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*

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

Objective: To evaluate the safety and efficacy of transcatheter aortic valve replacement (TAVR) with domestic prostheses in patients with severely stenotic bicuspid aortic valve (BAV). Methods: This study was a prospective single-center non-randomized controlled study. Patients with symptomatic severe aortic stenosis (AS), who underwent TAVR with domestic prostheses at the First Affiliated Hospital of Air Force Medical University from January 2016 to April 2020 were consecutively included in our study. Patients were divided into BAV group and tricuspid aortic valve (TAV) group according to the aortic valve morphology. Baseline characteristics, procedural outcomes were compared between the two groups, and the primary endpoint was one-month all-cause mortality. Results: A total of 100 patients aged (69.8±8.9) years were enrolled, including 71 (71%) males. There were 51 cases in BAV group and 49 cases in TAV group. Compared with TAV group, patient in the BAV group was younger ((67.1±8.6) years vs. (72.7±8.4) years, P=0.002) and had larger ascending aortic diameter at proximal part ((39.7±5.7) mm vs. (36.0±4.2) mm, P<0.001), lower Society of Thoracic Surgeons-Predicted Risk of Mortality (STS-PROM) score (3.1 (1.9, 5.4) % vs. 5.9 (2.6, 12.3) %, P=0.002). In BAV group and TAV group, the incidence of 2nd prosthesis implantation was 15.7% (8/51) and 18.4% (9/49) (P=0.721), the incidence of moderate or severe paravalvular regurgitation was 2.0% (1/51) and 0 (P=1.000), the rate of device success was 82.4% (42/51) and 81.6% (40/49) (P=0.925), respectively. One-month all-cause mortality was 2.0% (1/51) and 10.2% (5/49) (P=0.108), respectively. Echocardiography showed that postprocedural mean pressure gradient (PGmean) was higher in the BAV group (13.0 (10.0, 16.0) mmHg vs. 9.0 (7.0, 14.0) mmHg, P=0.003) (1 mmHg=0.133 kPa), but the PGmean decrease post procedure as compared with that before TAVR was similar between the two groups ((36.7±16.6) mmHg vs. (36.2±17.5) mmHg, P=0.893). Conclusion: Favorable safety and efficacy are evidenced in patients with severely stenotic BAV undergoing TAVR with domestic prostheses.

Purpose::Blast lung injury (BLI) is the most common damage resulted from explosion-derived shock wave in military, terrorism and industrial accidents. However, the molecular mechanisms underlying BLI induced by shock wave are still unclear.Methods::In this study, a goat BLI model was established by a fuel air explosive power. The key genes involved in were identified. The goats of the experimental group were fixed on the edge of the explosion cloud, while the goats of the control group were 3 km far away from the explosive environment. After successful modeling for 24 h, all the goats were sacrificed and the lung tissue was harvested for histopathological observation and RNA sequencing. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis were performed to identify the main enriched biological functions of differentially expressed genes (DEGs). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the consistency of gene expression.Results::Of the sampled goat lungs, 895 genes were identified to be significantly differentially expressed, and they were involved in 52 significantly enriched GO categories. KEGG analysis revealed that DEGs were highly enriched in 26 pathways, such as cytokine-cytokine receptor interaction, antifolate resistance, arachidonic acid metabolism, amoebiasis and bile secretion, JAK-STAT, and IL-17 signaling pathway. Furthermore, 15 key DEGs involved in the biological processes of BLI were confirmed by qRT-PCR, and the results were consistent with RNA sequencing.Conclusion::Gene expression profiling provide a better understanding of the molecular mechanisms of BLI, which will help to set strategy for treating lung injury and preventing secondary lung injury induced by shock wave.

