5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on i...5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials (RCTs) and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density (MVD) in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation.展开更多
Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihyd...Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihydrotestosterone(DHT),and excessive DHT will cause related diseases.Since BPH seriously affects the quality of life of patients,it is essential to discover effective 5α-reductase inhibitors.In this study,the simple analytical method of high performance thin layer chromatography(HPTLC)was used to screen active compounds,and seven compounds with strong activity were screened out.This research will provide a reference for studying the material basis of drugs for the treatment of BPH.展开更多
Objectives To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organsMethods The expression level of 5α-reductase type 2 gene inhuman testis, epididymis and vas deferens tissues wa...Objectives To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organsMethods The expression level of 5α-reductase type 2 gene inhuman testis, epididymis and vas deferens tissues was determined by in situ hybridization using Digoxin labeled 5α-reductase type 2 cRNA probe.Results The brown granules of hybridizing signals distributed in the cytoplasm of Sertoli and Leydig cells of the testis, the principle cells of epididymis and the epithelial cells of vas deferens, but there was no positive signal in the nuclei of above-mentioned cells. No positive signal was observed in germ cells, basement of the testis, interstium of epididymis and basement, as well as smooth muscle of vas deferens. Conclusion This study confirmed that the 5α-reductase type 2 gene expressed in Sertoli , Leydig cells of the testis, and the principle cells of epididymis. The expression pattern of the gene in these cells in human was similar to that of rat and monkey. The presence of 5α-reductase type 2 gene in epithelial cells of the vas deferens suggested it might possess an important physiological role in human reproduction.展开更多
Aim: To identify the genotype of two Indians with male pseudohermaphroditism. Methods: Standard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carded out fo...Aim: To identify the genotype of two Indians with male pseudohermaphroditism. Methods: Standard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carded out for diagnosing the genetic sex in these subjects with genital ambiguity. Molecular analysis was carried out by standard polymerase chain reaction procedure using different sets of primers and reaction conditions specific for the 5α- reductase type 2 gene (SRDSA2) gene. Direct sequencing was carried out using the ABI Prism dye terminator sequencing kit and the ABI 310 sequencing apparatus. Results: We found an SRDSA2 gene mutation in exon 5, where arginine is substituted with glutamine (R246Q), in two males with pseudohermaphroditism and ambiguous genitalia from unrelated families. This is the first time this mutation has been reported in individuals from India. Conclusion: Identification of the R246Q mutation of the SRDSA2 gene from two unrelated Indian families possibly extends the founder gene effect.展开更多
To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organs. Methods: The expression level of 5ct-reductase type 2 gene in human testis, epididymis and vas deferens tissues was deter...To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organs. Methods: The expression level of 5ct-reductase type 2 gene in human testis, epididymis and vas deferens tissues was determined by in situ hybridization using a digoxin-labeled 5α-reductase type 2 cRNA probe. Results: The brown granules of hybridizing signals distributed in the cytoplasm of the Sertoli and Leydig cells of the testis, the principle cells of epididymis and the epithelial cells