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Abstract Cirrhosis represents a significant global health challenge, characterized by high morbidity and mortality rates that severely impact human health. Timely and precise prognostic assessments of liver cirrhosis are crucial for improving patient outcomes and reducing mortality rates as they enable physicians to identify high-risk patients and implement early interventions. This paper features a thorough literature review on the prognostic assessment of liver cirrhosis, aiming to summarize and delineate the present status and constraints associated with the application of traditional prognostic tools in clinical settings. Among these tools, the Child–Pugh and Model for End-Stage Liver Disease (MELD) scoring systems are predominantly utilized. However, their accuracy varies significantly. These systems are generally suitable for broad assessments but lack condition-specific applicability and fail to capture the risks associated with dynamic changes in patient conditions. Future research in this field is poised for deep exploration into the integration of artificial intelligence (AI) with routine clinical and multi-omics data in patients with cirrhosis. The goal is to transition from static, unimodal assessment models to dynamic, multimodal frameworks. Such advancements will not only improve the precision of prognostic tools but also facilitate personalized medicine approaches, potentially revolutionizing clinical outcomes.

Abstract Background The impact of liver fibrosis on the clinical outcomes of patients with sepsis-induced coagulopathy (SIC) is not well understood. This study aimed to evaluate the association between liver fibrosis scores and in-hospital mortality in SIC patients. Methods In this retrospective observational cohort study, data were collected from patients diagnosed with sepsis and admitted to the ICU at the First Affiliated Hospital of Wenzhou Medical University between January 2017 and December 2023. Liver fibrosis was evaluated using three scores: Fibrosis-4 (Fib-4), Aspartate Aminotransferase–to–Platelet Ratio Index (APRI), and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Patients were divided into tertiles according to their liver fibrosis scores, and the primary outcome was in-hospital mortality. Multivariable logistic regression and restricted cubic spline regression analyses were used to assess associations, complemented by sensitivity analyses through subgroup evaluations. Results The cohort included 948 patients diagnosed with SIC with an in-hospital mortality of 26.16%. Multivariate logistic regression analysis revealed a significant association between higher liver fibrosis scores and increased in-hospital mortality. Specifically, patients in the highest tertile of Fib-4, APRI, and NFS scores had significantly higher odds of mortality (FIB-4: OR 3.62, 95% CI 1.03–12.69; APRI: OR 2.16, 95% CI 0.88–5.30; NFS: OR 6.80, 95% CI 2.11–21.93) compared to those in the lowest tertile. The restricted cubic spline regression model showed a linear increase in the risk of in-hospital mortality with increasing liver fibrosis score. Sensitivity analysis confirmed the consistency and stability of the results across the different subgroups. Conclusion Our study suggests that elevated liver fibrosis scores, particularly Fib-4 and NFS, are associated with higher in-hospital mortality in SIC patients. Further research, especially larger prospective studies, are needed to validate these findings.

Abstract Background Factor XI (FXI) deficiency is an autosomal hemorrhagic disorder characterized by reduced plasma FXI levels. Multiple ancestral variants in the F11 gene have been identified in Ashkenazi Jews and other selected European populations. However, there are few reports of predominant variants in Chinese and/or East Asian populations. The aim of this study is to characterize the genotypes and phenotypes of FXI deficiency and identify the predominant variants. Results Of the 41 FXI-deficient patients, 39 exhibited severe FXI defects, considerably more than those with partial defects. The APTT levels showed a negative correlation with FXI activity levels (coefficient=-0.584, P

