rate.

Aim To explore the role of zinc transporter 6(SLC30A6)on the proliferation,migration and inva-sion capabilities of hepatocellular carcinoma(HCC)cell line Huh7,and to identify potential traditional Chi-nese medicine(TCM)small-molecule inhibitors targe-ting SLC30A6 from the China Natural Products Data-base(CNPD)using virtual screening techniques.Methods The expression levels,clinical characteris-ticsand prognostic value of SLC30A6 in HCC were pre-dicted based on TCGA and ICGC datasets.SLC30A6 was knocked down in Huh7 cells using lentiviral trans-fection.The effects on cell proliferation,migration,and invasion were assessed using CCK-8,EdU,wound heal-ing,and Transwell assays.The regulation of HCC cancer stem cell markers(CD44,CD133,CD90)by SLC30A6 was also examined.Based on the CNPD,a docking-based virtual screening strategy was employed,including high-throughput virtual screening,standard precision virtual screening,and high-precision virtual screening,to identify the potential drug candidates with high specificity and favorable drug-likeness.Results SLC30A6 expression was upregulated in HCC tissues.Higher SLC30A6 levels were associated with advanced pathological stages,histological grades,alpha-fetopro-tein(AFP)levels,vascular invasion,and poor progno-sis in HCC patients.SLC30A6 knockdown significantly inhibited the proliferation,migration,and invasion of Huh7 cells and reduced the levels of HCC cancer stem cell markers.Virtual screening identified six potential TCM small-molecule inhibitors.Conclusions SLC30A6 can regulate the proliferation,migrationand invasion of HCC cells.SLC30A6 may serve as a poten-tial prognostic biomarker and therapeutic target for HCC.

This research investigated the contamination level,distribution of drug-resistant strains,and molecular epidemiologi-cal characteristics of Campylobacter,and further explored transmission pathways and prevention strategies.Cecum,chicken carcass,chicken product,and environmental samples,as well as swabs from workers'hands,were collected from a slaughterhouse in a large broiler group in the Jiaodong area between August 2023 and July 2024.Quantitative contamination assessment of Campylobacter in chicken carcasses and chicken products was performed.After microbial mass spectrometry identification,the representative strains of different links were selected for drug resistance testing and whole genome sequencing(WGS).On the basis of the sequencing results,the resistance genes,virulence genes,multilocus sequence typing(MLST),and phylogenetic characteristics of representative strains were analyzed.Homology comparisons were performed between isolates and strains from patients with diarrhea in the NCBI database.A total of 297 Campylobacter strains were isolated from 806 samples,and the overall detection rate was 36.85%.The detection rate of Campylobacter was highest in the evisceration process(47.33%),followed by the cutting process(35.64%).Overall,the Campylo-bacter detection rate first increased,then decreased,and subsequently increased.Drug sensitivity testing revealed that 90 isolates were resistant to nalidixic acid and ciprofloxacin,and 94.97%of isolates were resistant to tetracycline.WGS showed that both Campylo-bacter jejuni(C.jejuni)and Campylobacter coli(C.coli)carried many drug resistance and virulence genes.ST-14176 of C.jejuni was isolated for the first time herein.The predominant ST-8261 strain of C.jejuni and ST-860,ST-829,and ST-1586 strains of C.coli are known to cause human diarrhea.LOS expression genes associated with Guillain-Barré syndrome(GBS)were detected in both C.jejuni isolates from the slaughter chain and patients with GBS.Some strains exhibited close genetic relatedness to human-derived Campylo-bacter strains from the NCBI database.The detection rate of Campylobacter in the slaughterhouse first increased,then decreased,and subsequently increased,and the quantitative contamination level of each link was similar to the detection rate.Quantitative analysis of chicken carcasses/products revealed that the average bacterial load was highest in eviscerated carcasses(102.80 cfu/g),and the high-est amount of Campylobacter in chicken products reached 451.80 cfu/g.Abundant drug resistance genes and virulence genes were iden-tified,and the drug resistance genes were highly correlated with the drug resistance rate.Therefore,surveillance intensity and control measures for Campylobacter in slaughter processes should be strengthened.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Objective:To analyze and identify the expression profiles of oxidative stress-related genes and circular RNAs(circRNAs)in ricin toxin(RT)-induced pyroptosis of mouse mononuclear macrophages(RAW264.7)using transcriptome sequencing and bioinformatics technology,and to preliminarily analyze their potential functions.Methods:The macrophages(RAW264.7 cells)were treated with RT to establish a cell pyroptosis model and divided into control group,40 μg·L-1 RT group,and 80 ng/mL RT group.Transmission electron microscope(TEM)was used to observe the morphology of the RAW264.7 cells in various groups;Western blotting method was used to detect the expression levels of the pyroptosis pathway-related proteins in the cells in various groups;80 μg·L-1 RT was selected for subsequent experiments.Transcriptome sequencing(RNA-Seq)was performed to obtain the circRNA and mRNA expression profiles in the RAW264.7 cells in control group and RT-treated group,followed by bioinformatics analysis.Results:Compared with control group,the cells in 40 and 80 μg·L-1 RT groups underwent morphological changes;the cells in RT groups showed obvious pyroptosis-like morphological changes,characterized by significant swelling of dying cells and the appearance of characteristic large bubbles on the plasma membrane.Compared with control group,the expression level of gasdermin DN-terminal fragment(GSDMD-N)protein in 40 and 80 μg·L-1 RT groups was increased(P<0.05);compared with 40 μg·L-1 RT group,the expression level of GSDMD-N protein in the cells in 80 μg·L-1 RT group was increased(P<0.05);therefore,the subsequent experiments used the RT concentration of 80 μg·L-1.A total of 2930 differentially expressed messenger RNAs(mRNAs)and 24 differentially expressed circRNAs were identified.The constructed circRNA-microRNA(miRNA)-mRNA competing endogenous RNA(ceRNA)regulatory network consisted of 7 circRNAs,12 miRNAs and 13 mRNAs.Gene Ontology(GO)functional enrichment analysis showed that in biological process(BP),the functions regulated by differentially expressed genes mainly included immune response and oxidative stress response;in cellular component(CC),differentially expressed genes were mainly localized to the external side of plasma membrane and cell leading edge;in molecular function(MF),they were mainly involved in transporter transmembrane activity and hormone receptor binding.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that differentially expressed genes were mainly enriched in Toll-like receptor signaling pathway,Forkhead box O(FoxO)signaling pathway and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.In the protein-protein interaction(PPI)network,the top 10 hub genes with the highest connectivity were screened by CytoHubba,including matrix metalloproteinase 9(MMP9),superoxide dismutase 2(SOD2),and v-src sarcoma viral oncogene homolog(Src).Conclusion:The expression profiles of oxidative stress-related genes and circRNAs in RAW264.7 cells are altered after RT treatment.The screened differentially expressed circRNAs and mRNAs may serve as potential targets to regulate RT-induced pyroptosis in RAW264.7 cells through oxidative stress pathways.

Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.