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 investigate the feasibility and safety of suprapubic bladder puncture and gland fixation in transurethral enucleation of the prostate.Methods:The clinical data of 15 patients with benign prostatic hyperplasia admitted to the First Affiliated Hospital of Guangxi Medical University from January 2020 to June 2020 were retrospectively analyzed. The age was (70.27±5.35) years old, preoperative serum prostate-specific antigen (PSA) level was (3.03±1.37) ng/ml, preoperative total prostate weight was 80.3(70.49, 96.78)g, preoperative postvoid residual urine volume(PVR)was 80 (55, 108)ml, and the maximum urine flow rate (Q max) was (6.13±2.25) ml/s. The international prostate symptom score(IPSS) was 25(22, 27), quality of life (QOL)score was 5(5, 6), international erectile function index-5 (IIEF-5) score was (15.38±5.10). All 15 patients underwent conventional transurethral plasma enucleation of prostate by using the three-lobe method, and the enucleated gland was pushed into the bladder completely. Then a laparoscopic pneumoperitoneum needle was used to perform suprappubic cystipuncture, and ureteral grasping forceps were inserted through the outer sheath. The forceps were used to fix the enencied gland. A rapid harvesting electric resection was performed in the broad space of the bladder, and the Ellick was rinsed to remove the tissue fragments. Surgical indicators and complications were recorded. The improvement of subjective score (IPSS, QOL, IIEF-5) and objective index (Q max, PVR) was compared between preoperative and postoperative. Results:All the 15 operations were completed successfully and there were no complications such as blood transfusion, capsule perforation, transurethral resection syndrome, bladder injury, bladder puncture site laceration and bleeding. The weight of resected prostate tissue was 44(40, 60)g, with blood loss (79.20±18.93)ml.The time of enucleation operation was (54.13±10.88)min, with harvest cutting time (14.67±2.50)min, evisceration efficiency (0.89±0.08)g/min, harvesting efficiency (3.26±0.36)g/min, bladder irrigation time (2.47±0.52) d. The time of indwelling catheter was (3.73±0.80)d.The postoperative hospital stay was (4.40±0.91) d. Temporary urinary incontinence occurred in 1 case after operation. All patients were followed up for 6 months after operation. The IPSS score was 3(2, 3), QOL score was 0(0, 1), IIEF-5 score was (20.12±2.30), Q maxwas (21.80±2.14) ml/s and PVR was 10(5, 15)ml, which were all significantly different compared with those before surgery ( P<0.05). The symptoms of the patients were significantly improved. Conclusions:Transurethral plasma enucleation of prostate combined with suprapubic bladder puncture and fixed gland is effective in the treatment of benign prostatic hyperplasia. The subjective symptoms and objective examination of patients have been significantly improved, and no adverse operation-related complications have occurred. It is a suitable method for enucleation of prostate in units which are not equipped with transurethral tissue planer.

On the basis of systematic evaluation of 32 provincial capital cities and municipalities in their capacity for preventing and controlling emerging infectious diseases, focus analysis is made on Wuhan in relation to its advantages and disadvantages as follows:There has been a legal basis for epidemic prevention according to law, but it has not translated into effective action.There has been an organizational basis for responding to epidemic, but coordination mechanism has not been effectively established.The management mechanism has been complete, but the division of responsibilities among different departments has not been clear.The monitoring network has been set up, but its role of "predictive warning" has not been played.Insufficiency of public health service delivery was observed owing to lack of financial investment.In cities of China, advantages and disadvantages have been both existent in their capacity to prevent and control of emerging infectious disease.We should be vigilant in this regard. It is imperative to "fill defects, stop leaks and strengthen weakness".There is a Chinese saying:"It is not too late to mend a fold after the sheep have been stolen".

