Exploring the pathogenesis linking primary aldosteronism and obstructive sleep apnea via bioinformatic analysis.

Primary aldosteronism (PA) and obstructive sleep apnea (OSA) are both considered independent risk factors for hypertension, which can lead to an increase in cardiovascular disease incidence and mortality. Clinical studies have found a bidirectional relationship between OSA and PA. However, the underlying mechanism between them is not yet clear. This study aims to investigate the shared genetic characteristics and potential molecular mechanisms of PA and OSA. We obtained microarray datasets of aldosterone-producing adenoma (APA) and OSA from the gene expression omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to select co-expression modules associated with APA and OSA, and common genes of the two diseases were obtained by intersection. Subsequently, hub genes for APA and OSA were identified through functional enrichment analysis, protein-protein interaction (PPI), datasets, and public database. Finally, we predicted the transcription factors (TFs) and mirRNAs of the hub genes. In total, 52 common genes were obtained by WGCNA. The Gene Ontology (GO) of common genes includes interleukin-1 response, cytokine activity, and chemokine receptor binding. Functional enrichment analysis highlighted the TNF, IL-17 signaling, and cytokine-cytokine receptor interactions related to APA and OSA. Through PPI, datasets, and public databases verification, we identified 5 hub genes between APA and OSA (IL6, ATF3, PTGS2, CCL2, and CXCL2). Our study identified shared 5 hub genes between APA and OSA (IL6, ATF3, PTGS2, CCL2, and CXCL2). Through bioinformatics analysis, we found that the 2 disorders showed relative similarity in terms of inflammation, stress, and impaired immune function. The identification of hub genes may offer potential biomarkers for the diagnosis and prognosis of PA and OSA.

Living environment, service quality satisfaction and depression among Chinese older adults in elderly caring social organizations.

BACKGROUND: Older adults living in elderly caring social organizations (SOs) are prone to suffer from depression. Many studies have found correlations between environmental and quality-of-life factors and depression; however, evidence from elderly caring SOs is rare, particularly in China. METHODS: A cross-sectional study was conducted among service recipients in elderly caring SOs in Anhui and Chongqing, China. Data on demographic and health-related characteristics, living environment factors, and service quality satisfaction factors in 2171 older adults were used for analysis. The binary logistic regression model was conducted to estimate the association between living environment and service quality satisfaction factors and depression. RESULTS: Our results indicated that living environment factors in terms of exposure to suitable temperature and humidity (OR = 0.655; 95 % CI: 0.446, 0.963), green coverage >30 % (OR = 0.432; 95 % CI: 0.337, 0.553) were associated with lower odds of developing depression. Also, an opposite relationship was found in the noise factor (OR = 1.985; 95 % CI: 1.395, 2.823). Higher satisfaction with admission and discharge services, dietary services, entertainment services, and psychological support services were also found to be associated with a lower risk of depression. LIMITATIONS: A cross-sectional design precluded determining whether living environment, service quality satisfaction, and depression are causally related. Measurement of living environment factors and service quality satisfaction factors needs to be further clarified comprehensively. CONCLUSIONS: Enhancing the living environment and the quality of the services provided to seniors in the elderly caring SOs is conducive to the reduction of the likelihood of depression.

Revealing the enhancement effect of social capital on the individual performance of core members in elderly caring organizations: A study from Anhui, China.

Aging is a challenge to global development. This challenge is particularly significant for China because it has the largest elderly population worldwide. The proportion of aging population continues to increase, and solely relying on government efforts to meet the needs of the elderly is inadequate. Hence, involvement of social organizations in elderly care services is needed. Their core members exhibit higher sense of responsibility and identification with the organization than regular members, thus profoundly affecting organizational development. Based on the Social Capital Theory, this study employed a multistage stratified random sampling method to examine the social capital stock of elderly social organizations and their core members across six cities in Anhui Province, China. Chi-square tests analyzed the relationship between the core members' demographic factors and individual performance. Independent-sample t-tests assessed the relationship between social capital and individual performance. Finally, binary logistic regression models determined the factors influencing the individual performance of core members. Social networks within core members' social capital and the internal social capital of elderly caring social organizations (ESOs) affect the individual performance of core members. Therefore, organizations should provide more training opportunities for core members to expand their networks. Cultivating a shared language and vision as components of social capital can enhance organizational cohesion and operational stability.

