Sarcopenia is an age-related syndrome characterized by the progressive loss of skeletal muscle mass, strength, and function. It is associated with an increased risk of falls, disability, and mortality, as well as a significant healthcare burden. Traditional assessment of sarcopenia relies on imaging techniques and physical function tests, which have important limitations, including operational complexity, difficulty in early identification, and inability to reflect underlying molecular mechanisms. The emergence of candidate biomarkers—including muscle-specific factors, inflammation-related proteins, non-coding RNAs, and nutritional metabolites—has enabled a more precise elucidation of the pathophysiological mechanisms of the disease across multiple dimensions, such as protein homeostasis, chronic inflammation, post-transcriptional regulation, and energy metabolism. These advances provide new avenues for early identification, risk stratification, identification of disease subtypes, and the development of personalized intervention strategies. This article reviews the potential applications and current challenges of these candidate biomarkers in both clinical practice and research on sarcopenia.

Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection and remains a major global health challenge because of its high morbidity, mortality, and limited targeted therapeutic options. Accumulating evidence suggests that bile acids (BAs), endogenous metabolites synthesized in the liver and modified by the gut microbiota, are involved in inflammation, barrier integrity, and metabolic homeostasis. Sepsis is associated with alterations in multiple aspects of BA homeostasis, including hepatic synthesis, transporter activity, microbial biotransformation, and enterohepatic circulation. These alterations may influence hepatic function, gut barrier integrity, and immune responses, although their precise role in sepsis progression remains incompletely understood. This review summarizes current advances in BA biology relevant to sepsis, discusses the interactions between BA dysregulation and the liver–gut–microbiota–immune axis, and evaluates the potential and current limitations of BA-related biomarkers and therapeutic strategies. Particular emphasis is placed on unresolved issues, including disease heterogeneity, causality, and clinical translation. By synthesizing current evidence and knowledge gaps, this review provides an updated perspective on BA dysregulation within the broader immunometabolic landscape of sepsis and highlights priorities for future research.

This study aims to explore the effect of furosemide on the prognosis of patients with intra-abdominal hypertension (IAH). A retrospective cohort study was conducted utilizing data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The analysis encompassed adult patients diagnosed with intra-abdominal hypertension. The exposure factor in this study was defined as the administration of furosemide during the intensive care unit (ICU) stay. The primary outcome measured was all-cause mortality at 28 days, while the secondary outcomes included all-cause mortality at 7 days, 90 days, and 180 days. Both propensity score matching (PSM) and COX multivariate regression analysis were employed to adjust for potential confounding variables.​ A total of 859 critically ill patients with IAH were enrolled, with 534 receiving furosemide and 325 not. After PSM, mortality was significantly higher in the non-furosemide group across all time points (7 days: 6.7

The prognosis of patients with a concomitance of severe traumatic brain injury (sTBI) and acute respiratory distress syndrome (ARDS) is poor, and early identification of such patients can provide diagnostic and therapeutic assistance for clinical treatment. However, few studies have been conducted to identify the risk of ARDS in patients with sTBI. This study aimed to construct a risk prediction model for ARDS in patients with sTBI and evaluate its efficacy. From 2016 to 2023, 502 patients diagnosed with sTBI were selected from the Affiliated Hospital of Yangzhou University. All participants were randomly allocated to either the training or validation group. Feature selection for constructing the prediction model and developing a nomogram was carried out using the least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression analysis. The effectiveness and clinical relevance of the model were evaluated using receiver operating characteristic (ROC) curves, the area under the ROC curve (AUC), calibration curves, and the decision curve analysis (DCA). The study found that 32.9

