ObjectivesTo evaluate associations between endoscopic features and hospitalization outcomes in IgA vasculitis (IgAV) with gastrointestinal (GI) involvement, focusing on endoscopic subtypes associated with prolonged hospitalization.MethodsWe analyzed 132 IgAV patients with GI involvement and complete endoscopic data at a large-volume center (January 2019 to December 2024). Clinical manifestations, endoscopic characteristics, laboratory data, and abdominal imaging findings at admission were reviewed. Prolonged length of stay (LOS) was defined as LOS exceeding the 75th percentile (>13 days). Multivariable logistic regression and gamma regression (log link) were used to examine factors associated with prolonged LOS and LOS as a continuous outcome. Sensitivity analyses additionally adjusted for treatment variables and renal involvement. Laboratory parameters were compared across endoscopic subgroups in exploratory analyses.ResultsThe median age of the patients was 18 years (IQR: 15.0–45.5), with a male-to-female ratio of 2:1. Abdominal pain was the most common presenting symptom. Bowel wall thickening was the most frequent finding on abdominal imaging. The most prevalent endoscopic finding was congestion/edema, followed by erosions, ulcers, and petechiae/ecchymosis. Endoscopic ulceration (OR 2.40, 95% CI 1.09–5.27, p=0.029) and multi-segment GI involvement (OR 2.58, 95% CI 1.20–5.58, p=0.016) were independently associated with prolonged LOS. Gamma regression showed that ulceration was associated with a 27.7% longer LOS (RR 1.277, 95% CI 1.047–1.564, p=0.018) and multi-segment involvement with a 34.7% longer LOS (RR 1.347, 95% CI 1.035–1.748, p=0.025). The association with ulceration remained significant after adjusting for treatment factors, whereas the association with multi-segment involvement was attenuated. The association of ulceration with LOS was more pronounced in patients aged ≤18 years. In sensitivity analyses, additional adjustment for renal involvement did not materially change the associations between endoscopic features and LOS.ConclusionsIn IgAV with GI involvement, endoscopic ulceration is the endoscopic feature most consistently associated with longer hospitalization, and the association appears stronger in patients aged ≤18 years. Multi-segment involvement shows a weaker association that attenuates after treatment adjustment. Overall, these findings support the clinical value of endoscopic phenotyping to inform clinical assessment and should be interpreted as associations rather than prognostic predictions.

OBJECTIVES:Gastrointestinal (GI) bleeding is a serious complication of immunoglobulin A vasculitis (IgAV), but reliable predictors are still lacking. This study aimed to identify clinical risk factors and develop a prediction model for IgAV-related GI bleeding in a large patient cohort. METHODS:In this retrospective study, 968 patients with IgAV from the Affiliated Hospital of Southwest Medical University (2019-2024) were divided into GI bleeding (n=484) and non-bleeding (n=484) groups. We analysed seasonal onset patterns and used multivariate logistic regression with ROC curve validation to identify predictors. RESULTS:This retrospective study revealed that summer-onset disease was associated with a significantly higher risk of GI bleeding compared to other seasons (OR=1.67, 95% CI:1.15-2.45; p=0.007), representing a 13.8% absolute risk increase (p<0.001). The neutrophil-to-albumin ratio (NAR) was the strongest biochemical predictor (OR=1.79; 95% CI:1.33-2.47; AUC=0.723). High systemic immune-inflammation index levels also increased risk (OR=2.91, 95% CI:1.67-5.08), while mean platelet volume (MPV) was protective (OR=0.78, 95% CI:0.68-0.90). A combined model including seasonality, NAR, and MPV showed superior predictive performance (AUC=0.742, 95% CI:0.711-0.772). CONCLUSIONS:Summer onset, elevated NAR, and decreased MPV help identify IgAV patients at high risk of GI bleeding. A model combining these factors allows effective risk stratification and supports targeted monitoring in clinical practice, particularly for summer-admitted patients with high neutrophil-to-albumin ratios.

