MASH1 induces neuron transdifferentiation of adrenal medulla chromaffin cells. / MASH1ä»‹å¯¼è‚¾ä¸Šè ºé«“è´¨å—œé“¬ç»†èƒžå‘ç”Ÿç¥žç»å ƒè½¬åˆ†åŒ–.

OBJECTIVES: Nerve growth factor (NGF) induces neuron transdifferentiation of adrenal medulla chromaffin cells (AMCCs) and consequently downregulates the secretion of epinephrine (EPI), which may be involved in the pathogenesis of bronchial asthma. Mammalian achaete scute-homologous 1 (MASH1), a key regulator of neurogenesis in the nervous system, has been proved to be elevated in AMCCs with neuron transdifferentiation in vivo. This study aims to explore the role of MASH1 in the process of neuron transdifferentiation of AMCCs and the mechanisms. METHODS: Rat AMCCs were isolated and cultured. AMCCs were transfected with siMASH1 or MASH1 overexpression plasmid, then were stimulated with NGF and/or dexamethasone, PD98059 (a MAPK kinase-1 inhibitor) for 48 hours. Morphological changes were observed using light and electron microscope. Phenylethanolamine-N-methyltransferase (PNMT, the key enzyme for epinephrine synthesis) and tyrosine hydroxylase were detected by immunofluorescence. Western blotting was used to test the protein levels of PNMT, MASH1, peripherin (neuronal markers), extracellular regulated protein kinases (ERK), phosphorylated extracellular regulated protein kinases (pERK), and JMJD3. Real-time RT-PCR was applied to analyze the mRNA levels of MASH1 and JMJD3. EPI levels in the cellular supernatant were measured using ELISA. RESULTS: Cells with both tyrosine hydroxylase and PNMT positive by immunofluorescence were proved to be AMCCs. Exposure to NGF, AMCCs exhibited neurite-like processes concomitant with increases in pERK/ERK, peripherin, and MASH1 levels (all P<0.05). Additionally, impairment of endocrine phenotype was proved by a signifcant decrease in the PNMT level and the secretion of EPI from AMCCs (all P<0.01). MASH1 interference reversed the effect of NGF, causing increases in the levels of PNMT and EPI, conversely reduced the peripherin level and cell processes (all P<0.01). MASH1 overexpression significantly increased the number of cell processes and peripherin level, while decreased the levels of PNMT and EPI (all P<0.01). Compared with the NGF group, the levels of MASH1, JMJD3 protein and mRNA in AMCCs in the NGF+PD98059 group were decreased (all P<0.05). After treatment with PD98059 and dexamethasone, the effect of NGF on promoting the transdifferentiation of AMCCs was inhibited, and the number of cell processes and EPI levels were decreased (both P<0.05). In addition, the activity of the pERK/MASH1 pathway activated by NGF was also inhibited. CONCLUSIONS: MASH1 is the key factor in neuron transdifferentiation of AMCCs. NGF-induced neuron transdifferentiation is probably mediated via pERK/MASH1 signaling.

Factors influencing intercourse frequency among the young and middle-aged men. / å½±å“ä¸­é’å¹´ç”·æ€§æˆ¿äº‹é¢‘çŽ‡çš„å› ç´ .

OBJECTIVES: At present, there are few studies on the sexual activity of young and middle-aged men in China. This study aims to explore the factors that affect the frequency of intercourse among young and middle-aged men in China. METHODS: Data for 923 men aged 20-60 years were collected in the Health Management Center, Third Xiangya Hospital, Central South University from January 2019 to March 2019, and a questionnaire survey (including basic conditions and sexual function-related scales) was carried out in the subjects. Finally, the data were analyzed by multivariate logistic regression analysis. RESULTS: The age ( P <0.01), number of children ( P <0.01), total cholesterol ( P <0.05), low-density lipoprotein ( P <0.05), erectile function ( P <0.01) and premature ejaculation ( P <0.05) was significantly correlated with the frequency of intercourse in the young and middle-aged men in China. CONCLUSIONS: The sexual frequency in the middle-young men in China is closely related to factors such as age, number of children, total cholesterol, low-density lipoprotein, and sex function.

Role of an Exosomes-Related lncRNAs Signature in Tumor Immune Microenvironment of Gastric Cancer.

