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*

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.
Pregnancy ; Female ; Humans ; Male ; Vas Deferens/abnormalities* ; Azoospermia/surgery* ; Epididymis/surgery* ; Retrospective Studies ; Tertiary Care Centers ; China ; Semen

Optimal vision and ergonomics are essential factors contributing to the achievement of good results during microsurgery. The three-dimensional (3D) digital image microscope system with a better 3D depth of field can release strain on the surgeon's neck and back, which can improve outcomes in microsurgery. We report a randomized prospective study of vasoepididymostomy and vasovasostomy using a 3D digital image microscope system (3D-DIM) in rats. A total of 16 adult male rats were randomly divided into two groups of 8 each: the standard operating microscope (SOM) group and the 3D-DIM group. The outcomes measured included the operative time, real-time postoperative mechanical patency, and anastomosis leakage. Furthermore, a user-friendly microscope score was designed to evaluate the ergonomic design and equipment characteristics of the microscope. There were no differences in operative time between the two groups. The real-time postoperative mechanical patency rates were 100.0% for both groups. The percentage of vasoepididymostomy anastomosis leakage was 16.7% in the SOM group and 25.0% in the 3D-DIM group; however, no vasovasostomy anastomosis leakage was found in either group. In terms of the ergonomic design, the 3D-DIM group obtained better scores based on the surgeon's feelings; in terms of the equipment characteristics, the 3D-DIM group had lower scores for clarity and higher scores for flexibility and adaptivity. Based on our randomized prospective study in a rat model, we believe that the 3D-DIM can improve surgeon comfort without compromising outcomes in male infertility reconstructive microsurgery, so the 3D-DIM might be widely used in the future.

Alleles ; Asthma/genetics* ; Child ; Genetic Predisposition to Disease ; Genotype ; Glucocorticoids ; Humans ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Polymorphism, Genetic

Non-obstructive azoospermia (NOA), which is defined as the absence of spermatozoa in the ejaculate secondary to impaired spermatogenesis within the testis, may be caused by a variety of etiologies, including varicocele-induced testicular damage, cryptorchidism, prior testicular torsion, post-pubertal mumps orchitis, gonadotoxic effects from medications, genetic abnormalities, chemotherapy/radiation, and other unknown causes currently classified as idiopathic (Cocuzza et al., 2013). The microdissection testicular sperm extraction (micro-TESE) technique involves a meticulous microsurgical exploration of the testicular parenchyma to identify and selectively extract larger seminiferous tubules that carry a higher probability of complete spermatogenesis (Schlegel, 1999). The Cornell group evaluated the efficacy of micro-TESE in 152 NOA patients with an associated history of cryptorchidism. In their series, spermatozoa were successfully retrieved in 116/181 attempts (64%), and the resulting pregnancy rate was 50% with a delivery rate of 38% (Dabaja and Schlegel, 2013). Franco et al. (2016) described a stepwise micro-TESE approach in NOA patients, which was considered to reduce the cost, time, and effort associated with the surgery. Alrabeeah et al. (2016) further reported that a mini-incision micro-TESE, carried through a 1-cm equatorial testicular incision, can be useful for micro-TESE candidates, particularly in patients with cryptozoospermia. We conducted a retrospective study of 20 consecutive NOA patients with a history of orchidopexy from May 2015 to March 2017.
Adult ; Azoospermia/surgery* ; Humans ; Male ; Microdissection/methods* ; Middle Aged ; Orchiopexy ; Retrospective Studies ; Sperm Retrieval

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ(2)=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ(2)=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ(2)=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ(2)=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions: HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.
Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Myelodysplastic Syndromes ; Retrospective Studies ; Siblings ; Transplantation Conditioning ; Transplantation, Homologous

