Background: Previous studies demonstrated an important role for connexin 43 (Cx43) in the regulation of apoptosis by influencing mitochondrial functions. This study aimed to investigate the relationship between Cx43 and lipopolysaccharide (LPS)-induced oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs). Methods: Western blot was performed to determine mitochondrial Cx43 (MtCx43) protein level and phosphorylation (p-MtCx43). Gap19, a selective Cx43 inhibitor, was used to examine the effects of Cx43 on LPS-induced oxidative stress and apoptosis in HUVECs. Expression of regulatory genes associated with oxidative stress was examined by quantitative polymerase chain reaction (qPCR) and Western blot. Apoptosis was assessed by flow cytometry. Results: LPS stimulation resulted in increased levels of MtCx43 and p-MtCx43. Interestingly, Gap19 antagonized the upregulation of glutathione S-transferase Zeta 1 (GSTZ1) and cytochrome b alpha beta (CYBB), and the downregulation of antioxidant 1 (ATOX1), glutathione synthetase (GSS) and heme oxygenase 1 (HMOX1) induced by LPS or Cx43 overexpression. Moreover, the increased production of reactive oxygen species (ROS) and apoptosis elicited by LPS or Cx43 overexpression were reduced following treatment with Gap19. Conclusions: Selective inhibition of Cx43 hemichannels protects HUVECs from LPS-induced apoptosis and this may be via a reduction in oxidative stress production.

Background: Ventilator-associated pneumonia (VAP) is one of the common critical complications of nosocomial infection (NI) in invasive mechanically ventilated intensive care unit (ICU) patients. The efficacy of total parenteral nutrition (TPN), enteral nutrition and/or adjuvant peripheral parenteral nutrition (EPN) supplemented with or without probiotic, prebiotic, and synbiotic therapies in preventing VAP among these patients has been questioned. We aimed to systematically and comprehensively summarize all available studies to generate the best evidence of VAP prevention for invasive mechanically ventilated ICU patients.Methods: Randomized controlled trials (RCTs) for the administration of TPN, EPN, probiotics-supplemented EPN, prebiotics-supplemented EPN, and synbiotics-supplemented EPN for VAP prevention in invasive mechanically ventilated ICU patients were systematically retrieved from four electronic databases. The incidence of VAP was the primary outcome and was determined by the random-effects model of a Bayesian framework. The secondary outcomes were NI, ICU and hospital mortality, ICU and hospital length of stay, and mechanical ventilation duration. The registration number of Prospero is CRD42020195773.Results: A total of 8339 patients from 31 RCTs were finally included in network meta-analysis. The primary outcome showed that probiotic-supplemented EPN had a higher correlation with the alleviation of VAP than EPN in critically invasive mechanically ventilated patients (odds ratio [OR] 0.75; 95% credible intervals [CrI] 0.58–0.95). Subgroup analyses showed that probiotic-supplemented EPN prevented VAP in trauma patients (OR 0.30; 95% CrI 0.13–0.83), mixed probiotic strain therapy was more effective in preventing VAP than EPN therapy (OR 0.55; 95% CrI 0.31–0.97), and low-dose probiotic therapy (less than 10¹⁰ CFU per day) was more associated with lowered incidence of VAP than EPN therapy (OR 0.16; 95% CrI 0.04–0.64). Secondary outcomes indicated that synbiotic-supplemented EPN therapy was more significantly related to decreased incidence of NI than EPN therapy (OR 0.34; 95% CrI 0.11–0.85). Prebiotic-supplemented EPN administration was the most effective in preventing diarrhea (OR 0.05; 95% CrI 0.00–0.71).Conclusion: Probiotic supplementation shows promise in reducing the incidence of VAP in critically invasive mechanically ventilated patients. Currently, low quality of evidence reduces strong clinical recommendations. Further high-quality RCTs are needed to conclusively prove these findings.Systamatic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020195773], identifier [CRD42020195773].