Taxonomic and functional shifts of gut microbiome in immunoglobulin A vasculitis children and their mothers.

Objectives: To examine the gut microbiota characteristics in children with immunoglobulin A vasculitis and their interrelationships with the host, while evaluate the vertical inheritance of microbiota in the development and progression of IgA vasculitis. Methods: This study investigated the gut microbiome of 127 IgA vasculitis mother-child pairs and 62 matched healthy mother-child pairs, and compared the gut microbial composition of different groups. The pathway enrichment analysis evaluated potential gut microbiome-mediated pathways involved in the pathophysiology of IgA vasculitis. The Spearman correlation analysis illustrated the relationships between clinical variables and bacterial biomarkers. Results: This study identified distinct intestinal microbiome in IgA vasculitis children compared to healthy children, and further pointed out the association in gut microbiota between IgA vasculitis children's and their mother's. The relative abundance of Megamonas and Lactobacillus in IgAV children was positively correlated with that in their mothers. The pathway enrichment analysis found microbial biosynthesis of vitamins and essential amino acids was upregulated in children with IgA vasculitis. Correlation analysis showed bacterial biomarkers were correlated with indicators of blood coagulation. Conclusion: Children with IgA vasculitis have unique bacterial biomarkers and may affect coagulation function, and their gut microbiome was closely associated with that of their mothers. The observed association in gut microbiota between IgA vasculitis children and their mothers suggested a potential intergenerational influence of the maternal microbiota on the development or progression of IgA vasculitis in children.

Causal relationship between several autoimmune diseases and renal malignancies: A two-sample mendelian randomization study.

OBJECTIVE: Observational studies have shown an association between systemic autoimmune disease (AD) and multiple malignancies. However, due to the difficulty indetermining the temporal nature of the order, their causal relationship remains elusive. Based on pooled data from a large population-wide genome-wide association study (GWAS), this study explores the genetic causality between systemic autoimmune disease and renal malignancy. METHODS: We took a series of quality control steps from a large-scale genome-wide association study to select single nucleotide polymorphisms (SNPs) associated with systemic autoimmune disease as instrumental variables(IVs) to analyze genetic causality with renal malignancies. Inverse variance weighting (IVW), MR- Egger, weighted median, simple model and weighted model were used for analysis. The results were mainly based on IVW (Random Effects), followed by sensitivity analysis. Inverse-Variance Weighted(IVW) and MR-Egger were used to test for heterogeneity. MR- Egger is also used for pleiotropic testing. A single SNP analysis was used to identify single nucleotide polymorphisms (SNPs) with potential impact. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate causality, and sensitivity analysis was performed to evaluate pleiotropy and instrumental validity. RESULTS: Acute and subacute iridocylitis (P = 0.006, OR = 1.077), Ankylosing spondylitis (P = 0.002, OR = 1.051), and spondyloarthritis (P = 0.009, OR = 1.073) were positively associated with an increased risk of renal malignancy. Coxarthrosis (P = 0.008, OR = 0.483), Juvenile rheumatism (P = 0.011, OR = 0.897), and Systemic lupus erythematosus (P = 0.014, OR = 0.869) were negatively associated with an increased risk of renal malignancy. The results of sensitivity analysis were consistent without heterogeneity or pleiotropy. CONCLUSION: Our study suggests a causal relationship between different systemic autoimmune diseases and renal malignancies. These findings prompt health care providers to take seriously the potential risk of systemic autoimmune disease and provide new insights into the genetics of kidney malignancies.

Temporal development and potential interactions between the gut microbiome and resistome in early childhood.