We retrospectively reviewed data for 286 patients with varicocele who underwent microsurgical subinguinal varicocelectomy from March 2015 to May 2017 in Shanghai General Hospital (Shanghai, China). In this surgical approach, the testis was delivered, and the gubernacular and external cremasteric veins were stripped. In addition, the spermatic cord was delivered downward with continuous double traction away from the external ring. The remaining procedure was similar to the conventional approach. We followed patients for at least 3 months and evaluated postoperative semen parameters, pain symptoms, and complications. We excluded data for 32 men due to inadequate follow-up (<3 months). Of the remaining 254 patients, 73 had oligoasthenospermia, 121 had nonobstructive azoospermia, and 60 had symptomatic varicoceles. Total progressive sperm counts increased in the oligoasthenospermic patients from a median preoperative value of 9.15 × 10⁶ ml^-1 to 25.33 × 10⁶ ml^-1 (n= 34), and 35.6% (26/73) initially oligoasthenospermic men contributed to unassisted pregnancies. Sperm returned to the ejaculate in 12.4% (15/121) azoospermia patients. In patients with scrotal pain (n = 60), 43 (71.7%) reported complete resolution of pain, 16 (26.7%) reported partial resolution, and 1 (1.7%) reported no change. No patients experienced varicocele recurrence. This double-traction strategy avoids opening the external oblique aponeurosis, and results in less damage and faster recovery. In addition, the stripping strategy eliminates potential damage to the testis caused by the varicose veins. Our results showed that microsurgical subinguinal varicocelectomy using spermatic cord double traction in conjunction with testicular delivery for vein stripping is a safe and effective approach for varicocele repair.
Adolescent ; Adult ; Humans ; Male ; Microsurgery ; Middle Aged ; Retrospective Studies ; Spermatic Cord/surgery* ; Testis/blood supply* ; Treatment Outcome ; Urogenital Surgical Procedures/methods* ; Varicocele/surgery* ; Veins/surgery* ; Young Adult

Objective To evaluate the clinical efficacy of aerosolized inhalation of salbutamol suspension in the treatment of children with asthma and the influence of lung function,blood eosinophil (EOS) and immunoglobulin E(IgE).Methods A total of 160 children with asthma were randomly divided into treatment group (n =80 cases) and control group (n =80 cases).The control group was treated with inhaled budesonide 1.0 mg,5 min a time,twice a day,while the children in treatment group were treated combined with salbutamol 5 minutes a time,twice a day on the basis of control group.All patients were treated for 2 weeks.The clinical efficacy in two groups were observed.The changes of blood EOS and IgE at 3 months after treatment were observed.Results The total effective rate in treatment group was 98.68％ (75/76 cases),had significant difference with that in control group,which was 84.13％ (53/63 cases,P ＜ 0.05).And 3 months after treatment,the forced vital capacity (FVC),forced expiratory volume in first second(FEV1),peak expiratory flow (PEF),vital capacity(VC) in treatment group were (79.34 ± 6.52) L,(80.12 ± 3.32) L,(82.08 ±9.62) L· min-1,(83.42 ±4.10) L,had significant difference with those in control group,which were (70.20±3.34)L,(68.25 ±2.90)L,(71.21 ±4.52) L · min-1,(73.17 ±2.34) L (all P＜0.05).The absolute value of EOS and IgE in treatment group were (0.52 ± 0.13) × 109/L,(105.32 ± 62.35) ng · mL-1,had significant difference with those in control group,which were (0.96 ± 0.23) × 109/L,(222.58 ± 84.71) ng · mL-1(all P ＜ 0.05).The control group occurred 1 cases (1.59％) of nausea,while treatment group occurred 2 cases(2.63％) of hoarseness,with no significant difference (P ＞ 0.05).No drug allergy,nosocomial infections,rash and other adverse reactions occurred in two groups.Conclusion The application of glucocorticoid combined with salbutamol inhalation has significant effect on children with asthma,and can significantly reduce the levels of EOS and IgE in blood,and improve lung function.

OBJECTIVETo discuss the intervention effect of ligustrazine on ox-LDL-induced foam cells from the perspective of reverse cholesterol transport.

METHODRAW264.7 cultured in vitro was induced with 20 mg x L(-1) ox-LDL to establish the foam cell model, and intervened with ligustrazine. The lipid accumulation in cells was observed by the oil red O dyeing. The changes in total cholesterol and cholesterol ester in the cells were detected with the colorimetric method. The fluorescent quantitative PCR and Western blot were used to detect the mRNA expressions of PPARgamma, LXRalpha and ABCA1.

RESULTLigustrazine could reduce total cholesterol and cholesterol ester in foam cells, inhibit the lipid accumulation, and increase the mRNA and protein expressions of PPARgamma, LXRalpha and ABCA1.

CONCLUSIONLigustrazine can promote the reverse cholesterol transport by increasing the gene expressions of PPARgamma, LXRalpha and ABCA1.

ATP Binding Cassette Transporter 1 ; genetics ; metabolism ; Animals ; Biological Transport ; drug effects ; Cell Line ; Cholesterol ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Foam Cells ; drug effects ; metabolism ; Gene Expression ; drug effects ; Mice ; PPAR gamma ; genetics ; metabolism