BackgroundMixed-type IgA vasculitis (IgAV) is common in clinical practice, but its internal heterogeneity and prognostic significance, especially in renal involvement, remain unclear. This study aimed to characterize mixed-type IgAV, compare renal risk across mixed subtypes, and evaluate the additional predictive value of mixed subtype classification for clinically significant renal involvement.MethodsWe performed a retrospective cohort study of patients with clinically diagnosed IgAV treated between December 2018 and October 2025. Among 2,818 admissions/records screened, 2,416 unique patients were included after excluding repeated admissions, including 739 non-mixed and 1,677 mixed-type cases. Mixed type and mixed subtypes were defined according to organ involvement at first admission. Clinically significant renal involvement was defined from discharge diagnoses and renal-related clinical documentation, with available renal laboratory indicators used as supporting evidence. Laboratory-based component and sensitivity analyses were additionally performed using predefined proteinuria, eGFR, and serum creatinine criteria. Subtype-specific logistic regression, receiver operating characteristic (ROC) analysis, and a visit-order KM-like proteinuria analysis were performed.ResultsCompared with non-mixed disease, mixed-type IgAV was associated with lower BMI and albumin, higher white blood cell and platelet counts, longer hospital stay, and markedly higher frequencies of digestive, joint, and renal involvement. Within the mixed-type cohort, clinically significant renal involvement varied substantially across subgroups, ranging from 26.7% to 76.9%. Using Skin–Joint as the reference group, significantly higher odds of clinically significant renal involvement were observed in the Other/rare group, Skin–Renal, Skin–Joint–Renal, and Skin–Abdominal–Renal (all p < 0.001). In complete-case analysis (n=2,286), adding mixed subtype to a model based on routine demographic and laboratory variables improved the AUC from 0.596 to 0.745 (ΔAUC 0.148, DeLong p < 0.001). Mixed-type patients also showed a lower proteinuria-free probability across successive admissions.ConclusionsMixed-type IgAV is a heterogeneous phenotype with marked subtype-dependent differences in renal risk. Mixed subtype classification improves identification of clinically significant renal involvement and may support earlier and more individualized renal risk stratification.

Infliximab (IFX) for inflammatory bowel disease (IBD) treatment may increase the risk of hepatitis B virus (HBV) reactivation, particularly in areas with high HBV prevalence such as China. This study aimed to evaluate HBV reactivation/infection, liver dysfunction, vaccination efficacy and strategies in IBD patients undergoing IFX therapy. This retrospective, multicenter study included 4183 IBD patients from 15 hospitals across China, who were divided into six groups according to the HBV status. Demographic features, HBV vaccination status, reactivation/infection rates, and liver dysfunction outcomes were collected, with data collection performed from 2009 to 2022. We found that HBV reactivation rate was notably higher in HBsAg positive group than other groups (P < 0.05) despite antiviral treatment. Although only 29% of patients were immunized at IFX initiation and almost no patients got vaccinated against HBV during IFX treatment, no patients experienced HBV infection in the susceptible population group. The study underscores a critical need for rigorous HBV screening before IFX initiation. Despite antiviral prophylaxis, the importance of continuous monitoring of HBV DNA is necessary for HBsAg positive patients. HBsAg negative patients, including the susceptible population, had a very low risk of new HBV infection, thus reassuring patients and physicians of the safety of IFX in this cohort.

