Guoxing Wang

Background: Despite advances in post-cardiac arrest (CA) care, mortality rates remain high. Intestinal dysfunction following CA is associated with adverse clinical outcomes. While laxatives might be a potential therapeutic strategy for restoring intestinal function, there is currently a lack of evidence. Objective: This study aims to explore the safety and efficacy of laxatives as therapeutic agents for intestinal function recovery in CA, while further assessing the most suitable types of laxatives for this clinical context. Methods: Utilizing the MIMIC-IV database, we conducted a retrospective cohort study categorizing patients into laxative and non-laxative groups. Propensity score matching (PSM) was applied to balance baseline characteristics. We classified confounders into prehospital and hospitalization categories, establishing three hierarchical adjustment models. Through multivariable Cox and logistic regression analyses, we assessed 30-day and extended mortality risks while evaluating laxative-associated safety outcomes. Time-dependent Cox regression analysis was utilized to assess the time-varying effect of laxative administration. Furthermore, we also comparatively analyzed the risk–benefit profiles of commonly used laxatives. Results: 2604 patients were eligible for this study. After PSM, a total of 898 patients were average divided into two groups. Patients in the laxative group demonstrated a statistically significant reduction in 30-day mortality risk compared to the non-laxative group (HR = 0.686, 95%CI [0.550–0.855], P = 0.001). After applying time-dependent Cox regression analysis, the results remain consistent (HR = − 0.771 + 0.632 × ln[day + 1], 95%CI [0.528–0.835], P = 0.001). Meanwhile, laxative did not increase the risk of sepsis and Clostridium difficile infection but improved the bowel sounds recovery and increased the ICU-free day. Further subgroup analysis revealed that the use of docusate sodium (HR = 0.753, 95%CI [0.566–1.000], P = 0.050) may be associated with a decreased mortality risk. Conclusion: Early using laxative to improve intestinal function is associated with improved survival outcomes. However, clinical application may be guided by the bowel sounds recovery and demonstrated tolerance to enteral feeding. This still requires further studies to confirm.

To determine therapeutic effect of Qishen Huoxue Granule (QHG) on the myocardial injury in sepsis and whether it is through the inhibition of excessive autophagy by using network pharmacological analysis and in vitro.120 SPF male Wistar rats were divided into 6 groups. Firstly, the function of the heart were evaluated through echocardiography, and pathological changes of myocardial tissue was observed by Hematoxylin-eosin (H&E) and Transmission electron microscopy (TEM). Subsequently, enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of myocardial injury markers (cTnT and BNP) and inflammatory cytokines (TNF-α and IL-1β). Finally, the expression of proteins associated with the MasR/PI3K-AKT-mTOR pathway and autophagy-related proteins was evaluated using immunohistochemistry, immunofluorescence, RT-qPCR, and Western blot analysis.The results demonstrated that QHG significantly improved systolic function in rats, reduced levels of myocardial injury markers and inflammatory cytokines, and downregulated autophagy-related genes (ATG5, LC3, and Beclin1). However, when QHG was combined with inhibitors of the MasR/PI3K-AKT-mTOR pathway, the mRNA and protein expression levels of pathway components were reduced. Concurrently, the mRNA and protein expressions of autophagy indicators were upregulated, counteracting the inhibitory effect of QHG on excessive autophagy.QHG ameliorated the myocardial injury in sepsis rats by inhibiting the excessive autophagy in myocardial cells via activating the MasR/PI3K-AKT-mTOR pathway.

Background Aquaporin 2 (AQP2), a vasopressin-sensitive water channel in the renal collecting ducts, maintains body water homeostasis. Sepsis reduces AQP2 and vasopressin receptor 2 (V2R) levels, contributing to acute kidney injury. In a heritable nephrogenic diabetes insipidus mouse model with V2R mutation, Wnt-5a, a ligand for frizzled receptors (Fzds), enhances AQP2 expression and translocation through calcium/calmodulin/calcineurin signaling. However, the mechanism by which Wnt-5a reduces sepsis-induced AQP2 inhibition remains unclear. We assessed this mechanism and whether Wnt-5a alleviates sepsis-induced downregulation of renal AQP2. Methods Our study used in vitro and in vivo approaches. To study AQP2 trafficking, lipopolysaccharide (LPS) was applied to mouse inner medullary collecting duct 3 (mIMCD3) cells in vitro; subsequently, phosphorylated AQP2 and apical AQP2 expression as well as calcineurin activity and its upstream regulators (endogenous Wnt-5a, Fzds, and intracellular calcium intensity) were examined. In vivo, cecal ligation and puncture (CLP) mice were used to assess AQP2 levels and urine osmolality as indicators of urinary concentration. Results In mIMCD3 cells, LPS application was associated with reduced V2R expression, a vasopressin-irreversible reduction in AQP2, and increased Fzds turnover and Wnt-5a-stimulated intracellular calcium, enhancing calcineurin signaling. Subsequent application of Wnt-5a to LPS-exposed mIMCD3 cells prevented AQP2 reduction. Moreover, it increased phosphorylated AQP2 at residue Ser269 (Ser269-pAQP2) and decreased at Ser261-pAQP2 without affecting Ser256-pAQP2. These effects were reversed by the calcineurin inhibitor cyclosporin A. In CLP mice, Wnt-5a injection was associated with increased renal AQP2 and urine osmolality. Conclusion Wnt-5a attenuates sepsis-induced AQP2 downregulation through the calcineurin signaling pathway.

Background: There were limited studies investigating treatments of septic cardiomyopathy (SCM), which is a common complication during sepsis. A septic rat model created by cecal ligation and puncture (CLP) was used to investigate the effects of diminazene aceturate (DIZE) in SCM. Methods: A total of 151 Wistar rats were randomly assigned into the sham, CLP, or CLP + DIZE group. Data evaluated postoperatively at 6, 12, 24, and 48 hours included: cardiac function; plasma concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6, angiotensin-(1–7) [Ang-(1–7)], angiotensin II (AngII), troponin I, and brain natriuretic peptide; expression levels of myocardial Ang-(1–7), angiotensin-converting enzyme (ACE), ACE2, and angiotensin type 1 and Mas receptors; and histological changes. Results: We found that the CLP + DIZE group had a lower mortality compared to the CLP group (38.5% versus 61.5%) within 48 h postoperatively, although without statistical significance. In contrast to the sham group, the CLP group had decreased cardiac functions, increased myocardial injuries, and higher TNF-α levels, which were ameliorated in the CLP + DIZE group. Furthermore, administration of DIZE could reverse the decreases of myocardial Ang-(1–7) and ACE2 expressions in the CLP group, which finally minimized the myocardial microstructure disruptions. Conclusions: It was concluded that DIZE could mitigate the development of SCM and preserve cardiac function during sepsis possibly by interfering with the renin-angiotensin system through promoting myocardial ACE2 expression and restoring local Ang-(1–7) levels.

: A 20-year-old female resident of Beijing intended to consume the eggs of the parasitic worm, Taenia saginata, for weight loss; however, she apparently inadvertently ingested Taenia solium (pork tapeworm) eggs, which resulted in disseminated cysticercosis. Cysticerci developed in the brain, tongue, muscles, liver, peritoneum, and subcutaneous tissues. She was administered oral albendazole and praziquantel. After four 10-day courses of treatment, most of the cysts disappeared and she recovered. After 3 years, the patient remains in good health.