Intensive care unit-acquired weakness (ICU-AW) is a common complication in critically ill patients, associated with multiple risk factors and significantly impacting long-term patient outcomes. Currently, early diagnosis remains a key challenge in managing ICU-AW: clinical scales are limited by subjectivity, while muscle ultrasound and emerging biomarkers (such as the creatinine/cystatin C ratio, miR-451a, and MuRF1), though showing potential for early identification, have not yet been widely adopted in clinical practice. In terms of management, prevention is paramount. The ABCDEF bundle emphasizes early mobilization (initiated within 24-72 hours), while nutritional strategies targeting molecular pathways (such as HMB and ω-3 fatty acids) help regulate protein metabolism balance. Novel targeted therapies (eg, the myostatin inhibitor Bimagrumab) have demonstrated potential to increase muscle mass in clinical trials. Currently, early diagnosis remains the critical barrier. This review aims to synthesize the latest evidence on the risk factors, diagnostic challenges, and management strategies for ICU-AW, providing insights for clinical practice. It also underscores the need for future research to focus on developing highly sensitive diagnostic tools, optimizing preventive strategies, and promoting the clinical translation of targeted therapies. Ultimately, this will help establish a comprehensive and precise multi-level intervention framework to improve patient outcomes.

BackgroundSepsis is highly heterogeneous. Therefore, identifying biomarkers that can stratify patients with sepsis into more homogeneous cohorts to develop individualized treatment and care measures for patients and carry out early intervention to reduce the risk of death and improve the prognosis of patients has become a current research hotspot.MethodsUsing the MIMIC-IV database, we analyzed data from 1,575 adult patients with sepsis. Serum lactate levels were measured once daily for 5 consecutive days after admission. The GBTM model was used to stratify the risk of sepsis and explore the relationships between different lactate trajectories and 28-day mortality in septic patients.ResultsWe report a new method for identifying subphenotypes of sepsis patients based on lactate trajectories. Through group-based trajectory modeling, we identified and validated five groups of sepsis patients with different lactate trajectories, namely, “Low-stable group,” “low-slowly declining group,” “high-rapidly decline group,” “Moderate-slow declining group,” and “high-slow decline group.” The relationships between sepsis patients with different lactate trajectories and 28-day mortality were explored. Among them, patients with a “Low-stable group” had the lowest in-hospital 28-day mortality. Patients with a “high-slow decline group” had the highest 28-day mortality.ConclusionIn this study, different subtypes of sepsis were successfully identified by analyzing lactate trajectories. Combined with the dynamic changes in lactate levels, the GBTM model was used to stratify patients according to their risk of sepsis. This model provides a theoretical basis for clinicians to evaluate the prognosis of patients using the lactate change trajectory.

Background Previously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel clinical phenotypes in ARDS using trajectories of fluid balance, to test whether phenotypes respond differently to different treatment, and to develop a simplified model for phenotype identification. Methods FACTT (conservative vs liberal fluid management) trial was classified as a development cohort, joint latent class mixed models (JLCMMs) were employed to identify trajectories of fluid balance. Heterogeneity of treatment effect (HTE) for fluid management strategy across phenotypes was investigated. We also constructed a parsimonious probabilistic model using baseline data to predict the fluid trajectories in the development cohort. The trajectory groups and the probabilistic model were externally validated in EDEN (initial trophic vs full enteral feeding) trial. Results Using JLCMM, we identified two trajectory groups in the development cohort: Class 1 (n = 758, 76.4% of the cohort) had an early positive fluid balance, but achieved negative fluid balance rapidly, and Class 2 (n = 234, 24.6% of the cohort) was characterized by persistent positive fluid balance. Compared to Class 1 patients, patients in Class 2 had significantly higher 60-day mortality (53.5% vs. 17.8%, p < 0.001), and fewer ventilator-free days (0 vs. 20, p < 0.001). A significant HTE between phenotypes and fluid management strategies was observed in the FACTT. An 8-variables model was derived for phenotype assignment. Conclusions We identified and validated two novel clinical trajectories for ARDS patients, with both prognostic and predictive enrichment. The trajectories of ARDS can be identified with simple classifier models.

