Human-like adrenal features in Chinese tree shrews revealed by multi-omics analysis of adrenal cell populations and steroid synthesis

The Chinese tree shrew(Tupaia belangeri chinensis)has emerged as a promising model for investigating adrenal steroid synthesis,but it is unclear whether the same cells produce steroid hormones and whether their production is regulated in the same way as in humans.Here,we comprehensively mapped the cell types and pathways of steroid metabolism in the adrenal gland of Chinese tree shrews using single-cell RNA sequencing,spatial transcriptome analysis,mass spectrometry,and immunohistochemistry.We compared the transcriptomes of various adrenal cell types across tree shrews,humans,macaques,and mice.Results showed that tree shrew adrenal glands expressed many of the same key enzymes for steroid synthesis as humans,including CYP11B2,CYP11B1,CYB5A,and CHGA.Biochemical analysis confirmed the production of aldosterone,cortisol,and dehydroepiandrosterone but not dehydroepiandrosterone sulfate in the tree shrew adrenal glands.Furthermore,genes in adrenal cell types in tree shrews were correlated with genetic risk factors for polycystic ovary syndrome,primary aldosteronism,hypertension,and related disorders in humans based on genome-wide association studies.Overall,this study suggests that the adrenal glands of Chinese tree shrews may consist of closely related cell populations with functional similarity to those of the human adrenal gland.Our comprehensive results(publicly available at http://gxmujyzmolab.cn:16245/scAGMap/)should facilitate the advancement of this animal model for the investigation of adrenal gland disorders.

Diagnostic accuracy of cystoscopic biopsy for tumour grade in outpatients with urothelial carcinoma of the bladder and the risk factors of upgrading

Objective:To assess the concordance of tumour grade in specimens obtained from diagnostic cystoscopic biopsy and transurethral resection of bladder tumour(TURBT)and explore the risk factors of upgrading.Methods:The medical records of 205 outpatients who underwent diagnostic cystoscopic biopsy before initial TURBT were retrospectively reviewed.Comparative analysis of the tumour grade of biopsy and operation specimens was performed.Tumour grade changing from low-grade to high-grade with or without variant histology was defined as upgrading.Logistic regression an-alyses were performed to identify the risk factors of upgrading.Results:For the 205 patients,the concordance of tumour grade between specimens obtained from biopsy and operation was 0.639.The concordance for patients who were preoperatively diagnosed with low-grade and high-grade was 0.504 and 0.912,respectively.Univariate and multivariate logistic regression analyses showed that older age,tumour multifocality,high neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and low lymphocyte-to-monocyte ratio(LMR)were significantly associated with upgrading(odds ratio ranging from 0.412 to 4.364).The area under the curve of the different multivariate models was improved from 0.752 to 0.821,and decision curve analysis demonstrated a high net benefit when NLR,LMR,and PLR were added.Conclusion:Diagnostic cystoscopic biopsy may not accurately represent the true grade of primary bladder cancer,especially for outpatients with low-grade bladder cancer.Moreover,older age,tumour multifocality,high NLR,PLR,and low LMR are risk factors of upgrading,and systemic inflammatory markers improve the predictive ability.