Background: Exosomes plays a crucial role in intercellular communication of gastric cancer (GC), while long non-coding RNAs (lncRNAs) contributes to the tumorigenesis and progression of GC. This study aims to explore the prognostic exosomes-related lncRNAs of GC patients. Methods: Data of 375 GC patients were obtained from the TCGA database. The entire cohort was randomly divided into a training cohort and a validation cohort in a 2:1 ratio. Exosomes-related lncRNAs were identified by the Pearson correlation analysis with reported exosomes-related genes. LASSO Cox regression was used to construct the signature. Results: A prognostic signature consisting of 11 exosomes-related lncRNAs was identified, and patients with lower risk scores had a better prognosis than those with higher risk scores. ROC curves and multivariate Cox regression analysis showed that the signature was an independent risk factor for prognosis in both the training (HR: 3.254, 95% CI: 2.310-4.583) and validation cohorts (HR: 1.974, 95% CI: 1.108-3.517). Gene set enrichment analysis (GSEA) suggested associations between the signature and several immune-related pathways. The identified signature was shown to be associated with GC tumor microenvironment. The expression of two immune checkpoints was also increased in the high-risk group, including B7-H3 and VSIR, indicating the potential role of the identified signature in GC immunotherapies. Conclusion: A novel exosomes-related lncRNA signature, which may be associated with tumor immune microenvironment and potentially serve as an indicator for immunotherapy, has been identified to precisely predict the prognosis of GC patients.

Analysis of Clinical Features and Risk Factors in Pregnant Women With Miliary Pulmonary Tuberculosis After In Vitro Fertilization Embryo Transfer.

Purpose: Miliary pulmonary tuberculosis (TB) among pregnant women after in vitro fertilization embryo transfer (IVF-ET) causes poor outcomes but is rarely reported. This study analyzed the clinical characteristics and risk factors of these patients to provide hints for further studies. Method: The demographic characteristics, clinical manifestations, radiologic features, treatment, and outcomes of six patients diagnosed from May 2012 to August 2021 in Xiangya Hospital and 69 patients that were reported in English or Chinese literature from January 1980 to August 2021 were retrospectively analyzed. Continuous variables were compared between groups by t-test or Mann-Whitney U test, and categorical variables were compared between groups by chi-square test or Fisher exact test. Univariate and multiple logistic regression analyses were used to determine the predictors of respiratory failure. Results: A total of 75 patients were included. The average age of patients was about 30 years. All patients had tubal obstruction; 5 of them were diagnosed with pelvic TB before. Thirteen cases had a history of pulmonary or extrapulmonary TB, six out of them without any antituberculosis treatment history. All patients were in their first or second trimester during the onset of symptoms. The average interval between onset of symptoms and radiologic examination was about 21 days. The most common abnormalities on chest computed tomography scan were multiple nodules, pulmonary infiltrate, and consolidation. Merely 10 patients obtained bacteriological diagnosis by Mycobacterium tuberculosis culture or polymerase chain reaction test. The other patients were clinically diagnosed. All the patients received antituberculosis treatment. Although 44% of patients had fatal complications, all cases were cured or improved after antituberculosis treatment. Unfortunately, only eight fetuses survived (10.6%). The most frequent and severe complication was type I respiratory failure (20%). Patients with expectoration, dyspnea, coarse breath sounds, ground-glass opacity, and pulmonary infiltrate or consolidation were more likely to have respiratory failure (P < 0.05). Ground-glass opacity (OR = 48.545, 95% CI = 2.366-995.974, P = 0.012) and pulmonary infiltrate or consolidation (OR = 19.943, 95% CI = 2.159-184.213, P = 0.008) were independent predictors for respiratory failure. Conclusion: Tube infertility with underscreened or untreated TB is a risk factor for miliary TB during pregnancy after IVF-ET. Ground-glass opacity and pulmonary infiltrate or consolidation are predictors of respiratory failure. We demonstrate risk factors for incidence and complications to supply clues for future intervention and improve patient prognosis.

Downregulated Copper Homeostasis-Related Gene FOXO1 as a Novel Indicator for the Prognosis and Immune Response of Breast Cancer.

Copper (Cu) is one of the essential microelements for all living systems. Studies have illustrated the biological significance of Cu homeostasis in human cancers, including breast cancer (BRCA). Nevertheless, the detailed roles of Cu homeostasis in BRCA need to be further explored. Here, we identified a downregulated Cu homeostasis-related gene FOXO1 and investigated the potential functions of FOXO1 in BRCA through several bioinformation databases. The BRCA patients with high level of FOXO1 displayed favorable prognostic values. Subsequently, enrichment analysis of FOXO1 coexpressed genes revealed that the top three enriched KEGG pathways were spliceosome, oxidative phosphorylation, and ribosome. Immunoinfiltration analysis indicated that aberrantly expressed FOXO1 showed positive correlations with the subcellular infiltration of macrophages and neutrophils in BRCA. Moreover, FOXO1 expression was positively associated with multiple immune checkpoints, such as sialic acid-binding immunoglobulin-like lectin 15 (SIGLEC15), indoleamine 2,3-dioxygenase 1 (IDO1), programmed cell death 1 ligand 1 (PD-L1/CD274), hepatitis A virus cellular receptor 2 (HAVCR2), programmed cell death 1 (PDCD1), cytotoxic T lymphocyte antigen 4 (CTLA4), and programmed cell death 1 ligand 2 (PDCD1LG2). Overall, these findings would deepen our understanding of FOXO1 in BRCA prognosis and immunotherapy response, representing a promising therapeutic strategy for BRCA patients.