Antimicrobial resistance-associated infections have become a major threat to global health. The gut microbiome serves as a major reservoir of bacteria with antibiotic resistance genes; whereas, the temporal development of gut resistome during early childhood and the factors influencing it remain unclear. Moreover, the potential interactions between gut microbiome and resistome still need to be further explored. In this study, we found that antibiotic treatment led to destabilization of the gut microbiome and resistome structural communities, exhibiting a greater impact on the resistome than on the microbiome. The composition of the gut resistome at various developmental stages was influenced by the abundance and richness of different core microbes. First exposure to antibiotics led to a dramatic increase in the number of opportunistic pathogens carrying multidrug efflux pump encoding genes. Multiple factors could influence the gut microbiome and resistome formation. The data may provide new insights into early-life research.IMPORTANCEIn recent years, the irrational or inappropriate use of antibiotics, an important life-saving medical intervention, has led to the emergence and increase of drug-resistant and even multidrug-resistant bacteria. It remains unclear how antibiotic exposure affects various developmental stages of early childhood and how gut core microbes under antibiotic exposure affect the structural composition of the gut resistome. In this study, we focused on early antibiotic exposure and analyzed these questions in detail using samples from infants at various developmental stages. The significance of our research is to elucidate the impact of early antibiotic exposure on the dynamic patterns of the gut resistome in children and to provide new insights for early-life studies.

Synergistic horizontal transfer of antibiotic resistance genes and transposons in the infant gut microbial genome.

Transposons, plasmids, bacteriophages, and other mobile genetic elements facilitate horizontal gene transfer in the gut microbiota, allowing some pathogenic bacteria to acquire antibiotic resistance genes (ARGs). Currently, the relationship between specific ARGs and specific transposons in the comprehensive infant gut microbiome has not been elucidated. In this study, ARGs and transposons were annotated from the Unified Human Gastrointestinal Genome (UHGG) and the Early-Life Gut Genomes (ELGG). Association rules mining was used to explore the association between specific ARGs and specific transposons in UHGG, and the robustness of the association rules was validated using the external database in ELGG. Our results suggested that ARGs and transposons were more likely to be relevant in infant gut microbiota compared to adult gut microbiota, and nine robust association rules were identified, among which Klebsiella pneumoniae, Enterobacter hormaechei_A, and Escherichia coli_D played important roles in this association phenomenon. The emphasis of this study is to investigate the synergistic transfer of specific ARGs and specific transposons in the infant gut microbiota, which can contribute to the study of microbial pathogenesis and the ARG dissemination dynamics.IMPORTANCEThe transfer of transposons carrying antibiotic resistance genes (ARGs) among microorganisms accelerates antibiotic resistance dissemination among infant gut microbiota. Nonetheless, it is unclear what the relationship between specific ARGs and specific transposons within the infant gut microbiota. K. pneumoniae, E. hormaechei_A, and E. coli_D were identified as key players in the nine robust association rules we discovered. Meanwhile, we found that infant gut microorganisms were more susceptible to horizontal gene transfer events about specific ARGs and specific transposons than adult gut microorganisms. These discoveries could enhance the understanding of microbial pathogenesis and the ARG dissemination dynamics within the infant gut microbiota.

Mediation role of anxiety on social support and depression among diabetic patients in elderly caring social organizations in China during COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Diabetes has become a prominent global public health problem, which is an important cause of death, disease burden, and medical and health economic burden. Previous studies have reported that majority of persons diagnosed with diabetes later presented with psychological and mental health diseases. The study aimed to explore the mediation role of anxiety on social support and depression among diabetic patents in elderly caring social organizations (SOs). METHODS: A multi-stage stratified cluster random sampling method was used in this cross-sectional study, and a questionnaire consisting of demographic questionnaire, MSPSS, GAD-7, and CES-D-10 was utilized to gather data. SPSS 22.0 and MPLUS 7.4 were used for statistical analysis. Spearman correlation analysis was employed to investigate correlations of key variables. A generalized linear model was used to exam factors associated with depression. Finally, the mediation effect among study variables was investigated by structural equation modeling (SEM). RESULTS: The average scores of social support, anxiety, and depression were 58.41 ± 14.67, 2.95 ± 3.95, and 7.24 ± 5.53, respectively. The factors of gender, social support, and anxiety were identified as significantly influential factors related to depression among diabetic patients in elderly caring SOs. The effect of social support on depression was significantly mediated by anxiety (ß = -0.467, 95%CI: -0.813 to -0.251). Furthermore, anxiety partially mediated the relationship between family support and depression (ß = -0.112, 95%CI: -0.229 to -0.012), and anxiety functioned as a complete mediator in the effect of significant others' support and depression (ß = -0.135, 95%CI: -0.282 to -0.024). CONCLUSIONS: The indirect effect of social support on depression through anxiety among diabetic patients in elderly caring SOs was elucidated. Social support played a key role in maintaining and regulating their mental health, particularly from family and significant others. Social support provided by both family and significant others exerted an important influence on maintaining and regulating their mental health. In light of this pathway, the elderly caring SOs should enhance the magnitude of social support from these two sources, thereby diminishing the likelihood of experiencing anxiety and depression.