Expression and significance of ADAM12 in bladder cancer

Objective:To investigate the expression and significance of ADAM12 in bladder cancer.Methods:Transcriptome data and clinical data of bladder cancer and normal samples from TCGA database were downloaded to analyze the expression level and prognosis of ADAM12 in bladder cancer and normal tissues,and analyze its clinical correlation.Bladder cancer wax block samples were collected to detect the expression level of ADAM12 protein in cancer and adjacent cancer by immunohisto-chemistry.In vitro experiments,the experiments were divided into siNC group and siADAM12 group by transfection interference sequence,and the effect of knockdown ADAM12 on the proliferation and migration of bladder cancer cells was evaluated by CCK8,Transwell and scratch experiments.Western Blot was used to detect the expression level of EMT-related protein in each group of bladder cancer cells.Bioinformatics was used to explore the potential mechanism of ADAM12 in influencing the progression of bladder cancer.Results:ADAM12 expression in bladder cancer tissue is higher than normal tissue(P<0.05).Compared with the low expression group,the prognosis of high-expression ADAM12 was worse(P=0.007),and it was related to tumor stage,depth of invasion and lymph node metastasis(P<0.05).The immunohistochemical results showed that ADAM12 was expressed higher in bladder cancer tissues than in neighboring tissues(P<0.05).The results of in vitro experiments showed that knocking down ADAM12 could inhibit the proliferation and migration of bladder cancer cells compared with the control group.Compared with the NC group,the Western Blot test results showed that the expression of E-cadherin was increased in the siADAM12 group,while the expression of N-cadherin and Vimentin was decreased.Overexpression leads to the opposite.Bioinformatics analysis showed that ADAM12 may be involved in multiple cancer-related signaling pathways and is associated with the infiltration of various immune cell(P<0.05).Conclusion:ADAM12 is highly expressed in bladder cancer tissues and is associated with tumor immune cell infiltration and promotes the migration of bladder cancer cells by regulating EMT,which may be a prognostic marker and biotherapeutic target for bladder cancer.

What should be the future direction of development in the field of prostate cancer with lung metastasis?

BACKGROUND Since the start of the 21st century,prostate cancer with lung metastasis(PCLM)has accumulated significant scientific research output.However,a systematic knowledge framework for PCLM is still lacking.AIM To reconstruct the global knowledge system in the field of PCLM,sort out hot research directions,and provide reference for the clinical and mechanism research of PCLM.METHODS We retrieved 280 high-quality papers from the Web of Science Core Collection and conducted a bibliometric analysis of keywords,publication volume,and citation frequency.Additionally,we selected differentially expressed genes from global high-throughput datasets and performed enrichment analysis and proteinprotein interaction analysis to further summarize and explore the mechanisms of PCLM.RESULTS PCLM has received extensive attention over the past 22 years,but there is an uneven spatial distribution in PCLM research.In the clinical aspect,the treatment of PCLM is mainly based on chemotherapy and immunotherapy,while diagnosis relies on methods such as prostate-specific membrane antigen positron emission tomography/computed tomography.In the basic research aspect,the focus is on cell adhesion molecules and signal transducer and activator of transcription 3,among others.Traditional treatments,such as chemotherapy,remain the mainstay of PCLM treatment,while novel approaches such as immunotherapy have limited effectiveness in PCLM.This study reveals for the first time that pathways related to coronavirus disease 2019,cytokinecytokine receptor interaction,and ribosome are closely associated with PCLM.CONCLUSION Future research should focus on exploring and enhancing mechanisms such as cytokine-cytokine receptor interaction and ribosome and improve existing mechanisms like cadherin binding and cell adhesion molecules.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer

Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

TM9SF1 promotes bladder cancer cell growth and infiltration

BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.

MAPK9 as a therapeutic target:unveiling ferroptosis in localized prostate cancer progression

Background:Ferroptosis,a lipid peroxidation-mediated programmed cell death,is closely linked to tumor development,including prostate cancer(PCa).Despite established connections between ferroptosis and PCa,a comprehensive investigation is essential for understanding its impact on patient prognosis.Methods:A risk model incorporating four ferroptosis-related genes was developed and validated.Elevated risk scores correlated with an increased likelihood of biochemical recurrence(BCR),diminished immune infiltration,and adverse clinicopathological characteristics.To corroborate these results,we performed validation analyses utilizing datasets from both the Cancer Genome Atlas Cohort(TCGA)and the Gene Expression Synthesis Cohort(GEO).Moreover,we conducted further investigations into the pivotal gene identified in our model to explore its impact on tumor characteristics through cell proliferation and invasion assays,as well as animal studies conducted in vivo.Additionally,we conducted further experiments involving ferroptosis-related analysis to validate its association with ferroptosis.Results:The risk model demonstrated exceptional predictive capabilities for prognosis and therapeutic outcomes in PCa patients.Mitogen-activated protein kinase 9(MAPK9)emerged as a crucial gene within the model.In vivo and in vitro experiments explored MAPK9’s role in ferroptosis and its influence on tumor migration and proliferation.Conclusion:The findings provide a novel perspective for advancing ferroptosis exploration in PCa,bridging basic research and clinical applications.

Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats

The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.

Transgelin induces apoptosis of human prostate LNCaP cells through its interaction with p53

The androgen receptor （AR） and its coregulators have important roles in the carcinogenesis of prostate cancer.p53 is an important tumour suppressor gerte,and the absence of a fundamental p53 response may predispose to cancer. Transgelin,known as an ARA54-associated AR inhibitor,can suppress AR function in LNCaP cells. In addition to these effects,we aimed to elucidate the proapoptotic effects of the protein on LNCaP and its underlying mechanisms,especially the interaction between transgelin and p53. Cell counting,flow cytometric analysis and terminal deoxynucleotidyl transferase-dUTP nick-end labelling assays were applied to measure the proapoptotic effect of transgelin. Using western blotting of p53 and double immunofluorescence staining of p53 with transgelin,we show that transfection of transgelin results in increasing cytoplasmic translocation of p53 and upregulation of p53 expression. We also found an interaction between transgelin and p53 in vivo by mammalian two-hybrid and coimmunoprecipitation assays. The activation of the mitochondria-associated apoptosis pathway was observed in LNCaP cells after transfection with transgelin. These results are indicative of p53-mediated mitochondria-associated apoptotic effects of transgelin on LNCaP cells in addition to its known suppressive effects on the AR pathway.

Prostate cancer risk and aggressiveness associated with the CYPIB1 4326C/G （Leu432Val） polymorphism： a meta-analysis of 2788 cases and 2968 controls

To derive a precise estimation of the associations between the cytochrome P450 1B 1 （CYPIB1） 4326C/G variants and prostate cancer （PCa） risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYPIB1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians （OR= 1.52, 95% Ch 1.20-1.92）, and significant associations were also observed in a heterozygote comparison （OR= 1.40, 95% Ch 1.03-1.89）, a homozygote comparison （0R=2.38, 95% Ch 1.31-4.33） and in a dominant genetic model （OR = 1.52, 95% Ch 1.14-2.01）. Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa （OR= 1.13, 95% Ch 1.04-1.24）, and significant associations were observed in a heterozygote comparison （OR= 1.16, 95% Ch 1.02-1.33）, a homozygote comparison （OR= 1.24, 95% Ch 1.03-1.49） and a dominant genetic model （OR= 1.19, 95% Ch 1.05- 1.34）. The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYPIB1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.

Congenital agenesis of seminal vesicle

Congenital agenesis of the seminal vesicle （CASV） is frequently associated with congenital absence of the vas deferens （CAVD） or ipsilateral congenital vasoureteral communication. We reported two cases of a rare condition that the vas deferens open ectopically into Mullerian duct cyst associated with agenesis of the ipsilateral seminal vesicle. The diagnosis was confirmed by vasography. Transurethral unroofing of the Mullerian duct cyst was performed in both patients with favourable results, however, assisted reproductive technology （ART） was still necessary for them to father children.

Reduced expression of circulating microRNA-218 in gastric cancer and correlation with tumor invasion and prognosis

AIM:To investigate the expression of microRNA-218(miR-218)in serum from gastric cancer patients and its relationship with clinicopathological characteristics.METHODS:A total of 68 patients with pathologically diagnosed gastric cancer and 56 healthy individuals were recruited to this study.The expression of miR-218was detected in the serum of gastric cancer patients and healthy individuals by quantitative real-time polymerase chain reaction.The clinical data were collectedand analyzed by statistical software.RESULTS:miR-218 was reduced significantly in the serum of gastric cancer patients compared to healthy individuals(1.15±0.08 vs 0.37±0.023;P=0.026).In the gastric cancer group,serum expression of miR-218was lower in patients with metastasis and poorly differentiated cancer compared with non-metastatic and well-differentiated cancer(0.19±0.011 vs 0.45±0.021,P=0.031 and 0.21±0.019 vs 0.49±0.021,P=0.025).Serum miR-218 was found to be significantly associated with gastric cancer metastasis(P=0.003),tumor T stage(P=0.018)and tumor grade(P=0.012).Low serum expression of miR-218 was related to an increase in the stage of gastric cancer.The expression level of miR-218 in the serum was correlated with the3-year survival.Ninety-seven percent of patients with a high level of miR-218 expression survived for 3 years,while only 54%of those with low miR-218 expression survived.CONCLUSION:miR-218 is deregulated in gastric cancer patients and is strongly correlated with tumor stage,grade and metastasis.Serum expression of miR-218 may be a prognostic marker.

