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.

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.

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.

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.

Allergen-specific Th2 cells refer to a subset of Th2 cells that undergo substantial expansion following allergen stimulation. They play a crucial role in allergic diseases, and an increasing amount of research has revealed a close relationship between surface molecules on allergen-specific Th2 cells and allergic diseases. In comparison to other CD4+T cells or Th2 cells, allergen-specific Th2 cells exhibit low expression of CD27 but high expression of CD154, CD69, CRTH2, CD161, ST2, hPGDs, CD49d, and COX-2. They can be used for the identification of allergen-specific Th2 cells and serve as potential targets for the prevention and treatment of specific diseases. They hold significant value in preventing the onset and exacerbation of allergic diseases.
Humans ; Allergens ; Th2 Cells

Allergen-specific Th2 cells refer to a subset of Th2 cells that undergo substantial expansion following allergen stimulation. They play a crucial role in allergic diseases, and an increasing amount of research has revealed a close relationship between surface molecules on allergen-specific Th2 cells and allergic diseases. In comparison to other CD4+T cells or Th2 cells, allergen-specific Th2 cells exhibit low expression of CD27 but high expression of CD154, CD69, CRTH2, CD161, ST2, hPGDs, CD49d, and COX-2. They can be used for the identification of allergen-specific Th2 cells and serve as potential targets for the prevention and treatment of specific diseases. They hold significant value in preventing the onset and exacerbation of allergic diseases.
Humans ; Allergens ; Th2 Cells

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Pregnancy ; Female ; Humans ; Male ; Vas Deferens/abnormalities* ; Azoospermia/surgery* ; Epididymis/surgery* ; Retrospective Studies ; Tertiary Care Centers ; China ; Semen