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*

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

Objective To explore clinical effect and safety of N-acetyl cysteine(NAC)effervescent tablet combined with budesonide and formoterol fumarate powder for inhalation in the treatment of patients with moderate to severe chronic obstructive pulmonary disease(COPD).Methods Patients with moderate to severe COPD were randomly divided into NAC group,ST group and combination group.NAC group was treated with NAC effervescent tablets[NAC effervescent tablets 0.6 g was dissolved in warm water(≤40 ℃),one tablet/once,qd,take medicine at night],ST group was treated with budesonide and formoterol fumarate powder for inhalation(a inhalation/once,bid),combination group was treated with NAC effervescent tablets and budesonide and formoterol fumarate powder for inhalation.All patients were treated for 7 d.The clinical curative effect,peak expiratory flow(PEF),forced expiratory volume in 1 s(FEV1),FEV1/forced vital capacity(FVC),serum CRP,PCT,SAA,6 min walking test(6MWT)and safety in the three groups were evaluated.Results There were 40 cases in each group.After 7 d of treatment,total response rates of NAC group,ST group and combination group were 77.50％(31 cases/40 cases),80.00％(32 cases/40 cases)and 95.00％(38 cases/40 cases),the differences between combination group and NAC group or between combination group and ST group were statistically significant(P＜0.05),but the difference between NAC group and ST group was not statistically significant(P＞0.05).After 7 d of treatment,FVC levels in NAC group,ST group and combination group were(2.51±0.72),(2.59±0.76)and(3.01±0.82)L,PaO2 levels were(2.24±0.61),(2.29±0.64)and(2.87±0.72)L,FEV1/FVC levels were(89.24±4.28)％,(88.42±4.19)％and(95.35±4.27)％,levels of serum CRP were(19.52±2.12),(19.34±2.09)and(11.85±2.24)mg·L-1,PCT levels were(0.83±0.22),(0.87±0.24)and(0.51±0.13)μg·L-1,SAA levels were(28.95±3.48),(29.23±3.75)and(17.70±2.73)mg·L-1,the differences between combination group and NAC group or between combination group and ST group were statistically significant(all P＜0.05),but the difference between NAC group and ST group was not statistically significant(all P＞0.05).The adverse drug reactions were mainly on abdominal pain,diarrhea,headache,nausea and vomiting in the three groups.The total incidence of adverse drug reactions in NAC group,ST group and combination group was 2.50％,5.00％and 12.50％,the difference among the three groups was not statistically significant(all P＞0.05).Conclusion The curative effect of NAC effervescent tablet combined with budesonide and formoterol fumarate powder for inhalation is significant in patients with moderate to severe COPD,which can effectively improve pulmonary function,reduce levels of serum CRP,PCT and SAA,with good safety.

We reported a 59-year-old male with exertional angina pectoris, and the coronary angiography showed multiple vessel lesions. The initial strategy was coronary artery bypass grafting (CABG). The measurement of quantitative flow ration (QFR) before operation indicated that the posterior descending branch (PD) did not need to be treated. The left circumflex branch (LCX) was small, and the QFR of the left anterior descending branch (LAD) and the first diagonal branch (D1) was<0.8. Therefore, the LAD and D1 were re-vascularized. The operation strategy was changed to on-pump CABG through a small incision, and the final strategy was LIMA-D1-LAD (sequential), fractional flow reserve (FFR) of distal LAD and D1 after CABG were>0.8 by computed tomography FFR. SYNTAX scores after CABG were 20 and the functional SYNTAX scores after CABG were 3, indicating a good prognosis.

Aim To research the neuroprotective effect of Haikun Shenxi (HKSX) medicated serum on N2a/ App695 cells and the underlying mechanism. Methods HKSX medicated serum was prepared and carbohydrate components in it was analyzed using high performance thin layer chromatography (HPTLC) . N2a/ App695 cells were intervened with HKSX medicated serum, the cytotoxicity of HKSX medicated serum was measured by MTT; AP[_

AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P＜0.01);decreased retinal thickness(P＜0.01);decreased retinal blood perfusion(P＜0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P＜0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P＜0.01);increased retinal blood flow(P＜0.01);increased amplitudes of ERG a wave and b wave(P＜0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P＜0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

