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Background: Skeletal muscles are organs with high energy requirements, especially during vigorous exercise. Adequate mitochondrial function is essential to meet the high energy needs of skeletal muscle cells. Recent studies have reported that red ginseng can significantly improve chronic fatigue; however, the specific mechanism of action is still not clear.Methods: A chronic fatigue syndrome mouse model was developed using C57BL/6J mice through long-term compound stimulation of stress factors. Following this, the animals were orally administered 200, 400, or 600 mg/kg red ginseng extracts for 28 days. Skeletal muscle lactate acid, serum lactate dehydrogenase, urea concentrations, ATP level, mitochondrial membrane potential, activities of Na+-K+-ATPase and cytochrome c oxidase were determined using assay kits or an automatic biochemical analyser detection system. Skeletal muscle mitochondria morphology was observed using electron microscopy and the expression of p-AMPK, PGC-1α, ACO2 and complex I in skeletal muscle protein was determined by western blotting.Results: Oral administration of 400 or 600 mg/kg red ginseng extract in mice with chronic fatigue reduced lactic acid, lactate dehydrogenase and urea, rescued the density and morphology of skeletal muscle mitochondria, increased the activities of Na+-K+-ATPase and cytochrome c oxidase, and activated the AMPK/PGC-1α cascade pathway, resulting in improved skeletal muscle mitochondrial function by restoring ATP level, mitochondrial membrane potential, complex I and mitochondrial biogenesis.Conclusion: The anti-fatigue effects of red ginseng are partly related to its potent mitochondrial improving activity, including decreasing mitochondrial swelling and mitochondrial membrane permeability, increasing mitochondrial biogenesis, thus ameliorating mitochondrial dysfunction.

Background: TGF-β signaling pathway plays an essential role in tumor progression and immune responses. However, the link between TGF-β signaling pathway-related genes (TSRGs) and clinical prognosis, tumor microenvironment (TME), and immunotherapy in gastric cancer is unclear.Methods: Transcriptome data and related clinical data of gastric cancer were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and 54 TSRGs were obtained from the Molecular Signatures Database (MSigDB). We systematically analyzed the expression profile characteristics of 54 TSRGs in 804 gastric cancer samples and examined the differences in prognosis, clinicopathological features, and TME among different molecular subtypes. Subsequently, TGF-β-related prognostic models were constructed using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to quantify the degree of risk in each patient. Patients were divided into two high- and low-risk groups based on the median risk score. Finally, sensitivity to immune checkpoint inhibitors (ICIs) and anti-tumor agents was assessed in patients in high- and low-risk groups.Results: We identified two distinct TGF-β subgroups. Compared to TGF-β cluster B, TGF-β cluster A exhibits an immunosuppressive microenvironment with a shorter overall survival (OS). Then, a novel TGF-β-associated prognostic model, including SRPX2, SGCE, DES, MMP7, and KRT17, was constructed, and the risk score was demonstrated as an independent prognostic factor for gastric cancer patients. Further studies showed that gastric cancer patients in the low-risk group, characterized by higher tumor mutation burden (TMB), the proportion of high microsatellite instability (MSI-H), immunophenoscore (IPS), and lower tumor immune dysfunction and exclusion (TIDE) score, had a better prognosis, and linked to higher response rate to immunotherapy. In addition, the risk score and anti-tumor drug sensitivity were strongly correlated.Conclusion: These findings highlight the importance of TSRGs, deepen the understanding of tumor immune microenvironment, and guide individualized immunotherapy for gastric cancer patients.