Ferroptosis-Related Gene MT1G as a Novel Biomarker Correlated With Prognosis and Immune Infiltration in Colorectal Cancer.

Ferroptosis, a newly discovered way of cell death, has been proved to be involved in the oncogenesis and development of cancers, including colorectal cancer (CRC). Here, by identifying the differentially expressed genes (DEGs) from three CRC transcriptome microarray datasets (GSE20842, GSE23878, and GSE25070), we found that the expression of MT1G was significantly decreased in CRC tissues, and the patients with a high level of MT1G displayed a poor prognosis. Quantitative PCR (qPCR) further confirmed the downregulated MT1G in two CRC cells, HCT8 and HCT116. The colony-forming assay indicated that the MT1G overexpression exhibited a remarkable inhibition of cell proliferation in HCT8 and HCT116 cells. In addition, we explored the co-expressed genes of MT1G to gain a better understanding of its potential signaling pathways. Aberrantly expressed MT1G also affected the immune response of CRC patients. Collectively, these findings might deepen our comprehension on the potential biological implications of MT1G in CRC.

Prevalence, awareness, and associated factors of high blood pressure among female migrant workers in Central South China.

Background: Although many young Chinese women migrate to urban regions for better opportunities, little is known about the prevalence and awareness of having high blood pressure (HBP) in this population. This study investigated the prevalence, awareness, and factors associated with HBP among young female migrant workers in Central South China. Methods: We conducted a cross-sectional study to identify HBP (2017 ACC/AHA guidelines) among female migrant workers aged 18-45 years in Central South China. Demographics, anthropometric measurements, hypertension-related lifestyle, awareness of HBP, and blood pressure were recorded. Logistic regression analysis was used to identify the factors associated with HBP (blood pressure ≥ 130/80 mmHg). Results: Overall, 232 female migrants participated in the study (mean age 34.4; standard deviation: 6.4 years). The prevalence of HBP was 27.2% (95% CI [21.6-33.2]), and 88.9% of the participants were unaware of their HBP status. Having rural medical insurance (odds ratio [OR] = 20.7; 95% confidence interval 95% CI [2.1-204.8]), awareness of having HBP (OR = 5.1; 95% CI [1.4-18.5]), physical inactivity (OR = 2.9; 95% CI [1.1-7.9]), and being overweight/obese (OR = 2.7; 95% CI [1.3-6.1]) were independently associated with HBP. Conclusions: This study revealed a high prevalence of HBP among young Chinese female migrant workers, as well as a high frequency of being unaware of their condition and some associated factors (rural medical insurance, awareness of having HBP, physical inactivity, and overweight/obesity). The uncontrolled HBP among young Chinese female migrant workers suggested that health education needs further promotion in such a population.

Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease?

INTRODUCTION: Erectile dysfunction (ED) and cardiovascular diseases (CVDs) share many common risk factors. ED could be a strong independent predictive factor of CVDs. Furthermore, the treatment of ED had been shown to be beneficial for cardiovascular diseases. However, the association between ED and CVDs has been reported scarcely in the literature. AIM: To investigate urologists' perception, diagnosis, and treatment of CVDs in patients with ED. METHODS: The study was conducted as a prospective study from November 2018 through February 2019, including urologists aged 18-64 years. All participants completed a survey of the knowledge of ED via an online questionnaire platform in 7 WeChat groups of urologists. WeChat is the most popular multipurpose messaging and social media in China. MAIN OUTCOME MEASURE: The main outcomes were the answers that urologists chose or filled. RESULTS: 449 urologists were included. Most of participants (375, 83.5%) agreed that CVDs are associated with ED. Only 231 participants (51.4%) thought ED was an independent disorder. The awareness of the association between ED and CVDs is significantly higher among male urologists than their female counterparts. Although 378 (83.6%) participants believed that the progression of these 2 diseases was consistent, only 181 (44.9%) would do conjoined assessment of both CVDs and ED. In addition, most urologists only considered conventional treatment, such as psychological intervention (341, 75.4%) and phosphodiesterase type 5 inhibitor (PDE5i) therapy (318, 70.4%) for their patients, whereas 339 urologists (88.3%) claimed that they would treat CVDs in patients with both ED and CVDs. 344 (76.6%) urologists showed some concerns over PDE5is. CONCLUSION: Urologists' assessment of CVDs in patients with ED was disappointing especially among young and female urologists or those working in underserved areas. Besides, the urologists' treatments of ED were not updated, and their attitudes toward the safety and effectiveness of PDE5is for CVDs were not optimistic. Li D, Li X, Peng A, et al. Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease? Sex Med 2020;8:195-204.