The impact of minimally invasive surgeries for the treatment of symptomatic benign prostatic hyperplasia on male sexual function： a systematic review

A systematic review of randomized controlled trials and cohort studies was conducted to evaluate data for the effects of minimally invasive procedures for treatment of symptomatic benign prostatic hyperplasia （BPH） on male sexual function. The studies searched were trials that enrolled men with symptomatic BPH who were treated with laser surgeries, transurethral microwave therapy （TUMT）, transurethral needle ablation of the prostate （TUNA）, transurethral ethanol ablation of the prostate （TEAP） and high-intensity frequency ultrasound （HIFU）, in comparison with traditional transurethral resection of the prostate （TURP） or sham operations. A total of 72 studies were identified, of which 33 met the inclusion criteria. Of the 33 studies, 21 were concerned with laser surgeries, six with TUMT, four with TUNA and two with TEAP containing information regarding male sexual function. No study is available regarding the effect of HIFU for BPH on male sexual function. Our analysis shows that minimally invasive surgeries for BPH have comparable effects to those of TURP on male erectile function. Collectively, less than 15.4% or 15.2% of patients will have either decrease or increase, respectively, of erectile function after laser procedures, TUMT and TUNA. As observed with TURP, a high incidence of ejaculatory dysfunction （EjD） is common after treatment of BPH with holmium, potassium-titanyl-phosphate and thulium laser therapies （〉 33.6%）. TUMT, TUNA and neodymium：yttrium aluminum garnet visual laser ablation or interstitial laser coagulation for BPH has less incidence of EjD, but these procedures are considered less effective for BPH treatment when compared with TURP.

Penile rehabilitation with a vacuum erectile device in an animal model is related to an antihypoxic mechanism： blood gas evidence

Our previous study showed that vacuum erectile device （VED） therapy has improved erectile function in rats with bilateral cavernous nerve crush （BCNC） injuries. This study was designed to explore the mechanism of VED in penile rehabilitation by analyzing cavernous oxygen saturation （SO2） and to examine the effect of VED therapy on preventing penile shrinkage after BCNC. Thirty adult Sprague- Dawley rats were randomly assigned into three groups： group 1, sham surgery; group 2, BCNC; and group 3, BCNC＋VED. Penile length and diameter were measured on a weekly basis. After 4 weeks of therapy, the penile blood was extracted by three methods for blood gas analysis （BGA）： method 1, cavernous blood was aspirated at the flaccid state; method 2, cavernous blood was aspirated at the traction state; and method 3, cavernous blood was aspirated immediately after applying VED. SO2 values were tested by the blood gas analyzer. The results showed that VED therapy is effective in preventing penile shrinkage induced by BCNC （Penile shortening： BCNC group 1.9±1.1 mm; VED group 0.3±1.0 mm; P〈0.01. Penile diameter reduction： BCNC group 0.28±0.14 mm; VED group 0.04±0.14 mm; P〈0.01）. The mean SO2±s.d. values were increased by VED application （88.25%±4.94%） compared to the flaccid （76.53%±4.16%） or traction groups （78.93%±2.56%） （P〈0.05）. The calculated blood constructs in the corpus cavernosum right after VED application were 62% arterial and 38% venous blood. These findings suggest that VED therapy can effectively preserve penile size in rats with BCNC injury. The beneficial effect of VED therapy is related to antihypoxia by increasing cavernous blood SO2.