BackgroundDrug-induced upper gastrointestinal bleeding (UGIB) is a serious adverse event that deserves close attention. This study conducted a real-world pharmacovigilance research, aiming to enhance the understanding of drug safety and more effectively identify and prevent potential risks.MethodsThis study extracted data related to UGIB reported in the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases from the first quarter of 2004 to the second quarter of 2024. We selected the top 50 drugs with higher frequency and conducted safety analyses using four signal detection methods: Reporting Odds Ratio, Proportional Reporting Ratio, Empirical Bayes Geometric Mean, and Bayesian Confidence Propagation Neural Network.ResultsThrough data mining analysis, we found that the number of patients with UGIB reported was 62,941, including 57,414 in the FAERS and 5,527 in the JADER. It is particularly noteworthy that aspirin frequency and signal strength were among the top five in both databases. Rivaroxaban, warfarin, and pradaxa not only had the highest number of reports in the FAERS database but also showed highly in terms of their signal values. In the JADER database, clopidogrel, loxoprofen, apixaban, and bevacizumab had a higher number of reports, and it was also observed that esflurbiprofen/mentha oil and lornoxicam exhibited extremely high signal values. Meanwhile, meloxicam and prasugrel also had relatively high signal values.ConclusionThis study conducted a pharmacovigilance analysis of drug-related UGIB by integrating and analyzing multiple adverse drug reaction databases. In both the FAERS and JADER databases, we not only identified some common risk-signaling drugs but also discovered database-specific risk-associated medications. In particular, this study performed a systematic quantitative risk assessment of the selected high-reporting-frequency drugs. This analysis not only deepened our understanding of drug risk profiles but also provided important reference evidence for clinical medication safety decision-making.

BackgroundStatins, as an important class of lipid-lowering drugs, play a key role in the prevention and treatment of cardiovascular diseases. However, with their widespread use in clinical practice, some adverse events have gradually emerged. In particular, the hepatotoxicity associated with statins use has become one of the clinical concerns that require sufficient attention.MethodsIn this study, we conducted a comprehensive and detailed analysis of the hepatotoxicity of statins based on the data of the US Food and Drug Administration Adverse Event Reporting System database from the first quarter (Q1) of 2004 to the Q1 of 2024 and used Reporting Odds Ratios and Empirical Bayes Geometric Mean to mine the signal of adverse events.ResultsIn this study, hepatic disorder related seven statins all exhibited positive signals. Through signal mining, we identified a total of 14,511 cases of adverse events associated with hepatic disorder caused by these statin drugs, with atorvastatin, simvastatin, and rosuvastatin occurring at a higher rate. A total of 148 positive signals related to adverse events of hepatic disorder were captured. Autoimmune hepatitis and drug-induced liver injury both presented positive signals across multiple statin drugs. Notably, atorvastatin had the most significant signal strength in cholestatic pruritus and bilirubin conjugation abnormal. Fluvastatin also showed notable signal strength in autoimmune hepatitis, while simvastatin had a relatively weaker signal strength for hepatic enzyme increased.ConclusionThis study discovered specific adverse event signal values, revealing potential hepatotoxic risks associated with the use of statin drugs. The results provide an important reference for the safe clinical use of drugs, help to improve the understanding of the safety of statins, and also provide a scientific basis for clinicians to make more accurate and safe decisions when making treatment plans.

The Body Rounds Index (BRI) is an anthropometric indicator specifically developed to evaluate an individual's obesity level, particularly emphasizing central or abdominal obesity. This study aimed to explore the relationship between BRI and all-cause mortality in older U.S. adults. The research sample comprised individuals aged 65 and older from the National Health and Nutrition Examination Survey (NHANES), eligible for mortality analyses between 1999 and 2018. We utilized Cox regression analyses, restricted cubic spline (RCS), threshold effects analysis, Kaplan-Meier curves, and subgroup analyses were conducted to assess how the BRI correlates with all-cause mortality among older adults in the U.S. To further ensure the robustness of our findings, we conducted sensitivity analyses. Among 5371 U.S. older adults (age ≥ 65), with an average age of 72.45 (standard deviation [SD]:5.65) years, 2884 (60%) were women. During the follow-up period, there were 2781 deaths from all causes among the 5371 participants. After adjusting for all covariates, a U-shaped association was identified between BRI and the all cause mortality. Compared to a BRI of less than 4.457, a BRI between 4.457 and 5.538 was associated with a 19% reduction in the likelihood of mortality from any cause (HR = 0.81, 95% CI = 0.69-0.95). A BRI between 5.538 and 6.888 was linked to a 8% reduction in mortality risk (HR = 0.92, 95% CI = 0.79-1.07), while a BRI exceeding 6.888 showed a 1% increase in this risk (HR = 1.01, 95% CI = 0.87-1.17). RCS analysis indicated a U-shaped relationship between BRI and all-cause mortality. The turning point was located at 4.546, with correlations observed both before and after this point. This NHANES-based study highlights the U-shaped relationship between BRI and all-cause mortality among U.S. older adults, suggesting that the BRI has predictive value for mortality outcomes. The findings offer compelling support for utilizing BRI as a non-invasive mortality risk screening tool.