Danlu tongdu tablets (DLTD) is a listed Chinese patent medicine collected in the Pharmacopoeia of the People’s Republic of China (version 2020). This prescription has been applied in clinics in China for lumbar spinal stenosis and lumbosacral disc herniations. The wide application of Danlu tongdu in therapy has raised some clinical adverse reactions, such as significant elevation of alanine transaminase (ALT) and aspartate transaminase (AST) in individual patients after use. The present study aimed to investigate the safety of Danlu tongdu and analyze its adverse effects on the liver. The maximum feasible dose (MFD) was used to carry out the acute toxicity tests. Mortality, adverse effects, body weight and food consumption were recorded for up to 14 days post treatment. In the 6-month chronic toxicity test, sprague-dawley rats were randomly divided into four groups according body weight, the experimental groups were administrated to rats at the concentrations of 1.67, 3.34 and 6.67 g/kg/day, whereas the control group was received the ultrapure water (vehicle) only, 10 ml/kg, once a day. The animal’s body weight, food consumption was monitored weekly. In addition, their hematological and biochemical parameters, body and organ weights and histopathology, were all measured at specific observation time points. Additionally, we further explored the adverse effects mechanism of Danlu tongdu on the liver through transcriptome analysis. No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 1.67 g/kg and 3.34 g/kg, respectively. We found that mild hypertrophy and hyperplasia of hepatic interlobular bile ducts were detected in some rats with doses of 6.67 g/kg after repeated oral administration of Danlu tongdu for 13 and 26 weeks, but the above changes in liver were reversible. The results of transcriptome sequencing showed that Danlu tongdu had a significant effect on cytochrome P450 enzymes in rat liver, especially cytochrome P450 1 (CYP1) subtype. Therefore, the toxic target organ of Danlu tongdu is the liver and the mechanism of mild liver injury is closely related to the up-regulation of cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1A2 (CYP1A2) expression.

Background: This study aims to assess the clinical efficacy and adverse events of delafloxacin for the treatment of acute bacterial infections in adult patients through meta-analysis.Methods: The PubMed, Embase, Cochrane library, Web of Science, and Clinical trails databases were searched up to 26 March 2022. Only randomized controlled trials (RCTs) that evaluated delafloxacin and comparator antibiotics for treating acute bacterial infections in adult patients were included. The clinical cure rate and microbiological eradication rate at the posttreatment evaluation, while the secondary outcomes included the risk of adverse events (AEs).Results: In total, six randomized controlled trials (RCTs) involving 3,019 patients with acute bacterial infection were included. There were no significant differences in the clinical cure rate between delafloxacin and comparators (OR = 1.06%, 95% CI = 0.89–1.26, I2 = 0%). Overall, the results showed that delafloxacin had a microbiological eradication rate (documented and presumed) similar to the comparators (OR = 1.33%, 95% CI = 0.94–1.88, I2 = 0%) in the pooled analysis of the six studies. Any treatment-emergent adverse events (TEAEs) did not show significant differences between delafloxacin and the comparators (OR = 0.93%, 95% CI = 0.80–1.08, I2 = 75%). Serious adverse events (SAEs) did not differ between the delafloxacin and comparators (OR = 0.94%, 95% CI = 0.67–1.32, I2 = 0%). The results of gastrointestinal disorders were (OR = 1.26%, 95% CI = 1.01–1.56, I2 = 89%), and nausea, vomiting, and diarrhea were (OR = 0.77%, 95% CI = 0.45–1.34, I2 = 79%), (OR = 1.00%, 95% CI = 0.74–1.36, I2 = 72%), and (OR = 2.10%, 95% CI = 1.70–2.96, I2 = 0%), respectively. The results showed that there was no significant difference in the incidence of nausea and vomiting between delafloxacin and the comparator, but the incidence of diarrhea was higher. The analysis of neurological disorders indicated that the incidence of nervous system disorders was lower in the delafloxacin group (OR = 0.71%, 95% CI = 0.50–1.01, I2 = 52%).Conclusion: The clinical efficacy, microbiological eradication rate and the incidence of AEs of delafloxacin in the treatment of acute bacterial infections were similar to those of the comparators, as an alternative therapeutic agent.

The liver, a complex parenchymal organ, possesses a distinctive microcirculatory system crucial for its physiological functions. An intricate interplay exists between hepatic microcirculatory disturbance and the manifestation of pathological features in diverse liver diseases. This review updates the main characteristics of hepatic microcirculatory disturbance, including hepatic sinusoidal capillarization, narrowing of sinusoidal space, portal hypertension, and pathological angiogenesis, as well as their formation mechanisms. It also summarized the detection methods for hepatic microcirculation. Simultaneously, we have also reviewed the characteristics of microcirculatory disturbance in diverse liver diseases such as acute liver failure, hepatic ischemiareperfusion injury, viral hepatitis, non-alcoholic fatty liver disease, hepatic fibrosis, hepatic cirrhosis, and hepatocellular carcinoma. Finally, this review also summarizes the advancement in hepatic microcirculation attributed to traditional Chinese medicine (TCM) and its active metabolites, providing novel insights into the application of TCM in treating liver diseases. [ABSTRACT FROM AUTHOR]