The risks, degree of malignancy and clinical progression of prostate cancer associated with the MDM2 T309G polymorphism： a meta-analysis

To determine the risk, malignant degree and clinical progression of prostate cancer （PCa） associated with mouse double-minute 2 protein （MDM2） T309G variants, a meta-analysis was performed on all eligible published studies. Odds ratios （ORs） with 95% confidence intervals （CIs） were estimated to assess these associations in seven studies that included 5151 cases and 1003 controls. In the overall analysis, the 309G allele was significantly associated with a decreased PCa risk （0R=0.85, 95% CI： 0.74-0.97）; this was also the case for the homozygous comparison （0R--0.72, 95% Ch 0.55-0.95） and the dominant genetic model （0R=0.79, 95% Ch 0.65-0.96）. The 309G allele was also found to be significantly associated with lower degrees of PCa malignancy （0R=0.85, 95% Ch 0.75-0.96） in the overall analysis, as well as in the heterozygous comparison （0R=0.79, 95% Ch 0.65-0.96）, homozygous comparison （0R=0.76, 95% Ch 0.58-0.98） and dominant genetic model （0R=0.81, 95% CI： 0.68-0.96）. Furthermore, grouping analysis showed that the 309G allele in Caucasians was significantly correlated with a decreased PCa risk （0R=0.77, 95% Ch 0.61-0.96）; this was also the case in the homozygous comparison （0R=0.51, 95% Ch 0.31-0.86）. The grouping analysis also showed that the 309G variant in Caucasians was significantly associated with a lower degree of PCa malignancy in all of the genetic models. In addition, we found that the 309G variant in Caucasians was significantly associated with a slower PCa clinical progression in all of the genetic models. In summary, our meta-analysis showed that the MDM2 309G variant was significantly associated with a decreased PCa risk, lower malignant degree and slower clinical progression in Caucasians, but there was no obvious association in the Asian population.

Natural orifice transluminal endoscopic surgery in urology: The Chinese experience

Objective:To describe the Chinese experience of natural orifice transluminal endoscopic surgery(NOTES)in urology.Methods:From December 2008 to May 2017,35 animal experiments and 305 clinical surgeries of NOTES or natural orifices specimen extractions(NOSE)were performed in China.The animal experiments included five kidney biopsies,24 nephrectomies and six partial nephrectomies.The clinical surgeries included 12 transvaginal NOSE(TV-NOSE),266 hybrid transvaginal NOTES(TV-NOTES)and 27 pure TV-NOTES.The TV-NOSE procedure was performed in five transumbilical laparoendoscopic single-site(U-LESS)nephrectomies,four suprapubic-assisted laparoendoscopic single-site surgery(SA-LESS)nephroureterectomies,and three laparoscopic radical cystectomies.The hybrid TV-NOTES procedure included 210 nephrectomies,31 adrenalectomies,eight nephroureterectomies,13 partial nephrectomies,and four heminephrectomies.The pure TV-NOTES procedure included five renal cyst decortications and 22 nephrectomies.Results:A total of 29 animal experiments were successfully performed.One partial nephrectomy was converted to standard laparoscopic surgery.Two kidney biopsies and two nephrectomies were unsuccessful.A total of 297 clinical surgeries were successfully performed.Six patients who underwent hybrid TV-NOTES were converted to open surgery.Two patients who underwent pure TV-NOTES were converted to SA-LESS.There were 22 major complications,16 occurred intraoperatively and six postoperatively.The mean visual analog score(VAS)of 48 h after the operation was 2.5 points in TV-NOSE,2.3 points in hybrid TV-NOTES and 1.7 points in pure TV-NOTES.The mean follow-up of 50.6(3.0-87.0)months showed that all patients were in good condition.The umbilicus scars were nearly invisible in TV-NOSE and hybrid TV-NOTES.The vaginal incision healed well.Conclusions:TV-NOSE and TV-NOTES are feasible,safe,and effective with little injury,low pain,fast recovery,and good cosmetic outcomes in properly selected patients.They are worth consideration for urological clinical practice.

