Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization. The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4–6) in the oseltamivir group compared with 7 days (interquartile range 5–10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure. Thrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion. Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 .

Mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) are increasingly recognized for their therapeutic potential in regenerative medicine, driven by their capabilities in immunomodulation and tissue repair. However, MSCs present risks such as immunogenic responses, malignant transformation, and the potential to transmit infectious pathogens due to their intrinsic proliferative and differentiative abilities. In contrast, MSC-EVs, particularly exosomes (MSC-exosomes, 30–150 nm in diameter), offer a safer therapeutic profile. These acellular vesicles mitigate risks associated with immune rejection and tumorigenesis and are inherently incapable of forming ectopic tissues, thereby enhancing their clinical safety and applicability. This review highlights the therapeutic promise of MSC-exosomes especially focusing on the modulation of miRNA (one of bioactive molecules in MSC-EVs) profiles through various preconditioning strategies such as exposure to hypoxia, chemotherapeutic agents, inflammatory cytokines, and physical stimuli. Such conditioning is shown to optimize their therapeutic potential. Key miRNAs including miR-21, miR-146, miR-125a, miR-126, and miR-181a are particularly noted for their roles in facilitating tissue repair and modulating inflammatory responses. These functionalities position MSC-exosomes as a valuable tool in personalized medicine, particularly in the case of exosome-based interventions. Despite the potential of MSC-EVs, this review also acknowledged the limitations of traditional MSC therapies and advocates for a strategic pivot towards exosome-based modalities to enhance therapeutic outcomes. By discussing recent advances in detail and identifying remaining pitfalls, this review aims to guide future directions in improving the efficacy of MSC-exosome-based therapeutics. Additionally, miRNA variability in MSC-EVs presents challenges due to the diverse roles of miRNAs play in regulating gene expression and cell behavior. The miRNA content of MSC-EVs can be influenced by preconditioning strategies and differences in isolation and purification methods, which may alter the expression profiles of specific miRNAs, contributing to differences in their therapeutic effects.

Introduction: Sepsis associated acute kidney injury (SAKI) is a common complication of sepsis with high incidence and mortality around the world. SAKI characterized by low survival rate, poorlong-term prognosis and quality of life of patients, causes huge economic burden to family and society. A large amount of evidence indicates that early diagnosis and necessary treatment of SAKI can effectively improves the prognosis of patients. However, at present, laboratory indicators for early diagnosis of SAKI are limited. Therefore, understanding the risk factors associated with SAKI is crucial for early prediction of SAKI. Method: The meta-analysis was conducted with PRISMA statement. All studies are collected from PubMed, Web of Science, Cochrane library, Wiley online library and CNKI databases, and all published from the initiation of the database to Feb 11, 2022, were included. Result: A total of 25 studies were included in this meta-analysis, with statistically significant risk factors as follows: diabetes [1.79 (1.43 2.24)], hypotension (MAP < 65 mmHg) [2.25 (1.88 2.70)], coagulation dysfunction [1.14 (1.04 1.24)], liver disease [1.68 (1.28 2.20)], heart disease [1.89 (1.54 3.31)], high APACHEII scores [1.25 (1.02 1.53)], lactic acidosis [1.65 (1.38 1.97)], oliguria [ 1.45 (1.01 2.08), high serum creatinine (> 88 mol/l) [3.84 (2.10 7.04)]. Conclusion: Diabetes, hypotension (MAP < 65 mmHg), coagulation dysfunction, liver disease, heart disease, high APACHEII score, lactic acidosis, oliguria, high serum creatinine are the risk factors of SAKI.

Postoperative delirium (POD) after cardiac surgery correlates with adverse outcomes, increasing healthcare burdens and hindering patient recovery.The triglyceride-glucose (TyG) index, a marker of insulin resistance, shows cardiovascular prognostic value.This study sought to explore the association between the TyG index and the development of POD in patients undergoing cardiac surgery. This multicenter retrospective cohort study included 1,850 patients (MIMIC-IV: n = 1,461; Yuhuangding: n = 389). A four-knot restricted cubic spline (RCS) regression analyzed the nonlinear relationship to determine the TyG threshold. Multivariable logistic regression and propensity score matching (PSM) controlled for baseline differences.Subgroup analyses were conducted. Patients with POD exhibited significantly higher TyG indices compared to non-POD patients (MIMIC-IV cohort: 9.06 vs. 8.83, P < 0.001). Using the optimal threshold derived from RCS regression, participants were stratified into two groups: Q1 (< 8.91) and Q2 (≥ 8.91). Multivariable logistic regression revealed that a TyG index ≥ 8.91 was independently associated with an increased risk of POD (adjusted OR 1.767, 95% CI: 1.406–2.219, P < 0.001). This association remained statistically significant in PSM-adjusted analyses across multiple regression models. These findings were validated in the Yuhuangding Hospital cohort. Subgroup analyses demonstrated significant interaction effects in specific patient populations. This study establishes a robust and independent association between an elevated TyG index and increased risk of POD in cardiac surgery patients, suggesting that the TyG index may serve as a valuable biomarker for identifying patients at risk of postoperative delirium.