The Effects of Lactobacillus johnsonii on Diseases and Its Potential Applications.

Lactobacillus johnsonii has been used as a probiotic for decades to treat a wide range of illnesses, and has been found to have specific advantages in the treatment of a number of ailments. We reviewed the potential therapeutic effects and mechanisms of L. johnsonii in various diseases based on PubMed and the Web of Science databases. We obtained the information of 149 L. johnsonii from NCBI (as of 14 February 2023), and reviewed their comprehensive metadata, including information about the plasmids they contain. This review provides a basic characterization of different L. johnsonii and some of their potential therapeutic properties for various ailments. Although the mechanisms are not fully understood yet, it is hoped that they may provide some evidence for future studies. Furthermore, the antibiotic resistance of the various strains of L. johnsonii is not clear, and more complete and in-depth studies are needed. In summary, L. johnsonii presents significant research potential for the treatment or prevention of disease; however, more proof is required to justify its therapeutic application. An additional study on the antibiotic resistance genes it contains is also needed to reduce the antimicrobial resistance dissemination.

Dual growth factor-modified microspheres nesting human-derived umbilical cord mesenchymal stem cells for bone regeneration.

BACKGROUND: Modular tissue engineering (MTE) is a novel "bottom-up" approach that aims to mimic complex tissue microstructural features. The constructed micromodules are assembled into engineered biological tissues with repetitive functional microunits and form cellular networks. This is emerging as a promising strategy for reconstruction of biological tissue. RESULTS: Herein, we constructed a micromodule for MTE and developed engineered osteon-like microunits by inoculating human-derived umbilical cord mesenchymal stem cells (HUMSCs) onto nHA/PLGA microspheres with surface modification of dual growth factors (BMP2/bFGF). By evaluating the results of proliferation and osteogenic differentiation ability of HUMSCs in vitro, the optimal ratio of the dual growth factor (BMP2/bFGF) combination was derived as 5:5. In vivo assessments showed the great importance of HUMSCs for osteogneic differentiation. Ultimately, direct promotion of early osteo-differentiation manifested as upregulation of Runx-2 gene expression. The vascularization capability was evaluated by tube formation assays, demonstrating the importance of HUMSCs in the microunits for angiogenesis. CONCLUSIONS: The modification of growth factors and HUMSCs showed ideal biocompatibility and osteogenesis combined with nHA/PLGA scaffolds. The micromodules constructed in the current study provide an efficient stem cell therapy strategy for bone defect repair.

Bidirectional Mediation Effects between Intratumoral Microbiome and Host DNA Methylation Changes Contribute to Stomach Adenocarcinoma.