Objective :To study correlation between treadmill exercise test assessing myocardial ischemia and coronary stenosis .Methods :A total of 150 patients with stable angina pectoris in our hospital ,according to vascular stenosis by coronary CT were divided into group A (stenosis＜ 50%,n＝ 50) ,group B (stenosis 50% ～75%,n＝ 50) and group C (stenosis ＞75%,n＝50).Coronary stenotic rate and ST depression during exercise test were compared a-mong three groups.Spearman method was used to analyze correlation between treadmill exercise positive rate and coronary stenosis .Results :Compared with group B ,there were significant rise in coronary diameter stenotic rate [(63.64 ± 4.21)% vs.(66.71 ± 4.46)%] and vascular diameter of reference segment [(2.92 ± 0.23) mm vs.(3.03 ± 0.21) mm] in group C ,P＜0.05 or ＜0.01. Along with coronary stenosis aggravated ,there was significant re-duction in onset time of ST depression [(712.3 ± 202.7) s vs.(602.3 ± 210.4) s vs.(501.2 ± 236.1) s] ,and signif-icant rise in duration [ (425.4 ± 200.5) s vs.(520.8 ± 205.8) s vs.(603.4 ± 198.4) s] and treadmill exercise posi-tive rate (64.00% vs.82.00% vs .92.00%) ,in group A ,B ,C respectively ;and ST depression extent of group C was significantly higher than that of group A [(2.4 ± 1.1) mV vs.(1.9 ± 0.8) mV] ,P＜0.05 or ＜0.01. Spearman correlation analysis indicated that treadmill exercise positive rate (myocardial ischemia rate ) was not significantly correlated with coronary stenotic degree (r＝3.425 , P＝0.126).Conclusion :Although treadmill exercise test pos-sesses important significance in diagnosis of myocardial ischemia ,but coronary stenotic degree is not correlated with myocardial ischemic degree .which should raise clinical attention

OBJECTIVETo compare the clinical curative effect of thoracolumbar burst fracture treated by the posterior unilateral approach corpectomy fusion screw-rod fixation and anterior corpectomy bone fusion screw plate fixation.

METHODSFrom January 2008 to May 2014,36 cases of thoracolumbar burst fracture underwent operation of decompression, fusion, and internal fixation was retrospective analyzed. Among them, 16 patients were treated through posterior approach as posterior group, including 13 males and 3 females aged from 37 to 62 years old; 9 cases caused by falling injury, 3 cases by traffic accident injury,4 cases by heavy aboved;the injury segment was on T₁₂ in 2 cases, L₁ in 5 cases, L₂ in 7 cases, L₃ in 2 cases; according ASIA grade, 3 cases were grade A, 2 cases were grade B, 2 cases were grade C, 5 cases were grade D, 4 cases were grade E; the time between injury and operation ranged from 5 to 15 days. Other 20 patients were treated through anterior-lateral approach as anterior-lateral group, including 15 males and 5 females with age from 27 to 62 years old; 12 cases caused by falling injury, 4 cases by traffic accident injury, 4 cases by heavy aboved; the injury segment was on T₁₂ in 2 cases, L₁, in 7 cases, L₂ in 9 cases, L₃ in 2 cases; for ASIA grade: 4 cases were grade A, 2 cases were grade B, 4 cases were grade C, 6 cases were grade D, 4 cases were grade E; the time between injury and operation ranged from 4 to 12 days. The operation time, bleeding during operation and postoperative drainage volume were observed in two groups,and the changes of nerve function of ASIA grade, clinical efficacy,improved degree of thoracic and lumbar lordosis,and bony fusion were compared between two groups.

RESULTSAll patients were followed up from 12 to 24 months with an average of (15.8 ± 3.3) months. The operation time, bleeding during operation, and postoperative drainage volume had no significant different between two groups (P > 0.05). As compared with preoperative, ASIA grade of two groups at last follow-up had statistically significantly different (P < 0.01), the neural function of two groups after operation was recovered for different extent. The JOA score of two groups was compared between last follow-up and preoperative, the difference had statistically significant (P < 0.01), the two groups showed good clinical effect. The clinical results of ASIA grade, JOA score and RIS had no significant differences between two groups. All patients of two groups were obtained fusion. Thoracic and lumbar lordosis angle improvement degree had no significant difference between two groups ,it bad significant difference had statistical significance compared with preoperative, the two approaches could effectively restore the spinal sequence.

CONCLUSIONFor patients with thoracolumbar burst fracture just treated by anterior decompression and reconstruction of anterior column, according to the degree of operation performer' skill proficiency and the patient' condition to choose, but for patients must performed the spinal canal decompression anterior and posterior, the three column-reconstruction to required anterior-posterior approach, the posterior unilateral approach corpectomy fusion screw-rod fixation obviously shorten operation time, reduce the operation wound, it is worth the clinical promotion.