Genetic polymorphism of glutathione S-transferase T1 gene and susceptibility to idiopathic azoospermia or oligospermia in northwestern China

Aim： To investigate the association of glutathione S-transferase T1 （GSTT1） gene polymorphism in patients with idiopathic azoospermia or oligospermia in the northwestern China population. Methods： In the case-control study, GSTT1 genotypes were identified by multiplex polymerase chain reaction （PCR） with peripheral blood DNA samples from 78 patients with idiopathic azoospermia, 103 patients with idiopathic oligospermia and 156 age-matched controls with normal sperm concentration and motility, according to the criteria adapted from World Health Organization guidelines. All of the patients and controls were from northwestern China. Results： There is a significant association between GSTT1 null genotype with idiopathic azoospermia risk （odds ratio [OR]： 2.36, 95% confidence interval [CI]： 1.33-4.20, P = 0.003） or idiopathic oligospermia risk （OR： 2.00, 95% CI： 1.17-3.27, P = 0.010）. Conclusion： GSTT1 null genotype is a predisposing risk factor for sporadic idiopathic azoospermia or oligospermia in northwestern China. （Asian J Androl 2008 Mar; 10： 266-270）

Expression of Angiotensin Ⅱ Receptors in Aldosterone-producing Adenoma of the Adrenal Gland and Their Clinical Significance

The expression of angiotensin Ⅱ type 1 receptor (AT1R) and angiotensin Ⅱ type 2 receptor (AT2R) in aldosterone-producing adenoma (APA) of the adrenal gland was detected, and their relationship with clinical indexes of APA was analyzed. The mRNA expression of AT1R and AT2R in 50 cases of APA and tissues adjacent to tumors and 12 cases of normal adrenal tissues was detected by using reverse transcriptase polymerase chain reaction (RT-PCR). The expression of AT1R and AT2R proteins in paraffin-embedded slices of tissue was detected by immunohistochemistry. The expression of AT1R in adenoma, tissues adjacent to tumor, and normal tissues of the adrenal gland showed no significant differences. The expression of AT2R in APA tissue was lower than that in normal adrenal gland tissues (P<0.05). Correlation analysis of the mRNA expression level of AT2R and clinical data from patients demonstrated that AT2R expression was negatively related to plasma aldosterone concentration (PAC) (r=-0.467, P<0.05), but positively related with plasma renin activity (PRA) (r=0.604, P<0.05). It is concluded that down-regulation of the AT2R expression is possibly related with the tumorigenesis of APA.

Two case reports of bilateral adrenal myelolipomas

Primary adrenal myelolipoma is a rare, non-functioning adrenal benign tumor that is composed of mature adipose tissue and a variable amount of haemopoietic elements. Clinically, it is difficult to get diagnosed with adrenal myelolipoma because the patient usually doesn't have obvious symptoms and signs in early stage. In the present study, two cases of primary bilateral adrenal myelolipomas are reported. Clinical presentation, imaging diagnostic features, histopathological changes and surgical treatments of the two patients are discussed. Preoperative diagnostic imaging examinations(B-mode ultrasonography, computed tomography and magnetic resonance imaging sans) assisted getting a prediction diagnosis of bilateral adrenal myelolipomas. A two-stage surgery was used to successfully excise bilateral adrenal myelolipomas in the two patients. Conventional open adrenalectomy was applied to remove the adrenal myelolipomas greater than 6 cm, and laparoscopic adrenalectomy was performed to excise the adrenal tumors smaller than 6 cm. Bilateral adrenal myelolipomas of the two patients were finally confirmed by postoperative histopathological examinations. Understanding clinical, imaging diagnostic and histopathological features of bilateral adrenal myelolipomas will facilitate timely diagnosis and treatment of this condition. Surgical removal of bilateral adrenal myelolipomas is safe, curative and beneficial.The two-stage surgery appears to be the best treatment option for the patients with bilateral adrenal myelolipomas because it achieves optimal treatment effectiveness with minimized sequelae.