Background:Gastric cancer (GC), the fifth most common cancer worldwide, has high morbidity and mortality rates. Propionate metabolism, which plays a significant role in cancer progression, remains understudied in the context of GC development and progression. This study aimed to identify propanoate metabolism-related genes (PMRGs) with prognostic value, construct a predictive model for GC outcomes, and explore their associations with tumor microenvironment (TME) and therapeutic response. Methods:The data of GC patients included RNA-sequencing expression profiles, the clinical data, and mutation data gained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Data from GC patients in TCGA and GEO were used to develop and validate a prognostic model through univariate Cox and least absolute shrinkage and selection operator (LASSO) regression, by selecting key differentially expressed PMRGs (DE-PMRGs). Patients were divided into high- and low-risk groups by median risk scores. The prognostic model was evaluated by the Kaplan-Meier (K-M) curve and time-dependent receiver operating characteristic (ROC). A nomogram was created using PMRGs to predict 1-, 2-, and 3-year overall survival (OS), which was further validated with decision curve analysis (DCA) and calibration curves. Results:There were 63 DE-PMRGs were identified, with eight key hub PMRGs selected by LASSO and Cox regression for a prognostic model that predicted better survival in the low-risk group. A nomogram was constructed to predict the 1, 2 and 3 years survival rates of GC patients. In the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of high-risk groups, DE-PMRGs are primarily enriched in pathways related to muscle cells and cardiac diseases. Additionally, five immune cell types showed disparities between high and low-risk groups. Immune infiltration analysis suggested a higher potential for immune therapy response in the low-risk cohorts, and drug sensitivity prediction in GC indicates a broader sensitivity to chemotherapy drugs in the high-risk groups. Conclusions:We developed a prognostic model based on PMRGs to forecast clinical outcomes in GC patients independently. The model was refined to identify eight key genes, serving as a tool for prognosis and treatment planning in GC.

Background:Gastric cancer (GC) is a prevalent malignancy with high morbidity and mortality. Pyroptosis, a form of programmed cell death, plays a significant role in cancer progression and immune regulation. This study aimed to construct a pyroptosis-related prognostic signature (PRPS) and analyze its association with the tumor microenvironment in GC by integrating single-cell and bulk RNA sequencing data. Methods:Pyroptosis-related differentially expressed genes in GC were identified by integrating single-cell and bulk RNA sequencing data. The PRPS was constructed using univariate and multivariate Cox regression analyses, and evaluated by Kaplan-Meier curves, receiver operating characteristic curves, and nomogram analysis. Subsequently, genomic variations, immune landscapes, immune checkpoint inhibitors (ICIs) responses, and drug sensitivity were evaluated in different risk subgroups. Results:We constructed a PRPS in GC by integrating single-cell and bulk RNA sequencing data. The PRPS exhibited strong predictive efficiency, with the high-risk group showing significantly lower overall survival, progression-free survival, and disease-specific survival. Multivariate Cox regression validated the PRPS as an independent prognostic factor, while the PRPS-based nomogram showed high predictive accuracy. Functional enrichment and immune landscape analysis revealed the differences between the risk subgroups in immune pathways, gene mutations, immune cell infiltration, and tumor mutational burden. Analysis of ICIs responses and drug sensitivity showed the differences in treatment among different risk subgroups, providing a basis for personalized treatment. Conclusions:The PRPS provides a promising tool for the prognostic prediction, targeted prevention, and personalized treatment for GC, and may promote the precision medicine for GC patients.

