Abstract Background and aims Elucidating long-term mortality and risk determinants is critical for optimizing stroke care paradigms. In this study, we aimed to explore long-term mortality and associated risk factors of stroke patients over a median 16-year surveillance period in Shanghai, China. Methods A total of 1605 stroke patients enrolled in our registry from 2002 to 2007 were followed up until December 31, 2023 or the date of death. Standardized mortality ratios (SMRs) were calculated for the entire cohort and stratified by gender/age, with concurrent evaluation of risk factors associated with long-term mortality. Results Five hundred and forty-one (43.9%) stroke patients died during follow-up and the SMR was 4.47 (95% confidential interval [CI] 4.08–4.85). In the age group of < 60 years, the SMR was 2.15 (95% CI 1.63–2.67) for men, 0.94 (0.43–1.45) for women, respectively. In the patients aged ≥ 60 years, the SMR was 6.32 (95% CI 5.57–7.07) for men and 5.79 (4.93-6.65) for women. The older age at onset, history of hyperlipidemia and prior TIA/IS was independently associated with the long-term death. The Kaplan Meier plot depicted that those <60 years of age had better prognosis compared with the patients aged ≥60 years in both males and females. Conclusions The long-term mortality following acute stroke was higher compared with the general populations. The increasing age at onset, dyslipidemia and prior stroke history were associated with the long-term death. Aggressive public health interventions aimed at improving the control of risk factors and mitigating socioeconomic disparities are urgently needed. Conflict of interest all authors have nonting to disclose

Sepsis is a severe inflammatory condition often complicated by acute lung injury (ALI) with limited therapeutic options. S100 Calcium Binding Protein A9 (S100A9) as an alarmin is highly elevated in sepsis. We observed that S100A9 was lactylated in the lung tissues of septic mice, the role of which in regulating sepsis-related ALI remains unknown. S100A9 lactylation sites were identified in septic patients and CLP mice using immunoprecipitation and mass spectrometry. Mechanistic studies employed mutagenesis, co-immunoprecipitation, and luciferase assays. In this study, we confirmed that S100A9 was lactylated at K4 and K94 in septic patients. Lactylated S100A9 promoted its nuclear translocation, thereby enhancing its interaction with transcription factor CCAAT/enhancer-binding protein beta (Cebpb). The complex of S100A9 and Cebpb further promoted the transcriptional activation of downstream interleukin 1 beta (IL-1β), leading to sepsis-related ALI. Moreover, the knockout of S100A9 effectively alleviated sepsis-induced inflammatory response and lung injury. Our findings elucidated the importance of S100A9 lactylation in regulating inflammatory responses of macrophages in sepsis-induced ALI, providing novel insights into the pathophysiology of sepsis and potential therapeutic targets for sepsis-associated organ dysfunction.

This study evaluated the cost-effectiveness of bevifibatide versus eptifibatide for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in China. A 30-day decision tree and 15-year Markov model simulated outcomes using matching-adjusted indirect comparison data. Base-case analysis used current listed price of bevifibatide (¥1290/vial). Costs and quality-adjusted life-years (QALYs) were evaluated against willingness-to-pay (WTP) thresholds based on China's per capita gross domestic product (GDP). Base-case results showed bevifibatide added ¥12,909.24 and 0.0595 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of ¥216,899/QALY. This significantly exceeds the ¥76,599 WTP threshold (0.8 times GDP), indicating it is not cost-effective. Lifetime analysis confirmed these results (ICER: ¥159,541/QALY). Threshold analysis indicated a price reduction to approximately ¥595/vial is required to achieve cost-effectiveness. In conclusion, bevifibatide is not cost-effective for ACS patients undergoing PCI in China at its current price. A substantial price reduction is necessary to align cost with clinical value, providing an evidence-based threshold for future reimbursement negotiations.