Abstract Background In recent years, observational studies have been conducted to investigate the potential impact of vitamins on sepsis. However, many of these studies have produced inconsistent results. Our Mendelian randomization (MR) study aims to evaluate the causality between vitamins and sepsis from a genetic perspective. Methods Our MR study was designed following the STROBE-MR guidelines. Genetic instrumental variables for vitamins including folate, vitamin B12, B6, A (Retinol), C, D, and K were obtained from previous genome-wide association studies (GWAS) and MR studies. Five different sepsis severity levels were included in the analysis. The genetic instrumental variables were screened for potential confounders using PhenoScanner V2. MR analysis was performed using MR-egger, inverse-variance weighted multiplicative random effects (IVW-RE), inverse-variance weighted multiplicative fixed-effects (IVW-FE), and wald ratio methods to assess the relationship between vitamins and sepsis. Sensitivity analysis was performed using the MR-egger_intercept method, and the MR-PRESSO package and Cochran’s Q test were used to evaluate the heterogeneity of the instrumental variables. Results Our MR study found no statistically significant association between vitamins and sepsis risk, regardless of the type of vitamin (P-value > 0.05). The odds ratios (ORs) for folate, vitamin B6, vitamin B12, vitamin A, vitamin D, vitamin K, and vitamin C were 1.164 (95% CI: 0.895–1.514), 0.987 (95% CI: 0.969–1.005), 0.975 (95% CI: 0.914–1.041), 0.993 (95% CI: 0.797–1.238), 0.861 (95% CI: 0.522–1.42), 0.955 (95% CI: 0.86–1.059), and 1.049 (95% CI: 0.911–1.208), respectively. Similar results were observed in subgroups of different sepsis severity levels. Conclusions Our MR study found no evidence of a causal association between vitamins and sepsis risk from a genetic perspective. Further randomized controlled trials are necessary to confirm these results.

Abstract Background This study aimed to explore the association between the triglyceride-glucose (TyG) index and the risk of in-hospital mortality in critically ill patients with sepsis. Methods This was a retrospective observational cohort study and data were obtained from the Medical Information Mart for Intensive Care-IV (MIMIC IV2.2) database. The participants were grouped into three groups according to the TyG index tertiles. The primary outcome was in-hospital all-cause mortality. Multivariable logistics proportional regression analysis and restricted cubic spline regression was used to evaluate the association between the TyG index and in-hospital mortality in patients with sepsis. In sensitivity analysis, the feature importance of the TyG index was initially determined using machine learning algorithms and subgroup analysis based on different subgroups was also performed. Results 1,257 patients (56.88% men) were included in the study. The in-hospital, 28-day and intensive care unit (ICU) mortality were 21.40%, 26.17%, and 15.43% respectively. Multivariate logistics regression analysis showed that the TyG index was independently associated with an elevated risk of in-hospital mortality (OR 1.440 [95% CI 1.106–1.875]; P = 0.00673), 28-day mortality (OR 1.391; [95% CI 1.52–1.678]; P = 0.01414) and ICU mortality (OR 1.597; [95% CI 1.188–2.147]; P = 0.00266). The restricted cubic spline regression model revealed that the risks of in-hospital, 28-day, and ICU mortality increased linearly with increasing TyG index. Sensitivity analysis indicate that the effect size and direction in different subgroups are consistent, the results is stability. Additionally, the machine learning results suggest that TyG index is an important feature for the outcomes of sepsis. Conclusion Our study indicates that a high TyG index is associated with an increased in-hospital mortality in critically ill sepsis patients. Larger prospective studies are required to confirm these findings.

Abstract Background Sepsis is still a major public health concern and a medical emergency due to its high morbidity and mortality. Accurate and timely etiology diagnosis is crucial for sepsis management. As an emerging rapid and sensitive pathogen detection tool, digital droplet PCR (ddPCR) has shown promising potential in rapid identification of pathogens and antimicrobial resistance genes. However, the diagnostic value and clinical impact of ddPCR tests remains to be studied in patients with suspected sepsis. PROGRESS trial is aimed to evaluate the clinical effectiveness of a novel ddPCR assay compared with standard practice. Methods PROGRESS is a multicenter, open-label, pragmatic randomized controlled trial (pRCT) set in ten hospitals, including departments of infectious disease and intensive care units. In this study, a total of 2292 patients with suspected sepsis will be randomly assigned to two arms: the ddPCR group and the control group with a ratio of 3:1. The primary outcome is the diagnostic efficacy, that is, the sensitivity and specificity of the ddPCR assay compared with the synchronous blood culture. Secondary outcomes include the mortality rates and the mean Sequential Organ Failure Assessment (SOFA) score at follow-up time points, the length of stay in the hospital, the time to directed antimicrobial therapy, duration of broad-spectrum antibiotic use, and the EQ-5D-5L score on day 90. Discussion It is the first multicenter pragmatic RCT to explore the diagnostic efficacy and clinical impact of the ddPCR assay in patients with suspected sepsis, taking advantage of both RCT’s ability to establish causality and the feasibility of pragmatic approaches in real-world studies (RWS). This trial will help us to get a comprehensive view of the assay’s capacity for precise diagnosis and treatment of sepsis. It has the potential to monitor the pathogen load change and to guide the antimicrobial therapy, making a beneficial impact on the prognosis of sepsis patients. Trial registration: ClinicalTrial.gov, NCT05190861. Registered January 13, 2022—‘Retrospectively registered’, https://clinicaltrials.gov/ct2/show/NCT05190861 .