This study aimed to estimate the burden of digestive disorders in Asia from 1990 to 2019 using Global Burden of Disease Study (GBD) 2019 data. We calculated disability-adjusted life-years (DALYs), prevalence, incidence, deaths, and estimated annual percentage changes (EAPCs). We also examined the burden rankings, future projections for six selected countries, the association with Sociodemographic Index (SDI), and risk factors. Digestive diseases showed a downward trend in age-standardized DALY rates over the past 30 years, which was predicted to continue in the future among selected countries, except for Turkmenistan. DALYs for digestive diseases were higher in males than females, peaking at 50–54 years. Alcohol use was the most attributable risk factor for digestive diseases DALYs. There was a negative correlation between the burden of digestive diseases and SDI, with some exceptions. Despite reduced age-standardized DALYs rates, digestive diseases remained prevalent, necessitating effective prevention and treatment programs by Asian governments.

BackgroundEsomeprazole holds a significant position in the treatment of acid-related diseases. However, as with all drugs, it may also carry some potential risk of adverse effects. This study aims to further evaluate the safety of esomeprazole for clinical use.Research design and methodsThe data of esomeprazole-related adverse events was extracted from the FAERS database from the first quarter of 2004 to the first quarter of 2024 and used Reporting Odds Ratios (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean(EBGM) for data mining.ResultsA total of 67,712 esomeprazole-related adverse events were extracted from the FAERS database, involving 27 system organ class. The frequency of renal and urinary occurrence was the highest, and the signal was the strongest. Additionally, we detected 324 preferred terms: rebound acid hypersecretion, nephrogenic anemia, and hyperparathyroidism secondary showed significant high signal strength. In the elderly, adverse events were concentrated in the gastrointestinal disorders system, and the most common adverse events were dyspepsia and hyponatremia. Unexpected adverse events, such as vomiting, acute kidney injury, and anaphylactic reaction occurred in children.ConclusionsWe discovered some new and special esomeprazole-related adverse events, raising awareness of the safety of esomeprazole and further helping to mitigate associated risks.

Aim Our study aimed to report the burden of diseases attributable to high body mass index (BMI) in Asia from 1990 to 2019.Methods Utilizing data from the Global Burden of Disease (GBD) Study 2019, we calculated disability-adjusted life years (DALYs) and deaths, with trends quantified by the estimated annual percentage change (EAPC). We also made projections for selected countries and estimated the relationship between the Sociodemographic Index (SDI) and high BMI-related disease burden.Result From 1990 to 2019, high BMI-related diseases observed significant increases in the absolute number of deaths and DALYs, with EAPCs of 4.62 and 4.69, respectively, while the age-standardized rates of both deaths and DALYs also showed upward trends, with EAPCs of 1.39 and 1.80. Cardiovascular diseases, diabetes and kidney diseases, and neoplasms were the major contributors to the high BMI-related burden. The burden of high BMI-related diseases generally tended to be greater among males and older age groups. Predictions for selected countries indicated a continued rise in the number of deaths and DALYs for high BMI-related diseases, with a stabilization in the age-standardized rate. There was no significant association between SDI levels and the burden of high BMI-related diseases in Asia (coefficient=0.13, p = 0.39).Conclusion The burden of high BMI-related diseases, a major public health issue, was increasing in Asia. To address this problem, coordinated action by governments, civil society and other key stakeholders should be taken to enhance awareness of the risks associated with high BMI and effectively reduce its impact.

