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*

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

OBJECTIVE: To evaluate the efficacy of shockwave therapy, acupuncture, hyperthermia, biofeedback therapy, electrical nerve stimulation, magnetotherapy and ultrasound therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS), and to provide evidence-based support for clinical decision-making. METHODS: Two researchers independently searched PubMed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, VIP and Chinese Biomedical Literature databases for randomized controlled trials(RCTs) on the effects of different interventions on CP/CPPS from the establishment of the databases to August 2024. We evaluated the quality of the included literature and extracted the relevant data according to the Cochrane Handbook for Systematic Reviews of Interventions, followed by network meta-analysis using Revman 5.3, R 4.33 and Stata17 software. RESULTS: A total of 25 RCTs involving 1 794 cases were included. The results of network meta-analysis showed that electrical nerve stimulation, shockwave therapy, biofeedback therapy, magnetotherapy, ultrasound therapy and acupuncture were significantly superior to conventional medication and placebo in the total NIH-CPSI scores(P< 0.05), and so were electrical nerve stimulation and shockwave therapy to acupuncture and hyperthermia(P< 0.05), magnetic therapy to hyperthermia, and ultrasound therapy to placebo(P< 0.05). Shockwave therapy, biofeedback therapy, electrical nerve stimulation, magnetotherapy and ultrasound therapy achieved remarkably better clinical efficacy than conventional medication and placebo in the treatment of CP/CPPS, and so did shockwave therapy than electrical nerve stimulation, hyperthermia, ultrasonic therapy, magnetotherapy and acupuncture. CONCLUSION For the treatment of CP/CPPS, electrical nerve stimulation is advantageous over the other interventions in improving total NIH-CPSI scores, and shockwave therapy is advantageous in relieving pain symptoms and clinical efficacy. This conclusion, however, needs to be further verified by more high-quality clinical studies.
Humans ; Acupuncture Therapy ; Biofeedback, Psychology ; Chronic Disease ; Electric Stimulation Therapy ; Extracorporeal Shockwave Therapy ; Magnetic Field Therapy ; Pelvic Pain/therapy* ; Prostatitis/therapy* ; Randomized Controlled Trials as Topic ; Ultrasonic Therapy

Objective:To investigate the efficacy of sigmoid sinus constriction plus cartilage reconstruction technique for sigmoid sinus related pulsatile tinnitus. Methods:The clinical data of 31 patients with Sigmoid Sinus Diverticulum（SSD） who underwent surgical treatment from January 2020 to December 2023 were retrospectively analyzed. The surgical methods include transmastoid sigmoid sinus constriction and cartilage reconstruction, transmastoid sigmoid sinus（bone wax） return surgery. Among them, 15 patients had transmastoid sigmoid sinus strictation + cartilage reconstruction, and transmammary sigmoid sinus（bone wax） in 16 cases. The aesthetic of anesthesia include general and local anesthesia, 20 cases of general anesthesia, 11 cases of local anesthesia. The doctors of our team graded the degree of tinnitus in 1 week, 1 month and 3 months（Tinnitus Evaluation Questionnaire, TEQ）, and compared the degree of preoperative tinnitus to evaluate the surgical efficacy, and the intraoperative and postoperative complications were analyzed and summarized. Results:In 30 of 31 patients, tinnitus was cured or improved with satisfactory efficacy. Among the patients undergoing sigmoid sinus constrictation + cartilage reconstruction, one case had intraoperative sigmoid sinus rupture and bleeding; among the patients who underwent sigmoid sinus（bone wax） return, one patient did not improve postoperative tinnitus, and one patient had postoperative headache and blurred vision, which improved after 1 month of conservative treatment. Conclusion:In the treatment of intravenous pulsatile tinnitus caused by sigmoid sinus diverticulum, the precision of the return depth is difficult to control, and the insufficient and excessive return will cause poor efficacy and postoperative complications. Based on the observation of small sample size and recent curative effect, it is considered that the sigmoid sinus constriction + cartilage reconstruction technology has certain advantages in surgical efficacy, with few postoperative complications, but the operation is difficult, so pay attention to the prevention and emergency treatment of intraoperative sigmoid sinus rupture bleeding.
Humans ; Tinnitus/etiology* ; Retrospective Studies ; Cranial Sinuses/surgery* ; Male ; Plastic Surgery Procedures/methods* ; Female ; Cartilage/surgery* ; Diverticulum/complications* ; Middle Aged ; Treatment Outcome ; Adult

