Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.

Aim To investigate the expression of or-ganic anion transporting polypeptide 4C1(Oatp4c1)-P-glycoprotein(P-gp)in the kidneys of obese mice in-duced by high-fat diet(HFD),and its impact on the pharmacokinetic changes of digoxin.Methods C57BL/6 mice were randomly divided into the Chow group and the HFD group.Body weight and blood glu-cose were recorded weekly.After successful model es-tablishment,digoxin was intraperitoneally injected,and blood was collected at different time points.Part of the blood samples was used for LC-MS/MS detection,and the other part was used for the detection of other bio-chemical indicators.After 16 weeks,the organs were removed and weighed.HE and immunohistochemical staining was used to observe the renal pathology and the expression of Villin,a marker of proximal tubules.Western blot and qPCR were combined to detect the expression of Villin,Oatp4c1 and P-gp.Results In the HFD group,body weight and blood glucose in-creased significantly.The blood concentration of digox-in rose,the area under the curve increased,and the half-life was prolonged.The proximal tubular epithelial cells shed,and the protein expression of Villin,Oatp4c1 and P-gp decreased significantly.Conclu-sions The down-regulation of Oatp4c1-P-gp expres-sion in the kidneys of HFD mice leads to an increase in the blood concentration of digoxin and a decrease in re-nal clearance.

Neoadjuvant chemoradiotherapy combined with surgery is the standard treatment for patients with locally advanced esophageal cancer. However, there is significant variability in how patients respond to neoadjuvant chemoradiotherapy. The value of existing conventional diagnostic methods in predicting the effectiveness of neoadjuvant chemoradiotherapy is limited. Image-based artificial intelligence (AI), particularly radiomics and deep learning technologies, have shown great potential in predicting the efficacy of neoadjuvant chemoradiotherapy by automatically quantifying and analyzing a vast amount of information in medical images. This review summarizes AI research based on CT, positron emission computed tomography (PET-CT), and other imaging modalities, highlighting the current limitations and future directions of the research.

Objective To investigate the relationship between peripheral blood immunoglobulin,erythrocyte sedimentation rate(ESR),homocysteine(Hey)and the severity of central nervous system vasculitis(CNSV)in children,as well as its impact on prognosis.Methods A total of 103 children with CNSV from February 2018 to February 2023 were selected as the study group,and 103 healthy children as the control group.The peripheral blood levels of immunoglobulin A(IgA),immunoglobulin G(IgG),immunoglobulin M(IgM),ESR and Hcy were compared between the 2 groups to evaluate the relationship between each index and the degree of CNSV disease[Birmingham vasculitis disease activity score(BVAS)]and its predictive value for prognosis.Results The levels of peripheral blood IgA,IgG,IgM,ESR and Hcy in the study group were higher than those in the control group of healthy children(P＜0.05);the BVAS scores and the levels of peripheral blood IgA,IgG,IgM,ESR and Hcy in children with active disease were higher than those in children with inactive disease(P＜0.05);the levels of peripheral blood IgA,IgG,IgM,ESR and Hcy were positively correlated with the BVAS scores in children with CNSV(P＜0.05);two cases were lost to follow-up after 6 months.Among the children with CNSV,76 had good prognosis and 25 poor prognosis.The levels of peripheral blood IgA,IgG,IgM,ESR and Hcy in children with poor prognosis were higher than those in children with good prognosis(P＜0.05);before and after correcting for other factors,peripheral blood IgA,IgG,IgM,ESR and Hcy were all independent factors affecting the prognosis of children with CNSV(P＜0.05);the area under curve(AUC)of peripheral blood IgA,IgG,IgM,ESR and Hey for predicting the prognosis of children with CNSV was 0.747,0.808,0.841,0.839,and 0.746,respectively,with optimal cutoff values of 350.58 mg/dL,1513.06 mg/dL,124.84 mg/dL,51.22 mm/h,and 13.66 pmol/L,respectively;the AUC of peripheral blood IgA,IgG,IgM,ESR and Hey for jointly predicting the prognosis of children with CNSV was 0.943(95％CI 0.878-0.979),with a sensitivity of 92.00％and a specificity of 93.42％,which was superior to individual prediction of each indicator.Conclusion Peripheral blood IgA,IgG,IgM,ESR and Hey are positively correlated with the severity of CNSV.Abnormally high expression increases the risk of poor prognosis,and the combined predictive value is reliable.