Combination therapy for erectile dysfunction： an update review

The introduction of oral phosphodiesterase-5 inhibitors （PDE51s） in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE51s are currently first-line monotherapy for erectile dysfunction （ED）. However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE51 monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE51 therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE51 plus vacuum erectile device （VED）, intraurethral medication, intracavernosal injection （ICI）, androgen supplement, a-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorecal cancer patients with liver metastases who underwent hepatectomy.However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients.Patients and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients.The pathologic response was evaluated according to the tumor regression grade(TRG).The prognostic role of pathologic response in recurrence-free survival(RFS) and overall survival(OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests.Results: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy(median RFS: 9.9 vs.6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors,and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases(all P < 0.05). A decrease in the serum carcinoembryonic antigen(CEA) level after preoperative chemotherapy predicted an increased pathologic response rate(P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens.Conclusions: We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

Mobilisation of endothelial progenitor cells： one of the possible mechanisms involved in the chronic administration of melatonin preventing erectile dysfunction in diabetic rats

Diabetes-induced oxidative stress plays a critical role in the mobilisation of endothelial progenitor cells （EPCs） from the bone marrow to the circulation. This study was designed to explore the effects of chronic melatonin administration on the promotion of the mobilisation of EPCs and on the preservation of erectile function in type I diabetic rats. Melatonin was administered to streptozotocin-induced type I diabetic rats. EPCs levels were determined using flow cytometry. Oxidative stress in the bone marrow was indicated by the levels of superoxide dismutase and malondialdehyde. Erectile function was evaluated by measuring the intracavernous pressure during an electrostimulation of the cavernous nerve. The density of the endothelium and the proportions of smooth muscle and collagen in the corpus cavernosum were determined by immunohistochemistry. The administration of melatonin increased the superoxide dismutase level and decreased the malondialdehyde level in the bone marrow. This effect was accompanied by an increased level of circulating EPCs in the diabetic rats. The intracavernous pressure to mean arterial pressure ratio of the rats in the treatment group was significantly greater, compared with diabetic control rats. The histological analysis demonstrated an increase in the endothelial density of the corpus cavernosum after the administration of melatonin. However, melatonin treatment did not change the proportions of smooth muscle and collagen in the corpus cavernosum of diabetic rats. Chronic administration of melatonin has a beneficial effect on preventing erectile dysfunction （ED） in type I diabetic rats. Promoting the mobilisation of EPCs is one of the possible mechanisms involved in the improvement of ED.

The effects of long-term administration of tadalafil on STZ-induced diabetic rats with erectile dysfunction via a local antioxidative mechanism

Type 5 phosphodiesterase inhibitors （PDE51s） are well known being effective via the nitric oxide and cyclic guanosine monophosphate （NO-cGMP） pathway and are widely used in the treatment of diabetic erectile dysfunction （ED）. However, it is unclear whether other pathways may be involved in the treatment of diabetic ED with PDE51s. The purpose of this study was to clarify the role of antioxidants in diabetic ED treatment through the long-term administration of PDE51s. Three groups of Sprague-Dawley rats were utilized： Group N, the normal control; Group D, streptozotocin （STZ）-induced diabetic rats as a control; and Group D＋T, STZ-induced diabetic rats who received oral administration of tadalafil for 8 weeks. Erectile function was assessed by intracavernous pressure （ICP） and mean arterial pressure （MAP） during electrical stimulation of the cavernous nerve before euthanasia. The levels of malondialdehyde （MDA）, superoxide dismutase （SOD） and mitochondrial membrane potential （MMP） of cavernous tissue were assessed by biochemical analysis. The morphology of mitochondria was observed by electron microscopy. The ICP/MAP ratio was higher in Group D＋T than in Group D （P〈O.05）. The levels of MDA decreased and the activities of SOD increased in Group D＋T in comparison with Group D （P〈O.05）. The mitochondrial membrane potential level of cavernous tissue in diabetic rats was partially recovered by tadalafil treatment for 8 weeks. The morphology changes of mitochondria were also remarkably ameliorated in Group D＋T. Collectively, the long-term administration of tadalafil in diabetic rats partially reduced oxidative stress lesions of the penis via a local antioxidative stress pathway. Long-term dosages of tadalafil given once daily beginning soon after the onset of diabetes may aid in preventing rats from developing diabetic ED.