Objective To compare the fidelity of chronic obstructive pulmonary disease(COPD)models established using two methods:exposure to cigarette smoke(CS)and exposure to motor vehicle exhaust(MVE)in rats.Methods Twenty-four male SD rats were randomly divided into control,CS-exposed(CS),and MVE-exposed(MVE)groups,with 8 rats per group.Rats in CS and MVE groups were exposed to CS or MVE,respectively,to induce COPD models.After COPD model established,lung function of each group was assessed.Bronchoalveolar lavage fluid(BALF)was collected to measure inflammatory cell counts,levels of inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor(TNF)-α,and expression levels of mucin 5AC(MUC5AC).Lung tissue sections were stained with hematoxylin and eosin(HE)to observe pulmonary tissue and airway pathological changes.Periodic acid-Schiff(PAS)staining was used to detect goblet cell hyperplasia in airways.Results Compared with control group,rats in CS and MVE groups showed significantly increased inspiratory resistance(RI),total lung capacity(TLC),and lung static compliance(Cchord)(P<0.05),while expiratory flow parameters FEV50/FVC were significantly decreased(P<0.05).Compared with MVE group,rats in CS group had significantly higher RI,TLC,and Cchord(P<0.05),and lower FEV50/FVC(P<0.05).HE staining of lung tissues showed that mean linear intercept(MLI)was significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having higher MLI than MVE group(P<0.05).BALF analysis revealed that white blood cells,neutrophils,macrophages,lymphocytes,IL-6,and TNF-α levels were significantly higher in both CS and MVE groups compared with control group(P<0.05),and inflammatory cell counts,IL-6,and TNF-α levels were higher in CS group compared with MVE group(P<0.05).PAS staining of lung tissues indicated that goblet cells in large airways were significantly increased in both CS and MVE groups compared with control group(P<0.05),with CS group showing higher goblet cell counts than MVE group(P<0.05).Expression levels of MUC5AC in BALF were significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having significantly higher MUC5AC levels than MVE group(P<0.05).Conclusions Exposure to CS or MVE can establish a rat model of COPD,with CS exposure better mimicking characteristics of acute exacerbation of COPD compared to MVE exposure.

Objective To investigate the feasibility and value of a multi-parametric MRI radiomics-based nomogram model for pretreatment predicting the lymphovascular space invasion(LVSI)of endometrial endometrioid adenocarcinoma(EEA).Methods Preoperative MRI and baseline clinical characteristics of 205 EEA patients were prospectively collected from Oct 2020 to Jan 2022 in the Obstetrics and Gynecology Hospital,Fudan University,and randomly divided into training set(n=123)and validation set(n=82)in a 6∶4 ratio.The whole-tumor region of interest was manually drawn on T2-weighted imaging,diffusion-weighted imaging(apparent diffusion coefficient),and dynamic contrast-enhanced MRI,respectively,for radiomics features extraction.In the training set,univariate and multivariate Logistic regression analysis were used to select independent clinical predictors of LVSI(+)and construct the clinical model.The least absolute shrinkage and selection operator(LASSO)regression and multivariate Logistic regression analysis were used to select optimal radiomics features to form a radiomics signature.A combined nomogram model was established by integrating clinical independent predictors and the radiomics signature,and validated in the validation set.The predicting performance and clinical net benefit were evaluated by using the area under the receiver operating characteristic curve(AUC)and clinical decision curve analysis,respectively.Results Of the 205 EEA cases,144 cases were LVSI(-)and 61 cases were LVSI(+).Menopausal status,CA125,and CA199 were independent clinical predictors for the LVSI(+),and contributing to a clinical model with AUCs of 0.714(training)and 0.731(validation).From 8 240 extracted radiomics features,five were selected to construct a MRI radiomics signature after de-redundancy and LASSO dimensionality reduction,yielding AUCs of 0.860(training)and 0.759(validation).The combined nomogram model showed AUCs of 0.887(training)and 0.807(validation),outperforming others and achieving maximum clinical benefit in a large range of threshold probability in both training and validation sets.Conclusion The multi-parametric MRI-based nomogram model has the potential for pretreatment predicting the LVSI status of EEA,providing valuable information for clinical management decision-making and improving patient's clinical benefits.