Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

ObjectiveTo assess the relapse rate， clinical efficacy， and safety of a traditional Chinese medicine （TCM） sequential syndrome differentiation protocol for frequently relapsing/steroid-dependent nephrotic syndrome （FRNS/SDNS） in children. MethodsA total of 151 children with FRNS/SDNS treated in the First Affiliated Hospital of Henan University of Chinese Medicine from December 2020 to June 2024 were randomized into an observation group （77 cases） and a control group （74 cases）. Both groups received Western medicine （prednisone tablets and tacrolimus capsules）. In addition， the observation group additionally underwent TCM sequential syndrome differentiation and the control group received 1/10 of the TCM dose. The 6-month intervention was followed by a 12-month follow-up， totaling 18 months of observation across seven time points （before treatment and after 1， 2， 4， 24， 52， 76 weeks of treatment）. The evaluation was carried out based on the following indicators. ① The relapse rates were mainly recorded after 24， 52， 76 weeks of treatment. ② The efficacy was evaluated based on the clinical remission rates after 1， 2， 4 weeks of treatment， the time to proteinuria clearance， the levels of 24-hour urine total protein （24-h UTP）， serum total protein （TP）， serum albumin （ALB）， cholesterol （CHO）， and triglycerides （TG） and the TCM symptom scores before treatment and after 24 weeks of treatment. ③ The treatment safety was evaluated based on blood routine and levels of liver enzymes， renal function indicators and blood glucose （Glu） before treatment and after 24 weeks of treatment. Results① Relapse rate： After 24 weeks of treatment， no significant difference in relapse rate was found between the two groups. The observation group showed lower relapse rates than the control group after 52 weeks of treatment ［24.2% （16/66） vs. 52.5% （31/59）， χ²=10.634， P<0.01］ and 76 weeks of treatment ［42.4% （28/66） vs. 74.6% （44/59）， χ²=13.186， P<0.01］ than the control group. ② Efficacy indicators： The two groups showed no significant difference in remission rate after 1 week of treatment. The observation group demonstrated higher remission rates after 2 weeks of treatment ［88.2% （67/76） vs. 74.0% （54/73）， Z=-1.999， P<0.05］ and 4 weeks of treatment ［94.7% （72/76） vs. 82.2% （60/73）， Z=-2.3589， P<0.05）. In addition， the observation group had shorter time to proteinuria clearance （P<0.01）. After treatment， both groups showed declined 24 h-UTP， CHO， TG， and TCM symptom scores and elevated TP and ALB levels （P<0.01）， and the observation group had lower CHO， TG， and TCM symptom scores and higher TP and ALB than the control group （P<0.05）. ③ Safety indicators： After treatment， both groups showed declined white blood cell count （WBC）， red blood cell count （RBC）， hemoglobin （HB）， and alanine aminotransferase （ALT） （P<0.05， P<0.01） and elevated Glu （P<0.01） and blood urea nitrogen （BUN） （P<0.05）. After 24 weeks of treatment， none of WBC， RBC， HB， PLT， ALT， AST， BUN， Cr or Glu had significant differences between groups. Moreover， the incidence of adverse reactions showed no significant difference between the two groups. ConclusionThe TCM sequential syndrome differentiation protocol effectively reduces the relapse rate， improves the remission rate， shortens the time to proteinuria clearance， raised serum protein levels， lowers blood lipid levels， and alleviates symptoms， demonstrating good clinical safety in children with FRNS/SDNS.

OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

BACKGROUND: Hypertension is a serious chronic disease that can significantly lead to various cardiovascular diseases, affecting vital organs such as the heart, brain, and kidneys. Our goal is to predict the risk of new onset hypertension using machine learning algorithms and identify the characteristics of patients with new onset hypertension. METHODS: We analyzed data from the 2011 China Health and Nutrition Survey cohort of individuals who were not hypertensive at baseline and had follow-up results available for prediction by 2015. We tested and evaluated the performance of four traditional machine learning algorithms commonly used in epidemiological studies: Logistic Regression, Support Vector Machine, XGBoost, LightGBM, and two deep learning algorithms: TabNet and AMFormer model. We modeled using 16 and 29 features, respectively. SHAP values were applied to select key features associated with new onset hypertension. RESULTS: A total of 4,982 participants were included in the analysis, of whom 1,017 developed hypertension during the 4-year follow-up. Among the 16-feature models, Logistic Regression had the highest AUC of 0.784(0.775∼0.806). In the 29-feature prediction models, AMFormer performed the best with an AUC of 0.802(0.795∼0.820), and also scored the highest in MCC (0.417, 95%CI: 0.400∼0.434) and F1 (0.503, 95%CI: 0.484∼0.505) metrics, demonstrating superior overall performance compared to the other models. Additionally, key features selected based on the AMFormer, such as age, province, waist circumference, urban or rural location, education level, employment status, weight, WHR, and BMI, played significant roles. CONCLUSION We used the AMFormer model for the first time in predicting new onset hypertension and achieved the best results among the six algorithms tested. Key features associated with new onset hypertension can be determined through this algorithm. The practice of machine learning algorithms can further enhance the predictive efficacy of diseases and identify risk factors for diseases.
Humans ; China/epidemiology* ; Hypertension/diagnosis* ; Machine Learning ; Male ; Female ; Middle Aged ; Adult ; Nutrition Surveys ; Algorithms ; Aged ; Risk Factors

OBJECTIVES: According to the World Health Organization (WHO), infertility rates have been steadily rising worldwide. Identifying risk factors for contrast agent reflux into the myometrium during hysterosalpingo-contrast sonography (HyCoSy) is of clinical significance in reducing this complication and improving infertility treatment. However, there is currently no standardized pre-evaluation method for predicting intra-myometrial contrast reflux, with clinical assessment often relying on physician experience and patient symptoms. This study aims to identify imaging risk factors for contrast agent reflux into the myometrium using four-dimensional (4D) HyCoSy and to construct a nomogram-based predictive model to assist in clinical decision-making. METHODS: A retrospective analysis was conducted on 1 274 infertile women who underwent 4D HyCoSy at the Women and Children's Hospital of Hunan and the the Third Xiangya Hospital of Central South University from January 1, 2020, to December 15, 2022. Patients were divided into a reflux group (n=234) and a non-reflux group (n=1 040) based on the presence of intra-myometrial contrast reflux. Univariate and multivariable Logistic regression analyses were used to identify significant predictors, which were then used to construct a nomogram model. Internal validation was performed using 500 bootstrap resamples. RESULTS: The age of the reflux group was significantly higher than that of the non-reflux group [(31.82±5.27) years vs (30.66±4.83) years, P=0.001 1]. Primary infertility was more common in the non-reflux group (50.96%), while secondary infertility dominated in the reflux group (76.50%), with 72.65% having a history of gynecological surgery (P<0.001). Abnormal menstrual volume and discomfort during the procedure were more common in the reflux group, while the non-reflux group tolerated higher contrast agent doses (P<0.001). Imaging differences included endometrial thickness, tubal wall smoothness, and peritoneal contrast dispersion, with the non-reflux group showing thicker endometrium and smoother, more patent tubes. The nomogram model yielded an area under the curve (AUC) of 0.854, indicating good predictive performance. The AUC of the decision curve analysis (DCA) for internal validation of the model was 0.737. When the threshold probability for contrast agent reflux into the myometrium ranged from 0.05 to 0.95, the maximum net benefit reached 0.18. The net benefit of applying the nomogram predictive model exceeded that of either full intervention or no intervention, indicating that the model demonstrates good clinical predictive performance. CONCLUSIONS The nomogram model, based on infertility type, endometrial thickness, contrast agent dose, and discomfort symptoms, effectively predicts intra-myometrial contrast agent reflux after 4D HyCoSy. It provides a valuable tool for clinicians to implement early preventive measures and reduce the risk of contrast leakage and associated complications.
Humans ; Female ; Nomograms ; Contrast Media/adverse effects* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Hysterosalpingography/methods* ; Infertility, Female/diagnostic imaging* ; Myometrium/diagnostic imaging* ; Risk Factors

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.