Background:The function of liquid-liquid phase separation (LLPS) in the progression of hepatocellular carcinoma (HCC) has not been extensively clarified. This study aimed to assess the predictive value and immunotherapeutic response associated with an LLPS-related signature (LLPSRS) in HCC. Methods:LLPS was characterized via single-cell RNA sequencing. By using single-cell and transcriptome analysis, we applied The Cancer Genome Atlas (TCGA) data and the least absolute shrinkage and selection operator (LASSO) Cox regression to construct the LLPSRS. In order to enhance the practicality of LLPSRS, we established and externally validated a LLPSRS nomogram, providing a quantitative prognostic tool for patients with HCC. Furthermore, we investigated the mechanisms related to the LLPSRS at the transcriptome, genomic, and single-cell levels, revealing important connections between the LLPSRS, HCC prognosis, and the immune landscape. Finally, we examined the different responses of the risk subgroups to immune checkpoint inhibitors and their sensitivity to major LLPSRS-targeted drugs. Results:We developed a risk prediction scoring model based on the 9-gene LLPSRS. The high-risk group exhibited notably lower overall survival (OS) compared to the low-risk group. High area under the curve (AUC) values from time-dependent receiver operating characteristic (ROC) curves demonstrated the model's robust performance. A nomogram that integrated the risk score and clinical features showed excellent prognostic ability. The LLPSRS's associations with clinicopathological characteristics, tumor microenvironment, immunotherapy response, and chemotherapy sensitivity indicated their significant clinical relevance. Conclusions:We developed a model that can accurately predict the outcomes of patients with HCC, clarified the mechanisms underlying the LLPSRS's relationship to HCC, and generated findings that contribute to the personalized treatment and development of immunotherapy for patients with HCC.

Inflammation can influence the development of CRC as well as immunotherapy and plays a key role in CRC. Therefore, this study aimed to investigate the potential of inflammation-related genes in CRC risk prediction. Inflammation gene models were constructed and validated by combining transcriptomic and single-cell data from TCGA and GEO databases, and the expression of inflammation-related genes was verified by RT-qPCR. We identified two molecular subtypes and three genetic subtypes, two risk subgroups according to median risk values, constructed a prognostic model including thirteen genes (TIMP1, GDF15, UCN, KRT4, POU4F1, NXPH1, SIX2, NPC1L1, KLK12, IGFL1, FOXD1, ASPG, and CYP4F8), and validated the performance of each aspect of the model in an external database. Patients in the high-risk group had worse survival with reduced immune cell infiltration and a greater tumor mutational load. The risk score correlated strongly with the immune checkpoints PD1, PDL1, PDL2, and CTLA4, and it is possible that high-risk patients are more sensitive to treatment involving immune checkpoints. In the single-cell data, GDF15 was most significantly expressed in cancer cell populations. Therefore, we further validated their expression in cells and tissues using qPCR. In summary, we developed a prognostic marker associated with inflammatory genes to provide new directions for subsequent studies and to help clinicians assess the prognosis of CRC patients as well as to develop personalized treatment strategies.

AIM:This research was aimed to uncover the hepatitis B virus (HBV) and hepatitis C virus (HCV) related diseases burden in Asia over the past 3 decades, estimating from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS:Age-standardised rates, case numbers of prevalence, disability-adjusted life-years (DALYs), incidence and deaths with 95% uncertainty intervals (UI) for HBV/HCV-related diseases from 1990 to 2019 were derived from GBD 2019 database, with the estimated annual percentage changes (EAPCs) calculated. Our analysis also encompassed the association between the Sociodemographic Index (SDI) and the burden of HBV/HCV-related diseases, future disease burden predictions in six selected countries and various risk factors. RESULT:A general downward trend in the age-standardised rates of death, disability-adjusted life years (DALYs), prevalence and incidence for both HBV and HCV-related diseases was observed in Asia during the past 30 years. Despite overall declining trends, some analysed diseases experienced an increase. Compared with females, the disease burden was greater in the male population and peaked in the age of 50-54 for both sexes. It is significant for the HBV-related and HCV-related diseases burden in Afghanistan, Cambodia, Mongolia and Pakistan. Drug use and smoking were prominent contributors to HCV and HBV-related diseases. There was a negative relationship between the burden of HCV and HBV-related diseases and SDI. CONCLUSION:Although decreases were observed in Asia, the HBV- and HCV-associated diseases burden remained high, highlighting that imperative measures for prevention and treatment should be taken by governments in Asia.

