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 incidence and risk factors of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgeries and its correlation with preoperative risk assessment of cerebrovascular events,so as to guide perioperative risk management.Methods A retrospective study was conducted on 40 patients aged≥18 years who underwent non-cardiac and non-neurosurgical surgeries and experienced perioperative ischemic stroke in the First Affiliated Hospital of Henan University of Science and Technology from January 2015 to January 2022,forming the stroke group.A control group of 160 patients without perioperative ischemic stroke was selected in a 1:4 case-control ratio,matched for gender,age,date of operation,and the surgeon.Clinical data and preoperative risk assessment of cerebrovascular events(including the single or combined application of head CT/MRI,transcranial Doppler ultrasound,carotid ultrasound,and neurological consultation)of the two groups of patients were collected and statistically analyzed.Multiple logistic regression analysis was used to identify risk factors associated with perioperative ischemic stroke.Results The incidence of perioperative ischemic stroke was 0.042%.Multiple logistic analysis results showed that hypertension(OR=7.858,95%CI 2.175-28.388,P=0.002),hyperlipidemia(OR=4.457,95%CI 1.320-15.049,P=0.016),renal insufficiency(OR=8.277,95%CI 1.480-46.282,P=0.016),and intraoperative hypotension(OR=3.862,95%CI 1.211-12.317,P=0.022)were independent risk factors for perioperative ischemic stroke in non-cardiac and non-neurological surgeries;preoperative cerebrovascular risk assessment(OR=0.130,95%CI 0.031-0.542,P=0.005)was a protective factor against it.Conclusions The incidence of perioperative ischemic stroke in non-cardiac and non-neurosurgical surgery is low but has a poor prognosis.Hypertension,hyperlipidemia,renal insufficiency,and postoperative hypotension are risk factors for perioperative ischemic stroke,while preoperative cerebrovascular event risk assessment is beneficial to reducing its incidence.

An analytical method for 10 mycotoxins in Hippophae Fructus medicinal and edible products was established in this study, and the contamination of their mycotoxins was analyzed. First of all, the mixed reference solution of ten mycotoxins such as aflatoxin, ochratoxin, zearalenone, and dexoynivalenol was selected as the control, and the Hippophae Fructus medicinal and edible products were prepared. Secondly, based on the ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) technology, 10 mycotoxins in Hippophae Fructus medicinal and edible products were quantitatively investigated and their content was determined. Finally, the contamination of mycotoxins was analyzed and evaluated. The optimal analysis conditions were determined, and the methodological inspection results showed that the 10 mycotoxins established a good linear relationship(r>0.99). The method had good repeatability, test sample specificity, stability, and instrument precision. The average recovery rates of 10 mycotoxins in Hippophae Fructus medicinal products, edible solids, and edible liquids were 90.31%-109.4%, 87.86%-107.8%, and 85.61%-109.1%, respectively. Relative standard deviation(RSD) values were 0.22%-10%, 0.75%-13%, and 0.84%-8.5%, repsectively. Based on UPLC-MS/MS technology, the simultaneous determination method for the limits of 10 mycotoxins established in this study has fast detection speed, less matrix interference, high sensitivity, and accurate results, which is suitable for the limit examination of 10 mycoto-xins in Hippophae Fructus medicinal and edible products.
Mycotoxins/analysis* ; Chromatography, Liquid/methods* ; Tandem Mass Spectrometry/methods* ; Hippophae ; Limit of Detection ; Chromatography, High Pressure Liquid/methods*

Objective: To analyze the association of fasting plasma glucose (FPG) with mild cognitive impairment (MCI) in the Chinese middle-aged and elderly population from four provinces. Methods: Data were drawn from the baseline data of the Community-based Cohort Study on Nervous System Disease 2018-2019. We selected 3 272 subjects aged 55 and above with completed information on demographics, lifestyle, disease history, cognitive test, psychological assessment, and bio-chemistries measurement, and who were capable of performing basic activities of daily living but without Alzheimer's disease during recruitment. A multivariate logistic regression model was employed to analyze the association between FPG and MCI. Results: Median level of FPG in the study population was 5.5 mmol/L. The prevalence of MCI was 24.8%, and those in groups of the FPG quintile were 19.4%, 22.2%, 29.2%, 26.6%, and 26.1%, respectively, which significantly increased the trend (P=0.002). After adjustment of confounders, multivariate logistic regression analysis found that the MCI risk of subjects in the Q₃,Q₄ and Q₅ groups was 1.641 (95%CI: 1.226-2.131), 1.373 (95%CI: 1.036-1.825), 1.402 (95%CI: 1.054-1.871) times as high as that in the Q₁ group, respectively. Conclusion: High FPG level might serve as a risk factor for MCI in the middle-aged and elderly population, suggesting the importance of monitoring and controlling plasma glucose even without diabetes.
Middle Aged ; Humans ; Aged ; Fasting ; Blood Glucose ; Activities of Daily Living ; Cohort Studies ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment. Trial Registration ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.
Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; China ; Cyclophosphamide ; administration & dosage ; Doxorubicin ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Lymphoma, Follicular ; drug therapy ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; therapeutic use ; Vincristine ; administration & dosage