Abstract Background and objectives The clinical and pathological impact factors for renal function recovery in acute kidney injury (AKI) on the progression of renal function in primary membranous nephropathy (PMN) with AKI patients have not yet been reported, we sought to investigate the factors that may influence renal function recovery and develop a nomogram model for predicting renal function recovery in PMN with AKI patients. Methods Two PMN with AKI cohorts from the Nephrology Department, the First Affiliated Hospital of Wenzhou Medical University during 2012–2018 and 2019–2020 were included, i.e., a derivation cohort during 2012–2018 and a validation cohort during 2019–2020. Clinical characteristics and renal pathological features were obtained. The outcome measurement was the recovery of renal function within 12 months. Lasso regression was used for clinical and pathological features selection. Prediction model was built and nomogram was plotted. Model evaluations including calibration curves were performed. Result Renal function recovery was found in 72 of 124 (58.1%) patients and 41 of 72 (56.9%) patients in the derivation and validation cohorts, respectively. The prognostic nomogram model included determinants of sex, age, the comorbidity of hypertensive nephropathy, the stage of glomerular basement membrane and diuretic treatment with a reasonable concordance index of 0.773 (95%CI,0.716–0.830) in the derivation cohort and 0.773 (95%CI, 0.693–0.853) in the validation cohort. Diuretic use was a significant impact factor with decrease of renal function recovery in PMN with AKI patients. Conclusion The predictive nomogram model provides useful prognostic tool for renal function recovery in PMN patients with AKI.

Abstract Background Facilitating the primary health care (PHC) system and maintaining people’s reasonable healthcare-seeking behavior are key to establishing a sustainable healthcare system. China has employed a multitiered copayment system/medical insurance differentiated payment policies to incentivize the public to utilize PHC services through its hierarchical medical care system; however, most people still prefer visiting tertiary care hospitals. We question whether the quality gap in healthcare services reduces the effect of the multitiered copayment system, which is considered an important factor in the lack of reform in the Chinese healthcare system. Thus, we explore the effect and influencing factors of the multitiered copayment system that drives primary healthcare-seeking behavior under the current situation with a large quality gap. We also consider the hypothetical situation of a reduced gap in the future. Methods This study used the hypothetical quality improvement scenario to elicit people’s hypothetical behaviors, and a multistage stratified cluster random sampling method. This preliminary study was conducted in 2016 using 1829 individuals from four regions of Wenzhou in Zhejiang Province: Ouhai, Ruian, Yongjia, and Taishun. A descriptive statistical analysis, chi-square analysis, Fisher’s exact test, and multinomial logistic regression model were performed to introduce the effect of the multitiered copayment system, and to explore the factors affecting the selection of PHC institutions at pre- and post-change phases. Result The results show that compared with the large quality gap phase, the number of respondents who believed the multitiered copayment system had an effect on their selection of PHC institutions after the equalization of healthcare services quality increased threefold (from 14.0% to 50.8%). Moreover, the main determinants in people’s selection of PHC institutions changed from age and needs variables (self-rated health status) to age, needs variables (self-rated health status) and enabling variables (distance to a medical care facility). Conclusion The results indicate limited initial effects of the multitiered copayment system. However, they become more pronounced after the equalization of healthcare services quality. This study confirms that changes in the quality gap in healthcare services influence the effect of the multitiered copayment system. Hence, reducing this gap can help achieve the intended outcome of the tiered healthcare insurance schedule.

