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 analyze epidemiological characteristics and influencing factors of atrial fibrillation (AF) in Suqian in 2019-2023. Methods A total of 1 869 patients with AF admitted to medical institutions in Suqian from January 2019 to December 2023 were selected as the survey subjects. The diagnosis and treatment data of the AF patients were retrospectively analyzed to explore epidemiological characteristics. A total of 2 000 healthy controls during the same period were selected as the control group. The influencing factors of AF were analyzed by univariate and multivariate logistic regression models. Results The incidence of AF in Suqian increased with the increase of year, age and labor intensity. The incidence rate was higher (>50%) in patients with male gender, old age, education level of junior high school and below, city living, heavy physical labor, smoking history, drinking history and underlying diseases (coronary heart disease, stroke, heart failure, hyperuricemia, hyperthyroidism, hypertension, diabetes mellitus, and hyperlipidemia). Multivariate logistic regression analysis showed that hyperuricemia, hyperthyroidism, cognitive dysfunction and anxiety/depression were influencing factors of AF in Suqian (P<0.05). Conclusion From 2019 to 2023, AF risk is relatively high in patients in Suqian, which is closely related to hyperuricemia, hyperthyroidism, cognitive dysfunction and anxiety/depression.

ObjectiveTo explore the effectiveness of feedforward control mode on improving occupational burnout among operating room nurses through theoretical research and clinical practice， with a view to promoting their physical and mental health and enhancing the quality of surgical nursing. MethodsA total of 440 operating room nurses from different regions， scales， and nursing experiences in Shaanxi Province from November 2023 to December 2023 were randomly divided into an experimental group and a control group， with 220 nurses in each group. While the control group received routine intervention measures， the experimental group introduced a feedforward control mode based on the control group， with “emotional exhaustion，” “depersonalization，”and“personal achievement” as observation indicators. ResultsThe incidence of occupational burnout in the experimental group was 11.4%， while that in the control group was 20.0%. The experimental group showed a significantly lower incidence than the control group （P=0.013）. ConclusionThe feedforward control mode can significantly alleviate nurses’ sense of job burnout， promote the improvement of surgical nursing quality， as well as continuously improve the scientific rigor， advancement， and humanistic nature of nursing services， which is conducive to building a harmonious and efficient nursing team. The spirit of teamwork， reflected in mutual support， mutual trust， and joint efforts for surgical success and patient health， has become an important component of nurses’ professional ethics.

Objective:To explore mechanism of Caspase-11/GSDMD non-classical cell pyroptosis pathway in inflammatory response of RAW264.7 monocyte macrophages induced by ricin toxin.Methods:Cell pyroptosis model induced by LPS+Nigericin was used as a positive control,and cells were induced with 40 ng/ml and 80 ng/ml of ricin toxin for 8 hours.Cell release of lactate dehydro-genase(LDH)was measured by LDH cell release assay;cell viability was assessed by flow cytometry(Annexin Ⅴ/PI double staining);gene expressions of Caspase-11,GSDMD,IL-1β and IL-18 were measured by RT-qPCR;protein levels of Caspase-11 and GSDMD were measured by Western blot;secretion levels of inflammatory cytokines IL-1β and IL-18 in cell supernatant were measured by ELISA.Results:Compared with normal control group,RAW264.7 cells treated with ricin toxin showed swelling,cell membrane rupture,significantly increased LDH release(P<0.001),significantly increased pyroptosis rate(P<0.001),significantly increased expression of pyroptosis-related genes Caspase-11,GSDMD,IL-1β and IL-18(P<0.05),significantly increased protein expressions of Caspase-11 and GSDMD(P<0.05),and significantly increased secretion levels of IL-1β and IL-18 in cell supernatant(P<0.05).Results of ricin toxin treatment group were consistent with LPS+Nigericin cell pyroptosis positive control group.Conclu-sion:Ricin toxin may induce cell pyroptosis in RAW264.7 cells through Caspase-11/GSDMD non-classical pathway,thereby promoting inflammatory response.

To investigate the phenotype and genomic characterization of a mucoid-type Salmonella Saintpaul ST50 isolate from a urinary tract infection patient,promoting clinical diagnosis and treatment for urinary tract infections caused by Salmo-nella spp.Culture-based quantitative counts of midstream urine sample from the patient were conducted,and further biochemi-cal identification,mass spectrometry detection,serum agglutination test and antimicrobial susceptibility test(AST)were con-ducted on Salmonella isolate(2024JD5).Whole-genome sequencing(WGS)was performed on isolate 2024JD5 to predict sero-type,multilocus sequence type(MLST),resistance genes,and virulence genes.Two smooth-type of Salmonella Saintpaul ST50 were selected as comparative genomic reference strains from the Chinese local Salmonella genome database.The literature reviews of global Salmonella serotype of urinary tract infection were summarized.Specific serum agglutination confir-mation of isolate 2024JD5 failed due to characterization of the mucus type.The strain 2024JD5 was predicted as Salmonella Saintpaul(4,5,12:e,h:1,2)ST50 using WGS,and was resistant to ciprofloxacin,nalidixic acid,chloramphenicol and tetracy-cline with carrying aminoglycoside resistance genes aac(6')-Ⅰaa and aph(3)-Ⅱa,chloramphenicol resistance gene floR,tetra-cycline resistance gene tet,quinolone resistance gene qnrS1,and S83Y substitution in the gyrA gene was found in the quinolo-ne resistance determination region(QRDR).In addition,the strain 2024JD4 carried six types of non-plasmid-based mobile ge-netic elements and 144 virulence genes,including 71 secretion transporter genes and 58 fimbriae adhesion genes,respectively.Four types of fimbriae regulatory genes(csgB,csgC,fimW,fimY)were absent in comparison with smooth-type Salmonella Saintpaul.The literature reviews showed Salmonella Saintpaul was currently a rare Salmonella serotype in cases of urinary tract infections worldwide.Salmonella Saintpaul ST50 with mucoid-type is the pathogen of urinary tract infection with multi-drug resistant phenotypic and genotypic characteristics,and the high mucoid expression may be related to the compensatory mechanism of fimbriae regulatory genes absence in urinary tract colonization and adaptation.WGS combined with the Chinese local Salmonella genome database can effectively solve the diagnosis and biosafety assessments of rare Salmonella phenotypes.

