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Introduction: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. Methods: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. Results: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. Conclusion: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI. [ABSTRACT FROM AUTHOR]

Objective: This meta‐analysis aimed to determine the effect of mindfulness interventions on nurses' levels of depression and anxiety. Design: Meta‐analysis of randomised controlled trials. Methods: The following Chinese and English databases were searched: PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Internet (CNKI). The retrieval period was from database construction to 30 March 2022. Two researchers screened the relevant literature and extracted the data. After a cross‐check, data were input into Stata version 16.0 for meta‐analysis. Results: Twelve randomised controlled trials from 2017 to 2021 were included, which involved 807 subjects (405 and 402 in the intervention and control groups, respectively). Meta‐analysis results showed that nurses' anxiety reduced by mindfulness‐based interventions was significantly higher compared to that of the control group (SMD = 0.91, 95% CI: 0.27–1.55, p < 0.05). Furthermore, an 8‐week mindfulness‐based intervention (SMD = 1.43, 95% CI: 0.61–2.24) reduced the level of anxiety significantly more compared to a 4‐week intervention (SMD = 1.03, 95% CI: 0.36–1.71). Mindfulness‐based interventions were better compared to conventional intervention to reduce the level of depression (SMD = 1.02, 95% CI: 0.42–1.61, p < 0.05), and an 8‐week mindfulness intervention (SMD = 1.81, 95% CI: 0.78–2.84) reduced the level of depression significantly more compared to a 4‐week intervention (SMD = 0.82, 95% CI: 0.29–1.35). Since limited studies had interventions longer than 8 weeks, results on longer mindfulness interventions in reducing nurses' anxiety and depression are inconclusive. In conclusion, mindfulness intervention for 8 weeks or less can significantly reduce nurses' anxiety and depression levels. Patient or Public Contribution: None. [ABSTRACT FROM AUTHOR]

Introduction: Disseminated intravascular coagulation (DIC) is a syndrome characterized by coagulopathy, microthrombus, and multiple organ failure. The complement system in DIC is overactivated, and the functions of complement and coagulation pathways are closely related. Our previous screening revealed that salvianolic acid A (SAA) has anti-complement activity. The hyper-activated complement system was involved in the lipopolysaccharide (LPS) induced DIC in rats. The effects of SAA anti-complement action on LPS-induced DIC in rats were investigated. Methods: The complement activity of the classical pathway and alternative pathway was detected through an in vitro hemolysis assay. The binding sites of SAA and complement C3b were predicted by molecular docking. LPS-induced disseminated coagulation experiments were performed on male Wistar rats to assess coagulation function, complement activity, inflammation, biochemistry, blood routine, fibrinolysis, and survival. Results: SAA had an anti-complement activity in vivo and in vitro and inhibited the complement activation in the classical and alternative pathway of complement. The infusion of LPS into the rats impaired the coagulation function, increased the plasma inflammatory cytokine level, complemented activation, reduced the clotting factor levels, fibrinogen, and platelets, damaged renal, liver, and lung functions, and led to a high mortality rate (85%). SAA treatment of rats inhibited complement activation and attenuated the significant increase in D-dimer, interleukin-6, alanine aminotransferase, and creatinine. It ameliorated the decrease in plasma levels of fibrinogen and platelets and reversed the decline in activity of protein C and antithrombin III. The treatment reduced kidney, liver, and lung damage, and significantly improved the survival rate of rats (46.2 and 78.6% for the low- and high-dose groups, respectively). Conclusion: SAA reduced LPS-induced DIC by inhibiting complement activation. It has considerable potential in DIC treatment. [ABSTRACT FROM AUTHOR]

Background: Timely and accurate prediction of delayed cerebral ischemia is critical for improving the prognosis of patients with aneurysmal subarachnoid hemorrhage. Machine learning (ML) algorithms are increasingly regarded as having a higher prediction power than conventional logistic regression (LR). This study aims to construct LR and ML models and compare their prediction power on delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Methods: This was a multicenter, retrospective, observational cohort study that enrolled patients with aneurysmal subarachnoid hemorrhage from five hospitals in China. A total of 404 aSAH patients were prospectively enrolled. We randomly divided the patients into training (N = 303) and validation cohorts (N = 101) according to a ratio of 75–25%. One LR and six popular ML algorithms were used to construct models. The area under the receiver operating characteristic curve (AUC), accuracy, balanced accuracy, confusion matrix, sensitivity, specificity, calibration curve, and Hosmer–Lemeshow test were used to assess and compare the model performance. Finally, we calculated each feature of importance. Results: A total of 112 (27.7%) patients developed DCI. Our results showed that conventional LR with an AUC value of 0.824 (95%CI: 0.73–0.91) in the validation cohort outperformed k-nearest neighbor, decision tree, support vector machine, and extreme gradient boosting model with the AUCs of 0.792 (95%CI: 0.68–0.9, P = 0.46), 0.675 (95%CI: 0.56–0.79, P < 0.01), 0.677 (95%CI: 0.57–0.77, P < 0.01), and 0.78 (95%CI: 0.68–0.87, P = 0.50). However, random forest (RF) and artificial neural network model with the same AUC (0.858, 95%CI: 0.78–0.93, P = 0.26) were better than the LR. The accuracy and the balanced accuracy of the RF were 20.8% and 11% higher than the latter, and the RF also showed good calibration in the validation cohort (Hosmer-Lemeshow: P = 0.203). We found that the CT value of subarachnoid hemorrhage, WBC count, neutrophil count, CT value of cerebral edema, and monocyte count were the five most important features for DCI prediction in the RF model. We then developed an online prediction tool (https://dynamic-nomogram.shinyapps.io/DynNomapp-DCI/) based on important features to calculate DCI risk precisely. Conclusions: In this multicenter study, we found that several ML methods, particularly RF, outperformed conventional LR. Furthermore, an online prediction tool based on the RF model was developed to identify patients at high risk for DCI after SAH and facilitate timely interventions. Clinical Trial Registration: http://www.chictr.org.cn, Unique identifier: ChiCTR2100044448. [ABSTRACT FROM AUTHOR]