Vasopressor treatment strategies are essential for managing shock patients, yet determining optimal type, dosage, and timing of vasopressors remains challenging given variable clinician expertise and patient conditions. Applying existing reinforcement learning (RL) algorithms in treatment decision making risks Q-value overestimation and ignores the gap between artificial intelligence (AI)-driven recommendations and established clinical practices. This work introduces an offline RL algorithm called Safe Conservative Q-learning (SafeCQL), integrating conservative regularization and clinician-informed safety constraints. Patient trajectories from a large real-world intensive care database are modeled as a Markov decision process (MDP) to optimize vasopressor administration. Off-policy evaluations with model-based and model-free estimation methods demonstrate the superior performance of SafeCQL over clinician policies and existing RL models in improving survival rates and policy robustness. Findings show that SafeCQL improves the survival rate by 5.1% and raises expected returns from 45.78 to 69.15 (model-based) and 44.33 to 61.24 (model-free). SafeCQL can derive a treatment policy that aligns closely with clinician preferences while surpassing clinician expertise in decision quality. This work offers a deployable solution for personalized vasopressor management in dynamic critical care environments.

Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is a common cause of acute pancreatitis and is associated with worse clinical outcomes. Early prediction of prolonged hospitalization may facilitate clinical management and resource allocation. We aimed to develop and validate a web-based dynamic nomogram to predict prolonged length of stay (LOS) in patients with HTG-AP. We retrospectively analyzed 608 patients with HTG-AP admitted between 2014 and 2024. Patients were randomly divided into a training cohort (n = 487) and an internal validation cohort (n = 121). An independent external cohort of 39 patients (2021–2023) was used for external validation, and temporal validation was performed using a time-based split within the development cohort. Predictor variables were selected using LASSO regression and SHAP analysis. Independent predictors were identified by multivariate logistic regression and incorporated into a web-based nomogram. Model performance was assessed by discrimination, calibration, and decision curve analysis. Five independent predictors—systemic inflammatory response syndrome (SIRS), blood glucose, serum calcium, D-dimer, and APACHE II score—were included. Using LOS > 14 days as the endpoint, prolonged hospitalization occurred in 60.6

BackgroundAlthough the RNA-dependent RNA polymerase (RdRp) complex is a therapeutic target for influenza, evidence on the pharmacology, resistance, and clinical impact of RdRp-targeting inhibitors in high-risk populations remains fragmented. This scoping review on RdRp-targeting inhibitors identifies the research gaps and characterizes their mechanisms of action, pharmacokinetics, efficacy, safety, and resistance patterns.MethodsFollowing the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews” guidelines, a comprehensive search for studies was conducted across PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang, and ClinicalTrials.gov from inception to October 2025. Preclinical and clinical studies on influenza RdRp-targeting inhibitors were included, with data charted across eight domains.ResultsFrom 1,282 identified records (English: 1197; Chinese: 85), 156 articles were included. PA inhibitors emerged as the most extensively documented class. Preclinical findings demonstrated potent antiviral activity of PA inhibitors and emerging PB1/PB2 analogs, with variability in pharmacokinetic profiles. Clinical evidence showed PA inhibitors consistently shorten the time to symptom relief and accelerate viral RNA clearance compared with standard therapy. RdRp-targeting inhibitors showed an acceptable tolerability profile. Resistance was a notable challenge, primarily involving PA-I38 substitutions. Evidence on drug–drug interactions was limited to early-phase trials. A significant evidence gap remains for high-risk populations; baloxavir being the only agent widely studied in high-risk adults.ConclusionRdRp-targeting antivirals represent a promising frontier for influenza treatment, with PA inhibitors being the most extensively validated class. While PB1 and PB2 inhibitors diversify the therapeutic pipeline, their development is hindered by the need for multiple-dose regimens and the emergence of drug resistance. Future research should prioritize inhibitor designs that minimize resistance, as well as combination regimens, to accelerate clinical translation.

