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 explore the clinical efficacy of super-selective ophthalmic artery thrombolysis in the treatment of central retinal artery occlusion (CRAO).Methods:This is a retrospective case series study,based on the analysis of clinical data of 50 non-arteritic CRAO patients. The patients were advised to be treated with super-selective intra-ocular arterial thrombolysis at the Neurosurgery Department, Shenyang No. 4 People′s Hospital from May to December 2024, and treated with intra-arterial thrombolysis and postoperative management guidance by the Department of Neurosurgery, General Hospital of the Northern Theater Command. There were 36 males and 14 females, aged (59.5±10.2)years (range: 41 to 75 years). There were 5 cases of complete obstruction of the central retinal artery and 45 cases of subtotal obstruction.Before the operation, all patients underwent optical coherence tomography angiography (OCTA)+ocular vascular ultrasonography, and their visual acuity was measured using a standard visual acuity logarithmic scale, visual field was measured using the contrast visual field examination method;One week after the operation, all patients were rechecked for OCTA, visual acuity and visual field. The patients′ preoperative and postoperative visual field recovery status were compared. Significant effect was defined as an improvement of more than 3 lines of visual acuity or a complete improvement of visual field defects after treatment compared with pretreatment visual acuity; effectiveness was defined as an improvement of 1 to 2 lines of visual acuity or an improvement of visual field defects after treatment compared with pretreatment visual acuity.Results:The overall effective rate of 50 patients with CRAO treated with super-selective ophthalmic artery urokinase thrombolysis was 94.0% (47/50), with 29 very effective, 18 effective and 3 ineffective. The time from onset to surgery was 0 to 6 hours in 5 patients, with an effective rate of 5/5; >6 to 24 hours in 11 patients, with an effective rate of 10/11; >1 to 7 days in 21 patients, with an effective rate of 90.5%(19/21); >7 to 14 days in 9 patients, with an effective rate of 9/9; and >14 to 21 days in 4 patients, with an effective rate of 4/4, and the difference in effective rate between the different time windows of thrombolytic therapy was not statistically significant ( P=0.961). There were 3 cases of intraoperative and postoperative complications, including 1 case of ophthalmic artery entrapment, 1 case of femoral artery pseudoaneurysm and 1 case of fundus hemorrhage, but all of them were cured after symptomatic treatment. Conclusions:Intra-arterial thrombolysis for CRAO patients has a high effective rate and a low complication rate. The surgical time window can be extended to 21 days after the onset, which is of positive significance for the recovery and improvement of the patient′s final visual acuity.

Objective:To investigate the epidemiological trends of viral diarrhea pathogens in children in Baotou city, and to provide reference for controlling the prevalence of viral diarrhea and guiding the development of regional vaccines.Methods:Fecal samples were collected from children under five years old hospitalized with viral diarrhea at two sentinel hospitals in Baotou from June 2023 to May 2024. Real-time PCR was used to detect group A rotavirus, norovirus, adenovirus, and astrovirus. Statistical analysis was performed using SPSS 20.0 software, with Chi-square tests conducted to assess differences. A P value<0.05 was considered statistically significant. Results:A total of 246 fecal samples were collected, including 153 from males and 93 from females. Among these, 135 samples tested positive, yielding a positivity rate of 54.88% (135/246). There were 82 positive samples from male children and 53 from female children, with no significant difference between genders. Most positive samples (51.85%, 70/135) tested positive for two viruses. Specifically, co-infections of group A rotavirus with norovirus or adenovirus accounted for 98.57% (69/70) of all co-infected cases. Significant differences in detection rates were observed across age groups (χ 2=29.803, P<0.001), with the highest positivity rates in children under one year old and in the 1-year age group. Seasonality, viral diarrhea in Baotou was more prevalent in winter and spring. The G8P[8] genotype of group A rotavirus was the predominant strain. Conclusions:From June 2023 to May 2024, viral diarrhea in hospitalized children under five years old in Baotou is primarily caused by co-infections of group A rotavirus and norovirus, with a higher incidence in preschool-aged children. The G8P[8] genotype of group A rotavirus is the dominant strain. It is recommended to strengthen vaccination and surveillance efforts for viral diarrhea in preschool children, particularly during the winter and spring seasons.