Three new compounds, crotalariapallins A-C (1-3), were isolated from the 95% EtOH extract of the seeds of Crotalaria pallida. Their structures were established based on extensive spectroscopic methods, including HRESIMS, UV, 1D and 2D NMR. All compounds were evaluated for their inhibitory activities to tyrosinase. These compounds showed different degrees of inhibitory activities, among them, compound 3 exhibited the strongest inhibition activity (IC50 = 0.42 mM). [ABSTRACT FROM AUTHOR]

This study aims to investigate the relationship between body measures and the presence of two frailty‐related phenotypes, and the moderating effect of age on this relationship. This is a secondary data analysis of the baseline data of an interventional study. The participants were residents of seven districts in Hong Kong, aged 55 or older, able to ambulate independently and to function well cognitively. Pre‐frailty refers to the presence of two frailty‐related phenotypes: low physical activity or poor handgrip strength or both. Included in the study were 199 individuals with a mean age of 73.43 (SD 7.54). Regression models showed that body weight (OR = 0.95, 95% CI 0.92–0.99, p <.05) was significantly associated with pre‐frailty, as was body height (OR = 0.88, 95% CI 0.83–0.94, p <.001). Age is a significant moderator of the relationship between pre‐frailty and body weight and body height. The effect of body weight (beta = −0.044, p <.05) and height (beta = −0.16, p <.001) on pre‐frailty was significant and negative in the younger age groups. The findings indicate that raw body measures (i.e. body weight, body height) are more predictive of pre‐frailty than BMI in older Chinese people. However, in the old‐old group, these measures are not significant predictors of pre‐frailty in Chinese community‐dwelling adults. Practitioners should consider adopting body measures as predictors of pre‐frailty in the younger‐old population. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated an intergenerational interaction program set in a nonfamilial context to combat age-related stereotypes and to facilitate positive interactions between the young and elderly in Hong Kong. Method: A quasi-experimental design was adopted. A total of 312 participants were recruited: 73 older and 78 young participants in the intervention group and 77 older and 84 young participants in the comparison group. Standardized measurements of intergenerational attitude, sense of comfort with cross-age groups, and intergenerational interaction were used during pre- and posttest. Results: The intervention group showed positive change in intergenerational attitude and sense of comfort. There were also positive changes in most aspects of intergenerational interaction in the intervention group. Discussion: This research provides preliminary evidence of the effectiveness of the intervention model and offers many implications for service directions. The findings enrich cumulative knowledge about factors contributing to the reduction of age-related stereotypes. [ABSTRACT FROM AUTHOR]

Abstract Nine new prenylated flavan compounds with multi-chiral centers including two pairs of epimers were isolated from the stem and root bark of Daphne giraldii. Their structures were established by extensive NMR and HR-ESIMS spectroscopic data analyses. The in vitro cytotoxicity experiments indicated that compound 6 showed the most significant cytotoxicity against Hep3B cells, with an IC 50 value of 9.83 μ M. Hoechst 33258 and Annexin V-FITC/PI staining suggested that 6 could induce apoptosis of Hep3B cells in a concentration-dependent manner. Further mechanism study indicated that the apoptosis was associated with the up-regulations of Bax, cl-PARP and a decrease in Bcl-2 expression. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Background Overproduction of reactive oxygen species is associated with the development of alcoholic liver disease ( ALD). Plant polyphenols have been used as dietary interventions for multiple diseases including ALD. The objective of this study was to determine whether dietary supplementation with fisetin, a novel flavonoid, exerts beneficial effect on alcohol-induced liver injury. Methods C57 BL/6J mice were pair-fed with the Lieber-DeCarli control or ethanol (EtOH) diet for 4 weeks with or without fisetin supplementation at 10 mg/kg/d. Results Alcohol feeding induced lipid accumulation in the liver and increased plasma alanine aminotransferase and aspartate aminotransferase activities, which were attenuated by fisetin supplementation. The EtOH concentrations in the plasma and liver were significantly elevated by alcohol exposure but were reduced by fisetin supplementation. Although fisetin did not affect the protein expression of alcohol metabolism enzymes, the aldehyde dehydrogenase activities were significantly increased by fisetin compared to the alcohol alone group. In addition, fisetin supplementation remarkably reduced hepatic NADPH oxidase 4 levels along with decreased plasma hydrogen peroxide and hepatic superoxide and 4-hydroxynonenal levels after alcohol exposure. Alcohol-induced apoptosis and up-regulation of Fas and cleaved caspase-3 in the liver were prevented by fisetin. Moreover, fisetin supplementation attenuated alcohol-induced hepatic steatosis through increasing plasma adiponectin levels and hepatic protein levels of p- AMPK, ACOX1, CYP4A, and MTTP. Conclusions This study demonstrated that the protective effect of fisetin on ALD is achieved by accelerating EtOH clearance and inhibition of oxidative stress. The data suggest that fisetin has a therapeutical potential for treating ALD. [ABSTRACT FROM AUTHOR]

