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*

On March 19, 2021, the National Medical Products Administration(NMPA) issued the Regulations on the Supervision and Administration of Medical Devices (Order No. 739 of the State Council of the People's Republic of China), which clearly stipulated in Article 53 the basic definition and scope of use of in vitro diagnostic reagents developed by medical institutions. It also pointed out that the relevant administrative measures shall be formulated by the Drug Regulatory Department of the State Council in conjunction with the Health Department of the State Council. This initiative marks the re-incorporation of in vitro diagnostic reagents developed by medical institutions into China's regulatory system. This study reviewed the development of regulatory policies for self-developed in vitro diagnostic reagents at home and abroad, combined with the Key Points of On-site Verification of Self-developed In Vitro Diagnostic Reagents in Shanghai Medical Institutions issued by the Shanghai Municipal Drug Administration, in conjunction with the Shanghai Municipal Health Commission, and the specific verification work of pre-record evaluation, and sorted out the general requirements for the quality management system of self-developed in vitro diagnostic reagents. The purpose is to provide some references for the further development of this pilot work and its nationwide promotion.
China ; Quality Control ; Indicators and Reagents/standards* ; Reagent Kits, Diagnostic/standards*

Objective To investigate the effect of mirror therapy on upper limb function and cortical activity in patients with type I complex regional pain syndrome(CRPS)after stroke. Methods A total of 72 post-stroke patients with type I CRPS were recruited at the Third Rehabilitation Hospital Affiliat-ed to Shanghai University of Traditional Chinese Medicine from October,2017 to February,2022.They were ran-domly divided into control group(n=36)and mirror therapy group(n=36).The control group received conven-tional rehabilitation training,while the mirror therapy group received mirror therapy in addition.Before treat-ment,as well as at three and six weeks after treatment,they were evaluated using the Visual Analog Scale(VAS)for pain,modified Barthel Index(MBI),edema volume and Brunnstrom stage.Resting-state data were collected for 440 seconds using a 32-channel functional near-infrared spectroscopy(fNIRS)system. Results After treatment,VAS scores significantly improved in each group,showing better after six weeks than after three weeks(P<0.01).The mirror therapy group was better than the control group after six weeks(P<0.05).MBI scores also significantly improved in each group,showing better after six weeks than after three weeks(P<0.001).Edema volume significantly decreased in each group(Z>30.113,P<0.001),while the mirror therapy group was better than the control group after six weeks(Z=-3.347,P=0.001).Edema volume in the mirror therapy group significantly reduced at both three and six weeks(Z<-0.667,P<0.01),with a stronger effect ob-served after six weeks(Z=-0.667,P=0.005).Brunnstrom stages improved significantly in each group(Z>29.714,P<0.001),while the mirror therapy group was better than the control group after six weeks(Z=-2.046,P=0.041).After treatment,the control group showed strong connectivity between right M1 and right primary so-matosensory cortex,while the mirror therapy group demonstrated stronger connectivity between left M1 and right M1,right primary somatosensory cortex,right pre-motor and supplementary motor cortex.Connectivity be-tween left and right primary somatosensory cortex increased in mirror therapy group,as well as the connectivity between left pre-motor-supplementary motor cortex and right M1,right pre-motor-supplementary motor cortex and left primary somatosensory cortex,left M1 and left primary somatosensory cortex,and left primary somato-sensory cortex and right M1(∣t∣>3.402,P<0.01). Conclusion Mirror therapy may relieve pain and edema,and improve upper limb motor function in post-stroke patients with type I CRPS,which may associate with stonger connectivity between sensory regions on the unaffected side and sensory-motor regions on the affected side,promoting sensorimotor cortical reorganization.

Tezepelumab(AMG 157/MEDI9929)is a human monoclonal antibody against the epithelial cell-derived cytokine thymic stromal lymphopoietin(TSLP).It is primarily used to treat moderate to severe asthma,particularly in patients with a non-eosinophilic inflammatory phenotype,whose asthma remains uncontrolled despite the use of long-acting beta-agonists and moderate to high doses of inhaled glucocorticoids.This article will summarise the mechanism of action,clinical trial efficacy and safety and tolerability of Tezepelumab in order to provide a comprehensive understanding of the drug and inform clinical work.

