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 diagnostic value of ¹⁸F-FDG PET/CT in bone marrow infiltration (BMI) of newly diagnosed diffuse large B-cell lymphoma (DLBCL), compared with the results of bone marrow biopsy (BMB) and investigate whether the BMI diagnosed by ¹⁸F-FDG PET/CT and other factors have independent prognostic values. METHODS: Ninety-four newly diagnosed DLBCL patients who underwent PET/CT in Clinical Medical College of Shanghai General Hospital of Nanjing Medical University were included. BMB was performed within 2 weeks before or after PET/CT, and standardized treatment was performed after PET/CT. The manifestations of bone marrow (BM) FDG uptake were recorded. The diagnostic criteria of BMI were BMB positive or focal BM FDG uptake confirmed by imaging follow-up. The relationship between clinical features and BM FDG uptake and the values of PET/CT and BMB in the diagnosis of BMI was analyzed. The progression-free survival (PFS) was analyzed by Kaplan-Meier survival curves, log-rank test was used to compare PFS rate, and Cox regression model was used to analyze the independent risk factors affecting PFS. RESULTS: Among 94 DLBCL patients, 34 patients showed focal BM uptake (fPET), 7 patients showed super BM uptake (sBMU), 11 patients showed diffuse homogenous uptake higher than liver (dPET), and the other 42 patients had normal BM uptake (nPET) (lower than liver). BMB positive was found in all sBMU patients, in 20.6%(7/34) of fPET patients, and in 27.3% (3/11) of dPET patients. All nPET patients had negative BMB results. dPET patients were associated with lower hemoglobin level and leukocyte count compared with nPET group (P < 0.001, P =0.026). Compared with fPET patients, sBMU patients were more likely to have B symptoms and elevated lactate dehydrogenase (LDH). A total of 44 patients were diagnosed BMI, including 17 cases with BMB⁺. The sensitivity and specificity of BMB in the diagnosis of BMI was 38.6% (17/44) and 100% (50/50), respectively. Using fPET and sBMU as criteria of PET BMI, the diagnostic sensitivity and specificity of PET/CT was 93.2% (41/44) and 100% (50/50), respectively. Kaplan-Meier analysis showed that there was no significant difference in 2-year PFS rate between nPET and dPET patients (P >0.05), while sBMU patients had lower 2-year PFS rate compared with fPET patients (P < 0.001). Multivariate analysis showed that higher Ann Arbor stage (HR=9.010, P =0.04) and sBMU (HR=3.964, P =0.002) were independent risk factors affecting PFS. CONCLUSIONS Increased BM FDG uptake of DLBCL can be manifested as dPET, fPET and sBMU. fPET and sBMU can replace BMB to diagnose BMI. Although dPET cannot completely exclude the possibility of BMI, it does not affect the prognosis, so it can be diagnosed as PET BMI negative. sBMU is an independent prognostic risk factor.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Fluorodeoxyglucose F18 ; Prognosis ; Bone Marrow/pathology* ; Retrospective Studies ; China ; Positron-Emission Tomography/methods* ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Biopsy

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.

Brain Neoplasms/surgery* ; Cyclic AMP Response Element-Binding Protein ; Gene Fusion ; Humans ; Oncogene Proteins, Fusion/genetics* ; RNA-Binding Protein EWS/genetics*

Objective: To understand the incidence of pneumoconiosis in the non-coal mining industry in Jiangsu Province, and provide reference for the prevention and control of pneumoconiosis in the non-coal mining industry. Methods: The data of 7019 newly diagnosed pneumoconiosis patients in non-coal mining industry in Jiangsu Province from January 1956 to December 2019 were collected through the Jiangsu Province Pneumoconiosis Follow-up Network Report System, including the gender of the pneumoconiosis patients, the name of the employer and the location, the industry classification of the employer, the duration of dust exposure in dust exposure, the name of occupational pneumoconiosis disease, the date of diagnosis of pneumoconiosis, etc. The collected case data of patients with pneumoconiosis were entered into the statistical software, and the characteristics of the patients' diagnosis time, region and industry were analyzed. Results: The number of confirmed pneumoconiosis patients in the non-coal mining industry in Jiangsu Province was mostly in 2007 (395 cases) , concentrated in Wuxi City (40.96%, 2875/7019) and Suzhou City (27.72%, 1946/7019) . The industries to which the patients belonged were mainly non-metallic mining and dressing (60.95%, 4278/7019) , and the most common type of pneumoconiosis was silicosis (96.40%, 6766/7019) . The patients were mainly stageⅠpneumoconiosis (61.33%, 4305/7019) . There were statistically significant differences in the mean age of diagnosis and the average duration of dust exposure among patients with different pneumoconiosis stages (P<0.01) . The differences in the average diagnosis age and the average duration of dust exposure of patients with different types of pneumoconiosis were statistically significant (P<0.05) , the mean age of diagnosis and the average duration of dust exposure of electric welders were the smallest, which were (44.92±7.74) years old and (17.38±10.15) years, respectively. Conclusion: The regional and industry distribution characteristics of new pneumoconiosis patients in the non-coal mining industry in Jiangsu Province are obvious, and attention should be paid to the treatment of pneumoconiosis patients with young diagnosed age and short duration of dust exposure, as well as the personal protection and health protection of front-line workers such as electric welders who are exposed to productive dust in a short period of time.
Adult ; Coal Mining ; Dust ; Humans ; Middle Aged ; Occupational Diseases/epidemiology* ; Occupational Exposure/adverse effects* ; Pneumoconiosis/epidemiology* ; Silicosis/epidemiology*