Prospective and long-term evaluation of erect penile length obtained with inflatable penile prosthesis to that induced by intracavernosal injection

We compared erect penile length after inflatable penile prosthesis （IPP） implantation with that induced by intracavemosal injection （ICI） before surgery. A total of 11 patients with full erections induced by ICI of 0.25 mL of Trimix （papaverine, phentolamine and prostaglandin E 1） at the time of penile color duplex Doppler ultrasonograpby were enrolled in this study. The patients subsequently underwent IPP implantation as the ultimate treatment for their erectile dysfunction （ED）. Erect penile length consequent to IPP implantation was measured at 6 weeks, 6 months and at I year after surgery. The Sexual Health Inventory for Men （SHIM） was administered before, and at 6 months and 1 year after IPP implantation. Erect penile length （mean ± s.c.） as induced by ICI was 13.2 ± 0.4 cm, whereas the lengths attained with IPP were 12.4 ± 0.3, 12.5 ± 0.3 and 12.5 ± 0.4 cm at the sixth week, sixth month and 1-year follow-ups, respectively. There were 0.83 ± 0.25, 0.75 ± 0.20 and 0.74 ± 0.15 cm decreases in erect penile length at 6 weeks, 6 months and 1 year, respectively, after IPP implantation when compared with that after ICI （P 〈 0.05）. The SHIM scores for patients reporting shorter penises were the same as those for patients without complaints at the 6-month and 1-year follow-ups （P 〉 0.05）. To our knowledge, this is the first study to objectively show a significant decrease in erect penile length after IPP implantation when compared with that after ICI. However, this decrease did not affect the effectiveness of IPP in treating ED.

Should patients with erectile dysfunction be evaluated for cardiovascular disease？

The landmark Massachusetts Male Ageing Study shed new light on the prevalence of erectile dysfunction （ED） and drew attention to ED as a disease of ageing. Over the years, ED has been linked to the development of cardiovascular disease （CVD） in some patients. There is clear evidence that ED and CVD share and have a similar risk factor profile. CVD is one of the most recognizable causes of mortality and early detection coupled with prevention of mortality from CVD has been the prime interest of many researchers. Consequently, there has been a multidisciplinary curiosity regarding the proposal to use ED as a marker for future CVD. I n fact, there have been several proposals to use ED as a screening tool for future CVD. We performed a comprehensive Search of two main databases--PubMed and Cochrane Library using a combination of keywords such as acute myocardial infarction, coronary artery disease （CAD） and ED. Journal articles from January 2000 to June 2011 were reviewed. We included all articles discussing the relationship between ED and CVD in the English language. All the relevant randomized controlled trials, cohort and retrospective studies, and review articles were included in our overall analysis in an attempt to answer the question whether all patients with ED should be clinically evaluated for CVD. The results showed a link between ED and the development of future CVD in some patients, but ED was not shown to be an independent risk predictor that is any better than the traditional Framingham risk factors. Screening for CVD may, however, be rewarding in younger patients with severe ED and in patients with concurrent CVD risk factors.

Sperm retrieval rates and clinical outcomes for patients with different causes of azoospermia who undergo microdissection testicular sperm extraction-intracytoplasmic sperm injection

The aim of our study was to compare the sperm retrieval rates(SRRs)and clinical outcomes of patients with different causes of azoospermia who underwent microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI).We conducted a retrospective study at the Reproductive Medicine Center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.This study examined 769 patients with nonobstructive azoospermia who underwent 347 cycles of micro-TESE-ICSI.Patients with azoospermia were classified into Group A(Klinefelter syndrome,n=284,125 cycles),Group B(azoospermia Y chromosome factor c[AZFc]microdeletion,n=91,64 cycles),Group C(cryptorchidism,n=52,39 cycles),Group D(previous mumps and bilateral orchitis,n=23,23 cycles),and Group E(idiopathic azoospermia,n=319,96 cycles).Clinical characteristics,SRR,embryonic development,and pregnancy outcomes of the patients were compared between all groups.Patients in Group D had the highest and most successful SRR.The average SRR for all patients was 46.0%.The rates of clinical pregnancy,implantation,and live birth in Group D were 78.3%,65.0%,and 74.0%,respectively,which were higher than those in all other groups(P<0.05).Group B patients had the lowest clinical pregnancy,implantation,and live birth rates of all groups(P<0.05).No differences were found in the miscarriage rate or birth defects among the groups(P>0.05).Patients with orchitis had the highest SRR and best clinical outcomes.Although AZFc microdeletion patients had a higher SRR,their clinical outcomes were worse.

Clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection with fresh or cryopreserved sperm in patients with nonobstructive azoospermia

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI)treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia(NOA).A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles(Group A).Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles(Group B).We compared patient characteristics,embryonic development,and pregnancy outcomes between Groups A and B.There was no statistical difference in the patient characteristics,and no differences were observed with fertilization or quality embryo rates between Groups A and B.The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B(both P<0.05).In conclusion,fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.

Factors influencing the sperm retrieval rate of microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction(micro-TESE)in patients with nonmosaic Klinefelter syndrome(KS),64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital(Beijing,China)between January 2016 and December 2017 were included in the study.Data on medical history,physical examination and laboratory examination results,and micro-TESE outcomes were collected.Patients were divided into two groups according to micro-TESE outcomes.The following factors were compared between the two groups by the Mann‒Whitney U test or Student’s t-test based on the distribution(nonnormal or normal)of the factors:age,testicular size,follicle-stimulating hormone level,luteinizing hormone level,testosterone level,and anti-Müllerian hormone level.The overall success rate of sperm retrieval was 50.0%.Correlation analysis showed that testicular volume was positively correlated with testosterone level.Using a logistic regression model,age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.

Long-term tadalafil once daily in Chinese men with erectile dysfunction:a 2-year final analysis of a post-marketing,multicenter,randomized,open-label trial

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 months.Treatment-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and headache.Significant improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,P<0.001)and was maintained to month 24(LSM change:8.6,95%CI:8.1–9.0,P<0.001).The proportions of patients regaining normal erectile function(IIEF-EF score≥26)were 43.7%and 48.0%at months 12 and 24,respectively.Global Assessment Questionnaire results showed improved erection function in 97.5%ofpatients and improved ability to engage in sexual activity in 95.9%of patients at month 12;these values were 96.1%and 95.0%at month 24,respectively.The quality of sexual life score based on the Sexual Life Quality Questionnaire(SLQQ)was increased by52.2%at month 12 and by 55.3%at month 24(both P<0.001).The treatment satisfaction score determined by SLQQ(mean±standard deviation)was 62.4±21.0 at month 12 versus 65.9±20.2 at month 24.Two-year daily application of tadalafil 5mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

Evaluation of the long-term safety and effectiveness of tadalafil once daily in Chinese men with erectile dysfunction： interim results of a multicenter, randomized, open-label trial

Once-daily tadalafil administration has been well established; however, studies about tadalafil once-daily treatment in the Chinese population are lacking. In this phase 4, postmarketing study, we ascertained the long-term safety and effectiveness of tadalafil 2.5 mg and 5.0 mg once daily in Chinese men with erectile dysfunction （n = 635）. The primary endpoint of the study was safety at 12 months as assessed by the proportion of patients experiencing at least one treatment-emergent adverse event （serious or nonserious）. The secondary endpoints included safety and effectiveness, measured by the International Index of Erectile Function-Erectile Function （IIEF-EF） domain scores. Similar adverse events to the known safety profile of tadalafil, such as nasopharyngitis, upper respiratory tract infection, headache, and dizziness, were detected. No new cardiovascular safety concerns were observed. After 3 months of treatment, significant increases in IIEF-EF domain scores were detected for both 2.5-mg （least squares [LS] mean change： 6.3; 95% confidence interval [CI]： 5.4-7.1; P 〈 0.001） and 5.0-mg （LS mean change： 7.4; 95% CI： 6.8-7.9; P 〈 0.001） tadalafil doses, and significance was maintained up to 12 months. In addition, approximately 40% of patients regained normal erectile function （IIEF-EF 〉26） following 1 year of tadalafil once-daily treatment. The findings in this study provide evidence for the extended effectiveness and tolerability of tadalafil, demonstrating no new safety concerns, in a Chinese population and make once-daily tadalafil administration a viable option for improving sexual performance and satisfaction in Chinese men with erectile dysfunction.