The induction of aberrant DNA methylation is the major pathway by which Helicobacter pylori infection induces stomach adenocarcinoma (STAD). The involvement of the non-H. pylori gastric microbiota in this mechanism remains to be examined. RNA sequencing data, clinical information, and DNA methylation data were obtained from The Cancer Genome Atlas (TCGA) STAD project. The Kraken 2 pipeline was employed to explore the microbiome profiles. The microbiome was associated with occurrence, distal metastasis, and prognosis, and differential methylation changes related to distal metastasis and prognosis were analyzed. Bi-directional mediation effects of the intratumoral microbiome and host DNA methylation changes on the metastasis and prognosis of STAD were identified by mediation analysis. The expression of the ZNF215 gene was verified by real-time quantitative PCR (RT-qPCR). A cell counting kit 8 (CCK8) cell proliferation experiment and a cell clone formation experiment were used to evaluate the proliferation and invasion abilities of gastric cells. Our analysis revealed that H. pylori and other cancer-related microorganisms were related to the occurrence, progression, or prognosis of STAD. The related methylated genes were particularly enriched in related cancer pathways. Kytococcus sedentarius and Actinomyces oris, which interacted strongly with methylation changes in immune genes, were associated with prognosis. Cell experiments verified that Staphylococcus saccharolyticus could promote the proliferation and cloning of gastric cells by regulating the gene expression level of the ZNF215 gene. Our study suggested that the bi-directional mediation effect between intratumoral microorganisms and host epigenetics was key to the distal metastasis of cancer cells and survival deterioration in the tumor microenvironment of stomach tissues of patients with STAD. IMPORTANCE The burgeoning field of oncobiome research declared that members of the intratumoral microbiome besides Helicobacter pylori existed in tumor tissues and participated in the occurrence and development of gastric cancer, and the methylation of host DNA may be a potential target of microbes and their metabolites. Current research focuses mostly on species composition, but the functional genes of the members of the microbiota are also key to their interaction with the host. Therefore, we focused on characterizing the species composition and functional gene composition of microbes in gastric cancer, and we suggest that microbes may further participate in the occurrence and development of cancer by influencing abnormal epigenetic changes in the host. Some key bioinformatics analysis results were verified by in vitro experiments. Thus, we consider that the tumor microbiota-host epigenetic axis of gastric cancer microorganisms and the host explains the mechanism of the microbiota participating in cancer occurrence and development, and we make some verifiable experimental predictions.

The satisfaction of elderly people with elderly caring social organizations and its relationship with social support and anxiety during the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: With the deepening of China's aging population, higher demands have been placed on the supply of elderly care services. As one of the main sources of providing elderly care services, the quality of service provided by elderly caring social organizations (SOs) directly affects the quality of life of the elderly. In recent years, mental health issues among the elderly have become increasingly prominent, especially with the onset of the COVID-19 pandemic. Necessitating the need to pay much more attention to the social support and mental health of this population. This study, therefore, explores the mediating role of institutional satisfaction between the social support and anxiety levels of elderly people in Chongqing's elderly caring SOs. METHOD: This study employed a multi-stage stratified random sampling method to survey 1004 service recipients in elderly caring social organizations from July to August 2022. The self-made sociodemographic questionnaire, institutional satisfaction questionnaire, MSPSS, and GAD-7 were used to collect data on sociodemographic characteristics, institutional satisfaction, social support, and anxiety levels of older adults. Exploratory Factor Analysis and Cronbach's alpha were used to test construct validity and scale reliability, respectively. Data features were described with One-Way Analysis of Variance, while Multiple Linear Regression and Structural Equation Modeling were used to evaluate relationships between social support, institutional satisfaction, and anxiety levels. RESULTS: The average institutional satisfaction score for elderly people in elderly caring SOs was 48.14 ± 6.75. Specifically, the satisfaction score for environmental quality and the satisfaction score for service quality were 16.63 ± 2.56 and 31.52 ± 4.76, respectively. In terms of socio-demographic variables, the presence of visits from relatives, personal annual average income, and self-rated health status all have significant effects on anxiety. Elders who receive visits from relatives have lower levels of anxiety compared to those who do not. Personal annual average income and self-rated health status are negatively correlated with anxiety levels. Social support had significant positive effect on institutional satisfaction, while institutional satisfaction had significant negative effect on anxiety. Institutional satisfaction partially mediated the relationship between social support and anxiety. CONCLUSIONS: Our research demonstrates that improving the quality of organizational services in elderly caring SOs and increasing institutional satisfaction among the elders has significant potential for reducing anxiety levels among the elderly. Additionally, the social support by visits from family members cannot be overlooked. We encourage increasing the frequency of family visits through various means to enhance the support provided to elderly individuals.

Study on prenatal diagnosis and pregnancy outcome analysis of fetuses with cardiac rhabdomyoma.

OBJECTIVE: To investigate the prenatal imaging characteristics, genetic characteristics and pregnancy outcome of fetuses with cardiac rhabdomyoma. STUDY DESIGN: The prenatal ultrasound, cranial MRI imaging information and genetic test results of 35 fetuses prenatally diagnosed with cardiac rhabdomyoma were collected and retrospectively analyzed, and the pregnancy outcome was followed up. RESULT: Cardiac rhabdomyomas mainly occurred in left ventricular wall and ventricular septum; cranial MRI imaging was found abnormal in 38.1% (8/21) of the fetuses; genetic test was found abnormal in 58.82% (10/17) of the fetuses; the fetus was born in 12 cases and the pregnancy was terminated in 23 cases. CONCLUSION: TRIO whole exome sequencing (TrioWES) is recommended as the genetic test regime for cardiac rhabdomyoma. The comprehensive evaluation of prognosis of fetuses needs to consider the genetic results and whether the brain is involved; the prognosis of fetuses with simple cardiac rhabdomyoma is good.