Cancer remains a leading cause of mortality worldwide, with human exonuclease 1 (EXO1) emerging as a key player in DNA repair and damage response pathways, critical for genomic stability and tumor evolution. The aim of this study was to conduct a comprehensive pan-cancer analysis to elucidate the multifaceted roles of EXO1 in various malignancies. Leveraging public databases including TCGA, GTEx, HPA, cBioPortal, UALCAN, STRING, CancerSEA and TISIDB database, we examined EXO1's expression, diagnostic potential, prognostic significance, mutational characteristics, functional roles, and immunological effects across different cancer types. EXO1 was found to be upregulated in multiple cancers, with significant diagnostic potential as indicated by high AUC values in ROC analyses. Elevated EXO1 expression correlated with adverse prognosis in several cancer types, including breast, lung, and pancreatic cancers. Epigenetic alterations, including DNA methylation and mRNA modifications, were also associated with EXO1 expression. Enrichment analyses identified EXO1-related genes involved in DNA recombination, replication, and repair, with GSEA implicating EXO1 in cell cycle regulation and DNA processing pathways. Importantly, immunogenomic analyses revealed EXO1's significant role in modulating the tumor microenvironment, as it is associated with immune cell infiltration and cytokine expression, suggesting its involvement in tumor immunology and immune response regulation. These results implied that EXO1 as a significant biomarker with prognostic and diagnostic potential across various malignancies, suggesting its potential as a therapeutic target and its involvement in immunomodulatory processes within the tumor microenvironment.

Objective This study evaluates the predictive value of the lactate/albumin ratio (LAR) for all-cause mortality in cirrhosis patients. Design Retrospective observational study. Setting Intensive care unit (ICU). Patients or participants 626 first-time ICU-admitted cirrhosis patients in the USA (MIMIC-IV v2.2). Interventions None. Main variables of interest LAR index, 28-day, and 90-day all-cause mortality. Results Of 626 patients (60.86% male), 27.80% and 39.14% died within 28 and 90 days, respectively. Multivariate Cox analysis showed a significant association between higher LAR and mortality. Adjusted for confounders, elevated LAR increased the 28-day mortality risk [HR: 1.31 (1.21–1.42), P < 0.001]. A restricted cubic spline analysis revealed non-linear relationships between LAR and mortality. For 28-day mortality, the inflection point was 1.583: below this, HR was 2.29 (95% CI: 1.61–3.27, P < 0.001); above, HR was 1.16 (95% CI: 1.02–1.31, P = 0.021; P = 0.002). For 90-day mortality, the inflection point was 1.423: below, HR was 1.60 (95% CI: 1.04–2.47, P = 0.033); above, HR was 0.94 (95% CI: 0.75–1.16, P = 0.542; P = 0.012). Conclusions LAR predicts 28-day and 90-day mortality with a segmented effect. An LAR ≥1.583 signals high 28-day mortality risk, necessitating intensified monitoring and potential ICU admission. For 90-day mortality, LAR near 1.423 serves as an early warning for high-risk patients and guides interventions. Continuous LAR monitoring aids management, but prospective studies are needed to confirm clinical utility.

Non-alcoholic fatty liver disease (NAFLD) is a global health challenge with complex pathogenesis and limited diagnostic biomarkers. Palmitoylation, a post-translational modification, has emerged as a critical regulator in metabolic disorders, yet its role in NAFLD remains underexplored. This study integrated bioinformatics analysis and machine learning to identify palmitoylation-related biomarkers for NAFLD. Transcriptomic datasets from human liver tissues were analyzed to identify differentially expressed genes (DEGs) and co-expression modules via WGCNA. Intersection analysis revealed 60 palmitoylation-related DEGs (PR-DEGs). Seven machine learning models were employed, with Neural Network (NNET) and Decision Tree (DT) outperforming others, identifying three hub genes: TYMS, WNT5A, and ZFP36. A nomogram integrating these genes demonstrated robust diagnostic accuracy (AUC = 0.976). The pivotal role of these genes in diagnosing NAFLD was confirmed using the validation dataset (AUC = 0.903). Functional enrichment linked these genes to TNF signaling, lipid metabolism, and immune pathways. Single-cell RNA-seq analysis highlighted their expression in hepatocytes and immune cells, with altered intercellular communication patterns. Immune infiltration analysis revealed significant shifts in monocytes, dendritic cells, and macrophages in NAFLD. Regulatory network analysis highlighted that hsa-let-7b-5p might be pivotal co-regulator of the three hub gene expressions. Finally, the top 10 potential gene-targeted drugs were screened. This study unveils novel palmitoylation-related biomarkers and provides insights into NAFLD pathogenesis, offering diagnostic and therapeutic avenues.