Objectives Previous studies had reported that frailty and loneliness were associated with increased risk of cardiovascular disease (CVD). The aim of present study was to evaluate the combined effect of frailty and loneliness on the risk of CVD. Methods A total of 9,674 participants from the China Health and Retirement Longitudinal Study were included. Multivariate Cox proportional hazards regression model was used to explore the associations between frailty, loneliness and new-onset CVD, stroke and cardiac events. Results During the 7-year follow-up, a total of 1,758 respondents experienced CVD (including 584 stroke and 1,324 cardiac events). Compared to those without loneliness or frailty, individuals with loneliness alone, or with frailty alone, or with both loneliness and frailty were significantly associated with increased risk of CVD, with corresponding HRs (95%CIs) were 1.21(1.07–1.37), 1.57(1.32–1.86) and 1.78(1.52–2.10), respectively. Similarly, participants with loneliness alone, or with frailty alone, or with both loneliness and frailty were associated with higher risk of cardiac events. The significant associations were consistent in age subgroups (participants aged less or more than 60 years). Conclusion Our study indicated that there was a combined effect of effect of frailty and loneliness on the risk of CVD, stroke and cardiac events. These findings highlighted the importance of identifying loneliness and frailty, and intervening much earlier both in older and younger population.

Introduction: Acute pancreatitis (AP) is a prevalent inflammatory disease that can lead to severe abdominal pain and multiple organ failure, potentially resulting in pancreatic necrosis and persistent dysfunction. A nomogram prediction model was developed to accurately evaluate the prognosis and provide therapy guidance to AP patients.Material and methods: Retrospective data extraction was performed using MIMIC-IV, an open-source clinical database, to obtain 1344 AP patient records, of which the primary dataset included 1030 patients after the removal of repeated hospitalizations. The prediction of in-hospital mortality (IHM) used the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection. A multivariate logistic regression analysis was used to build a prediction model incorporating the selected features, and the C-index, calibration plot, and decision curve analysis (DCA) were utilized to evaluate the discrimination, calibration, and clinical applicability of the prediction model.Results: The nomogram utilized a combination of indicators, including the SAPS II score, RDW, MBP, RR, PTT, and fluid-electrolyte disorders. Impressively, the model exhibited a satisfactory diagnostic performance, with area under the curve values of 0.892 and 0.856 for the training cohort and internal validation, respectively. Moreover, the calibration plots and the Hosmer-Lemeshow goodness-of-fit (HL) test revealed a strong correlation between the predicted and actual outcomes (p = 0.73), further confirming the reliability of our model. Notably, the results of the decision curve analysis (DCA) highlighted the superiority of our model over previously described scoring methods in terms of net clinical benefit, solidifying its value in clinical applications.Conclusions: Our novel nomogram is a simple tool for accurately predicting IHM in ICU patients with AP. Treatment methods that enhance the factors involved in the model may contribute to increased in-hospital survival for these ICU patients.

BACKGROUND According to clinical data, a significant percentage of patients experience pain after surgery, highlighting the importance of alleviating postoperative pain. The current approach involves intravenous self-control analgesia, often utilizing opioid analgesics such as morphine, sufentanil, and fentanyl. Surgery for colorectal cancer typically involves general anesthesia. Therefore, optimizing anesthetic management and postoperative analgesic programs can effectively reduce perioperative stress and enhance postoperative recovery. The study aims to analyze the impact of different anesthesia modalities with multimodal analgesia on patients' postoperative pain. AIM To explore the effects of different anesthesia methods coupled with multi-mode analgesia on postoperative pain in patients with colorectal cancer. METHODS Following the inclusion criteria and exclusion criteria, a total of 126 patients with colorectal cancer admitted to our hospital from January 2020 to December 2022 were included, of which 63 received general anesthesia coupled with multi-mode labor pain and were set as the control group, and 63 received general anesthesia associated with epidural anesthesia coupled with multi-mode labor pain and were set as the research group. After data collection, the effects of postoperative analgesia, sedation, and recovery were compared. RESULTS Compared to the control group, the research group had shorter recovery times for orientation, extubation, eye-opening, and spontaneous respiration (P < 0.05). The research group also showed lower Visual analog scale scores at 24 h and 48 h, higher Ramany scores at 6 h and 12 h, and improved cognitive function at 24 h, 48 h, and 72 h (P < 0.05). Additionally, interleukin-6 and interleukin-10 levels were significantly reduced at various time points in the research group compared to the control group (P < 0.05). Levels of CD3+, CD4+, and CD4+/CD8+ were also lower in the research group at multiple time points (P < 0.05). CONCLUSION For patients with colorectal cancer, general anesthesia coupled with epidural anesthesia and multi-mode analgesia can achieve better postoperative analgesia and sedation effects, promote postoperative rehabilitation of patients, improve inflammatory stress and immune status, and have higher safety.