Objective:To investigate the epidemiological trends of viral diarrhea pathogens in children in Baotou city, and to provide reference for controlling the prevalence of viral diarrhea and guiding the development of regional vaccines.Methods:Fecal samples were collected from children under five years old hospitalized with viral diarrhea at two sentinel hospitals in Baotou from June 2023 to May 2024. Real-time PCR was used to detect group A rotavirus, norovirus, adenovirus, and astrovirus. Statistical analysis was performed using SPSS 20.0 software, with Chi-square tests conducted to assess differences. A P value<0.05 was considered statistically significant. Results:A total of 246 fecal samples were collected, including 153 from males and 93 from females. Among these, 135 samples tested positive, yielding a positivity rate of 54.88% (135/246). There were 82 positive samples from male children and 53 from female children, with no significant difference between genders. Most positive samples (51.85%, 70/135) tested positive for two viruses. Specifically, co-infections of group A rotavirus with norovirus or adenovirus accounted for 98.57% (69/70) of all co-infected cases. Significant differences in detection rates were observed across age groups (χ 2=29.803, P<0.001), with the highest positivity rates in children under one year old and in the 1-year age group. Seasonality, viral diarrhea in Baotou was more prevalent in winter and spring. The G8P[8] genotype of group A rotavirus was the predominant strain. Conclusions:From June 2023 to May 2024, viral diarrhea in hospitalized children under five years old in Baotou is primarily caused by co-infections of group A rotavirus and norovirus, with a higher incidence in preschool-aged children. The G8P[8] genotype of group A rotavirus is the dominant strain. It is recommended to strengthen vaccination and surveillance efforts for viral diarrhea in preschool children, particularly during the winter and spring seasons.

Objective:To explore the clinical efficacy of super-selective ophthalmic artery thrombolysis in the treatment of central retinal artery occlusion (CRAO).Methods:This is a retrospective case series study,based on the analysis of clinical data of 50 non-arteritic CRAO patients. The patients were advised to be treated with super-selective intra-ocular arterial thrombolysis at the Neurosurgery Department, Shenyang No. 4 People′s Hospital from May to December 2024, and treated with intra-arterial thrombolysis and postoperative management guidance by the Department of Neurosurgery, General Hospital of the Northern Theater Command. There were 36 males and 14 females, aged (59.5±10.2)years (range: 41 to 75 years). There were 5 cases of complete obstruction of the central retinal artery and 45 cases of subtotal obstruction.Before the operation, all patients underwent optical coherence tomography angiography (OCTA)+ocular vascular ultrasonography, and their visual acuity was measured using a standard visual acuity logarithmic scale, visual field was measured using the contrast visual field examination method;One week after the operation, all patients were rechecked for OCTA, visual acuity and visual field. The patients′ preoperative and postoperative visual field recovery status were compared. Significant effect was defined as an improvement of more than 3 lines of visual acuity or a complete improvement of visual field defects after treatment compared with pretreatment visual acuity; effectiveness was defined as an improvement of 1 to 2 lines of visual acuity or an improvement of visual field defects after treatment compared with pretreatment visual acuity.Results:The overall effective rate of 50 patients with CRAO treated with super-selective ophthalmic artery urokinase thrombolysis was 94.0% (47/50), with 29 very effective, 18 effective and 3 ineffective. The time from onset to surgery was 0 to 6 hours in 5 patients, with an effective rate of 5/5; >6 to 24 hours in 11 patients, with an effective rate of 10/11; >1 to 7 days in 21 patients, with an effective rate of 90.5%(19/21); >7 to 14 days in 9 patients, with an effective rate of 9/9; and >14 to 21 days in 4 patients, with an effective rate of 4/4, and the difference in effective rate between the different time windows of thrombolytic therapy was not statistically significant ( P=0.961). There were 3 cases of intraoperative and postoperative complications, including 1 case of ophthalmic artery entrapment, 1 case of femoral artery pseudoaneurysm and 1 case of fundus hemorrhage, but all of them were cured after symptomatic treatment. Conclusions:Intra-arterial thrombolysis for CRAO patients has a high effective rate and a low complication rate. The surgical time window can be extended to 21 days after the onset, which is of positive significance for the recovery and improvement of the patient′s final visual acuity.