Gut microbiota diversity of hospitalized older adult patients with and without antibiotic-associated diarrhea.

BACKGROUND: The incidence of antibiotic-related diarrhea (AAD) is high in older adults. AIM: To examine the gut microbiota changes in older adults who received antibiotics to identify the microbial signatures associated with antibiotic use and AAD. METHODS: A nested prospective observational cohort study was conducted between December 2019 and June 2021 in patients ≥ 65 years old at Huashan Hospital affiliated with Fudan University. The patients were grouped as antibiotic-treated (HA group) and no antibiotics (HC group); the HA group was subdivided as with vs. without AAD. Fecal samples were collected at admission (i.e., before eventual antibiotics) and after 7 days. RESULT: Thirty-eight and 19 participants were included in the HA and HC groups. There were significant differences in gut microbiota between the HA after antibiotics vs. HC groups, with a higher Firmicutes/Bacteroidetes ratio. Before antibiotics in the HA group, the relative abundances of Akkermansia and Alistipes were lower in the AAD subgroup than the no-AAD subgroup, while the relative abundance of Actinomyces was higher. After antibiotics in the HA group, specific bacterial species were decreased in the AAD subgroup compared with the no-AAD subgroup. Among HA participants without probiotics, the abundance of Akkermansia in the patients without AAD was higher than in the patients with AAD at baseline (P = 0.007). CONCLUSION: Patients with or without AAD have different gut microbiota compositions before antibiotics. Antibiotics can lead to dysbiosis, with a decrease in beneficial bacteria and an increase in Enterococcus.

The Interaction between Intratumoral Microbiome and Immunity Is Related to the Prognosis of Ovarian Cancer.

Microbiota can influence the occurrence, development, and therapeutic response of a wide variety of cancer types by modulating immune responses to tumors. Recent studies have demonstrated the existence of intratumor bacteria inside ovarian cancer (OV). However, whether intratumor microbes are associated with tumor microenvironment (TME) and prognosis of OV still remains unknown. The RNA-sequencing data and clinical and survival data of 373 patients with OV in The Cancer Genome Atlas (TCGA) were collected and downloaded. According to the knowledge-based functional gene expression signatures (Fges), OV was classified into two subtypes, termed immune-enriched and immune-deficient subtypes. The immune-enriched subtype, which had higher immune infiltration enriched with CD8+ T cells and the M1 type of macrophages (M1) and higher tumor mutational burden, exhibited a better prognosis. Based on the Kraken2 pipeline, the microbiome profiles were explored and found to be significantly different between the two subtypes. A prediction model consisting of 32 microbial signatures was constructed using the Cox proportional-hazard model and showed great prognostic value for OV patients. The prognostic microbial signatures were strongly associated with the hosts' immune factors. Especially, M1 was strongly associated with five species (Achromobacter deleyi and Microcella alkaliphila, Devosia sp. strain LEGU1, Ancylobacter pratisalsi, and Acinetobacter seifertii). Cell experiments demonstrated that Acinetobacter seifertii can inhibit macrophage migration. Our study demonstrated that OV could be classified into immune-enriched and immune-deficient subtypes and that the intratumoral microbiota profiles were different between the two subtypes. Furthermore, the intratumoral microbiome was closely associated with the tumor immune microenvironment and OV prognosis. IMPORTANCE Recent studies have demonstrated the existence of intratumoral microorganisms. However, the role of intratumoral microbes in the development of ovarian cancer and their interaction with the tumor microenvironment are largely unknown. Our study demonstrated that OV could be classified into immune-enriched and -deficient subtypes and that the immune enrichment subtype had a better prognosis. Microbiome analysis showed that intratumor microbiota profiles were different between the two subtypes. Furthermore, the intratumor microbiome was an independent predictor of OV prognosis that could interact with immune gene expression. Especially, M1 was closely associated with intratumoral microbes, and Acinetobacter seifertii could inhibit macrophage migration. Together, the findings of our study highlight the important roles of intratumoral microbes in the TME and prognosis of OV, paving the way for further investigation into its underlying mechanisms.