The outbreak of COVID-19 has exposed many shortcomings in disease control and prevention system (DCPS) of China.Resolving the problems and strengthening the DCPS became the top priority on China′s public policy agenda.This paper reveals the problems of the DCPS system regarding policy-making, regulations, operation mechanism and staff, and proposes several strategies from three aspects of legal construction, management system, and operation mechanism, including:"Prevention first" should be incorporated into the national legal system, all the departments should be engaged in "Healthy China 2030" initiative, laws and regulations should be amended, new disease prevention and control management institutions should be set up, a high-quality professional team should be retained, the regional health information exchange channels should be strengthened, the coordinated mechanism for disease prevention and control should be normalized, the long-term investment mechanism should be established, and the equipment renewal and reserve system should be improved.

Background::Regulatory policy (RP) is known as a major factor to improve health care system performance. A significant difference in maternal mortality rates (MMRs) was observed between New York city (NYC) and Shanghai (SH), both first-class international metropolises. This study aims to adopt a quantitative evaluation model to analyze whether RP differences contribute to the different MMRs of the two cities.Methods::Based on collection of all publicly released policy documents regarding maternal health in the two cities, we assessed and compared the status of their maternal health care RPs from 2006 to 2017 through a series of quantitative indicators as regulatory elements coverage rate (RECR), departmental responsibility clarity rate (DRCR), and accountability mechanism clarity rate (AMCR), based on two characteristics of comprehensiveness and effectiveness of RPs. Pearson correlation analysis, principal component analysis, and linear regression analysis were used to test the relationships between the indicators and MMR in SH and NYC.Results::By 2017, disparities of maternal health care RP are found between SH and NYC, from the indicators of RECR (100% vs. 77.0%), DRCR (38.9% vs. 45.1%), and AMCR (29.2% vs. 22.5%). From 2006 to 2017, RECR, DRCR, and AMCR in SH have shown a higher growth of 8.7%, 53.2%, and 45.2%, compared with growth of 25.0%, 12.5%, and 2.9% in NYC. The three indicators were found all negatively correlated with MMR in SH (Coefficients = －0.831, －0.833, and －0.909, and P < 0.01), while only RECR and DRCR had negative correlation with MMR in NYC (Coefficients = －0.736 and －0.683, and P < 0.05). Linear regression showed that the principal components of the three indicators were found with significant impact on MMRs both in SH ( R = 0.914, R2 = 0.836, P < 0.001) and NYC ( R = 0.854, R2 = 0.357, P = 0.04). Conclusion::Compared with NYC, the more comprehensive and effective maternal health care RPs in SH had a stronger impact on MMR control, which contributed to the differences between the two cities’ MMRs to some extent. The methods and indicators we adopted for assessment are reasonable and comparable.

[Objective]To explore the diagnostic value of urine ErbB3 protein in clear cell renal cell carcinoma.[Methods]We collected 31 urine samples of clear cell renal cell carcinoma patients who received operations in the Urology Department of the First Affiliated Hospital of Sun Yat-Sen University from April 2,2016 to August 31,2016.Meanwhile we collected 50 urine samples of normal people as control.We tested the expression of urine ErbB3 protein in experimen-tal group and control group,and analyzed the differences between the two groups.Then we established the ROC curve of which diagnosing clear cell renal carcinoma by urine ErbB3 protein. Also,we analyzed the relation between ErbB3 pro-tein in urine and the patients'BMI,preoperative creatinine,tumor diameter and underlying diseases such as hyperten-sion and hyperglycemia.[Results]①The expression of urine ErbB3 protein in clear cell renal cell carcinoma group was significantly lower than normal group(P<0.001). ② When diagnosing clear cell renal carcinoma by ErbB3 protein,the AUC of ROC was 0.802(P<0.001). When setting the cutoff as 13.98 pg/mL,the max Youden index was 0.525,the sensitivity was 0.645 and the specificity was 0.880. The Kappa value of diagnostic test was 0.542(P<0.001). ③ There was no correlation between the ErbB3 content and patients'BMI,tumor diameter or preoperative creatinine by correlation analysis. Also,there was no correlation between the urine ErbB3 protein content and blood pressure or blood glucose.[Conclusion]The urine ErbB3 protein of clear cell renal cell carcinoma was significantly lower than normal people,and it is meaningful for applying urine ErbB3 protein to early diagnosis of clear cell renal cell carcinoma.

