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: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Background and Aims:Surgical treatment is a cornerstone of breast cancer management;however,the physical trauma and psychological burden associated with surgery may adversely affect patients'quality of life(QoL).Based on data from a prospective cohort,this study was conducted to evaluate changes in postoperative QoL among breast cancer patients and to identify mediating factors influencing QoL,thereby providing evidence for perioperative rehabilitation strategies.Methods:Female breast cancer patients who underwent local surgical treatment at Suining Central Hospital between June 2024 and January 2025 were enrolled.The Constant-Murley Shoulder Score,EORTC QLQ-C30,and QLQ-BR23 questionnaires were used pre-and postoperatively to assess shoulder joint function,and QoL.Paired t-tests were used to analyze changes in scores before and after surgery.A mediation model was applied to explore the indirect pathways through which surgery impacts QoL.Additionally,subgroup analyses were conducted to compare QoL changes across different surgical modalities.Results:A total of 148 patients were included,with median age of 54(46-60)years old Postoperative psychological health significantly improved,while shoulder function and overall QoL scores markedly declined(all P<0.001).According to QLQ-C30,functional domains such as physical and role functioning worsened,while symptom burden increased.The QLQ-BR23 revealed significantly higher scores for breast and upper limb symptoms postoperatively(both P<0.001).Subgroup analyses showed that patients undergoing axillary lymph node dissection experienced greater declines in shoulder function and QoL compared to those receiving sentinel lymph node biopsy(both P<0.05).QoL deterioration was comparable between mastectomy and breast-conserving surgery,although the former was associated with more prominent pain and breast symptoms.Mediation analysis indicated that shoulder function,breast symptoms,and physical functioning served as mediators in the impact of surgery on QoL,while better psychological health exerted a protective effect.Conclusion:Surgical treatment significantly affects postoperative QoL in breast cancer patients,with local functional impairment and symptom exacerbation serving as key mediators.Different surgical approaches have varying impacts on QoL.Enhancing postoperative shoulder rehabilitation,symptom management,and psychological support may improve patients'QoL.

Background and Aims:Surgical treatment is a cornerstone of breast cancer management;however,the physical trauma and psychological burden associated with surgery may adversely affect patients'quality of life(QoL).Based on data from a prospective cohort,this study was conducted to evaluate changes in postoperative QoL among breast cancer patients and to identify mediating factors influencing QoL,thereby providing evidence for perioperative rehabilitation strategies.Methods:Female breast cancer patients who underwent local surgical treatment at Suining Central Hospital between June 2024 and January 2025 were enrolled.The Constant-Murley Shoulder Score,EORTC QLQ-C30,and QLQ-BR23 questionnaires were used pre-and postoperatively to assess shoulder joint function,and QoL.Paired t-tests were used to analyze changes in scores before and after surgery.A mediation model was applied to explore the indirect pathways through which surgery impacts QoL.Additionally,subgroup analyses were conducted to compare QoL changes across different surgical modalities.Results:A total of 148 patients were included,with median age of 54(46-60)years old Postoperative psychological health significantly improved,while shoulder function and overall QoL scores markedly declined(all P<0.001).According to QLQ-C30,functional domains such as physical and role functioning worsened,while symptom burden increased.The QLQ-BR23 revealed significantly higher scores for breast and upper limb symptoms postoperatively(both P<0.001).Subgroup analyses showed that patients undergoing axillary lymph node dissection experienced greater declines in shoulder function and QoL compared to those receiving sentinel lymph node biopsy(both P<0.05).QoL deterioration was comparable between mastectomy and breast-conserving surgery,although the former was associated with more prominent pain and breast symptoms.Mediation analysis indicated that shoulder function,breast symptoms,and physical functioning served as mediators in the impact of surgery on QoL,while better psychological health exerted a protective effect.Conclusion:Surgical treatment significantly affects postoperative QoL in breast cancer patients,with local functional impairment and symptom exacerbation serving as key mediators.Different surgical approaches have varying impacts on QoL.Enhancing postoperative shoulder rehabilitation,symptom management,and psychological support may improve patients'QoL.

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.