Pathogenic/likely pathogenic copy number variations and regions of homozygosity in fetal central nervous system malformations.

OBJECTIVE: To explore pathogenic/likely pathogenic copy number variations (P/LP CNVs) and regions of homozygosity (ROHs) in fetal central nervous system (CNS) malformations. METHODS: A cohort of 539 fetuses with CNS malformations diagnosed by ultrasound/MRI was retrospectively analyzed between January 2016 and December 2019. All fetuses were analyzed by chromosomal microarray analysis (CMA). Three cases with ROHs detected by CMA were subjected to whole-exome sequencing (WES). The fetuses were divided into two groups according to whether they had other structural abnormalities. The CNS phenotypes of the two groups were further classified as simple (one type) or complicated (≥ 2 types). RESULTS: (1) A total of 35 cases with P/LP CNVs were found. The incidence of P/LP CNVs was higher in the extra-CNS group [18.00% (9/50)] than in the isolated group [5.32% (26/489)] (P < 0.01), while there was no significant difference between the simpletype and complicated-type groups. (2) In the simple-type group, the three most common P/LP CNV phenotypes were holoprosencephaly, Dandy-Walker syndrome, and exencephaly. There were no P/LP CNVs associated with anencephaly, microcephaly, arachnoid cysts, ependymal cysts, or intracranial hemorrhage. (3) Only four cases with ROHs were found, and there were no cases of uniparental disomy or autosomal diseases. CONCLUSION: The P/LP CNV detection rates varied significantly among the different phenotypes of CNS malformations, although simple CNS abnormalities may also be associated with genetic abnormalities.

Follicle-Stimulating Hormone Promotes the Development of Endometrial Cancer In Vitro and In Vivo.

Endocrine disruptors as risk factors for endometrial cancer (EC) are positively correlated with serum follicle-stimulating hormone (FSH) levels. Additionally, increased FSH is associated with EC. However, its exact mechanism is not yet clear. Therefore, this study investigated how FSH affects the occurrence of EC. Using immunohistochemistry (IHC), immunofluorescence (IF), and Western blot (WB), we found that FSH receptor (FSHR) was expressed in both EC tissues and cell lines. To explore the effect of FSH on EC in vitro, Ishikawa (ISK) cells were cultured in different doses of FSH, and it was found that FSH could promote the proliferation and migration of ISK cells. Furthermore, the detection of key molecules of migration and apoptosis by WB showed that FSH promoted cell migration and inhibited apoptosis. Additionally, FSH decreased AMPK activation. To clarify the effect of FSH on EC in vivo, we subcutaneously planted ISK cells into ovariectomized mice and then gave two of the groups oestradiol (E2). In comparison with the OE (ovariectomy plus E2) and sham groups, the growth rates and weights of the tumors in the OE plus FSH group were significantly higher. The findings above suggest that FSH promotes the proliferation and metastasis of EC, providing a new strategy for the treatment of EC.

Pivotal interplays between fecal metabolome and gut microbiome reveal functional signatures in cerebral ischemic stroke.