Background Peroxisome proliferator-activated receptor gamma ( PPAR γ) signaling has been shown to regulate lipogenesis and lipid accumulation. Previous studies have shown that hepatic PPAR γ is up-regulated in steatotic liver of both animal and human. However, the effects of hepatic PPAR γ signaling on alcoholic liver disease ( ALD) remain elusive. Methods To determine the role of hepatic PPAR γ signaling on ALD, wild-type ( WT) and hepatocyte-specific PPAR γ knockdown ( PPAR γ∆ Hep) mice were fed a modified Lieber- De Carli alcohol or isocaloric maltose dextrin control liquid diet for 8 weeks to induce ALD. Blood parameters, hepatic steatosis, and inflammation were measured after 8-week alcohol feeding. Results Alcohol feeding to WT mice resulted in liver damage (alanine aminotransferase [ ALT], 94.68 ± 17.05 U/L; aspartate aminotransferase [ AST], 55.87 ± 11.29 U/L), which was significantly alleviated by hepatic PPAR γ knockdown ( ALT, 57.36 ± 14.98 U/L; AST, 38.06 ± 3.35 U/L). Alcohol feeding led to marked lipid accumulation and up-regulation of lipogenic genes including fatty acid transport protein 1 ( FATP1), acetyl- Co A carboxylase ( ACC), fatty acid synthase ( FASN), lipin1 (LIPIN1), diacylglycerol acyltransferase 1 ( DGAT1), and diacylglycerol acyltransferase 2 ( DGAT2) in the livers of WT mice. Knockdown of hepatic PPAR γ significantly alleviated alcohol-induced lipid accumulation and abolished the up-regulation of FASN, DGAT1, and DGAT2. Silencing of PPAR γ in FL83 B cells significantly decreased ethanol ( Et OH)-, linoleic acid-, and Et OH plus linoleic acid-induced lipid accumulation. Knockdown of hepatic PPAR γ also significantly reduced alcohol-induced inflammatory chemokine (monocyte chemotactic protein 1 [ MCP1], keratinocyte-derived chemokine [ KC], interferon gamma-induced protein 10 [ IP-10]) and inflammatory infiltration (lymphocyte antigen 6 complex, locus G [ Ly6 G], and F4/80). Conclusions The results suggest that hepatic PPAR γ signaling contributes to alcohol-induced liver injury by promoting hepatic steatosis and inflammation. [ABSTRACT FROM AUTHOR]

Background Chronic alcohol exposure causes lipid dyshomeostasis at the adipose-liver axis, reducing lipid storage in white fat and increasing lipid deposit in the liver. Previous studies have shown that visceral fat, rather than subcutaneous fat, is a risk factor for metabolic diseases. This study was conducted to determine whether chronic alcohol exposure differentially affects lipid metabolism in visceral (epididymal) and subcutaneous fat, and the mechanisms underlying the alcohol effects. Methods Male Wistar rats were pair-fed the Lieber-DeCarli control or alcohol liquid diet for 12 weeks to determine the effects of alcohol on the white fat. Tissue explants culture and 3T3-L1 culture were conducted to define the role of acetaldehyde in alcohol-induced adipose tissue dysfunction. Results Chronic alcohol feeding significantly reduced visceral fat mass and down-regulated peroxisome proliferator activator receptor- γ and CCAAT/enhancer binding protein- α, 2 important transcription factors in regulation of lipogenesis. The protein levels of lipogenic enzymes including phospho- ATP-citrate lyase, acetyl-CoA carboxylase, fatty acid synthase, lipin1, and diacylglycerol acyltransferase 2 in the visceral fat were reduced. In contrast, chronic alcohol exposure did not affect subcutaneous fat mass and had less effect on the protein levels of lipogenic enzymes and regulators. Accordingly, the visceral fat showed a lower protein level of aldehyde detoxification enzymes compared to the subcutaneous fat. Acetaldehyde treatment to either visceral fat explants or 3T3-L1 adipocytes produced similar effects on lipogenic enzymes and regulators as observed in animal model. Conclusions These results demonstrated that visceral fat is more susceptible to alcohol toxicity compared to subcutaneous fat, and disruption of adipose lipogenesis contributes to the pathogenesis of alcoholic lipodystrophy. [ABSTRACT FROM AUTHOR]