Purpose:Septic cardiomyopathy (SCM) is a significant global public health concern characterized by substantial morbidity and mortality, which has not been improved for decades due to lack of early diagnosis and effective therapies. This study aimed to identify hub biomarkers in SCM and explore their potential mechanisms. Methods:We utilized the GSE53007 and GSE207363 datasets for transcriptome analysis of normal and SCM mice. Hub biomarkers were identified through a protein-protein interaction (PPI) network and validated using LPS-treated C57/BL6 mice. Functional enrichment analysis was performed to uncover relevant signaling pathways, while single-cell RNA sequencing was used to examine key genes and regulatory mechanisms associated with SCM. Results:A total of 374 differentially expressed genes (DEGs) were identified, with 268 genes up-regulated and 106 genes down-regulated. Functional enrichment highlighted chemokine activity and receptor binding, with KEGG pathways revealing significant involvement of the TNF and IL-7 signaling pathways. Deterioration of cardiac function, elevated inflammatory markers such as IL-1β, IL-6, and increased cardiac injury biomarkers such as cTnI indicated the successful establishment of our SCM model. Subsequently, qPCR was conducted to validate the expression of the top 10 genes, through which we identified Cd40, Tlr2, Cxcl10, Ccl5, Cxcl1, Cd14, Gbp2, Ifit2, and Vegfa as key biomarkers. Single-cell sequencing indicated increased neutrophil and macrophage populations, with decreased B cells and cardiomyocytes. Additionally, transcription regulators Irf1 and Stat1 were found to potentially regulate the expression of Gbp2, Cxcl10, Ccl5, and Cd40, linking SCM to immune response, ferroptosis, pyroptosis, cuproptosis, and m6A RNA methylation modification. Conclusion:This study identified nine hub biomarkers and two transcription regulators associated with SCM. Exploring the connections between SCM and immunity, ferroptosis, pyroptosis, cuproptosis, and m6A RNA methylation might provide insights into the underlying mechanisms. These findings enhanced our understanding of SCM's underlying mechanisms and might pave the way for novel therapeutic strategies to improve clinical outcomes.

IntroductionMyocardial infarction (MI), a leading cause of heart failure, is characterized by the loss of cardiomyocytes, which severely limits the heart’s regenerative capacity. The Hippo pathway, which regulates cell proliferation and apoptosis, presents a therapeutic target for cardiac regeneration. This study explores the efficacy of Lats-IN-1, a LATS1/2 kinase inhibitor targeting the Hippo pathway, as a novel treatment for MI.MethodsUsing male C57BL/6 mice subjected to surgically induced MI, we administered Lats-IN-1 and evaluated the effects on cardiac function, infarct size, cardiomyocyte proliferation, and apoptosis through various assays and echocardiographic assessments.ResultsOur results demonstrate that Lats-IN-1 significantly improves cardiac function, as evidenced by enhanced ejection fraction and reduced ventricular dimensions. Additionally, Lats-IN-1 decreased infarct size and apoptosis rates while promoting cardiomyocyte proliferation. These findings suggest that Lats-IN-1 promotes cardiac repair and regeneration.DiscussionBy modulating the Hippo pathway and reducing apoptosis markers, Lats-IN-1 represents a promising therapeutic strategy for improving outcomes in heart diseases characterized by cardiomyocyte loss. This study highlights the critical role of the Hippo pathway in facilitating cardiac regeneration.

BackgroundSepsis is a heterogeneous syndrome, and enrollment of more homogeneous patients is essential to improve the efficiency of clinical trials. Artificial intelligence (AI) has facilitated the identification of homogeneous subgroups, but how to estimate the uncertainty of the model outputs when applying AI to clinical decision-making remains unknown. ObjectiveWe aimed to design an AI-based model for purposeful patient enrollment, ensuring that a patient with sepsis recruited into a trial would still be persistently ill by the time the proposed therapy could impact patient outcome. We also expected that the model could provide interpretable factors and estimate the uncertainty of the model outputs at a customized confidence level. MethodsIn this retrospective study, 9135 patients with sepsis requiring vasopressor treatment within 24 hours after sepsis onset were enrolled from Beth Israel Deaconess Medical Center. This cohort was used for model development, and 10-fold cross-validation with 50 repeats was used for internal validation. In total, 3743 patients with sepsis from the eICU Collaborative Research Database were used as the external validation cohort. All included patients with sepsis were stratified based on disease progression trajectories: rapid death, recovery, and persistent ill. A total of 148 variables were selected for predicting the 3 trajectories. Four machine learning algorithms with 3 different setups were used. We estimated the uncertainty of the model outputs using conformal prediction (CP). The Shapley Additive Explanations method was used to explain the model. ResultsThe multiclass gradient boosting machine was identified as the best-performing model with good discrimination and calibration performance in both validation cohorts. The mean area under the receiver operating characteristic curve with SD was 0.906 (0.018) for rapid death, 0.843 (0.008) for recovery, and 0.807 (0.010) for persistent ill in the internal validation cohort. In the external validation cohort, the mean area under the receiver operating characteristic curve (SD) was 0.878 (0.003) for rapid death, 0.764 (0.008) for recovery, and 0.696 (0.007) for persistent ill. The maximum norepinephrine equivalence, total urine output, Acute Physiology Score III, mean systolic blood pressure, and the coefficient of variation of oxygen saturation contributed the most. Compared to the model without CP, using the model with CP at a mixed confidence approach reduced overall prediction errors by 27.6% (n=62) and 30.7% (n=412) in the internal and external validation cohorts, respectively, as well as enabled the identification of more potentially persistent ill patients. ConclusionsThe implementation of our model has the potential to reduce heterogeneity and enroll more homogeneous patients in sepsis clinical trials. The use of CP for estimating the uncertainty of the model outputs allows for a more comprehensive understanding of the model’s reliability and assists in making informed decisions based on the predicted outcomes.