Adult ; Decompression, Surgical ; methods ; Female ; Humans ; Lumbar Vertebrae ; injuries ; surgery ; Male ; Middle Aged ; Pedicle Screws ; Reconstructive Surgical Procedures ; Retrospective Studies ; Spinal Fractures ; surgery ; Spinal Fusion ; methods ; Thoracic Vertebrae ; injuries ; surgery

Objective:To compare the clinical curative effect of thoracolumbar burst fracture treated by the posterior uni-lateral approach corpectomy fusion screw rod fixation and anterior corpectomy bone fusion screw plate fixation. Methods:From January 2008 to May 2014,36 cases of thoracolumbar burst fracture underwent operation of decompression,fusion,and internal fixation was retrospective analyzed. Among them ,16 patients were treated through posterior approach as posterior group,including 13 males and 3 females aged from 37 to 62 years old;9 cases caused by falling injury,3 cases by traffic acci-dent injury,4 cases by heavy aboved;the injury segment was on T12 in 2 cases,L1 in 5 cases,L2 in 7 cases,L3 in 2 cases;ac-cording ASIA grade,3 cases were grade A,2 cases were grade B,2 cases were grade C,5 cases were grade D,4 cases were grade E;the time between injury and operation ranged from 5 to 15 days. Other 20 patients were treated through anterior later-al approach as anterior lateral group,including 15 males and 5 females with age from 27 to 62 years old;12 cases caused by falling injury,4 cases by traffic accident injury,4 cases by heavy aboved;the injury segment was on T12 in 2 cases,L1 in 7 cas-es,L2 in 9 cases,L3 in 2 cases;for ASIA grade:4 cases were grade A,2 cases were grade B,4 cases were grade C,6 cases were grade D,4 cases were grade E;the time between injury and operation ranged from 4 to 12 days. The operation time ,bleeding during operation and postoperative drainage volume were observed in two groups ,and the changes of nerve function of ASIA grade,clinical efficacy,improved degree of thoracic and lumbar lordosis,and bony fusion were compared between two groups. Results:All patients were followed up from 12 to 24 months with an average of (15.8±3.3) months. The operation time,bleed-ing during operation,and postoperative drainage volume had no significant different between two groups (P>0.05). As com-pared with preoperative,ASIA grade of two groups at last follow up had statistically significantly different (P<0.01),the neural function of two groups after operation was recovered for different extent. The JOA score of two groups was compared between last follow-up and preoperative,the difference had statistically significant (P<0.01),the two groups showed good clinical ef-fect. The clinical results of ASIA grade,JOA score and RIS had no significant differences between two groups. All patients of two groups were obtained fusion. Thoracic and lumbar lordosis angle improvement degree had no significant difference between two groups,it had significant difference had statistical significance compared with preoperative ,the two approaches could ef-fectively restore the spinal sequence. Conclusion:For patients with thoracolumbar burst fracture just treated by anterior de-compression and reconstruction of anterior column ,according to the degree of operation performer'skill proficiency and the pa-tient'condition to choose,but for patients must performed the spinal canal decompression anterior and posterior,the three col-umn reconstruction to required anterior posterior approach,the posterior unilateral approach corpectomy fusion screw-rod fixa-tion obviously shorten operation time,reduce the operation wound,it is worth the clinical promotion.

BACKGROUNDSerum expression of cytokines may provide information about the clinical outcome of advanced non-small cell lung cancer (NSCLC) patients. This study aimed to investigate the relationship between serum cytokine levels and the clinical outcome of erlotinib treatment in a second or third line setting in patients with advanced NSCLC.

METHODSA total of 162 patients with advanced NSCLC who received erlotinib as either second or third line therapy were enrolled in this study. Blood samples were collected before the initiation of erlotinib treatment, and the levels of IL-1, IL- 2R, IL-6, and tumor necrosis factor (TNF)-α were assessed by enzyme-linked immunosorbent assay (ELISA). Cutoff points were defined as the median levels of IL-1 (low (≥26.5 pg/ml) and high (>26.5 pg/ml)), IL-2R (low ( = 115 pmol/L) and high (>15 pmol/L)), IL-6 (low (≤49.5 pg/ml) and high (>49.5 pg/ml)), and TNF-α (low (≤48.5 pg/ml) and high (>48.5 pg/ml)). Kaplan-Meier analysis was used to estimate the survival time, and Cox regression analyses were used to correlate cytokines and baseline clinical characteristics with clinical outcomes, including time to progression (TTP) and overall survival (OS).

RESULTSBetween January 2007 and May 2011, 162 patients were enrolled. Their median age was 58 years. In this group, 109 were males and 53 were females, 74 were former or current smokers and 88 were non-smokers. A total of 122 patients had adenocarcinoma, 27 had squamous cell carcinoma, and 13 had tumors with other types of histology. And 139 patients had an Eastern cooperative oncology group (ECOG) performance status of 0-1, while 23 scored at 2-3. Expression of IL-1, IL-2R, and IL-6 was not significantly associated with age, gender, ECOG performance status, smoking status, or histology and stage of tumor. Only TNF-α was associated with smoking status (P = 0.045). Survival analysis showed that patients with low levels of either IL-6 or TNF-α had a statistically longer TTP and OS than patients with high expression (P < 0.05). These cytokines remained significant upon multivariate analysis (P < 0.05).

