ObjectiveTo evaluate the protective effect of Xuebijing injection against renal injury in patients with sepsis, and to explore its possible mechanism.Methods A prospective randomized controlled trial (RCT) was conducted in which 62 severe patients with sepsis and septic shock admitted in Department of Critical Care Medicine of Jiangsu Province Traditional Chinese Medicine Hospital from June 2013 to December 2013 were randomly divided into control group and Xuebijing group, with 31 patients in each group. The patients in both groups received basic treatment for sepsis, and the patients in Xuebijing group were additionally given intravenous injection of Xuebijing 100 mL once a day for 7 days. In both groups, the changes in acute physiology and chronic health evaluationⅡ (APACHEⅡ) score were observed before treatment and 1, 3, 7 days after treatment, and the changes in the levels of interleukins (IL-6, IL-10), prothrombin time (PT), fibrinogen (Fib), activated partial thromboplastin time (APTT), serum creatinine (SCr), and Cystain C (Cys C) were determined before treatment and 1 day and 3 days after treatment.Results There was no statistically significant difference in APACHEⅡ score before treatment between two groups, however, the APACHEⅡ scores were significantly decreased in both groups 3 days and 7 days after treatment compared with those before treatment, and the degree of decrease in Xuebijing group was more obvious 7 days after treatment (13.61±7.62 vs. 16.34±8.70,P< 0.05). Serum concentrations of Cys C, SCr, IL-6, IL-10, PT, APTT, and Fib showed no difference between two groups before treatment (allP> 0.05), while after treatment the degrees of improvement of above indexes in Xuebijing group were obviously superior to those in control group, especially 3 days after treatment[Cys C (mg/L):1.12±0.11 vs. 1.35±0.14, SCr (μmol/L): 115.0±31.0 vs. 135.0±24.0, IL-6 (ng/L): 54.27±28.79 vs. 73.35±31.01,PT (s): 13.50±0.11 vs. 15.71±0.11, APTT (s): 43.66±0.31 vs. 48.03±0.55, Fib (g/L): 1.91±0.51 vs. 1.51±0.52, P< 0.05 orP< 0.01].ConclusionXuebijing injection has certain renal protective effect in patients with sepsis, and its mechanism is possibly related to the regulation and improvement of uncontrolled inflammatory response and coagulation function in sepsis.

[Summary] All patients with cholesterol side-chain cleavage enzyme ( P450scc) deficiency that have been reported presented with early adrenal failure. Here we described a 35-year-old male presented with infertility as the only initial presenting complaint. He had received two separate surgeries to remove bilateral testicular masses. We reevaluated the resected tumors and found testicular adrenal rest tumor ( TART) pathology in the resected tumor. We profiled steroid hormones and found significantly elevated ACTH. CT scan revealed bilateral adrenal hyperplasia. Mutation screening identified compound heterozygous mutations (R353W and P432L) in the P450scc encoding gene (CYP11A1). The patient was finally diagnosed as congenital adrenal hyperplasia.

Background::Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies.Methods::Seven patients with UC were included who underwent curative surgery at our hospital between July 2020 and October 2020. We performed single-cell RNA sequencing (scRNA-seq) analysis in seven tumors with six matched adjacent normal tissues and integrated the results with two public scRNA-seq datasets. The functional properties and intercellular interactions between single cells were characterized, and the results were validated using multiplex immunofluorescence staining, flow cytometry, and bulk transcriptomic datasets. All statistical analyses were performed using the R package with two-sided tests. Wilcoxon-rank test, log-rank test, one-way analysis of variance test, and Pearson correlation analysis were used properly.Results::Unsupervised t-distributed stochastic neighbor embedding clustering analysis identified ten main cellular subclusters in urothelial tissues. Of them, seven urothelial subtypes were noted, and malignant urothelial cells were characterized with enhanced cellular proliferation and reduced immunogenicity. CD8 + T cell subclusters exhibited enhanced cellular cytotoxicity activities along with increased exhaustion signature in UC tissues, and the recruitment of CD4 + T regulatory cells was also increased in tumor tissues. Regarding myeloid cells, coordinated reprogramming of infiltrated neutrophils, M2-type polarized macrophages, and LAMP3 + dendritic cells contribute to immunosuppressive TME in UC tissues. Tumor tissues demonstrated enhanced angiogenesis mediated by KDR + endothelial cells and RGS5 +/ACTA2 + pericytes. Through deconvolution analysis, we identified multiple cellular subtypes may influence the programmed death-ligand 1 (PD-L1) immunotherapy response in patients with UC. Conclusion::Our scRNA-seq analysis clarified intra-tumoral heterogeneity and delineated the pro-tumoral and immunosuppressive microenvironment in UC tissues, which may provide novel therapeutic targets.

Periodontitis is the most widespread oral disease and is closely related to the oral microbiota. The oral microbiota is adversely affected by some pharmacologic treatments. Systemic antibiotics are widely used for infectious diseases but can lead to gut dysbiosis, causing negative effects on the human body. Whether systemic antibiotic-induced gut dysbiosis can affect the oral microbiota or even periodontitis has not yet been addressed. In this research, mice were exposed to drinking water containing a cocktail of four antibiotics to explore how systemic antibiotics affect microbiota pathogenicity and oral bone loss. The results demonstrated, for the first time, that gut dysbiosis caused by long-term use of antibiotics can disturb the oral microbiota and aggravate periodontitis. Moreover, the expression of cytokines related to Th17 was increased while transcription factors and cytokines related to Treg were decreased in the periodontal tissue. Fecal microbiota transplantation with normal mice feces restored the gut microbiota and barrier, decreased the pathogenicity of the oral microbiota, reversed the Th17/Treg imbalance in periodontal tissue, and alleviated alveolar bone loss. This study highlights the potential adverse effects of long-term systemic antibiotics-induced gut dysbiosis on the oral microbiota and periodontitis. A Th17/Treg imbalance might be related to this relationship. Importantly, these results reveal that the periodontal condition of patients should be assessed regularly when using systemic antibiotics in clinical practice.
Humans ; Mice ; Animals ; Dysbiosis ; Anti-Bacterial Agents/pharmacology* ; Virulence ; Microbiota ; Periodontitis/chemically induced* ; Cytokines