The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases

Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and peritoneal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over-represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that surveying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.Shenzhen Municipal Government of China [JCYJ20160229172757249, JCYJ20150601090833370]; Danish Strategic Research Council [2106-07-0021]; Ole Romer grant from Danish Natural Science Research Council; Solexa project [272-07-0196]SCI(E)ARTICLE

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Vacuum sealing drainage combined with eggshell-like debridement antibiotic-loaded calcium sulphate for calcaneal osteomyelitis

Abstract Background To compare the clinical efficacy of vacuum sealing drainage, eggshell-like debridement combined with antibiotic calcium sulphate implantation and conventional debridement combined with antibiotic calcium sulphate implantation in the treatment of calcaneal osteomyelitis. Methods Sixty-six patients with calcaneal osteomyelitis who were treated in our department between January 2017 and August 2021 were included in this study. Thirty-one patients underwent VSD and eggshell-like debridement combined with antibiotic calcium sulphate implantation. Thirty-five patients underwent conventional debridement combined with antibiotic calcium sulphate implantation. The inflammatory markers, operation time, wound healing time, hospital stay, full weight bearing time after operation, recurrence rate of infection, complications, and American Orthopedic Foot and Ankle Society (AOFAS) scores were compared between the two groups. Results The operation time and full weight bearing time after operation of observation group were longer than that of control group. Compared with preoperative results, WBC, ESR, CRP and PCT in both groups were significantly decreased at 14 days after operation, and there was no statistical significance between the two groups. The wound healing time and hospital stay in the observation group were shorter than those in the control group (P < 0.05). There were four patients with aseptic exudation in the observation group and ten patients with aseptic exudation in the control group, and the wounds healed well after multiple dressing changes. Seven patients in the observation group underwent secondary bone grafting due to bone defects, and four patients in the control group received secondary bone grafting due to bone defects. In the observation group, three patients received debridement combined with antibiotic calcium sulphate implantation again due to recurrent infection, compared with seven patients in the control group. One year after operation, the observation group had a better AOFAS scores than the control group, especially in terms of foot function (P < 0.05). Conclusion Compared with conventional debridement and antibiotic calcium sulphate implantation, VSD and eggshell-like debridement combined with antibiotic calcium sulphate implantation in the treatment of calcaneal osteomyelitis can shorten the wound healing and hospital stay of patients, reduce postoperative aseptic exudation complications and infection recurrence rate, and better preserve the foot function, which is a simple and effective method

Insights into Human Astrocyte Response to H5N1 Infection by Microarray Analysis

Influenza virus infects not only the respiratory system but also the central nervous system (CNS), leading to influenza-associated encephalopathy and encephalitis. Astrocytes are essential for brain homeostasis and neuronal function. These cells can also be infected by influenza virus. However, genome-wide changes in response to influenza viral infection in astrocytes have not been defined. In this study, we performed gene profiling of human astrocytes in response to H5N1. Innate immune and pro-inflammatory responses were strongly activated at 24 h post-infection (hpi). Antiviral genes, as well as several cytokines and chemokines, including CXCL9, CXCL10, and CXCL11, were robustly induced. Phosphorylation of p65 and p38 can be activated by viral infection, suggesting their potential critical roles in H5N1-induced pro-inflammatory response. Moreover, H5N1 infection significantly upregulated the gene expressions related to the neuroactive ligand-receptor interaction pathway at 24 hpi, such as MC2R, CHRNG, P2RY13, GABRA1, and HRH2, which participant in synaptic transmission and may take part in CNS disorders induced by H5N1 infection. Targeting key components of innate immune response and the neuroactive ligand-receptor interaction pathway may provide a strategy to control H5N1-induced encephalopathy and encephalitis. This research can contribute to the understanding of H5N1 pathogenesis in astrocytes

Multidisciplinary Treatment on a Case of ROSAH Syndrome

A 15-year-old female was referred to the hospital with intermittent fever, where multiple systemic abnormalities were found, such as splenomegaly, secondary hypersplenism, retinitis pigmentosa, and ectodermal dysplasia. Medical history revealed that she had suffered recurrent respiratory infections, blurred vision at night, and dysplasia of teeth and nail beds since childhood. Then she was suspected to be experiencing ROSAH syndrome, a rare disease newly recognized in recent years, which was finally confirmed by gene sequencing results. During a course of treatment with tumor necrosis factor inhibitors, recurrent fever with elevated inflammatory markers reappeared, and the child developed headaches. To guide the comprehensive treatment and improve the patient's quality of life, the multidisciplinary team in Peking Union Medical College Hospital discussed together and directed the following treatment

Interfacial Self-Assembly Driven Formation of Hierarchically Structured Nanocrystals with Photocatalytic Activity

We report the synthesis of hierarchical structured nanocrystals through an interfacial self-assembly driven microemulsion (μ-emulsion) process. An optically active macrocyclic building block Sn (IV) <i>meso</i>-tetraphenylporphine dichloride (tin porphyrin) is used to initiate noncovalent self-assembly confined within μ-emulsion droplets. <i>In-situ</i> studies of dynamic light scattering, UV–vis spectroscopy, and electron microscopy, as well as optical imaging of reaction processes suggest an evaporation-induced nucleation and growth self-assembly mechanism. The resulted nanocrystals exhibit uniform shapes and sizes from ten to a hundred nanometers. Because of the spatial ordering of tin porphyrin, the hierarchical nanocrystals exhibit collective optical properties resulting from the coupling of molecular tin porphyrin and photocatalytic activities in the reduction of platinum nanoparticles and networks and in photodegradation of methyl orange (MO) pollutants

Quantitative dynamic contrast-enhanced parameters and intravoxel incoherent motion facilitate the prediction of TP53 status and risk stratification of early-stage endometrial carcinoma

The aim of the study was to investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and intravoxel incoherent motion (IVIM) in differentiating TP53-mutant from wild type, low-risk from non-low-risk early-stage endometrial carcinoma (EC)