Adult ; Humans ; Male ; Paraganglioma ; diagnosis ; surgery ; Seminal Vesicles ; pathology ; surgery ; Tomography, X-Ray Computed

OBJECTIVETo develop a 96-microwell plate DNA diagnostic chip for simultaneous detection of 9 major foodborne bacteria.

METHODSType-specific PCR primers labeled with biotin and oligonucleotide probes were designed according to the conservative genes of 9 major foodborne bacteria Staphylococcus aureus, Salmonella spp., Escherichia coli O157:H7 (Stx1 and Stx2), Shigella spp., Listeria monocytogenes, Bacillus cereus, Yersinia enterocolitica, Vibrio cholerae and Vibrio parahaemolyticus. A one-tube multiplex PCR system for simultaneous amplification of these bacteria was established, and the DNA probes were spotted and immobilized in the wells of the plate in 5x5 array format. Stable hybridization system between PCR products and oligonucleotide probes in the microwell was established after condition optimization. Alkaline phosphatase-conjugated streptavidin and NBT/BCIP were used to detect the hybridized PCR products.

RESULTSTwenty standard bacteria strains were used to validate the 96 microwell plate DNA diagnostic chip and highly specific and stable experiment results were obtained. Using this chip assay, the causal pathogen Staphylococcus aureus was identified within 12 h after the sampling from an incident of food poisoning, and the result was consistent with that obtained using conventional bacterial culture and biochemical identification.

CONCLUSIONThe novel 96 microwell plate DNA diagnostic chip allows rapid, accurate, automated and high-throughput bacterial detection and is especially valuable for quick response to such public health emergencies as food poisoning.

Bacteria ; classification ; genetics ; isolation & purification ; DNA, Bacterial ; analysis ; Food Contamination ; analysis ; Food Microbiology ; methods ; Foodborne Diseases ; microbiology ; Humans ; Oligonucleotide Array Sequence Analysis ; methods

AIMTo explore the intestinal absorption characteristics of lumbrokinase (YJM-I) in the absence or presence of various absorption enhancers and to find the optimum intestinal site for YJM-I absorption.

METHODSThe absorption kinetics and absorption intestinal sites for YJM-I absorption were investigated with the method of diffusion cell in vitro, duodenum bolus injection, recirculating perfusion and in situ duodenum perfusion in vivo.

RESULTSYJM-I could be transported into blood and kept its biological activity across intestinal endothelial membrane after administration via duodenum site, whereas with lower bioavailability. Some of the absorption enhancers were shown good enhancement effects on intestinal absorption of YJM-I in vitro and in situ experiments. The order of enhanced efficiencies of various enhancers on duodenum, ileum and jejunum in vitro permeation experiments were shown as follows: 1% chitosan > 1% SDCh > 1% Na2EDTA > 1% SDS > 1% sodium caprylate > 1% poloxamer > 1% HP-beta-CD. The order of enhanced efficiencies of various enhancers on duodenum absorption of YJM-I in vivo were as follows: 2.5% SDCh > 2.5% Na2EDTA > 2.0% chitosan > 2.5% SDS > 2.5% sodium caprylate > 2.5% Poloxamer > 2.5% HP-beta-CD.

CONCLUSIONThe results indicated that the absorption of YJM-I could be enhanced by various enhancers, and duodenum was the optimum absorption site of YJM-I. Furthermore, bio-adhesive chitosan might be a potential enhancer of intestinal YJM-I absorption.

Administration, Oral ; Animals ; Area Under Curve ; Caprylates ; pharmacology ; Chitosan ; pharmacology ; Deoxycholic Acid ; pharmacology ; Duodenum ; drug effects ; metabolism ; Edetic Acid ; pharmacology ; Endopeptidases ; administration & dosage ; pharmacokinetics ; Injections, Intravenous ; Intestinal Absorption ; Male ; Metabolic Clearance Rate ; Poloxamer ; pharmacology ; Rats ; Rats, Sprague-Dawley