Objective To investigate the changes in the concentration of endothelial cell-specific molecule-1(ESM-1)in cerebrospinal fluid during the acute phase of patients with moderate to severe traumatic brain injury(TBI)and its relationship with injury severity and outcomes.Methods Eighty-four patients with moderate to severe TBI who underwent ventriculostomy for intracranial pressure(ICP)monitoring at Department of Neurosurgery,Jinshan Hospital,Fudan University from Jan 2020 to Dec 2023 were selected as the study subjects,and their clinical data were collected.Based on the Glasgow Coma Scale(GCS)upon admission,TBI patients were divided into moderate TBI group(GCS 9-12,n=48)and severe TBI group(GCS 3-8,n=36).According to the Glasgow Outcome Scale(GOS)at three months post-injury,the moderate to severe TBI patients were categorized into poor outcome group(GOS 1-3)and good outcome group(GOS 4-5).Patients were also classified based on ICP monitoring values into a normal ICP group(ICP≤15 mmHg),a mildly elevated ICP group(15 mmHg

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

The endoplasmic reticulum is an important organelle responsible for the synthesis,folding and processing of proteins.When the endoplasmic reticulum protein folding ability is affect-ed,internal unfolded proteins or misfolded proteins accumulate in the endoplasmic reticulum accumulation,leading to endoplasmic reticulum structural dysfunction resulting in endoplasmic reticu-lum stress.Autophagy is the process by which cells selectively remove stress endoplasmic reticulum and error proteins.Under stress,the endoplasmic reticulum can maintain normal physiolog-ical functions through unfolded protein responses and autophagy.Postmenopausal osteoporosis is mainly due to an imbalance be-tween bone resorption by osteoclasts and bone formation by oste-oblasts.Endoplasmic reticulum stress and autophagy both modu-late bone cells status with consequences for bone homeostasis.This article provides a review of the progress of research on en-doplasmic reticulum stress and autophagy interaction in the path-ogenesis of postmenopausal osteoporosis.

Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.

To investigate the phenotype and genomic characterization of a mucoid-type Salmonella Saintpaul ST50 isolate from a urinary tract infection patient,promoting clinical diagnosis and treatment for urinary tract infections caused by Salmo-nella spp.Culture-based quantitative counts of midstream urine sample from the patient were conducted,and further biochemi-cal identification,mass spectrometry detection,serum agglutination test and antimicrobial susceptibility test(AST)were con-ducted on Salmonella isolate(2024JD5).Whole-genome sequencing(WGS)was performed on isolate 2024JD5 to predict sero-type,multilocus sequence type(MLST),resistance genes,and virulence genes.Two smooth-type of Salmonella Saintpaul ST50 were selected as comparative genomic reference strains from the Chinese local Salmonella genome database.The literature reviews of global Salmonella serotype of urinary tract infection were summarized.Specific serum agglutination confir-mation of isolate 2024JD5 failed due to characterization of the mucus type.The strain 2024JD5 was predicted as Salmonella Saintpaul(4,5,12:e,h:1,2)ST50 using WGS,and was resistant to ciprofloxacin,nalidixic acid,chloramphenicol and tetracy-cline with carrying aminoglycoside resistance genes aac(6')-Ⅰaa and aph(3)-Ⅱa,chloramphenicol resistance gene floR,tetra-cycline resistance gene tet,quinolone resistance gene qnrS1,and S83Y substitution in the gyrA gene was found in the quinolo-ne resistance determination region(QRDR).In addition,the strain 2024JD4 carried six types of non-plasmid-based mobile ge-netic elements and 144 virulence genes,including 71 secretion transporter genes and 58 fimbriae adhesion genes,respectively.Four types of fimbriae regulatory genes(csgB,csgC,fimW,fimY)were absent in comparison with smooth-type Salmonella Saintpaul.The literature reviews showed Salmonella Saintpaul was currently a rare Salmonella serotype in cases of urinary tract infections worldwide.Salmonella Saintpaul ST50 with mucoid-type is the pathogen of urinary tract infection with multi-drug resistant phenotypic and genotypic characteristics,and the high mucoid expression may be related to the compensatory mechanism of fimbriae regulatory genes absence in urinary tract colonization and adaptation.WGS combined with the Chinese local Salmonella genome database can effectively solve the diagnosis and biosafety assessments of rare Salmonella phenotypes.