CONCLUSIONIL-6 or TNF-α may serve as potential predictive biomarker for the efficacy of erlotinib.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; blood ; drug therapy ; Cytokines ; blood ; Erlotinib Hydrochloride ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; Male ; Middle Aged ; Protein Kinase Inhibitors ; therapeutic use ; Quinazolines ; therapeutic use

OBJECTIVE: Over-expression of thrombin in ovarian cancer cells is associated with poor prognosis. In this study, we investigated the role of thrombin in inducing epithelial-mesenchymal transition (EMT) in SKOV3 epithelial ovarian cancer cells. METHODS: After thrombin treatment SKOV3 cells were subjected to western blots, reverse-transcription PCR, and enzyme-linked immunosorbent assay to quantify EMT-related proteins, mRNA expression of SMAD2, DKK1, and sFRP1, and the secretion of matrix metalloproteinases (MMPs) and cytokines. Meanwhile, invasion ability was evaluated using transwell assays. RESULTS: The results indicated a dose- and time-dependent down-regulation of E-cadherin and upregulation of N-cadherin and vimentin in thrombin-treated SKOV3 cells, compared with the thrombin-free control group (p<0.05). There was a dose- and time-dependent increase in the levels of SMAD2 and DKK1 mRNAs and a decrease in the levels of sFRP1 mRNA in thrombin-treated SKOV3 cells compared to control cells (p<0.05). Thrombin-treated SKOV3 cells exhibited increased secretion of MMP-9, MMP-2, interleukin (IL)-8, and IL-6 and increased invasion compared to untreated cells (p<0.05). Thrombin altered the morphology of SKOV3 cells to a spindle-like phenotype. Addition of hirudin to thrombin-treated cells reversed the effects of thrombin. CONCLUSION: Thrombin induced EMT and promoted the invasion of SKOV3 cells, possibly via distinct signaling pathways. Hirudin inhibited the effects of thrombin, suggesting that anticoagulant therapy could be a novel therapeutic strategy for ovarian carcinoma.
Blotting, Western ; Cadherins ; Cytokines ; Down-Regulation ; Enzyme-Linked Immunosorbent Assay ; Epithelial-Mesenchymal Transition ; Hirudins ; Interleukin-6 ; Interleukins ; Matrix Metalloproteinases ; Neoplasms, Glandular and Epithelial ; Ovarian Neoplasms ; Phenotype ; Polymerase Chain Reaction ; Prognosis ; Proteins ; RNA, Messenger ; Thrombin ; Up-Regulation ; Vimentin

OBJECTIVETo evaluate the effect on pre-exposure prophylaxis (PrEP) to prevent HIV infection in high risk populations.

METHODSA computerized literature searching had been carried out in PubMed, EMbase, Ovid, Web of Science, Science Direct, Wanfang, Tsinghua Tongfang database and related websites to collect relevant papers (from establishment to June 2012) with the key words of pre-exposure prophylaxis, HIV, AIDS, high risk populations, relative risk, reduction. All randomized controlled trials (RCT) papers about using single or compound antiretroviral drugs (ARVs) orally or topically before HIV exposure or during HIV exposure in high risk populations were enrolled. Meta-analysis was conducted using Stata 10.0 to calculate the pooled RR value (95%CI). Consistency test was performed and publication bias was evaluated.

RESULTSFinally 5 RCT papers were enrolled, including 10 271 persons who were at high risk of HIV infection. The number of the experimental group was 5929, among which 116(1.96%) became infected. The number of the control group was 4342, among which 201(4.63%) became infected. Meta-analysis showed that the pooled relative risk (RR) and 95%CI was 0.49 (0.39 - 0.61), P < 0.05, indicating that the persons in experimental group had a 0.49 times lower risk of HIV infected, as compared with the control group. Publication bias analysis revealed a symmetry funnel plot. The fail-safe number was 825.

CONCLUSIONPrEP was an effective and safe protection measure to reduce HIV infection in high risk populations.

Anti-HIV Agents ; administration & dosage ; therapeutic use ; HIV Infections ; prevention & control ; Humans ; Randomized Controlled Trials as Topic ; Risk