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: This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022. METHODS: Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality. RESULTS: Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities. CONCLUSION Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.
Cross-Sectional Studies ; Drugs, Chinese Herbal/administration & dosage* ; Systematic Reviews as Topic/standards* ; Humans ; China ; Administration, Oral ; Medicine, Chinese Traditional

Gorham-Stout disease(GSD)is a sporadic chronic disease characterized by progressive bone dissolution,absorption,and disappearance along with lymphatic vessel infiltration in bone-marrow cavities.Although the osteolytic mechanism of GSD has been widely studied,the cause of lymphatic hyperplasia in GSD is rarely investigated.In this study,by comparing the RNA expression profile of osteoclasts(OCs)with that of OC precursors(OCPs)by RNA sequencing,we identified a new factor,semaphorin 3A(Sema3A),which is an osteoprotective factor involved in the lymphatic expansion of GSD.Compared to OCPs,OCs enhanced the growth,migration,and tube formation of lymphatic endothelial cells(LECs),in which the expression of Sema3A is low compared to that in OCPs.In the presence of recombinant Sema3A,the growth,migration,and tube formation of LECs were inhibited,further confirming the inhibitory effect of Sema3A on LECs in vitro.Using an LEC-induced GSD mouse model,the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo.We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss,whereas the injection of lentivirus expressing Sema3A short hairpin RNA(shRNA)into the tibiae caused GSD-like phenotypes.Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment,compared with the control.Based on the above results,we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

Objective: To investigate the protective effect of neurotrophic factor(MANF) derived from midbrain astrocytes on myocardial injury induced by sepsis by activating SIRT1/AMPK signaling pathway. Methods: 48 mice were randomly divided into 4 groups: control group, recombinant mouse MANF(rmMANF) group, cecal ligation and puncture(CLP) group and CLP+rmMANF group, with 12 mice in each group.The survival rate, sepsis score, anal temperature, blood biochemical indexes, pathological indexes of myocardial injury and the expression of endoplasmic reticulum stress(ERS) related proteins were detected 8 h after CLP.H9C2 cells were divided into control group(Con),LPS group, LPS+rmMANF group, LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group.The cells were collected after 24 h treatment with LPS,and the expression of ERS protein and apoptosis in cells were analyzed. Results: Compared with CLP group, the sepsis score and serum Lactate dehydrogenase(LDH),creatine kinase(CK),aspartateaminotransferase(AST) and blood urea nitrogen(BUN) levels in CLP+rmMANF group decreased significantly(P<0.01),and the anal temperature and serum albumin(ALB) levels increased significantly(P<0.05).Compared with CLP group, the expression of MANF in CLP+rmMANF group increased significantly(P<0.01),and the expression of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP) and the percentage of TUNEL positive cells decreased significantly(P<0.05).In vitro, LPS stimulation down-regulated the expression of SIRT1 and AMPK in H9C2 cells, while rmMANF further increased the expression level of SIRT1 and AMPK.Compared with LPS+rmMANF group, the expression of GRP78 and CHOP protein and the apoptosis rate of H9C2 cells in LPS+rmMANF+EX527 group and LPS+rmMANF+Cpd C group increased significantly(P<0.05). Conclusion rmMANF inhibits ERS related to sepsis-induced myocardial injury by activating SIRT1/AMPK signaling pathway, thereby protecting myocardial injury.

Objective:To investigate the efficacy and prognosis of different surgical approaches in sporadic medullary thyroid carcinoma.Methods:A retrospective analysis was conducted on 101 patients with sporadic medullary thyroid carcinoma (MTC) who underwent surgical treatment at the Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, from Feb. 2009 to Nov. 2023. The patients included 36 males and 75 females, with a male-to-female ratio of 1:2.1. The median age of the patients was 47 years old, with an age range of 21 to 72 years old. The study divided participants into two groups based on their surgical methods: an observation group (78 cases) and a control group (23 cases). The observation group received surgical methods in accordance with expert consensus, while the control group did not. The study compared the efficacy and prognosis of the two groups.Results:Statistical differences were found between the two groups in terms of stage II and III in TNM staging, intraoperative frozen pathological findings, number of lymph node resections in the central group, number of lymph node metastases in the central group, number of lymph node resections in the lateral cervical region, postoperative follow-up time, and five-year postoperative serum procalcitonin (Ctn) levels ( P<0.05) .Both groups of patients obtained a significant decrease in Ctn after surgical treatment. In the observation group, Ctn was at the remission level in 57 cases (73.1%), at the stable level in 13 cases (16.7%), and at the progression level in 8 cases (10.2%), while in the control group, Ctn was at the remission level in 20 cases (86.9%), at the progression level in 3 cases (13.1%), and there were no patients at the stable level after the operation.One patient (1.3 per cent) in the observation group had a recurrence after surgery; Two patients (8.7 per cent) in the control group had a recurrence. Conclusions:Standardised and thorough surgery can maximise the clearance of metastatic lymph nodes, effectively reduce the recurrence rate, achieve better efficacy, and improve the long-term prognosis of patients without increasing the risk of surgery and postoperative complications.