BACKGROUND: Integrative analysis approaches of metagenomics and metabolomics have been widely developed to understand the association between disease and the gut microbiome. However, the different profiling patterns of different metabolic samples in the association analysis make it a matter of concern which type of sample is the most closely associated with gut microbes and disease. To address this lack of knowledge, we investigated the association between the gut microbiome and metabolomic profiles of stool, urine, and plasma samples from ischemic stroke patients and healthy subjects. METHODS: We performed metagenomic sequencing (feces) and untargeted metabolomics analysis (feces, plasma, and urine) from ischemic stroke patients and healthy volunteers. Differential analyses were conducted to find key differential microbiota and metabolites for ischemic stroke. Meanwhile, Spearman's rank correlation and linear regression analyses were used to study the association between microbiota and metabolites of different metabolic mixtures. RESULTS: Untargeted metabolomics analysis shows that feces had the most abundant features and identified metabolites, followed by urine and plasma. Feces had the highest number of differential metabolites between ischemic stroke patients and the healthy group. Based on the association analysis between metagenomics and metabolomics of fecal, urine, and plasma, fecal metabolome showed the strongest association with the gut microbiome. There are 1073, 191, and 81 statistically significant pairs (P < 0.05) in the correlation analysis for fecal, urine, and plasma metabolome. Fecal metabolites explained the variance of alpha-diversity of the gut microbiome up to 31.1%, while urine and plasma metabolites only explained the variance of alpha-diversity up to 13.5% and 10.6%. Meanwhile, there were more significant differential metabolites in feces than urine and plasma associated with the stroke marker bacteria. CONCLUSIONS: The systematic association analysis between gut microbiome and metabolomics reveals that fecal metabolites show the strongest association with the gut microbiome, followed by urine and plasma. The findings would promote the association study between the gut microbiome and fecal metabolome to explore key factors that are associated with diseases. We also provide a user-friendly web server and a R package to facilitate researchers to conduct the association analysis of gut microbiome and metabolomics.

The Relationship between Social Support and Anxiety among Rural Older People in Elderly Caring Social Organizations: A Cross-Sectional Study.

BACKGROUND: Social support and anxiety have a major impact on later life quality in rural, older people in elderly caring social organizations (SOs). This study aimed to explore the relationship between social support and anxiety and their relevant influential factors among rural older people in elderly caring SOs in Anhui Province, China. METHODS: This cross-sectional study was conducted through a multi-stage stratified cluster random sampling method. Independent t-tests, one-way ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, and a generalized linear model were employed. RESULTS: A significantly negative association between friends' support and anxiety were found among rural older people in elderly caring SOs. Statistically significant relationships were found between social support and gender, marital status, education level, whether visited by relatives, and institutional satisfaction. Similarly, anxiety was associated with gender, institutional satisfaction, comorbid chronic diseases, and friends' support. CONCLUSIONS: Social support from friends plays an important role in preventing and regulating anxiety among rural older people, especially those from elderly caring SOs. To reduce the occurrence and level of anxiety among rural elderly in elderly caring SOs, an effort should be given to strengthening social support, improving institutional satisfaction, and emphasizing comorbid chronic diseases.

Downregulation of LINC00221 promotes angiopoiesis in HUVEC and inhibits recruitment of macrophages by augmenting miR-542-3p in trophoblast cells.

PURPOSE: To investigate the effects of long intergenic non-protein coding RNA 221 (LINC00221) on preeclampsia (PE) and its mechanism. METHODS: The expression of LINC00221 was detected in placental tissues from PE patients and normal pregnant women (non-PE). Next, the effects of LINC00221 silencing on trophoblast cells (HTR-8/SVneo and JEG-3) and co-cultured HUVECs or macrophages were evaluated. Afterwards, miR-542-3p was confirmed to bind to LINC00221 directly, and miR-542-3p mimics and inhibitors were transfected into trophoblast cells. Next, a rescue experiment was performed to examine the effect of LINC00221/miR-542-3p axis. Finally, the effect of LINC00221 was also verified in vivo in rat PE models. RESULTS: The expression of LINC00221 was higher in placental tissues of PE patients than those of non-PE. LINC00221 silencing significantly reduced MCP1 level and increased the VEGF level in trophoblast cells. LINC00221 knockdown in trophoblast cells remarkably enhanced VEGFR expression and the angiopoiesis of HUVECs, and decreased the migration and invasion of macrophages and reduced TNF-α level. Besides, LINC00221 knockdown decreased CHOP, p-IREα, p-PERK, and iNOS expression and increased Trx expression. Notably, LINC00221 negatively regulated miR-542-3p expression. MiR-542-3p overexpression had an effect to that of LINC00221 knockdown, while miR-542-3p inhibition had the opposite effect. Treatment with miR-542-3p inhibitors partially reversed the protective effect of LINC00221 silencing. PE rat model results were consistent with those of in vitro experiments. CONCLUSIONS: Downregulation of LINC00221 might reduce dysfunction, inflammatory responses, endoplasmic reticulum stress, and oxidative stress, and thereby protect against PE by augmenting miR-542-3p.