Ambient ozone pollution is associated with decreased semen quality:longitudinal analysis of 8945 semen samples from 2015 to 2018 and during pollution-control period in Beijing,China

Previous studies suggest that air pollution has a negative effect on semen quality.However,most studies are cross-sectional and the results are controversial.This study investigated the associations between air pollutants(PM25,PM10,SO2,NO2,CO,and O3)and seme n quality among sperm donation candidates,especially when the air pollution was artificially con trolled in Beijing,China.We an a lyzed 8945 semen samples in the human sperm bank of Peki ng Un iversity Third Hospital(Beijing,China)from October 2015 to May 2018.Air pollution data during the entire period(0-90 days prior)and key stages(0-9,10-14,and 70-90 days prior)of sperm development were collected from the China National Environmental Monitoring Centre.The association between air pollutants and seme n parameters(sperm con centrati on and progressive motility)was an a lyzed by a mixed model adjusted for age,abstinence duration,month,and average ambient temperature.Only O3 during key stages of 0-9 days and 10-14 days and the entire period was negatively associated with sperm concentration between 2015 and 2018(P v 0.01).During the period of air pollution control from November 2017 to January 2018,except for the in crease in O3 concentration,other five pollutants'concentrations decreased compared to those in previous years.In this period,the sperm concentration decreased(P<0.001).During the pollution-control period,O3 exposure 10-14 days prior was negatively associated with sperm concentration(95%Cl:-0.399—0.111;P<0.001).No significant association was found between the other five pollutants and semen quality during that period?Our study suggested that only O3 exposure was harmful to semen quality.Therefore,O3 should not be neglected during pollution control operation.

Nanotechnology-assisted adipose-derived stem cell （ADSC） therapy for erectile dysfunction of cavernous nerve injury： In vivo cell tracking, optimized injection dosage, and functional evaluation

Stem cell therapy is a potentially promising option for erectile dysfunction; however, its risk of tumorigenicity is a clinical hurdle and the risk is positively related to the number of injected cells. Our previous study showed that nanotechnology improved adipose-derived stem cell （ADSC） therapy for erectile dysfunction of cavernous nerve injury （CNI） by attracting cells in the corpus cavernosum. These results indicated the possibility of using a reduced dosage of ADSCs for intracavernous injection. In this exploratory study, we used lower dosage （2 × 105 cells） of ADSCs for intracavernous injection （ICI） and the nanotechnology approach. Intracavernous pressure and mean arterial pressure were measured at day 28 to assess erectile function. The low-dose ADSC therapy group showed favorable treatment effects, and nanotechnology further improved these effects. In vivo imaging of ICI cells revealed that the fluorescein signals of NanoShuttle-bound ADSCs （NanoADSCs） were much stronger than those of ADSCs at days 0, 1, and 3. Both immunofluorescence and Western blot analysis showed a significant increase in smooth muscle, endothelium, and nerve tissue in the ADSC group compared to that in the CNI group; further improvement was achieved with assisted nanotechnology. These findings demonstrate that nanotechnology can be used to further improve the effect of small dosage of ADSCs to improve erectile function. Abundant NanoADSCs remain in the corpus cavernosum in vivo for at least 3 days. The mechanism of erectile function improvement may be related to the regeneration of the smooth muscle, endothelium, and nerve tissues.

