Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*

Erectile dysfunction (ED) is prevalent among men, but its relationship with dietary habits is uncertain. The aim of our study was to assess whether dietary patterns enhance erectile function by reviewing the literature published before August 1, 2022, via PubMed, Web of Science, and EMBASE databases. The data compiled included author details; publication dates, countries, treatments, patient numbers, ages, follow-ups, and clinical trial outcomes, such as ED cases, odds ratios (ORs), confidence intervals (CIs), and International Index of Erectile Function-5 (IIEF-5) scores with means and standard deviations. An analysis of 14 studies with 27 389 participants revealed that plant-based diets (OR = 0.71, 95% CI: 0.66-0.75; P < 0.00001), low-fat diets (OR = 0.27, 95% CI: 0.13-0.53; P = 0.0002), and alternative diets such as intermittent fasting and organic diets (OR = 0.54, 95% CI: 0.36-0.80; P = 0.002) significantly reduced ED risk. High-protein low-fat diets (hazard ratio [HR] = 1.38, 95% CI: 1.12-1.64; P < 0.00001) and high-carb low-fat diets (HR = 0.79, 95% CI: 0.55-1.04; P < 0.00001) improved IIEF-5 scores. Combined diet and exercise interventions decreased the likelihood of ED (OR = 0.49, 95% CI: 0.28-0.85; P = 0.01) and increased the IIEF-5 score (OR = 3.40, 95% CI: 1.69-5.11; P < 0.0001). Diets abundant in fruits and vegetables (OR = 0.97, 95% CI: 0.96-0.98; P < 0.00001) and nuts (OR = 0.54, 95% CI: 0.37-0.80; P = 0.002) were also correlated with lower ED risk. Our meta-analysis underscores a strong dietary-ED association, suggesting that low-fat/Mediterranean diets rich in produce and nuts could benefit ED management.
Humans ; Male ; Erectile Dysfunction/epidemiology* ; Diet ; Diet, Fat-Restricted ; Feeding Behavior ; Penile Erection/physiology* ; Diet, Vegetarian

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Nitrogen narcosis is a neurological syndrome that manifests when humans or animals encounter hyperbaric nitrogen, resulting in a range of motor, emotional, and cognitive abnormalities. The anterior cingulate cortex (ACC) is known for its significant involvement in regulating motivation, cognition, and action. However, its specific contribution to nitrogen narcosis-induced hyperlocomotion and the underlying mechanisms remain poorly understood. Here we report that exposure to hyperbaric nitrogen notably increased the locomotor activity of mice in a pressure-dependent manner. Concurrently, this exposure induced heightened activation among neurons in both the ACC and dorsal medial striatum (DMS). Notably, chemogenetic inhibition of ACC neurons effectively suppressed hyperlocomotion. Conversely, chemogenetic excitation lowered the hyperbaric pressure threshold required to induce hyperlocomotion. Moreover, both chemogenetic inhibition and genetic ablation of activity-dependent neurons within the ACC reduced the hyperlocomotion. Further investigation revealed that ACC neurons project to the DMS, and chemogenetic inhibition of ACC-DMS projections resulted in a reduction in hyperlocomotion. Finally, nitrogen narcosis led to an increase in local field potentials in the theta frequency band and a decrease in the alpha frequency band in both the ACC and DMS. These results collectively suggest that excitatory neurons within the ACC, along with their projections to the DMS, play a pivotal role in regulating the hyperlocomotion induced by exposure to hyperbaric nitrogen.
Animals ; Gyrus Cinguli/drug effects* ; Male ; Mice, Inbred C57BL ; Locomotion/drug effects* ; Neurons/drug effects* ; Mice ; Nitrogen/toxicity* ; Inert Gas Narcosis/physiopathology* ; Corpus Striatum/physiopathology*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective:To investigate the clinical and genetic characteristics of a child with microcephaly-capillary malformation syndrome due to a STAMBP mutation. Methods:The clinical data of a case of microcephaly-capillary malformation syndrome caused by STAMBP gene mutation admitted to Anhui Children′s Hospital in August 2023 were collected. The genes of the child and his parents were detected by whole exome sequencing, and the risk was predicted by biological software. At the same time, the clinical characteristics of the child were analyzed and the literature was reviewed. Results:The patient is a male child aged 2 years and 7 months. The patient had special features, microcephaly, refractory epilepsy, severe comprehensive developmental delay, and capillary malformations. The results of genetic testing showed that the STAMBP gene in the child had complex heterozygous mutations NM_001353967: c.367delG[p.E123fs *27(p.Glu123fsTer27) and c.159A>C(p.Glu53Asp)], inherited from his mother and father respectively. The mutations have not been recorded in the HGMD, dbSNP and gnomAD databases,etc. The protein structure of the STAMBP gene was modeled that predicted c.367del(p.Glu123Lysfs *27) and c.159A>C (p.Glu53Asp) had a negative effect on the function of STAMBP protein. Conclusion:The STAMBP gene complex heterozygous mutations c.367delG(p.Glu123fsTer27) and c.159A>C(p.Glu53Asp) may be the pathogenic factor of this child, which further expands the variation spectrum of the STAMBP gene and the genotype of microcephaly-capillary malformation syndrome, and provides guidance for family genetic counseling.

BACKGROUND: Stress cardiomyopathy (SCM) currently has a high incidence in older adults, and the theories regarding its causes include "catecholamine myocardial toxicity" and "sympathetic hyperactivation". However, the role of the central nervous system in the pathogenesis of SCM remains unknown. We investigated the role of microglia activation in the paraventricular hypothalamic nucleus (PVN) in the development of SCM. METHODS: An SCM model was created using male Sprague-Dawley (SD) rats, immobilized for 6 h every day for a week. Electrocardiogram, cardiac electrophysiology, and echocardiography examinations were performed to verify the changes in cardiac structure and function in rats with SCM. RNA sequencing was used to explore the changes in the hypothalamus during SCM. In addition, brain and heart tissues were collected to detect microglial activation and sympathetic activity. RESULTS: The main findings were as follows: (1) immobilization stress successfully induced SCM in SD rats; (2) microglia were significantly activated in the hypothalamus, as evidenced by cytosol thickening, increases in the number of microglial branches, and microglia enriched in the PVN; (3) in SCM, the microglia in the PVN exhibited increased central and peripheral cardiac sympathetic activity and increased the expression of neuroinflammatory factors; and (4) it is possible that inhibiting microglial activation could suppress the sympathetic activity of the central nervous system and heart and increase cardiac electrical stability in SCM rats. CONCLUSIONS SCM was induced in SD rats by immobilization stress, acting through the activation of the hypothalamic microglia. The activated microglia were specifically enriched in the PVN, increasing the activity of the central and peripheral sympathetic nervous systems by regulating the expression of neuro-inflammatory factors, mediating dysfunction of the left ventricle, and increasing the susceptibility to ventricular arrhythmias.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Aim To investigate whether catechin can play against CCl

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.
Pregnancy ; Female ; Humans ; Young Adult ; Adult ; Retrospective Studies ; Altitude ; China/epidemiology* ; Heart Defects, Congenital/diagnostic imaging* ; Heart Septal Defects, Ventricular ; Echocardiography ; Fetal Heart/diagnostic imaging*