Accurate methods for identifying pelvic lymph node metastasis (LNM) of prostate cancer (PCa) prior to surgery are still lacking. We aimed to investigate the predictive value of peripheral monocyte count (PMC) for LNM of PCa in this study. Two hundred and ninety-eight patients from three centers were divided into a training set (n = 125) and a validation set (n = 173). In the training set, the independent predictors of LNM were analyzed using univariate and multivariate logistic regression analyses, and the optimal cutoff value was calculated by the receiver operating characteristic (ROC) curve. The sensitivity and specificity of the optimal cutoff were authenticated in the validation cohort. Finally, a nomogram based on the PMC was constructed for predicting LNM. Multivariate analyses of the training cohort demonstrated that clinical T stage, preoperative Gleason score, and PMC were independent risk factors for LNM. The subsequent ROC analysis showed that the optimal cutoff value of PMC for diagnosing LNM was 0.405 × 109 l

OBJECTIVE: To discuss the clinical effects of clomiphene citrate combined with low molecular weight heparin calcium in the treatment of patients with polycystic ovarian syndrome(PCOS)infertility. METHODS: A total of 105 patients with PCOS infertility who were admitted to the Outpatient Department of Women and Children's Hospital of Qingdao University from September 2016 to April 2018 were taken as research subjects.They were randomly divided into observation group(57 cases)and control group(48 cases).The control group received clomiphene citrate for ovulation treatment,the observation group was given clomiphene citrate combined with low molecular weight heparin calcium for ovulation treatment,and the endometrial receptivity changes,pregnancy rate and the incidence of adverse reactions of patients were compared between the two groups.RESULTS: In the observation group,the endometrial thickness,blood flow index(FI),endometrial spiral arterial blood flow resistance index(RI)and pulsatility index(PI)decreased,and the pregnancy rate was better than that in the control group;the difference was statistically significan(t P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).CONCLUSION: Clomiphene citrate combined with low molecular weight heparin calcium in the treatment of polycystic ovary syndrome infertility can improve the treatment efficiency,and is safe and reliable.It is worthy of clinical promotion.

Objective To observe the clinical efficacy of Tiao Shen Jie Jing needling (regulating the mind and release spasm) in treating post-stroke upper-limb spastic palsy. Method Ninety patients with post-stroke upper-limb spastic palsy were randomized into an observation group and a control group, 45 cases each. The observation group was intervened by Tiao Shen Jie Jing needling, while the control group was given ordinary acupuncture. The Modified Ashworth Scale (MAS), short-form Fugl-Meyer Assessment (SFMA) and Barthel Index (BI) were evaluated and recorded prior to the treatment, after 2-week and 4-week treatment and 3 months later after the intervention; the serumγ-aminobutyric acid (GABA) was detected before and after the treatment. Result The total effective rate was 83.3% in the observation group versus 61.0% in the control group, and the efficacy of the observation group was superior to that of the control group (P<0.05). The scores of each scale showed improvements after the treatment in both groups (P<0.05), and the improvements in the observation group were more significant (P < 0.05). The follow-up showed continuing improvements in the scales in the observation group, which were superior to those in the control group (P<0.05); after the treatment, the content of GABA in the observation group was significantly higher than that in the control group (P<0.05). Conclusion Tiao Shen Jie Jing needling can effectively ameliorate the upper-limb spasm,as well as the motor function of the upper extremities, improve the activities of daily living and maintain a long-term efficacy, better than ordinary acupuncture. The action mechanism is related to the regulation of GABA content in serum.

Objective To analyze the relationship between 18F-FDG PET/CT manifestations,tumor differentiation and PSA for the patients with bone metastases from prostate cancer.Methods Retrospective analysis was executed on the distribution,number and density of bone metastases tumor and FDG uptake as well as the relationship between serum PSA,FDG uptake of bone metastases focus,type of bone metastases and the involved range.Results Of the 25 cases,there were 8 ones of poorly differentiated carcinoma and 17 ones of moderately differentiated carcinoma.All the patients had serum PSA higher than 10 μg/ml,of whom there were 19 ones had the PSA not lower than 20 μg/ml.Eight patients with bone metastases restrained in the pelvis and lower lumbar vertebra,and the remained 17 ones had multiple or diffuse bone metastases.Fisher's exact test showed that non-osteoblastic metastases were more common in low-and medium-differentiation patients (P=0.022),the typing of bone metastases had no relationship with the enhancement of PSA,and there were no statistical differences between the involved ranges of the patients.Conclusion Bone metastases from prostate cancer often occurs in the patient with obviously enhanced PSA and poorly differentiation.18F-FDG PET/CT behaves well in the early diagnosis of bone metastases from prostate cancer.18F-FDG PET/CT manifestations differ with the differentiation of carcinoma,poorly differentiated carcinoma shows non-osteoblastic metastases and high FDG uptake,and moderately differentiated carcinoma appears as osteoblastic metastases and low FDG uptake.There is no confirmed correlation between PET/CT manifestation and total serum PSA for the patients with bone metastases from prostate cancer.