Abstract Background Albumin is the primary body protein, which can predict the poor prognosis of several critical diseases. However, there are a few scientific studies on the relationship between albumin and the prognosis of dialysis patients. This study aims to explore the impact of hypoalbuminemia on the prognosis of critically ill patients with acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). Methods This was a secondary study. Clinical, biochemical, and 28-day and 90-day mortality rates for critical patients with AKI who received CRRT between 2009 and 2016 were searched from the database to determine the effect of hypoalbuminemia on poor outcomes by univariate, multivariate, smooth curve fitting, and subgroup analysis. Results A total of 837 participants were enrolled in this study. Multivariate Cox proportional hazard regression analysis showed that hypoalbuminemia was associated with both 28-day and 90-day mortality risks after full adjustment for confounding variables, with an adjusted hazard ratio (95% confidence interval) of 0.63 (0.50–0.80) and 0.63 (0.51–0.78), respectively for each 1 g/dL increase of albumin. Stratified analysis showed that hypoalbuminemia was not associated with poor prognosis in oliguria. Conclusion Hypoalbuminemia is associated with poor prognosis in critically ill AKI patients with CRRT; therefore, measuring albumin may be helpful for predicting the prognosis. However, in those with oliguria, this conclusion is not valid.

Abstract Background Acute lung injury (ALI), which is induced by numerous pathogenic factors, especially sepsis, can generate alveolar damage, pulmonary edema and vascular hyper-permeability ultimately leading to severe hypoxemia. Fibroblast growth factor-2 (FGF2) is an important member of the FGF family associated with endothelial cell migration and proliferation, and injury repairment. Here, we conducted this study aiming to evaluate the therapeutic effect of FGF2 in sepsis-induced ALI. Methods Recombinant FGF2 was abdominally injected into septic mice induced by cecal ligation and puncture (CLP), and then the inflammatory factors of lung tissue, vascular permeability and lung injury-related indicators based on protein levels and gene expression were detected. In vitro, human pulmonary microvascular endothelial cells (HPMEC) and mouse peritoneal macrophages (PMs) were challenged by lipopolysaccharides (LPS) with or without FGF2 administration in different groups, and then changes in inflammation indicators and cell permeability ability were tested. Results The results revealed that FGF2 treatment reduced inflammation response, attenuated pulmonary capillary leakage, alleviated lung injury and improved survival in septic mice. The endothelial injury and macrophages inflammation induced by LPS were inhibited by FGF2 administration via AKT/P38/NF-κB signaling pathways. Conclusion These findings indicated a therapeutic role of FGF2 in ALI through ameliorating capillary leakage and inflammation.

Abstract Background Accumulation of iron is associated with oxidative stress, inflammation, and regulated cell death processes that contribute to the development of acute kidney injury (AKI). We aimed to investigate the association between serum iron levels and prognosis in intensive care unit (ICU) patients with AKI. Methods A total of 483 patients with AKI defined as per the Kidney Disease: Improving Global Guidelines were included in this retrospective study. The data was extracted from the single-centre Medical Information Mart for Intensive Care III database. AKI patients with serum iron parameters measured upon ICU admission were included and divided into two groups (low group and high group). The prognostic value of serum iron was analysed using univariate and multivariate Cox regression analysis. Results The optimal cut-off value for serum iron was calculated to be 60 μg/dl. Univariable Cox regression analysis showed that serum iron levels were significantly correlated with prognosis of AKI patients. After adjusting for possible confounding variables, serum iron levels higher than 60 μg/dl were associated with increases in 28-day (hazard [HR] 1.832; P

Abstract Background Sepsis is an infection-induced aggressive and life-threatening organ dysfunction with high morbidity and mortality worldwide. Infection-associated inflammation and coagulation promote the progression of adverse outcomes in sepsis. Here, we report that phospho-Tyr705 of STAT3 (pY-STAT3), not total STAT3, contributes to systemic inflammation and coagulopathy in sepsis. Methods Cecal ligation and puncture (CLP)-induced septic mice were treated with BP-1-102, Napabucasin, or vehicle control respectively and then assessed for systemic inflammation, coagulation response, lung function and survival. Human pulmonary microvascular endothelial cells (HPMECs) and Raw264.7 cells were exposed to lipopolysaccharide (LPS) with pharmacological or genetic inhibition of pY-STAT3. Cells were assessed for inflammatory and coagulant factor expression, cell function and signaling. Results Pharmacological inhibition of pY-STAT3 expression by BP-1-102 reduced the proinflammatory factors, suppressed coagulation activation, attenuated lung injury, alleviated vascular leakage and improved the survival rate in septic mice. Pharmacological or genetic inhibition of pY-STAT3 diminished LPS-induced cytokine production in macrophages and protected pulmonary endothelial cells via the IL-6/JAK2/STAT3, NF-κB and MAPK signaling pathways. Moreover, the increase in procoagulant indicators induced by sepsis such as tissue factor (TF), the thrombin-antithrombin complex (TAT) and D-Dimer were down-regulated by pY-STAT3 inhibition. Conclusions Our results revealed a therapeutic role of pY-STAT3 in modulating the inflammatory response and defective coagulation during sepsis. Video Abstract