Background: Fufang Yinhua Jiedu (FFYH) granules are recommended for treating coronavirus pneumonia (COVID-19) in China. However, its anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity and clinical efficacy against COVID-19 remain to be confirmed. Aims: Our study aimed to investigate the anti-SARS-CoV-2 effect and potential mechanism of FFYH. Materials and Methods: The activity of FFYH against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was evaluated via cell pathogenic effects, immunoblotting, immunofluorescence staining, and qRT-PCR. The potential mechanism of FFYH against SARS-CoV-2 was investigated by immunoblotting. One head-to-head randomized controlled trial was designed to evaluate the clinical efficacy of FFYH in mild COVID-19. Two hundred patients were randomly recruited to receive either FFYH or LHQW (Lianhua Qingwen) granules. Results: The in vitro results indicated that FFYH effectively inhibited SARS-CoV-2 replication by suppressing CPE and decreasing viral RNA and protein expression. A time-of-drug-addition assay confirmed that FFYH mainly targeted the binding and replication stages of the SARS-CoV-2 life cycle. Mechanistic studies revealed that blocking SARS-CoV-2-triggered autophagy may be the primary mechanism by which FFYH protects against SARS-CoV-2 infection by regulating the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway. Clinical results confirmed that FFYH effectively shortened the recovery time of clinical symptoms and viral nucleic acid negativity, improved abnormal hematology parameters, and controlled excessive cytokine responses in mild COVID-19 patients. Subgroup analysis revealed that FFYH improved the recovery time of clinical symptoms, improved hematological parameters, and controlled excessive cytokine storms to a greater extent in the mild COVID-19 male subgroup, abnormal hematology subgroup, and 32-42-year-old subgroup than in the corresponding LHQW subgroup (P < 0.05). No patients progressed to severe or critical cases. Conclusion: Our results indicate that FFYH not only has good anti-viral activity against SARS-CoV-2 but also has significant efficacy against COVID-19, indicating that FFYH may be a novel complementary option for treating COVID-19.

Amniotic fluid embolism (AFE) is a rare critical and severe obstetric crisis characterized by acute onset, rapid disease progression, and poor maternal prognosis. Although its etiology has been better defined, the pathogenesis is still not completely understood. There are no unified laboratory or clinical diagnostic criteria, and the risk factors of AFE are mostly unavoidable, with the proportion of AFE increasing year by year in most countries. Therefore, early diagnosis and timely and effective treatment of AFE play a decisive role in maternal prognosis and survival. This author mainly reviews the various clinical manifestations and the related treatment strategies of AFE.