Objective:To investigate the effect of the virtual simulation system-based teaching method for the experimental course of oral local nerve block anesthesia in improving the effect of traditional teaching methods.Methods:One hundred and eighteen undergraduate dental students were randomly divided into two groups, the experimental group was taught using a virtual simulation-based system, and the control group was taught using traditional teaching. The results of the teaching were comprehensively evaluated through course feedback questionnaires, analysis of theoretical test scores, evaluations of the trainees administering and receiving anesthesia on the current anesthesia, and faculty evaluations of the success of the anesthesia, and t-tests and chi-square tests were performed using SPSS 23.0.Results:There was no significant difference in baseline level between the two groups. The students in the experimental group thought that the learning was more vivid ( t=4.24, P=0.005) and had more self-confidence in local anesthesia ( t=4.99, P<0.001). The students in the experimental group felt less needle tip jitter during injection ( t=2.22, P=0.048) and better contact with the medial surface of the mandible ( t=2.22, P=0.020). The students who received anesthesia reported less pain during injection ( t=1.99, P=0.029) and better anesthesia of the inferior alveolar nerve ( t=3.36, P=0.039) in the experimental group. Teacher assessment revealed that the experimental group had a significantly lower failure rate of inferior alveolar nerve block than the control group ( χ2=4.40, P=0.036). Conclusions:The virtual simulation system can optimize the experimental teaching of oral local nerve block anesthesia and can achieve a satisfactory teaching effect.

OBJECTIVE To assess the efficacy， safety and cost-effectiveness of tenecteplase in the treatment of acute ischemic stroke， and to provide a basis for clinical rational drug use and related decision-making. METHODS The related literature in the PubMed， the Cochrane Library， CNKI， Wanfang data and health technology assessment （HTA） databases were searched from the establishment of the database to June 30th， 2024. Systematic reviews/meta-analyses， pharmacoeconomic studies and HTA reports on tenecteplase in the treatment of acute ischemic stroke were collected. After data extraction and quality assessment， descriptive analysis of the included studies was carried out. RESULTS A total of 31 articles were included， involving 28 systematic reviews/ meta-analysis and 3 pharmacoeconomic studies. In terms of effectiveness， compared with alteplase， tenecteplase （0.25 mg/kg） could significantly increase the early neurological improvement； the 90 d excellent neurological recovery rate， 90 d good neurological recovery rate， and recanalization were not inferior to alteplase. For safety， compared with alteplase， tenecteplase did not increase the incidence of hemorrhage， symptomatic intracranial hemorrhage， 3-month mortality， or intracranial hemorrhage. In terms of cost-effectiveness， foreign research results showed that tenecteplase had economic advantages over alteplase. CONCLUSIONS Compared with alteplase， tenecteplase is effective and safe in the treatment of acute ischemic stroke， and it is cost-effective.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

AIM:To evaluate and analyze the post-marketing adverse drug reaction(ADR)signals of polatuzumab vedotin,so as to provide reference for clinical safety management.METHODS:Using the FDA adverse drug event reporting system(FAERS)database and OpenVigil data platform,the ADR reports of polatuzumab vedotin were collect-ed from June 10,2019(FDA approval for market-ing)to the March 31,2023.The ADR signals were detected by using the reporting odds ratio(ROR)and proportional reporting ratio(PRR)in the pro-portional imbalance method.To increase the threshold and obtain stronger and more frequently occurring ADRs,a second screening of signals was performed.RESULTS:A total of 2 408 ADR reports related to polatuzumab vedotin were collected,and 83 ADR signals were detected after secondary screening.26 ADR signals were not mentioned in the drug instructions such as abnormal spinal mag-netic resonance imaging,increased bone resorp-tion,osteolysis,decreased aspartate aminotransfer-ase,decreased alanine aminotransferase,hypofibri-nogenemia,and pulmonary embolism.The system organ classes with a high signal counts or cumula-tive number of cases included infections and inva-sive diseases(24 signals,632 cases),various exami-nations(17 signals,675 cases),blood and lymphat-ic system diseases(11 signals,734 cases),various nervous system diseases(7 signals,153 cases),im-mune system diseases(3 signals,95 cases),system-ic diseases and various reactions at the site of ad-ministration(2 signals,145 cases),and systemic dis-eases and various reactions at the site of adminis-tration(2 signals,87 cases),etc.CONCLUSION:In addition to the common ADRs suggested by the in-structions,this study identified new ADR risk sig-nals for polatuzumab vedotin.In the clinical appli-cation of polatuzumab vedotin,in addition to the ADR mentioned in the instructions such as infec-tions,myelosuppression,peripheral neuropathies,infusion-related reactions,and abnormal liver func-tion,attention should also be paid to the risk sig-nals not mentioned such as abnormal spinal mag-netic resonance imaging,and increased bone re-sorption.