Objectives: The evidence connecting polyunsaturated fatty acids (PUFAs) to biliary problems is still highly contested and speculative despite the fact that biliary diseases are common and PUFAs have long been studied for their potential health benefits. This work used Mendelian randomization (MR) techniques in conjunction with genome-wide association study (GWAS) data to clarify the causal relationships between PUFAs and biliary tract diseases. Methods: We compiled data on PUFAs, including Omega -3 fatty acids, Omega -6 fatty acids, and the ratio of Omega -6 to Omega -3 fatty acids (Omega-6:Omega-3), using GWAS. MR was used to examine biliary tract problems (cholecystitis, cholelithiasis, gallbladder cancer, primary biliary cholangitis, primary sclerosing cholangitis, and disorders of gallbladder, biliary tract and pancreas). Single nucleotide polymorphisms significantly associated with PUFAs were selected as instrumental variables to estimate causal effects on biliary tract diseases. The final results were analyzed using five MR analysis techniques. Inverse variance weighting (IVW) was used as the primary outcome. And IVW was utilized in conjunction with the other MR analysis techniques (MR -Egger, weighted median, simple mode, and weighted mode). Additionally, we evaluated heterogeneity and horizontal multiplicity using the MREgger intercept test and Cochrane's Q test, respectively. Finally, to increase the accuracy and precision of the study outcomes, we carried out a number of sensitivity analyses. Results: We found that Omega -3 fatty acids reduced the risk of cholecystitis (OR: 0.851, P = 0.009), cholelithiasis (OR: 0.787, P = 8.76e-5), and disorders of gallbladder, biliary tract and pancreas (OR: 0.842, P = 1.828e-4) but increased the primary biliary cholangitis (OR: 2.220, P = 0.004). There was no significant association between Omega -3 fatty acids and risk of gallbladder cancer (OR: 3.127, P = 0.530) and primary sclerosing cholangitis (OR: 0.919, P = 0.294). Omega -6 fatty acids were associated with a reduced risk of cholecystitis (OR: 0.845, P = 0.040). However, they were not linked to an increased or decreased risk of cholelithiasis (OR: 0.878, P = 0.14), gallbladder cancer (OR: 4.670, P = 0.515), primary sclerosing cholangitis (OR: 0.993, P = 0.962), primary cholestatic biliary cholangitis (OR: 1.404, P = 0.509), or disorders of gallbladder, biliary tract and pancreas. Omega-6:Omega-3 fatty acids were linked to a greater risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas (OR:1.168, P = 0.009, OR:1.191, P = 1.60e-6, and OR:1.160, P = 4.11e-6, respectively). But (OR: 0.315, P = 0.010) was linked to a decreased risk of primary biliary cholangitis. Not linked to risk of primary sclerosing cholangitis (OR: 1.079, P = 0.078) or gallbladder cancer (OR: 0.046, P = 0.402). According to the MR -Egger intercept, our MR examination did not appear to be impacted by any pleiotropy (all P > 0.05). Additionally, sensitivity studies validated the accuracy of the calculated causation. Conclusion: Inconsistent causative relationships between PUFAs and biliary tract diseases were revealed in our investigation. However, Omega -3 fatty acids were found to causally lower the risk of cholecystitis, cholelithiasis, and disorders of gallbladder, biliary tract and pancreas. Omega -3 fatty acids increased the risk of primary biliary cholangitis in a causative way. Omega -3 fatty acids with the risk of gallbladder cancer and primary sclerosing cholangitis did not have any statistically significant relationships. Omega6 fatty acids were not significantly causally connected with the risk of cholelithiasis, gallbladder cancer, primary sclerosing cholangitis, or disorders of gallbladder, biliary tract and pancreas. However, they did play a causative role in lowering the risk of cholecystitis. Omega-6:Omega-3 fatty acids decreased the risk of primary biliary cholangitis but increased the risk of cholecystitis, gallstone disease, and disorders of gallbladder, biliary tract and pancreas. They had no effect on the risk of gallbladder cancer or primary sclerosing cholangitis. Therefore, additional research should be done to examine the probable processes mediating the link between polyunsaturated fatty acids and the risk of biliary tract diseases. (c) 2024 Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.

Objective. Computed tomography (CT) scan is a method to predict the progression and prognosis of COVID-19. It is not sufficient merely to measure the prognosis of COVID-19 without other clinical methods. The purpose of this study was to investigate the association between the CT scan and clinical laboratory indicators as well as clinical manifestations. Method. A total of 335 patients were enrolled from January 26, 2020, to February 26, 2020, in Shandong province and Huanggang city. Demographic and clinical characteristics, laboratory variables, and the data from the CT scans were collected for analysis. Scatter plot analysis and correlation analysis were used to calculate the relationship between CT evaluation and other indicators. Multivariable linear regression analysis was used to establish a model for diagnostic and prognostic prediction. Age, CRP, LDH, and lymphocyte counts as independent variables were selected to develop a predictive model, and the results from the CT scans to reflect the degree of lung injury were taken as the dependent variable. Result. The median age was 44 years (IQR: 34–56); among them, 188 (56%) were male. Severe patients were older (56 vs. 40, ). There were statistically significant differences in lymphocyte counts, platelet counts, C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT), and creatine kinase (CK) between the general patients and severe patients. We found that, without effective antiviral treatment, mild patients had a 6-day interval from symptom onset to CRP elevation, but in severe patients, CRP started to increase from day 2. Lung injury score from a chest CT scan and incidence of acute respiratory distress syndrome (ARDS) were significantly higher in severe patients than in mild patients. Lung injury score from a chest CT scan was closely correlated with CRP (r_s = 0.704, ), and they reflected the severity of the disease. The receiver operating curve (ROC) value of the injury score from the chest CT scan was 0.854 (95% CI: 0.808–0.901), and the area under the curve (AUC) value of CRP was 0.823 (95% CI: 0.769–0.878). Conclusion. The results from CRP and chest CT scans were indicators of the severity of COVID-19. Combining patient age, CRP, LDH, and lymphocyte counts, we developed a model that could help to predict lung injury/function of patients with COVID-19.