目的:探讨急性胰腺炎（acute pancreatitis, AP）合并休克患者的Δ平均动脉压（ΔMAP：院前与早期液体复苏后MAP之间的差值）与急性肾损伤（acute kidney injury, AKI）发生率之间的关系。方法:本研究是一项单中心回顾性观察性研究。收集2015年8月至2021年10月在扬州大学附属医院就诊的AP合并休克的216例患者，依据ΔMAP四分位数分为ΔMAP四分位数第1组（54例）和ΔMAP四分位数第2~4组（162例）；依据是否发生AKI，分为AKI组（148例）和非AKI组（68例）。分析比较两组人口学资料、基础疾病、体重指数(入院24 h内)、临床评分（入院24 h内）、病因、生化指标（入院24 h内）、院前和复苏后MAP、住院前6个月至7天的基线血肌酐水平、住院期间的血肌酐水平、血管活性药物使用、血管加压素使用和液体平衡等临床资料。采用逐步Logistic回归分析AKI的独立危险因素，并计算优势比( OR)。 结果:本研究中，患者男性112例（51.9%）；年龄52（40，62）岁；AKI组与非AKI组患者ΔMAP差异无统计学意义（ P>0.05）；ΔMAP四分位数第1组与第2~4组患者的AKI发生率（53.7% vs. 73.5%）差异有统计学意义（ P<0.05）；逐步Logistic回归分析结果示，ΔMAP四分位数第1组（ OR=0.23，95% CI:0.11~0.51）对AKI发生率有影响（ P<0.05）；高血压亚组分析示基本一致的结果。 结论:ΔMAP四分位数第1组（-25.3~4.0 mmHg）AP患者AKI发生率显著降低；APACHEⅢ评分、SOFA评分、乳酸初始值、院前的MAP、ΔMAP四分位数第1组是AKI发生率的独立危险因素；建议临床医生根据AP患者院前的MAP水平，制定早期液体复苏阶段的个体化目标MAP。

Background: Previous studies have shown that arterial stiffness (AS) was a risk factor for heart failure (HF) in nondiabetic patients. We aimed to analyze this impact in a community-based diabetic population.Methods: Our study excluded those who had HF before brachial-ankle pulse wave velocity (baPWV) measurement and included 9041 participants finally. Subjects were divided into the normal (<14 m/s), intermediate (14-18 m/s), and elevated baPWV groups (>18 m/s) based on baPWV values. Multivariate Cox proportional hazard model was used to analyze the effect of AS on HF risk.Results: During the median follow-up of 4.19 years, 213 patients had HF. The results of Cox model showed that HF risk in the elevated baPWV group was 2.25 times higher than that in the normal baPWV group (95% con-fidence interval [CI]: 1.24-4.11). HF risk increased by 18% (95% CI:1.03-1.35) for every 1 additional standard deviation(SD)of baPWV. Restricted cubic spline results showed statistically significant overall and non-linear associations between AS and HF risk (P < 0.05). The subgroup analysis and sensitivity analysis were consis-tent with that of total population.Conclusions: AS is an independent risk factor for developing HF in the diabetic population, and AS exhibits a dose-response relationship with HF risk.

Date palm (Phoenix dactylifera L.) has a significant role in our daily life due to its diverse nutritional composition and potential health benefits. This study was designed to evaluate the phytochemicals, antioxidant, and antidiarrheal potential of various extracts of Ajwa whole fruit, date palm pit, and flesh. The extracts with the highest phytochemical quantities were further subjected to bio-assay assessment against castor oil-induced diarrhea using different animal models. The results indicated that Ajwa whole fruit extract (AWFE) exhibited higher amount of total phenolic contents (TPC: 36 & PLUSMN; 16 mg/g GAE), total flavonoid contents (TFC: 360 & PLUSMN; 135 mg/g RE), and 2, 2-diphenyl-1-picrylhydrazyl (DPPH: 60 & PLUSMN; 7%) in hydro-ethanolic extracts. In vivo results revealed that Ajwa whole fruit 60% hydro-ethanolic extract at high dose (2000 mg/kg) showed significantly (p < .05) highest protective effect against diarrheal changes in mice. In case of AWFE, the intestinal contents % inhibition was slightly higher (72%) as compared to that of loperamide control (70%). High dose of Ajwa whole (2000 mg/kg) demonstrated less effectiveness (66 & PLUSMN; 11%) in comparison with loperamide (78 & PLUSMN; 8%) regarding % inhibition of fluid accumulation in enteropooling studies. High dose (2000 mg/kg) of Ajwa also reduced intestinal transit time by decreasing the % distance (53 & PLUSMN; 1%) in comparison with loperamide (57 & PLUSMN; 1%). The % inhibition of charcoal meal traveling of AWFE (38 & PLUSMN; 2%) was also significantly higher as compared to loperamide (26 & PLUSMN; 1%). The findings of the current study reveal that AWFE might be consumed as an ingredient in daily food products to counter effect the symptoms of diarrhea.