Major adverse kidney events within 30 days (MAKE30) are associated with poor outcomes in patients with sepsis-associated acute kidney injury (SA-AKI). This study aimed to develop and validate a nomogram-based prediction model for MAKE30 in SA-AKI patients. Clinical and laboratory data were collected from SA-AKI patients admitted to eight tertiary Grade-A hospitals in Shanghai between January 2021 and October 2022, forming the development cohort. External validation was performed using data from SA-AKI patients treated at Ruijin Hospital between January 2017 and December 2019. A predictive nomogram was constructed using LASSO regression followed by multivariate logistic regression. Model performance was assessed using area under the curve (AUC), calibration plots, decision curve analysis (DCA), and clinical impact curves (CIC). The model was subsequently validated in the external validation cohort. A total of 531 SA-AKI patients were included, with 372 in the development cohort and 159 in the validation cohort. The incidence of MAKE30 was 55.6

BACKGROUND:Sepsis, a life-threatening condition marked by organ dysfunction due to a dysregulated host response to infection, involves complex physiological and biochemical abnormalities. AIM:To develop a multivariate model to predict 4-, 6-, and 8-week mortality risks in intensive care units (ICUs). STUDY DESIGN:A retrospective cohort of 2389 sepsis patients was analysed using data captured by a clinical decision support system. Patients were randomly allocated into training (n = 1673) and validation (n = 716) sets at a 7:3 ratio. Least Absolute Shrinkage and Selection Operator (LASSO) regression identified variables incorporated into a multivariate Cox proportional hazards regression model to construct a prognostic nomogram. The area under the receiver operating characteristic curve (AUROC) assessed model accuracy, while performance was evaluated for discrimination, calibration and clinical utility. RESULTS:A risk score was developed based on 11 independent predictors from 35 initial factors. Key predictors included minimum Acute Physiology and Chronic Health Evaluation II (APACHE II) score as having the greatest impact on prognosis, followed by days of mechanical ventilation, number of vasopressors, maximum and minimum Sequential Organ Failure Assessment (SOFA) scores, infection sources, Gram-positive or Gram-negative bacteria and malignancy. The nomogram demonstrated superior discriminative ability, with AUROC values of 0.882 (95% confidence interval [CI], 0.855-0.909) and 0.851 (95% CI, 0.804-0.899) at 4 weeks; 0.836 (95% CI, 0.798-0.874) and 0.820 (95% CI, 0.761-0.878) at 6 weeks; and 0.843 (95% CI, 0.800-0.887) and 0.794 (95% CI, 0.720-0.867) at 8 weeks for training and validation sets, respectively. CONCLUSION:A validated nomogram and web-based calculator were developed to predict in-hospital mortality in ICU sepsis patients. Targeting identified risk factors may improve outcomes for critically ill patients. RELEVANCE TO CLINICAL PRACTICE:The developed prediction model and nomogram offer a tool for assessing in-hospital mortality risk in ICU patients with sepsis, potentially aiding in nursing decisions and resource allocation.

Primary cardiac angiosarcoma is a relatively rare tumor that frequently metastasizes by the time of diagnosis, with a poor prognosis. Currently, there is no uniform treatment, with surgical resection, radiotherapy, and chemotherapy being the mainstays of treatment. We report the case of a man in his early 30s who presented to the emergency department with hemoptysis and was found to have massive pericardial effusion and right atrial occupancy upon investigation. Subsequent examination revealed hypermetabolic foci in the lungs and femur, and a final biopsy confirmed the presence of a primary cardiac angiosarcoma. The patient died 3 days after diagnosis due to cardiopulmonary failure, with a survival period of 4 months from symptom onset to death. This report describes one of the few cases of cardiac tumor with respiratory symptoms.