Bombesin receptor subtype-3 (BRS3) is an orphan G protein-coupled receptor (GPCR) that plays critical roles in energy homeostasis, glucose metabolism, and insulin secretion. Recent structural studies have elucidated BRS3 signaling mechanisms using synthetic ligands, including BA1 and MK-5046. However, the molecular basis of BRS3 activation by bioactive natural compounds and their derivatives, particularly those derived from traditional Chinese medicine, remains unclear. Here, we present high-resolution cryogenic electron microscopy (cryo-EM) structures of the human BRS3-G_q complex in both unliganded and active states bound by two herb-derived compounds (DSO-5a and oridonin), at resolutions of 2.9, 2.8, and 2.9 Å, respectively. These structures display distinct ligand recognition patterns between DSO-5a and oridonin. Although both compounds bind to the orthosteric pocket, they differentially engage the interaction network of BRS3, as demonstrated by mutagenesis studies assessing calcium mobilization and inositol phosphate 1 (IP1) accumulation. These findings enhance our understanding of BRS3 activation and provide valuable insights into the development of small-molecule BRS3 modulators with therapeutic potential.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective:To explore the application value of a novel separated magnetic-controlled forceps in transumbilical single-incision laparoscopic cholecystectomy (SILC).Methods:This is a prospective case series study. Data from patients who underwent SILC at the Department of General Surgery, the Second Affiliated Hospital of Air Force Medical University from March to August 2023 were prospectively collected, based on inclusion and exclusion criteria. All patients underwent cholecystectomy assisted by a novel separated magnetic-controlled forceps. Surgical time, intraoperative blood loss, the need for additional incisions during surgery, and the length of hospital stay were recorded to assess surgical difficulty and effectiveness. Postoperative pain scores and complications were documented to evaluate the safety of the procedure. The collaboration experience of the surgeon and assistant was evaluated using a 5-point Likert scale to assess the feasibility of this surgical approach. Informed consent was obtained from all patients in accordance with medical ethical regulations. Patients were followed up through outpatient visits or telephone calls, with follow-up at 7 days and 1 month after surgery, and evaluation of incisional scar healing and completion of satisfaction questionnaires. Follow-up was conducted until September 30, 2023.Results:A total of 45 patients were included in the study,including 19 males and 26 females,aged (42.7±4.2)years(range:32 to 61 years). The difficulty of the operation was evaluated as grade 1 or 2 in 38 cases(84.4%) and grade 3 in 7 cases(15.6%). Operation time was (37.3±5.3) minutes(range: 25 to 80 minutes),and intraoperative blood loss( M(IQR)) was 17.8(35.0) ml (range:10 to 60 ml). All surgical procedures proceeded smoothly without intraoperative incidents, and the overall satisfaction of the surgeon and assistants was high. All patients underwent successful day surgery management and were discharged within 48 hours of hospitalization. The postoperative pain scores at 1, 7, and 30 days were 3 (4), 1 (3), and 0 (2), respectively. The follow-up time was 5.0(2.2) weeks (range: 3 to 7 weeks), with no occurrence of grade 3 to 4 adverse reactions, and the patients were satisfied with the cosmetic effect of the umbilical incision. Conclusions:The novel separated magnetic-controlled forceps can be applied in transumbilical SILC. It has the advantages of convenient operation, and patients are satisfied with the surgical results.