The increase in heart failure risk in the diabetic population when hypertension and atherosclerosis are both present is still inconclusive. The aim of this study was to explore the effects of hypertension combined with atherosclerosis in diabetic population on the risk of heart failure. We selected 10,711 patients with diabetes who participated in the Kailuan study and completed brachial-ankle pulse wave velocity (baPWV) testing for statistical analysis. The subjects were divided into the non-hypertensive non-atherosclerotic, hypertensive, atherosclerotic, and hypertensive atherosclerotic groups based on their history of hypertension and atherosclerosis. At a median follow-up of 4.15 years, 227 cases of heart failure occurred. Compared with the non-hypertensive non-atherosclerotic group, the multifactorial Cox proportional risk regression model showed that the hazard ratio (HR) for heart failure in the hypertensive atherosclerotic group was 3.08 (95% confidence interval [CI]: 1.32-7.16), whereas the HR decreased to 2.38 (95% CI: 1.01-5.63) after gradual correction of lipid-lowering, glucose-lowering, and antihypertensive drugs. The subgroup analysis and sensitivity analysis were consistent with that of total population. In conclusion, patients with diabetes exposed to both hypertension and atherosclerosis had an increased heart failure risk, which was attenuated by the use of lipid-lowering, glucose-lowering, and antihypertensive drugs.

Objective:To investigate the effect of galactose lectin 3 (Gal-3) on the pathogenesis of atrial fibrillation.Methods:This study adopts a case-control study method. 55 patients with non valvular atrial fibrillation (atrial fibrillation group) admitted to the First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from February to July 2019 were selected, and another 55 healthy individuals who underwent physical examination at our hospital during the same period were selected as the control group. Compare the general data and levels of various laboratory indicators between two groups, including blood routine, fasting blood glucose, blood lipids, liver and kidney function, and plasma Gal-3. Analyze the influencing factors of atrial fibrillation and the predictive value of plasma Gal-3 levels for the onset of atrial fibrillation. The measurement data with normal distribution and the measurement data converted to normal distribution after taking natural logarithm are expressed in xˉ± s. The comparison between the two groups is performed by independent sample t test; The measurement data of non normal distribution is represented by [ M ( Q1, Q3)], and Wilcoxon signed rank sum test is used for inter group comparison; The counting data is represented by examples (%), and the comparison between groups is conducted using χ 2 test. The influencing factors of atrial fibrillation were analyzed using logistic regression analysis. Results:The age, NLR, and blood creatinine levels in the atrial fibrillation group were higher than those in the control group [(71.16±9.17) years vs (60.71±10.11) years, (2.32±0.85) vs (1.74±0.81), (74.18±21.61) μmol/L vs (64.69±18.30) μmol/L, t-values are 5.68, 3.66, 2.48, P-values are <0.001, <0.001, 0.015], total cholesterol, HDL-C, LDL-C Albumin and eGFR water were on average lower than those in the control group [(4.31±1.67) mmol/L vs (5.13±0.78) mmol/L, (0.96±0.21) mmol/L vs (1.21±0.32) mmol/L, (2.35±0.65) mmol/L vs (3.04±0.62) mmol/L, (39.58±3.83) g/L vs (44.66±5.61) g/L, (94.84±29.22) mL/(min·1.73 m 2) vs (111.77±21.51) mL/(min·1.73 m 2)] ,The t-values are 3.30, 4.87, 5.69, 5.54, 3.46, and the P-values are 0.001,<0.001,<0.001,<0.001, 0.001, respectively. The plasma Gal-3 levels in the atrial fibrillation group were higher than those in the control group [(12.79±4.24)] μg/L vs (7.31±2.28) μg/L], the difference was statistically significant ( t=8.43, P<0.001), and the plasma Gal-3 level in the persistent atrial fibrillation group was higher than that in the paroxysmal atrial fibrillation group [(14.03±3.95) μg/L vs (11.51±4.21) μg/L], the difference was statistically significant ( t=2.29, P=0.026). The results of multivariate logistic regression analysis showed that after excluding other factors, Gal-3 remained an independent influencing factor for atrial fibrillation (odds ratio=1.66, 95% confidence interval: 1.29-2.12, P<0.001). Conclusions:Plasma Gal-3 is an influencing factor for the onset of atrial fibrillation. After excluding other factors, Gal-3 remains an independent influencing factor for atrial fibrillation, with an increase of 1 μg/L in Gal-3 increases the risk of atrial fibrillation by 1.66 times.