Prostaglandin (PG) E2 is an active substance in pathological and physiological mechanisms, such as inflammation and pain. The in vitro high-throughput assay for screening the inhibitors of reducing PEG2 production is a useful method for finding out antiphlogistic and analgesic candidates. The assay was based on LPS-induced PGE2 production model using a homogeneous time-resolved fluorescence(HTRF) PGE2 testing kit combined with liquid handling automation and detection instruments. The critical steps, including the cell density optimization and IC50 values determination of a positive compound, were taken to verify the stability and sensibility of the assay. Low intra-plate, inter-plate and day-to-day variability were observed in this 384-well, high-throughput format assay. Totally 5 121 samples were selected from the company's traditional Chinese medicine(TCM) material base library and used to screen PGE2 inhibitors. In this model, the cell plating density was 2 000 cells for each well; the average IC₅₀ value for positive compounds was (7.3±0.1) μmol; the Z' factor for test plates was more than 0.5 and averaged at 0.7. Among the 5 121 samples, 228 components exhibited a PGE2 production prohibition rate of more than 50%, and 23 components exhibited more than 80%. This model reached the expected standards in data stability and accuracy, indicating the reliability and authenticity of the screening results. The automated screening system was introduced to make the model fast and efficient, with a average daily screening amount exceeding 14 000 data points and provide a new model for discovering new anti-inflammatory and analgesic drug and quickly screening effective constituents of TCM in the early stage.

Objective To evaluate the safety and efficacy of cross-linked hyaluronic acid Revanesse Ultra for treatment of nasolabial folds in Chinese population .Methods A total of 120 participants were enrolled in this prospective , randomized , positive controlled , non-inferiority clinical trial in accordance to inclusion and ex-clusion criteria , and signed informed consents were obtained .The participants were numbered in the order of en-rollment and randomized into Restylane group and Revanesse group , receiving hyaluronic acid injection to correct bilateral nasolabial folds .Each person received 1 or 2 times of injection ( a touch-up injection could be adminis-tered 4 weeks post the first injection ) .According to the original depth of the wrinkles , no more than 2 ml hyalu-ronic acid was injected into each side .All the participants were followed up at 1, 3, 6, and 12 months after the last injection and standardized photographs were taken at each visit .All the participants were asked to fill the form of local adverse events within the first 15 days after injection.Investigators and the participants both evalu-ated wrinkles based on Wrinkle Severity Rating Scale ( WSRS) .The WSRS score according to the pictures of 6 months post-injection were compared with the pictures which were taken before the injection ( baseline) by in-dependent staff at the end of the trial .One or more grades of WSRS improvement compared with the baseline was considered as effective .Laboratory tests including blood and urine routine , liver and renal function tests were carried out at screening visit and 6 months after injection.Results The baseline features between the two groups were comparable (all P>0.05).There was no significant difference in the WSRS 6 months after injec-tion between the two groups ( P>0.05 ) .There was no significant difference in the WSRS improvement com-pared with baseline between the two groups ( P=0.105 ) .There was no significant difference in the rate of ef-fectiveness between the two groups ( 93.0% vs.96.7%, P=0.431 ) .Two participants reported minor ad-verse events, although both of which might not be associated with the product or procedure .No laboratory test change was found during the trial .Conclusions No severe adverse event associated with the injection material was observed during this clinical trial .According to the result , Revanesse Ultra may have good histocompati-bility and tolerance .It could provide obvious improvement in the nasolabial folds , with effectiveness comparable to that of Restylane .