Abstract Background The long-term predictive ability of acute kidney injury (AKI) classification based on “Kidney Disease: Improving Global Outcomes”(KDIGO) AKI diagnosis criteria has not been clinically validated in diffuse proliferative lupus nephritis (DPLN) patients with AKI. Our objective was to assess the long-term predictive value of KDIGO AKI classification in DPLN patients with AKI. Methods Retrospective cohort study was conducted by reviewing medical records of biopsy-proven DPLN patients with AKI from the First Affiliated Hospital of Wenzhou Medical University between Jan 1, 2000 and Dec 31, 2014. Multivariate Cox regression and survival analysis were performed. Results One hundred sixty-seven DPLN patients were enrolled,82(49%) patients were normal renal function (No AKI), 40(24%) patients entered AKI-1 stage (AKI-1), 26(16%) patients entered AKI-2 stage (AKI-2) and 19(16%) patients entered AKI-3 stage (AKI-3). The mean follow-up of all patients was 5.1 ± 3.8 years. The patient survival without ESRD of all patients was 86% at 5 years and 79% at 10 years. The patient survival rate without ESRD at 10 yr was 94.5% for No AKI patients, 81.8% for AKI-1 patients, 44.9% for AKI-2 patients and 14.6% for AKI-3 patients. The area under the ROC curve for KDIGO AKI classification to predict the primary end point was 0.83 (95% CI: 0.73–0.93) (P

Abstract Background Sepsis is a major challenge in critical care and is associated with high mortality. Current management of sepsis and septic shock remains mainly supportive. Both basic and clinical research has shown that ulinastatin can improve the prognosis of sepsis. The aim of this trial is to evaluate the efficacy and safety profiles of ulinastatin compared with placebo. Methods/design In this multi-center, double-blind, randomized placebo-controlled trial we are recruiting a total of 348 subjects meeting “The Third International Consensus Definitions for Sepsis and Septic Shock” (Sepsis-3). Subjects will be randomized (1:1) to receive ulinastatin 400,000 IU three times a day for 10 days or matching placebo and usual care simultaneously. The primary outcome is 28-day all-cause mortality. Adverse events and serious adverse events will be monitored closely. Discussion ADJUST is a large, multi-center, double-blind, randomized, parallel-group, placebo-controlled trial of ulinastatin in mainland China and is well-designed on the basis of previous studies. The results of this trial may help to provide evidence-based recommendations for treatment of sepsis. Trial registration ClinicalTrials.gov, ID: NCT02647554. First registered on 27 December 2015, and last verified in December of 2016. Protocol version: 2.1, verified on 19 July 2016.

Abstract Background The six-minute walk test (6MWT) is a safe, simple, inexpensive tool for evaluating the functional exercise capacity. However, there is a lack of standard reference equations for the six-minute walk distance (6MWD) in the healthy Chinese Han population with an age of 18–30 years. The aims of the present study were as follows: 1) to measure the anthropometric data and the walking distance in a sample of healthy Chinese Han population, aged 18–30 years; 2) to construct reference equations for the 6MWD; 3) to compare the measured 6MWD of our cohort with previously published equations. Methods The anthropometric data, demographic, lung function and the walking distance of Chinese Han population, aged 18–30 years, were prospectively measured using a standardized protocol. Informed consent was obtained from each participant and the approval was obtained from the ethics committee of Wenzhou People’s Hospital. The 6MWT was performed twice and the longer 6MWD was used for further analysis. Results A total of 355 subjects (176 female and 179 male) completed the 6MWT, and the average walking distance was 627.3 ± 52.88 m. The walking distance was achieved by females compared with males (607.4 ± 51.00 m vs. 646.9 ± 47.15 m; p