Background:Colorectal cancer (CRC) is among the most common and lethal cancers worldwide. Recent advances in tumor immunotherapy have highlighted the importance of T-cell subsets and the tumor microenvironment (TME) in CRC, both critical for mounting a successful anti-tumor immune response. Thus, there is an urgent need for comprehensive research in these areas to accelerate the development of personalized immunotherapeutic strategies for CRC patients. Therefore, this study aims to explore T-cell heterogeneity, identify characteristic genes, and develop a reliable prognostic model to predict patient outcomes and immunotherapy responses. Methods:CRC single-cell RNA sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database. We identified T cell feature genes and employed Cox and least absolute shrinkage and selection operator (LASSO) regression methods to construct a prognostic model using The Cancer Genome Atlas (TCGA) dataset, while GEO dataset was utilized for validation. Additionally, we analyzed the immune microenvironment, immune checkpoints, and drug sensitivity between the high-risk and low-risk groups. Results:Based on scRNA-seq data, we identified 4,440 T cell marker genes. There were also interactions between T cells and various other cell types. The results of the enrichment analysis revealed that these marker genes were primarily involved in immune-related pathways. After conducting univariate Cox and LASSO analyses, we developed a prognostic model based on the expression levels of three prognostic genes: TIMP1, HMMR, and HIST1H1C. The feasibility of the model was validated using external validation cohort. In addition, the high-risk group exhibited higher immune scores, stromal scores, ESTIMATE scores, and Tumor Immune Dysfunction and Exclusion (TIDE) prediction scores compared to the low-risk group, indicating a poorer response to immunotherapy. Conclusions:This study discovered three key genes with prognostic relevance in CRC, providing valuable insights into T-cell heterogeneity and the associated prognostic risk model. The results demonstrated that this model accurately predicts patient prognosis and responses to immunotherapy.

IntroductionChina has experienced unprecedented transformations unseen in a century and is gradually progressing toward an emerging superpower. The epidemiological trends of digestive diseases in the United States (the US) have significant prescient effects on China.MethodsWe extracted data on 18 digestive diseases from the Global Burden of Diseases 2019 Data Resource. Linear regression analysis conducted by the JoinPoint software assessed the average annual percentage change of the burden. We performed subgroup analyses based on sex and age group.ResultsIn 2019, there were 836.01 and 180.91 million new cases of digestive diseases in China and the US, causing 1558.01 and 339.54 thousand deaths. The age-standardized incidence rates of digestive diseases in China and the US were 58417.87/100,000 and 55018.65/100,000 respectively, resulting in age-standardized mortality rates of 81.52/100,000 and 60.88/100,000. The rates in China annually decreased by 2.149% for mortality and 2.611% for disability-adjusted life of year (DALY). The mortality and DALY rates of the US, respectively, had average annual percentage changes of −0.219 and −0.251. Enteric infections and cirrhosis and other chronic liver diseases accounted for the highest incidence and prevalence in both counties, respectively. The burden of multiple digestive diseases exhibited notable sex disparities. The middle-old persons had higher age-standardized prevalence rates.ConclusionChina bore a greater burden of digestive diseases, and the evolving patterns were more noticeable. Targeted interventions and urgent measures should be taken in both countries to address the specific burden of digestive diseases based on their different epidemic degree.