Hearing loss (HL) usually indicates high risk of cognitive decline. We intend to investigate whether hearing aids fitting reduces cognitive decline of participants with hearing loss and mild cognitive impairment (MCI) by Chinese Hearing Solution for Improvement of Cognition in Elders-randomized controlled trial (CHOICE-RCT), a multicenter, parallel randomized controlled trial. We screened and enrolled participants aged above 60 years with moderate to severe sensorineural hearing loss and mild cognitive impairment from CHOICE project, outpatients in subcenters and high-risk population. After collection and quality control, the baseline data was stored in our platform called CRIP. In addition to baseline analysis, we will use statistical methods to explore correlations within it. Participant recruitment began from May 2021 to February 2024. We screened 20786 participants. 703 were enrolled finally with 408 from CHOICE Cohort, 230 from outpatients and 65 from high-risk population. Baseline characteristics: mean age was 74.52±7.15 years, 35.7% female; mean MMSE was 23.48±3.05. Enrolment of study has met the sample size. Follow-up data collecting is ongoing as planned, which will be completed at 2026.

PURPOSE:This study aimed to develop a nomogram for predicting acute kidney injury (AKI) in patients with moderate severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). METHODS:This study enrolled a total of 1,077 patients with MSAP and SAP, categorizing them into three groups: training (n = 646), internal validation (n = 278), and external validation (n = 153). In the training cohort, logistic regression analysis identified independent predictors of AKI in patients with MSAP and SAP. A nomogram was developed based on these independent predictors. The model's performance was assessed using the receiver operating characteristics (ROC) curve, precision-recall (PR) curve, calibration curve, and decision curve analysis (DCA). RESULTS:The incidence rates of AKI in the training set, internal validation set, and external validation set were 32.82%, 32.01%, and 27.45%, respectively. Independent predictors of AKI in patients with MSAP and SAP included: shock index (odds ratio [OR] = 7.42, 95% confidence interval [CI] 2.18-25.19), blood urea nitrogen (OR = 1.32, 95% CI 1.22-1.43), uric acid (OR = 1.002, 95% CI 1.000-1.003), serum calcium (OR = 0.38, 95% CI 0.18-0.79), triglycerides (OR = 1.02, 95% CI 1.004-1.041), hematocrit > 0.5 (OR = 3.24, 95% CI 1.10-9.59), serum sodium < 135 mmol/L (OR = 2.01, 95% CI 1.15-3.49), creatine kinase isoenzyme > 4 ng/mL (OR = 2.61, 95% CI 1.48-4.61), and thrombin time < 14 s (OR = 2.83, 95% CI 1.28-6.27). In the training, internal validation, and external validation sets, the areas under the ROC curves for the nomogram were 0.841, 0.789, and 0.853, respectively. Similarly, the areas under the PR curves were 0.807, 0.733, and 0.770. The calibration curves demonstrated that the predicted outcomes were well-aligned with the actual results. The decision curve analysis (DCA) indicated that the model had satisfactory clinical applicability. CONCLUSIONS:Nine indicators have been identified as independent predictors of AKI in patients with MSAP and SAP. The developed nomogram exhibits robust predictive capability and shows promise for clinical application.

Background:Peptic ulcer disease (PUD) constitutes a significant global health concern, particularly in women of childbearing age (WCBA), who face elevated risks of severe pregnancy-associated complications. This investigation aimed to map the temporal dynamics and forecast the future incidence of PUD in this demographic to inform targeted prevention and control initiatives. Methods:This analysis drew on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, extracting data on PUD incidence and mortality across seven age groups (15-49 years) in WCBA. Age-standardized incidence and mortality rates were calculated using the direct method of age standardization. Temporal trends from 1992 to 2021 were analyzed using joinpoint regression. The study further employed age-period-cohort analysis to discriminate the effects of these variables on incidence and mortality, and frontier analysis to evaluate potential reductions in burden by country based on developmental status. Nordpred modeling was used to project epidemiological trends up to 2044. Results:In 2021, the global age-standardized incidence rates (ASIR) and death rates (ASDR) for PUD among WCBA were 24.18 per 100,000 (95% CI: 14.72-36.38) and 0.54 per 100,000 (95% CI: 0.42-0.66), respectively. The highest incidence rates were observed in Oceania, while the greatest mortality rates were recorded in South Asia. Over the period from 1992 to 2021, global age-standardized mortality rates showed a significant decline. Conversely, after an initial drop, age-standardized incidence rates began to rise, with considerable regional and country-specific variation. This increase was particularly marked in regions with high Socio-demographic Index (SDI). Frontier analyses indicate that countries or regions in the middle SDI quintiles possess significant untapped potential to enhance both access to and quality of healthcare. Despite predictions of declining age-standardized incidence and mortality rates, total case numbers are expected to continue rising modestly through 2044. Conclusions:The study underscores substantial global disparities in PUD trends in WCBA, with increasing case numbers and regional inequalities. The findings highlight the need for focused attention on high SDI regions and older WCBA cohorts to refine disease management and prevention strategies, aiding in the mitigation of PUD's public health impact.