Objective: To investigate the influencing factors of lumbar disc herniation (LDH) among elderly patients with osteoporosis (OP), so as to provide the basis for early prevention of LDH in OP patients. Methods: The patients aged 60 years and above with OP who were treated in the clinic of Beijing Jishuitan Hospital from December 2022 to December 2023 were recruited as the study subjects. The data of demographic and clinical information were collected through the hospital medical record system. LDH was diagnosed according to the LDH Diagnosis and Treatment Guidelines. Factors affecting LDH among elderly patients with OP were identified using a multivariable logistic regression model. Results: A total of 500 patients with OP were included, with 188 males (37.60%) and 312 females (62.40%). The mean age was (69.05±3.28) years, and the course of OP was (6.37±2.11) years. There were 196 patients living alone, accounting for 39.20%. LDH among elderly patients with OP were detected in 78 cases, accourcing for 15.60%. Multivariable logistic regression analysis showed that the patients who were at ages of 70 years and above (OR=1.465, 95%CI: 1.197-1.793), lived alone (OR=1.777, 95%CI: 1.093-2.889), had a history of fracture (OR=1.799, 95%CI: 1.070-3.023) and scored higher in quality of life (OR=1.405, 95%CI: 1.230-1.605) were at higher risks of LDH, while the patients who had a history of taking calcium supplements (OR=0.562, 95%CI: 0.345-0.915) were at lower risks of LDH. Conclusion Age, living situation, history of fracture, history of taking calcium supplements and quality of life were influencing factors for LDH among elderly patients with OP.

Neck dissection and reconstruction are two important aspects of oral cancer treatment.There are various surgical methods for neck dissection and reconstruction,but all of them are performed by open surgery.This article reports a full endoscopic neck dis-section through the retroauricular hairline approach,the radical resection of the intraoral tumor and the repair of the defect by superfi-cial circumflex iliac artery perforator flap with in situ vascular anastomosis intraorally.The incision is located in the hairline,hidden and invisible,and there is no exposed surgical scar on the neck after surgery.This paper introduces the technique of scarless neck dissection combined with free skin flap repair for the treatment of oral cancer and discusses its advantages and disadvantages.

Grassroots communities, as the forefront of the transformation of national system and mechanism, the reformation of social structure, the change of interest pattern, and the transition of ideological consciousness, have long been the focus of government work, academic research, and social practitioners. Based on the theory of collaborative governance, aiming at the problems existing in the emergency management of public health emergencies in grassroots communities at present, this paper put forward the construction measures of public health emergency collaborative governance system with grassroots communities as the core, including improving the grassroots community emergency management organizational structure, consolidating the standardized foundation of grassroots community emergency collaborative management, enhancing the awareness of grassroots community emergency collaborative management, and strengthening the interactivity of the grassroots community information communication system. It is hoped to provide necessary reference for promoting the reform of public health emergency governance system.

This study aimed to evaluate the ability of rete testis thickness (RTT) and testicular shear wave elastography (SWE) to differentiate obstructive azoospermia (OA) from nonobstructive azoospermia (NOA). We assessed 290 testes of 145 infertile males with azoospermia and 94 testes of 47 healthy volunteers at Shanghai General Hospital (Shanghai, China) between August 2019 and October 2021. The testicular volume (TV), SWE, and RTT were compared among patients with OA and NOA and healthy controls. The diagnostic performances of the three variables were evaluated using the receiver operating characteristic curve. The TV, SWE, and RTT in OA differed significantly from those in NOA (all P ≤ 0.001) but were similar to those in healthy controls. Males with OA and NOA were similar at TVs of 9-11 cm 3 ( P = 0.838), with sensitivity, specificity, Youden index, and area under the curve of 50.0%, 84.2%, 0.34, and 0.662 (95% confidence interval [CI]: 0.502-0.799), respectively, for SWE cut-off of 3.1 kPa; and 94.1%, 79.2%, 0.74, and 0.904 (95% CI: 0.811-0.996), respectively, for RTT cut-off of 1.6 mm. The results showed that RTT performed significantly better than SWE in differentiating OA from NOA in the TV overlap range. In conclusion, ultrasonographic RTT evaluation proved a promising diagnostic approach to differentiate OA from NOA, particularly in the TV overlap range.
Male ; Humans ; Azoospermia ; Rete Testis ; China ; Testis

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.
Animals ; Humans ; Male ; Female ; Sertoli Cells/metabolism* ; Klinefelter Syndrome/genetics* ; Endothelial Cells ; Testis/metabolism* ; X Chromosome/metabolism* ; Mammals/genetics*