The ejaculatory duct ectopically invading the bladder with multiple congenital malformations of the homolateral urogenital system： a report of a rare case and an embryological review

We report a rare case of a left ejaculatory duct that allotropically protrudes towards or invades the left vesicle triangular area with its dead end. The patient simultaneously exhibited multiple congenital malformations of the homolateral urogenital system, such as absence of the left kidney, dysplasia and allotopia of the left seminal vesicle, absence of the left ureterostoma, separation between the left testis and the epididymis tail, and maldevelopment of the left testis. According to all clinical and laboratory evidence, the case represented a new syndrome, which we named Wuyang＇s syndrome. It involved a rare phenomenon in embryonic development; the dysplastic proximal vas precursor, having intruded into a common mesonephric duct and accidentally encroaching on the ureteric bud position, resulted in the absence or dysplasia of the homolateral urinary tract and ectopic invasion of the bladder by the homolateral seminal tract.

Localization of epididymal protease inhibitor in adult rat and its transcription profile in testis during postnatal development

To investigate the expression pattern of rat Eppin （epididymal protease inhibitor; official symbol Spinlwl）, we detected mRNA transcripts and subsequent protein translation of Eppin in several sorts of tissues by RT-PCR and westem blotting. Then immunohistochemistry was performed for more detailed observation. The testicular transcription level was monitored by real-time PCR throughout postnatal development. We found that rat Eppin was specifically expressed in the testis and epididymis. The testicular transcription was slight in neonatal （1-day） and infantile stages （5-, 7- and 10-day）. It increased sharply thereafter, with maximum expression level （about 38- fold compared with that of 1-day old rat） detected in prepubertal stage （15-day）. Then a slightly declined but stable level （about 20-fold compared with that of 1-day old rat） was kept in pubertal-early adult （30-day） and adult （60-day） stages of postnatal maturation. In the adult rat, EPPIN protein was mainly localized in the elongated spermatids and epididymal epithelial cells. Sperm in the epididymal duct were all covered with EPPIN and its level kept constant during incubation under conditions used to achieve capacitation. Its stage-specific expression in the testis suggests that EPPIN may be important during spermatogenesis especially for the spermatid elongation. The abundant production of epididymal EPPIN indicated indirectly that it might play a role in the function of the epididymis.

Efficacy and safety of degarelix in patients with prostate cancer:Results from a phase III study in China

Objective:To establish non-inferiority of gonadotropin-releasing hormone degarelix compared with goserelin in suppressing and maintaining castrate testosterone levels from Day 28 to Day 364 in Chinese patients with prostate cancer.Methods:This is an open-label,multi-centre study in which men aged18 years were randomised in a 1:1 ratio to once-a-month subcutaneous injection of either degarelix(240/80 mg)or goserelin(3.6 mg)for 12 months.The primary endpoint was difference in 1-year cumulative probability of suppressing testosterone to ≤0.5 ng/mL.Non-inferiority was to be established if the lower 95% confidence interval(CI)limit for difference in cumulative probability between the treatment arms was greater than -10%.Secondary endpoints included cumulative probability of prostate-specific-antigen-progression-free-survival(PSA-PFS).Safety was also assessed.Results:Baseline demographics and disease characteristics were similar between degarelix(n=142)and goserelin(n=141)treatment arms.The difference in cumulative probability of maintaining castrate levels from Day 28-364 was 3.6%(95%CI:-1.5%,8.7%),demonstrating non-inferiority of degarelix.The cumulative probability of PSA-PFS at Day 364 was higher for degarelix(82.3%,95%CI:74.7%,87.7%)versus goserelin(71.7%,95%CI:63.2%,78.5%,p=0.038).Adverse events(AEs)were similar between treatment arms,except for more injection site reactions with degarelix versus goserelin.Four(2.8%)and nine(6.4%)patients discontinued due to AEs in degarelix and goserelin groups,respectively.