Although significant progressions in antiviral studies of IFNβ have been demonstrated, the role of the proteasome in modulating cross-talk between TBK1-IFNβ signaling and viral replication during viral infection is not fully elucidated. Here, we discover that deficiency of REGγ, a proteasome activator, significantly reduces IFNβ production and increases viral replications in mice, leading to increased mortality in virus infection models. Our mechanistic study indicates that REGγ interacts with and degrades the protein phosphatase subunit Protein Phosphatase 2 Catalytic Subunit Beta (PPP2CB). This degradation disrupts the dephosphorylation of TBK1 and its interaction with IRF3, resulting in the activation of IFNβ-mediated antiviral signaling. In response to viral infection, up-regulation of REGγ in macrophages accelerates the degradation of PPP2CB, which increases the activation of TBK1-IRF3-IFNβ axis and thereby restricts viral replications and pathology. Interestingly, IFNβ enhances REGγ expression in viral infection, forming a positive feedback regulatory loop. In conclusion, our work demonstrates that REGγ is a positive modulator of IFNβ signaling during antiviral response, highlighting that this procedure is regulated via REGγ degradation of PPP2CB and provides a new insight into the coordination between antiviral response and proteasome activity. Thus, REGγ-proteasome activity and phosphatase PPP2CB may be potential targets in host defense against viruses.

Sepsis is a severe disease and induces skeletal muscle atrophy, which has a significant impact on patients. Moreover, the onset and severity of muscle atrophy can vary across different anatomical regions during sepsis. Our previous study demonstrated that ZBED6 knockout not only promotes skeletal muscle growth under physiological conditions, but also alleviates systemic muscle atrophy during sepsis. However, its region-specific effects on sepsis-induced muscle atrophy have not been analyzed. In this study, we performed RNA sequencing for 54 samples of skeletal muscle from nine different anatomical regions from male ZBED6 knockout and wild-type (WT) minipigs subjected to sepsis. We generated 364.63 Gb of high-quality bulk RNA sequencing data from the skeletal muscle samples (approximately 6.75 Gb per sample). This dataset provided insightful gene expression information to understand the role of ZBED6 in region-specific muscle atrophy during sepsis. In addition, this dataset can be used for heterogeneity analysis between skeletal muscle tissues from multiple species or female pigs.

BACKGROUND:Botulinum toxin type A is widely used to block acetylcholine release in the treatment of chronic sialorrhea, muscle spasticity, and dystonia. We aim to develop a user-friendly method for detecting cases of medical botulinum toxin poisoning. METHODS:The mice poisoning model was established by injecting or gavage with Botulax®, and the poisoning dose and symptoms were observed. The residual levels of toxin in poisoned mice were detected by high-resolution mass spectrometry and sandwich ELISA, respectively. RESULTS:Two hours after poisoning, no residual botulinum toxin was found by mass spectrometry (MS) under our specific untargeted workflow and sample preparation conditions, but ELISA detected residual toxin in various tissues of mice. Among them, the muscle tissue had the highest level. There is no noticeable difference in the levels of toxin residues in the same organs of mice, regardless of the route of poisoning. The sandwich ELISA method is user-friendly for detecting medical botulinum toxin poisoning. The presence of toxin residues can be detected in various tissues two hours after exposure, with muscle being the optimal sampling tissue. CONCLUSIONS:Our research indicates that under specific sample preparation, chromatographic separation, and untargeted detection conditions, mass spectrometry may not be effective for detecting Botulinum toxin at concentrations below the ng/ml level. The study demonstrates that ELISA is a sensitive and practical alternative for early detection. Positive results can be detected within 2 h of poisoning, especially when taken from muscle tissue.