Altered microRNA profiles of testicular biopsies from patients with nonobstructive azoospermia

Many studies have shown that microRNAs(miRNAs)play vital roles during the spermatogenesis.However,little is known about the altered miRNA profiles of testicular tissues in nonobstructive azoospermia(NOA).Using microarray technology,the miRNA expression profiles of testicular biopsies from patients with NOA and of normal testicular tissues were determined.Bioinformatics analyses were conducted to predict the enriched biological processes and functions of identified miRNAs.The microarray data were validated by quantitative reverse transcriptase polymerase chain reaction(qRT-PCR),the results of which were then validated with a larger sample size.Correlations between the miRNA expression levels and clinical characteristics were analyzed.Receiver operating characteristic(ROC)curve analysis was used to evaluate the diagnostic ability of miRNAs for azoospermia.Hierarchical clustering showed that 129 miRNAs were significantly differentially expressed between the NOA and control groups.Bioinformatics analysis indicated that the differentially expressed miRNAs were involved in spermatogenesis,cell cycle,and mitotic prometaphase.In the subsequent qRT-PCR assays,the selected miRNA expression levels were consistent with the microarray results,and similar validated results were obtained with a larger sample size.Some clinical characteristics were significantly associated with the expression of certain miRNAs.In particular,we identified a combination of two miRNAs(miR-10b-3p and miR-34b-5p)that could serve as a predictive biomarker of azoospermia.This study provides altered miRNA profiles of testicular biopsies from NOA patients and examines the roles of miRNAs in spermatogenesis.These profiles may be useful for predicting and diagnosing the presence of testicular sperm in individuals with azoospermia.

Development of a predictive model for increasing sperm retrieval sucpess by microdissection testicular sperm extraction in patients with nonobstructive azoospermia

Microdissection testicular sperm extraction(micro-TESE)is widely used to treat nonobstructive azoospermia.However,a good prediction model is required to anticipate a successful sperm retrieval rate before performing micro-TESE.This retrospective study analyzed the clinical records of 200 nonobstructive azoospermia patients between January 2021 and December 2021.The backward method was used to perform binary logistic regression analysis and identify factors that predicted a successful micro-TESE sperm retrieval.The prediction model was constructed using acquired regression coefficients,and its predictive performance was assessed using the receiver operating characteristic curve.In all,67 patients(sperm retrieval rate:33.5%)underwent successful micro-TESE.Follicle-stimulating hormone,anti-Miillerian hormone,and inhibin B levels varied significantly between patients who underwent successful and unsuccessful micro-TESE.Binary logistic regression analysis yielded the following six predictors:anti-Mullerian hormone(odds ratio[OR]=0.902,95%confidence interval[Cl]:0.821-0.990),inhibin B(OR=1.012,95%Cl:1.001-1.024),Klinefelter’s syndrome(OR=0.022,95%Cl:0.002-0.243),Y chromosome microdeletion(OR=0.050,95%Cl:0.005-0.504),cryptorchidism with orchiopexy(OR=0.085,95%Cl:0.008-0.929),and idiopathic nonobstructive azoospermia(OR=0.031,95%Cl:0.003-0.277).The prediction model had an area under the curve of 0.720(95%Cl:0.645-0.794),sensitivity of 65.7%,specificity of 72.2%,Youden index of 0.379,and cut-off value of 0.305 overall,indicating good predictive value and accuracy.This model can assist clinicians and nonobstructive azoospermia patients in decision-making and avoiding negative micro-TESE results.

Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development(DSD)patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1(NR5A1)gene.Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1.The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development.The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis.Microfluidic-based single-cell RNA sequencing(scRNA-seq)analysis found that the fibroblast cells were significantly increased(approximately 46.5%),whereas the number of main epididymal epithelial cells(approximately 9.2%),such as principal cells and basal cells,was dramatically decreased.Bioinformatics analysis of cell–cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition(EMT)process.The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.