BACKGROUND:Negative pressure wound therapy has been extensively used, but most people only knew the superiority of negative pressure wound therapy based on clinical experiences or subjective judgment.
OBJECTIVE:To observe the effects of negative pressure wound therapy on the wound on the body surface, and to compare with contemporaneous conventional method.
METHODS:A total of 45 patients with wound on the body surface treated in the Peking Union Medical Col ege Hospital from January 2006 to December 2011 were enrol ed in this study, including 25 patients undergoing negative pressure wound therapy and 20 patients undergoing conventional change dressing method. Al clinical data were recorded.
RESULTS AND CONCLUSION:Negative pressure wound therapy was better than conventional method (P<0.05), on terms of preoperative preparation period, wound granulation, bacterial scavenging, labor intensity of working staff and incidence of postoperative complications. However, no significant difference in therapy cost was detectable (P>0.05). These results suggested that compared with conventional method, negative pressure wound therapy positively contributed to the healing, obviously shortened preoperative preparation, accelerated the diminution of wound, decreased the incidence of complications of reconstruction, lessened patient’s distress, reduced their economic cost, and diminished labor intensity of working staff. Negative pressure wound therapy has been proven an excellent tool of to promote wound healing.

OBJECTIVETo explore the effect of anhydroicaritin phytosomes (AIP) in preventing and treating bone loss and enhancing bone quality in ovariectomized osteoporosis rats.

METHODSeventy-two SD female rats were randomly divided into 6 groups: the sham group, the model group, the estrogen group and AIP groups (low, middle, high). The sham group was only sham operated, and the remaining five groups were ovariectomized. One week after the ovariectomy, the rats were given 17 beta-estrogen and AIP (15, 30, 60 mg x kg(-1)) for consecutively three months, during which period their serum calcium (s-Ca), serum phosphorus(s-P), alkaline phosphate (ALP), urine calcium (u-Ca), urine phosphorus(u-P), urinary deoxypyridinoline (D-Pyr) and creatinine (Cr) were detected. Subsequently, rats were sacrificed, and their thighbone, second lumbar vertebrate and forth lumbar vertebrate were collected to detect bone mineral density (BMD), bone calcium (b-Ca) and phosphorus (b-P), biomechanical properties and bone histomorphometric parameters.

RESULTCompared with the sham group, the model group showed a significant increase in serum ALP, u-Ca and D-Pyr /Cr, and reduction in BMD of femur, b-Ca and b-P, biomechanical properties (elastic load, maximum load, break load, stiffness), static parameters (total tissue area, trabecular area, trabecular perimeter) and dynamic parameters (% L Pm, BFR/BV and BFR/ TV), with metratrophia. Compared with the model group, ALP high and middle-dose groups and the estrogen group showed a decrease in serum ALP, u-Ca and D-Pyr/Cr, and growth in BMD of femur, b-Ca and b-P, biomechanical properties of the forth lumbar vertebrae (elastic load, maximum load, break load, stiffness), static parameters (total tissue area, trabecular area, trabecular perimeter) and dynamic parameters (% L Pm, BFR/BV and BFR/TV). The beta-estrogen group showed endometrial hyperplasia, whereas AIP groups showed no hyperplastic change.

CONCLUSIONAIP could inhibit enhanced bone turnover induced by ovariectomy, improve BMD the biomechanical properties of vertebrae, without any stimulation on uterus.

Animals ; Benzopyrans ; therapeutic use ; Bone Density ; drug effects ; Calcium ; blood ; Female ; Osteoporosis ; drug therapy ; prevention & control ; Ovariectomy ; Phospholipids ; therapeutic use ; Phosphorus ; blood ; Rats ; Rats, Sprague-Dawley

BACKGROUND:Negative pressure wound therapy has been widely recognized, the currently published papers are limited in academic value and lack of scientific, objective, qualified index to confirm the therapy effectiveness. OBJECTIVE:To systemical y evaluate the clinical effect of negative pressure wound therapy, provide more evidence for its clinical application, and guide clinical research.
METHODS:Fifteen articles were screened out of peer-reviewed publications (Cochran library, Embase, PubMed-Medline and Chinese BioMedical Literature Database). Scientific data were col ected and evaluated by two researchers. The data were statistical y analyzed with RevMan software.
RESULTS AND CONCLUSION:Only 15 random-control ed trials were final y preserved, including 10 as B-grade moderate bias risk and focused on the effect of negative pressure wound therapy on chronic wounds, and 5 as C-grade high bias risk and focused on the effect of negative pressure wound therapy on acute wounds. There were significant differences in the main outcome measures between negative pressure wound therapy and conventional wound therapy. As for chronic wound patients, no significant difference was observed in the operation-preparing period, reducing wound area, promoting wound granulation, and amputation rate between two therapies. As for acute wound patients, the differences were significant in the operation-preparing period, promoting wound granulation, wound infection rate, and cost materials between two therapies. However, no difference was significant in the healing of wound and hospitalization time. Our findings indicate that, negative pressure wound therapy is an effective means for both acute and chronic wounds, it can shorten operation-preparing period, promote wound granulation, and reduce amputation rate and infection rate, thus providing evidence for clinical application. The wel-designed study is needed to develop high-quality random control ed trails.