Objective:To analyze the imaging features of testicular conventional ultrasonography（US），shear wave elastography（SWE），and contrast-enhanced ultrasonography（CEUS）in subtypes of spermatogenic dysfunction（focal，arrest，and exhausted），and to evaluate the diagnostic efficacy of testicular multimodal ultrasound.Methods:A prospective study enrolled 310 spermatogenic dysfunction patients（focal type group： n=77，arrest type group： n=20，exhaustive type group： n=213）and 30 healthy volunteers（control group）at Shanghai General Hospital between October 2023 and December 2024. All patients underwent preoperative testicular US，SWE，and CEUS examinations，followed by microdissection testicular sperm extraction. Ultrasound parameters were compared among groups，and receiver operating characteristic（ROC）curves were plotted to assess the diagnostic efficacy of multimodal ultrasound for different subtypes. Results:①Testicular volume：The arrest group exhibited significantly greater volume compared to the focal group and the exhausted group（all P<0.05）. No statistically significant difference was observed between the arrest group and the normal group（ P>0.05）. ②Mean Young's modulus（Emean）：The arrest group exhibited significantly lower Emean compared with both the focal and exhausted groups（all P<0.05），but showed no significant difference versus the normal group（ P>0.05）. ③CEUS quantitative parameters：The arrival time（AT）and time to peak（TTP）in the exhausted group were higher than those in the normal group，while the peak intensity（PI）and area under the time-intensity curve（AUC）were lower（all P<0.05）. No significant differences were found in AT，TTP，or AUC among the three spermatogenic dysfunction subgroups（all P>0.05）. ④CEUS perfusion patterns：The focal group predominantly exhibited a mottled pattern（70.13%，54/77）. Both the arrest group（90.00%，18/20）and the normal group（93.33%，28/30）predominantly exhibited an rich pattern. The exhausted group predominantly exhibited a sparse pattern（56.34%，120/213）. ⑤ROC curve analysis showed that for differentiating the arrest group from the focal type group and the exhaustive type group，the combination of Emean，testicular volume，and CEUS perfusion pattern yielded an AUC of 0.931，with a sensitivity of 95.00% and specificity of 85.86%. For differentiating the focal type group from the exhaustive type group，the combination of testicular echogenicity，CEUS perfusion pattern，and Emean yielded an AUC of 0.833，with a sensitivity of 81.82% and specificity of 75.12%. Conclusions:Multimodal ultrasonography can comprehensively characterize the imaging features of different subtypes of spermatogenic dysfunction，holding promise as a noninvasive predictive tool.

Abstract Background and aims Hepatic ischemia-reperfusion injury (HIRI) is a major contributor to liver dysfunction and failure, particularly in the context of liver transplantation. Its pathogenesis is primarily driven by ferroptosis, oxidative stress, and mitochondrial dysfunction. Given the interplay among these mechanisms through redox imbalance and disrupted energy metabolism, nicotinic acid (NA)—recognized for its antioxidative and metabolic regulatory properties—emerges as a promising therapeutic candidate. This study aims to investigate the protective effects of NA on HIRI and elucidate its underlying mechanisms. Methods An HIRI model in mice and a hypoxia/reoxygenation (H/R) model in primary hepatocytes were established to evaluate the effects of NA treatment on oxidative stress. NA was administered prior to model induction. N-acetylcysteine (NAC) was used as a comparator. Comprehensive assessments of ferroptosis, oxidative stress, mitophagy, and mitochondrial biogenesis markers were conducted using Western blotting, immunohistochemistry, immunofluorescence, and biochemical assays. Results NA pretreatment reduced serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase (LDH) levels, suppressed inflammation by decreasing neutrophil infiltration and macrophage activation, and mitigated oxidative stress by lowering reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It enhanced antioxidant defenses, inhibited ferroptosis, and improved mitochondrial health through increased mitophagy, mitochondrial biogenesis, and mitochondrial permeability transition pore (mPTP) stabilization, leading to enhanced ATP production and mitochondrial function in HIRI. Conclusions NA improves mitochondrial function by promoting mitophagy and mitochondrial biogenesis, which reduces ferroptosis and oxidative stress, thereby alleviating HIRI.

Blood from a case of group B epidemic cerebrospinal meningitis identified in February 2024 in Ganzhou City,Jiangxi Province,and throat swabs from close contacts were collected for isolation and culture.The isolates were subjected to serogrouping,drug sensitivity testing,and whole genome sequencing and analysis,to provide a basis for epidemiological inves-tigation and clinical drug use.One strain of Neisseria meningitidis was isolated from the blood of the case and denoted group B.The MLST type was ST-7962,with no clonal group attribution.The phylogenetic tree showed that it was genetically close to the 1977 Shanghai carrier isolate(id-52231).Drug sensitivity results indicated that the strain was sensitive to 8 drugs:azithro-mycin,cefotaxime,minocycline,ceftriaxone,chloramphenicol,meropenem,rifampicin,and benzylpenicillin;resistant to cot-rimoxazole,levofloxacin,and ciprofloxacin;and showed an intermediate response to penicillin.This report describes the first case of ST-7962 group B meningoencephalitis found in Jiangxi Province.Monitoring of Neisseria meningitidis carriage,drug re-sistance,and molecular characteristics of strains in the healthy population in this region should be strengthened,to provide la-boratory support for the clinical use of medications,traceability,and control of the pathogen underlying meningoencephalitis infection.