The author analyzed the characteristics of phase Ⅰ clinical trials of macromolecular drugs,the characteristics of evaluation indicators of phase Ⅰ clinical trials of macromolecular drugs,such as safety evaluation,pharmacokinetic and pharmacodynamic evaluation,and efficacy evaluation.And the control points of subjects management,management of experimental macromolecule drugs,and identified and potential risk factors of macromolecule drugs in the implementation of risk management for phase Ⅰ clinical trials of macromolecule drugs were discussed in depth based on previous clinical trial research experience.Through discussion and analysis,the author suggests that each research center can formulate risk control strategies according to the actual situation,improve the efficiency of risk control,and facilitate the smooth implementation of clinical trials and improve the quality of clinical trials.

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases.The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared.The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group,while the postoperative satisfaction was higher in the endoscopic group than in the open group.This set of instruments has advantage of novel design,scientific structure,safe application.It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures,which can promote the development and popularization of laparoscopic technology.

Objective:To retrieve, evaluate, and summarize the best domestic and international evidence on non-pharmacological management of sleep disorders in breast cancer patients undergoing chemotherapy, providing evidence-based guidance for healthcare professionals to conduct standardized assessment and management of sleep disorders in these patients.Methods:Clinical questions were translated into evidence-based questions using the PIPOST model. A systematic search of domestic and international databases and professional association websites was conducted for literature related to non-pharmacological management of sleep disorders in breast cancer patients undergoing chemotherapy, including clinical decisions, evidence summaries, guidelines, and systematic reviews. The search covered publications up to December 17, 2022. Two researchers trained in evidence-based nursing independently completed the quality assessment, evidence extraction, and summary of the included literature.Results:A total of 16 publications were included, comprising two clinical decisions, one evidence summary, five guidelines, six systematic reviews, and two randomized controlled studies. The best evidence was summarized from seven aspects: multidisciplinary collaboration, identification of risk factors, assessment and monitoring, referral, psychological behavioral interventions, exercise management, and complementary therapies, resulting in 25 key recommendations.Conclusions:This study summarizes the current best evidence for non-pharmacological management of sleep disorders in breast cancer patients undergoing chemotherapy. Healthcare professionals can follow these best evidence practices to standardize the assessment of patient sleep disorder symptoms and choose appropriate intervention plans based on clinical context and patient preferences, thereby improving patient sleep quality.

With the development of population aging, the incidence of lower limb artery ischemic diseases is gradually increasing. Although various treatments such as medication and endovascular surgery are currently available, patients with compromised microcirculation in the distal limbs and poor outflow pathways often do not achieve satisfactory results. Additionally, these treatments can be costly, and long-term patency rates are not ideal. The amendment in situ autologous great saphenous vein arterialization surgery utilizes the patient′s great saphenous vein to provide arterial blood in a retrograde manner and re-establishes blood supply to the tissues through the venous microcirculation system in the distal foot. This approach can achieve good limb salvage results and long-term patency. Therefore, this article aims to elaborate on the methods and value of amendment in situ autologous great saphenous vein arterialization surgery.

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.

Objective:To summarize the evidence of cognitive training in breast cancer patients with chemotherapy-related cognitive impairment, so as to provide evidence-based evidence for clinical decision-making and practice.Methods:The literature about the relevant cognitive training in breast cancer patients with chemotherapy-related cognitive impairment were searched for CNKI, VIP database, Wanfang, SinoMed, PubMed, Web of Science, CINAHL, Embase, Cochrane Library, JBI as well as home and abroad official website of relevant professional institutes, including clinical decisions, guidelines, evidence summaries, systematic reviews, best practice information manuals, expert consensuses, and high-quality original studies. The literature retrieval period was from the database construction to March 1, 2023. Two researchers screened and evaluated the quality of the included literature, and extracted, generalized and summarized evidence according to the topic.Results:A total of 17 articles were involved, including 3 clinical decisions, 4 guidelines, 2 evidence summaries, and 8 systematic reviews. Finally, 6 evidence topics and 25 pieces of best evidences were formed, including screening and evaluation, training principles, training time, training place, training content, training effect.Conclusions:Cognitive training can effectively improve cognitive function in breast cancer patients with chemotherapy-related cognitive impairment. Medical staff should carefully select the best evidence, early screen and dynamically evaluate the cognitive changes of patients, follow the principle of step by step and dynamic adjustment, and carry out individualized cognitive training as soon as possible according to the treatment cycle and patients wishes, so as to prevent or delay chemotherapy-related cognitive impairment and improve the quality of life of patients.