Intra-abdominal hypertension (IAH) is a common complication in patients with acute pancreatitis (AP) and can lead to multiple organ failure. The efficacy of anticoagulant therapy for IAH in patients with acute pancreatitis is unclear. The objective of this study aimed to investigate the effects of anticoagulant therapy on IAH in patients with acute pancreatitis. A total of 49 AP patients with IAH were included in this retrospective study, with 34 patients in the anticoagulant group and 15 patients in the non-anticoagulant group. The effects of anticoagulant therapy on intra-abdominal pressure, inflammation markers, disease severity, and imaging indices were compared between the two groups. The anticoagulant group had significantly lower intra-abdominal pressure at 60 h of therapy compared to the non-anticoagulant group. In addition, inflammation markers and modified Marshall score were significantly improved in the anticoagulant group after 7 days of therapy. There was no significant difference in imaging indices, length of stay and mortality in hospital between the two groups. No adverse bleeding events or allergic reactions occurred during the treatment period. No significant difference was found in the rate of splanchnic vein thrombosis and portal hypertension between the two groups six months after the onset of the disease. Anticoagulant therapy may be a potential treatment option for IAH in patients with acute pancreatitis.

Age-related hearing impairment is a prevalent condition among the elderly and has been proven associated with cognitive decline. The Chinese Hearing Solution for Improvement of Cognitive Function in Elders - Cohort (CHOICE-C) is a multi-center, prospective cohort designed to explore the link between hearing impairment and cognitive decline. This paper outlines the recruitment, quality control, and data management processes of CHOICE-C study, presenting baseline and first-year follow-up results Recruitment was conducted via routine physical exams at community health centers, along with community outreach and social media campaigns. Participants were instructed to complete a questionnaire covering demographic details, hearing history and symptoms, as well as Mini-Mental State Examination (MMSE) for cognitive assessment. A battery of audiological assessments were performed, including acoustic immittance, pure-tone audiometry, and Speech-in-Quiet Test (SIQT). And multi-stage quality control measures were implemented to ensure the reliability and accuracy of the collected data From May 2021 to September 2024, 18,982 elderly aged over 60 years old were recruited. After exclusion of individuals with missing questionnaire or audio-metric data, 18,714 participants were retained (mean age: 69.6± 6.26 yrs; 56% female). 53.3% of baseline participants have completed the first follow-up. Among the participants, 73% have hearing impairment with a better-ear pure tone average (BPTA) above 20 dB HL. Compared to individuals with normal hearing, they were more likely to be older, male, less educated, to report tinnitus, and to exhibit lower MMSE scores. We found that alcohol consumption (OR=1.28, 95% CI 1.03-1.58) and self-reported hearing impairment (OR=1.21, 95% CI 1.06-1.40) were associated with improved hearing and cognition when setting group as reference with constant/decreased hearing and constant cognitive level. Approximately 5–17.3% of questionnaire interviews and 5% of audiometric evaluations were audited separately. 268 samples (1.41%) were excluded due to missing data, primarily resulting from prolonged waiting times or participants being unable to complete the full test Alcohol consumption and self-reported hearing impairment were linked to improvements in hearing and cognition, while age and smoking were risk factors. Data management implementation highlighted the necessity of multi-stage quality control measures