Objective:To analyze the imaging features of testicular conventional ultrasonography（US），shear wave elastography（SWE），and contrast-enhanced ultrasonography（CEUS）in subtypes of spermatogenic dysfunction（focal，arrest，and exhausted），and to evaluate the diagnostic efficacy of testicular multimodal ultrasound.Methods:A prospective study enrolled 310 spermatogenic dysfunction patients（focal type group： n=77，arrest type group： n=20，exhaustive type group： n=213）and 30 healthy volunteers（control group）at Shanghai General Hospital between October 2023 and December 2024. All patients underwent preoperative testicular US，SWE，and CEUS examinations，followed by microdissection testicular sperm extraction. Ultrasound parameters were compared among groups，and receiver operating characteristic（ROC）curves were plotted to assess the diagnostic efficacy of multimodal ultrasound for different subtypes. Results:①Testicular volume：The arrest group exhibited significantly greater volume compared to the focal group and the exhausted group（all P<0.05）. No statistically significant difference was observed between the arrest group and the normal group（ P>0.05）. ②Mean Young's modulus（Emean）：The arrest group exhibited significantly lower Emean compared with both the focal and exhausted groups（all P<0.05），but showed no significant difference versus the normal group（ P>0.05）. ③CEUS quantitative parameters：The arrival time（AT）and time to peak（TTP）in the exhausted group were higher than those in the normal group，while the peak intensity（PI）and area under the time-intensity curve（AUC）were lower（all P<0.05）. No significant differences were found in AT，TTP，or AUC among the three spermatogenic dysfunction subgroups（all P>0.05）. ④CEUS perfusion patterns：The focal group predominantly exhibited a mottled pattern（70.13%，54/77）. Both the arrest group（90.00%，18/20）and the normal group（93.33%，28/30）predominantly exhibited an rich pattern. The exhausted group predominantly exhibited a sparse pattern（56.34%，120/213）. ⑤ROC curve analysis showed that for differentiating the arrest group from the focal type group and the exhaustive type group，the combination of Emean，testicular volume，and CEUS perfusion pattern yielded an AUC of 0.931，with a sensitivity of 95.00% and specificity of 85.86%. For differentiating the focal type group from the exhaustive type group，the combination of testicular echogenicity，CEUS perfusion pattern，and Emean yielded an AUC of 0.833，with a sensitivity of 81.82% and specificity of 75.12%. Conclusions:Multimodal ultrasonography can comprehensively characterize the imaging features of different subtypes of spermatogenic dysfunction，holding promise as a noninvasive predictive tool.

Objective To investigate the dosimetric effects of different calculation grid size(CGS)in helical tomotherapy(HT)planning system on stereotactic body radiation therapy(SBRT)for non-small cell lung cancer(NSCLC).Methods Nine NSCLC patients receiving radiation therapy for the first time at some hospital from March 2019 to December 2022 were selected as the subjects.SBRT planning was carried out through the HT system with three different CGS plans(Fine,Normal,and Coarse)and the same pitch,modulation factor(MF)and optimization conditions,and the target area indexes of the three CGS plans were compared including conformity index(CI),homogeneity index(HI),dosimetric parameters of the organ at risk(OAR),point dose verification pass rate,treatment time,number of monitor units and Sinograms.SPSS 22.0 was used for statistical analysis.Results For target area HI,there weres significant differences between CGS Fine plan and Coarse plan and between CGS Normal plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan(P＞0.05).For target area CI,there were significant differences between CGS Fine plan and Coarse plan(P＜0.05),while no statistical differences were found between CGS Fine plan and Normal plan and between CGS Normal plan and Coarse plan(P＞0.05).For OAR dosimetric parameters,CGS Fine plan and Coarse plan had significant differences in heart Dmax and Dmean,esophageal Dmax and Dmean,V5,V20,V30 and Dmean of the whole lung and affected lung,V5 and Dmax of the affected lung and heart V10 and V30(P＜0.05),CGS Normal plan and Coarse plan had obvious differences in esophageal Dmax(P＜0.05),and the remained dosimetric parameters were not statistically significant(P＞0.05).Fine,Normal and Coarse plans had the point dose verifica-tion pass rates being 0.96％,1.50％and 1.77％,respectively.In terms of treatment time and number of monitor units,there were significant differences between Fine plan and Coarse plan(P＜0.05)while no statistical differences were found between Fine and Normal plans and between Normal and Coarse plans(P＞0.05).Sinograms analyses showed Fine plan had evenly distributed segment color gradient,Coarse plan had areas of very dark and very light color gradients and Normal plan was somewhere in between.Conclusion Low CGS has to be used as much as possible to obtain accurate dose distribution during SBRT planning for NSCLC patients,which contributes to the execution of the radiation therapy plan and the prevention of ad-verse effects.[Chinese Medical Equipment Journal,2024,45(2):52-57]