BACKGROUND:To investigate the prognostic value of the peripheral perfusion index(PPI)in patients with septic shock. METHODS:This prospective cohort study,conducted at the emergency intensive care unit of Peking University People's Hospital,recruited 200 patients with septic shock between January 2023 and August 2023.These patients were divided into survival(n=84)and death(n=116)groups based on 28-day outcomes.Clinical evaluations included laboratory tests and clinical scores,with lactate and PPI values assessed upon admission to the emergency room and at 6 h and 12 h after admission.Risk factors associated with mortality were analyzed using univariate and multivariate Cox regression analyses.Receiver operator characteristic(ROC)curve was used to assess predictive performance.Mortality rates were compared,and Kaplan-Meier survival plots were created. RESULTS:Compared to the survival group,patients in the death group were older and had more severe liver damage and coagulation dysfunction,necessitating higher norepinephrine doses and increased fluid replacement.Higher lactate levels and lower PPI levels at 0 h,6 h,and 12 h were observed in the death group.Multivariate Cox regression identified prolonged prothrombin time(PT),decreased 6-h PPI and 12-h PPI as independent risk factors for death.The area under the curves for 6-h PPI and 12-h PPI were 0.802(95%CI 0.742-0.863,P<0.001)and 0.945(95%CI 0.915-0.974,P<0.001),respectively,which were superior to Glasgow Coma Scale(GCS),Sequential Organ Failure Assessment(SOFA)scores(0.864 and 0.928).Cumulative mortality in the low PPI groups at 6 h and 12 h was significantly higher than in the high PPI groups(6-h PPI:77.52%vs.22.54%;12-h PPI:92.04%vs.13.79%,P<0.001). CONCLUSION:PPI may have value in predicting 28-day mortality in patients with septic shock.

This paper discusses the mechanism of acupuncture for diabetes mellitus from the perspective of molecular biology, aiming to reveal the potential rules of restoring the balance in the body and fighting against diabetes mellitus (DM). By searching the basic research literature of acupuncture treatment for DM, it is found that the molecular biological mechanism of acupuncture treatment for DM is closely related to the regulation of insulin signaling pathway, the modulation of inflammatory response, the protection and regeneration of islet β-cells, fat metabolism and energy balance. It points out that there are few studies of acupuncture on the type 1 diabetes mellitus and the large-scale randomized controlled trials, as well as the studies on the upstream regulation mechanism, the specific cellular molecules and the interaction mechanism of various molecules. It needs to deepen the multi-level, multi-target and multi-dimensional exploration on the molecular biological mechanism of acupuncture for diabetes mellitus.
Humans ; Acupuncture Therapy ; Diabetes Mellitus/genetics* ; Animals ; Insulin/metabolism* ; Signal Transduction

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration ( n = 36), sperm morphology ( n = 26), and sperm motility ( n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% ( n = 48), 25.6% ( n = 23), and 21.1% ( n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.
Humans ; Male ; Antioxidants/therapeutic use* ; Infertility, Male/therapy* ; Meta-Analysis as Topic ; Sperm Count ; Sperm Motility ; Systematic Reviews as Topic

Based on data mining technology, the acupoints compatibility rules of acupuncture for depression diseases were explored. The randomized controlled trial (RCT) articles regarding acupuncture for depression diseases published from establishment of database to September 2nd, 2022 were searched in CNKI database, Wangfang database, VIP database, SinoMed database, PubMed, EMbase, Web of Science and Cochrane Library. The use frequency of acupoints, meridian tropism, selection of special acupoints and acupoint association rules for five common depression diseases, including primary depression, post-stroke depression, menopausal syndrome, psychoneurosis and anxiety disorder, were analyzed by Python programming language. Cytoscape software was used to analyze the acupoint association and the disease-acupoint co-occurrence network. As a result, totally 387 articles were included, and 319 acupoints prescriptions for the above five common depression diseases were extracted, involving 159 acupoints. The use frequency of acupoints was 2 574 times in total. The frequently-used acupoints were Baihui (GV 20), Sanyinjiao (SP 6), Taichong (LR 3), Neiguan (PC 6), Shenmen (HT 7), Yintang (GV 24⁺), Zusanli (ST 36), Hegu (LI 4), Sishencong (EX-HN 1) and Taixi (KI 3), etc. The frequently involved meridians were the governor vessel, foot-taiyang bladder meridian, foot-taiyin spleen meridian, and foot-jueyin liver meridian. The frequency of the special acupoints from high to low was crossing points, five-shu points, yuan-primary points, back-shu points, luo-connecting points, and eight confluent points, etc, which were often used in combination with "Baihui (GV 20)-Yintang (GV 24⁺)" (the highest degree of association). At the same time, the analysis of the co-occurrence network of depression diseases and acupoints showed that the core acupoints group of acupuncture for depression diseases were Baihui (GV 20), Taichong (LR 3), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6) and Sanyinjiao (SP 6). In conclusion, acupuncture treatment for depression diseases has gradually formed a rule of acupoint compatibility, with special acupoint as the main body and "unblocking the governor vessel, and regulating the spirit and qi " as the main therapeutic principle.
Acupuncture Points ; Acupuncture Therapy ; Data Mining ; Depression ; Meridians ; Randomized Controlled Trials as Topic

With the continuous development of evidence-based medicine, increasing attention has been paid to the construction of a large medical database to ensure a source of high quality real-world data. The Chinese Medical Association Colorectal Surgery Group created the Chinese Colorectal Cancer Surgery Database (CCCD), whose objective is to promote the development of colorectal surgery and improve patient prognosis with evidence-based medicine theory. Compared to major databases around the world, CCCD contains more comprehensive information on colorectal cancer surgical cases, recording the main epidemiological characteristics and detailed surgical information, but perioperative treatment data still need to be strengthened. It is necessary to continuously expand the coverage, enrich perioperative data and strengthen data, quality control. In the future, CCCD is expected to play a role in promoting homogenization of medical services, promoting smooth and effective graded diagnosis and treatment, giving full role to the characteristics of each center to achieve integrated development, and connecting real-world data and artificial intelligence.