Ischemia/reperfusion (I/R) injury induces irreversible oxidative stress damage to the cardiac myocytes. Many studies have revealed that propofol alleviates the important organelle-mediated injury from oxidative stress in vitro. However, it remains unclear whether propofol prevents I/R-induced DNA damage in cardiomyocytes. In our study, we established an oxygen glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells and found that propofol decreased reactive oxygen species (ROS) levels and suppressed cell apoptosis induced by OGD/R in H9c2 cells. In addition, propofol significantly reduced the molecular marker of DNA damage and inhibited double-strand breaks of DNA damage induced by OGD/R in H9c2 cells in a dose-dependent manner. Furthermore, we investigated the molecular mechanisms and demonstrated that propofol inhibited forkhead box O 1 (FoxO1) phosphorylation and increased FoxO1 nuclear translocation through inhibition of protein kinase B (Akt) and adenosine 5'-monophosphate-activated protein kinase (AMPK) pathways. The protective effects of propofol against oxidative stress-induced DNA damage were reversed by silencing FoxO1. Taken together, our results suggest that oxidative stress aggravates DNA damage and apoptosis in H9C2 cells, which can be reversed by propofol via FoxO1 nuclear translocation.

OBJECTIVE:Cardiac dysfunction and remodeling are serious complications of sepsis and are the main causes of death in sepsis. RCAN1 is a feedback regulator of cardiac hypertrophy. Here, we aim to investigate the role of RCAN1 in septic cardiomyopathy.METHODS:Mice were randomly divided into control-WT, control-RCAN1-/-, LPS-induced WT and LPS-induced RCAN1-/- groups, some with Midiv-1 or KN93 treatment. The protein levels of RCAN1, p-ERK1/2, NFAT3, Drp1, p-Drp1, p-CaMKII in mouse hearts or cultured cardiomyocytes were determined by Western blotting. Myocardial function was assessed by echocardiography. Cardiac hypertrophy and fibrosis were detected by H&E and Masson's trichrome staining. Mitochondrial morphology was examined by transmission electron microscope. Serum level of LDH was detected by ELISA.RESULTS:Our data show that RCAN1 was downregulated in septic mouse heart and LPS-induced cardiomyocytes. RCAN1-/- mice showed a severe impairment of cardiac function, and increased myocardial hypertrophy and fibrosis. The protein levels of NFAT3 and p-ERK1/2 were significantly increased in the heart tissues of RCAN1-/- mice. Further, RCAN1 deficiency aggravated sepsis-induced cardiac mitochondrial injury as indicated by increased ROS production, pathological fission and the loss of mitochondrial membrane potential. Inhibition of fission with Mdivi-1 reversed LPS-induced cardiac hypertrophy, fibrosis and dysfunction in RCAN1-/- mice. Moreover, RCAN1 depletion promoted mitochondrial translocation of CaMKII, which enhanced fission and septic hypertrophy, while inhibition of CaMKII with KN93 reduced excessive fission, improved LPS-mediated cardiac remodeling and dysfunction in RCAN1-/- mice.CONCLUSIONS:Our finding demonstrated that RCAN1 deficiency aggravated mitochondrial injury and septic cardiomyopathy through activating CaMKII. RCAN1 serves as a novel therapeutic target for treatment of sepsis-related cardiac remodeling and dysfunction.