of vas deferens, but there was no positive signal in the nuclei of these cells. No positive signal was observed in the germ cells, basement of the testis, interstium of the epididymis and basement and the smooth muscle cells of vas deferens. Conclusion: This study confirmed that the 5a-reductase type 2 gene expressed in the Sertoli and Leydig cells of the testis and the principle cells of the epididymis. The expression pattem of the gene in these cells in the human was similar to that in the rat and monkey. The presence of 5α-reductase type 2 gene in the epithelial cells of the vas deferens suggests that it may play a physiological role in human reproduction. [Reprod Contracep (in English) 2002; 13: 67]展开更多
The changes in 5α-reductase (type 2 ) gene expression in the epi-didymis of puberty diabetic rats were studied by the Northern blot and Dotblot method. Rats were divided into 3 groups: the control group (C), thediabe...The changes in 5α-reductase (type 2 ) gene expression in the epi-didymis of puberty diabetic rats were studied by the Northern blot and Dotblot method. Rats were divided into 3 groups: the control group (C), thediabetic group (D), and the diabetic group with insulin treatment (DI).Results: The Northern blot intensity of the caput epididymis in Group D is展开更多
Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed s...Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed soft extract (active ingredients of GRANUFINK? Prosta forte 500 mg), seed oil and isolated Δ7-sterols could inhibit the conversion of [1,2,6,7-3H(N)]-testosterone to DHT by 5α-reductases. Also, we tested competition with [3H]-DHT for binding to the androgen receptor (AR). Pumpkin seed oil and pumpkin seed soft extract were identified as moderately active inhibitors of 5α-R1 and 5α-R2, with almost similar inhibitory capacities (IC50 5 mg/ml for 5α-R1 and about IC50 = 6 mg/ml for 5α-R2). The isolated Δ7-sterols were more active inhibitors (IC50 = 0.3 mg/ml for 5α-R1, IC50 = 1.0 mg/ml for 5α-R2). All three test compounds bound to the AR dose-dependently, with strong binding by Δ7-sterols (IC50 = 0.2 mg/ml) and weaker binding by pumpkin seed oil (IC50 = 0.4 mg/ml) and pumpkin seed soft extract (IC50 = 1.1 mg/ml). We propose that inhibition of 5α-reductases and competitive binding to the AR are mechanisms of action, by which the Uromedic? pumpkin seed derived test compounds, most specifically Δ7-sterols, counteract DHT and thereby exert clinically positive effects on the prostate, as well as bladder-strengthening effects.展开更多
5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone,which causes abnormal urogenital sinus development.The aim of this study was to analyze the relationship between genotype–p...5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone,which causes abnormal urogenital sinus development.The aim of this study was to analyze the relationship between genotype–phenotype,surgical selections,and postoperative complications of 5α-reductase 2-deficient patients with hypospadias.We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children’s Hospital,Capital Medical University(Beijing,China),from April 2007 to December 2021.A total of 69 patients were included in this study;the mean age at surgery was 34.1 months,and the average follow-up time was 54.1 months.Sixty children were treated with preoperative hormone stimulation(PHS)to promote penile growth.The average penis length and glans width were increased by 1.46 cm and 0.62 cm,respectively.The most frequent mutations were p.R227Q(39.1%,54/138),p.Q6^(*)(15.2%,21/138),p.G203S(12.3%,17/138),and p.R246Q(11.6%,16/138).In 64 patients who were followed up,43 had a one-stage operation and 21 had a staged operation,and there were significant differences in external masculinization score(EMS)(P=0.008)and the average number of operation required to cure(P<0.001)between one-stage and staged operations.PHS had a positive effect(P<0.001)on penile development.The p.R227Q mutation was associated with higher EMS and less severe hypospadias.One-stage surgery can be selected if conditions permit.The growth and development of children are acceptable in the long term,but penis growth remains unsatisfactory.Longterm complications of hypospadias should be considered during puberty.展开更多
Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats...Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P 〈 0.01); DHT concentrations of group D rats were significantly decreased (P 〈 0.01 ) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.展开更多
Importance:Children with 5-alpha-reductase deficiency(5α-RD)and hypospadias present with micropenis,which makes it difficult to obtain sufficient tissue for urethral reconstruction.Objective:We investigated the thera...Importance:Children with 5-alpha-reductase deficiency(5α-RD)and hypospadias present with micropenis,which makes it difficult to obtain sufficient tissue for urethral reconstruction.Objective:We investigated the therapeutic effects of oral testosterone undecanoate and established a standard androgen treatment protocol for patients with 5α-RD with micropenis.Methods:Patients with 5α-RD were treated with oral testosterone undecanoate for 3 months as a course.All patients were treated with no more than 3 courses.If the penile length(PL)reached 2.5 cm(the minimum criterion for surgery)or greater than or equal to−2.5 standard deviations(SDs)(lower limit of normal),testosterone undecanoate was considered to be effective.Results:The median age of 90 patients with 5α-RD was 1.7 years(0.9,3.1 years).The baseline PL was 1.9±0.6 cm before treatment.At the end of the first course,the PL of 63 patients(70%)reached 2.5 cm,and 49 patients(54%)reached greater than or equal to−2.5 SDs.After two treatment courses,the PL of 81 patients(90%)reached 2.5 cm,and 90 patients(100%)reached greater than or equal to−2.5 SDs.After three courses,the PL of all patients reached 2.5 cm,and all patients reached a PL greater than or equal to−2.5 SDs.No abnormal increase was observed in height-SD score,weight-SD score,or ratio of bone age to chronological age during the 1-3-year follow-up.Interpretation:After 3-9 months of treatment,PL increased to the target length.No severe adverse reactions were observed during follow-up.Testosterone undecanoate was safe and effective in children with 5α-RD with micropenis.展开更多
目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的s...目的探讨甲基转移酶5(methyltransferase-like 5,METTL5)在三阴乳腺癌(triple-negative breast cancer,TNBC)中的作用和潜在机制。方法采用免疫组织化学方法和Western blot检测TNBC肿瘤组织和细胞系中METTL5的表达情况。用靶向METTL5的shRNA(shRNA-METTL5)转染TNBC细胞后,用CCK-8、集落形成、伤口愈合以及Transwell实验分别检测细胞增殖活性、迁移与侵袭,Western blot检测Wnt/β-catenin信号关键蛋白的表达。构建异种移植瘤模型,验证敲降METTL5对TNBC细胞在体内生长以及Wnt/β-catenin信号活性的影响。结果METTL5在TNBC肿瘤组织和细胞系中表达上调(P<0.01)。敲降METTL5可抑制TNBC细胞的增殖、迁移和侵袭并降低了Wnt/β-catenin信号分子β-catenin、细胞周期蛋白(Cyclin)D1、基质金属蛋白酶(MMP)-2和MMP-7的表达(均P<0.01)。体内实验显示,敲降METTL5减缓了移植瘤生长和Wnt/β-catenin信号活性。结论敲降METTL5能抑制TNBC细胞的增殖、迁移与侵袭,其作用可能与抑制Wnt/β-catenin信号通路有关。展开更多
目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结...目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结肠癌组织、正常结肠细胞系(NCM460)和结直肠癌细胞系(SW620、HCT116、HT29、Lovo和SW480)中的表达。将SCL6A9过表达质粒及阴性对照(SLC6A9 OE、Vector)转染HT29细胞,将SCL6A9小干扰RNA及阴性对照(SLC6A9 siRNA1#、siRNA2#和Scramble)转染SW620细胞。划痕愈合实验和Transwell实验检测各组细胞的迁移、侵袭能力。Western blot和细胞免疫荧光检测EMT相关蛋白E-cadherin、Vimentin的表达水平。利用CCK-8法和构建裸鼠移植瘤模型检测SLC6A9过表达对结直肠癌细胞5-FU药物敏感性的影响。结果:与正常结肠组织和NCM460细胞相比,SLC6A9在结肠癌组织和结直肠癌细胞系中低表达(均P<0.05)。SLC6A9过表达引起E-cadherin蛋白表达增加,Vimentin蛋白水平降低,抑制结直肠癌细胞的迁移、侵袭(P<0.05)。SLC6A9低表达引起E-cadherin蛋白表达降低,Vimentin蛋白水平增加,促进结直肠癌细胞的迁移、侵袭能力(P<0.05)。SLC6A9过表达提高了5-FU的药物敏感性,并使肿瘤生长缓慢,质量减轻(P<0.05)。而SLC6A9低表达降低了5-FU的药物敏感性(P<0.05)。结论:SLC6A9过表达能够抑制结直肠癌细胞的迁移、侵袭和EMT进程,并增强5-FU对结直肠癌细胞的药物敏感性。展开更多
食品加工过程中的美拉德反应有助于形成一些热诱导毒性产物,包括晚期糖基化终末产物(advanced glycation end products,AGEs)和5-羟甲基糠醛(5-hydroxymethylfurfural,5-HMF)。食源性AGEs在体内的积累和循环与糖尿病并发症的发生有关,...食品加工过程中的美拉德反应有助于形成一些热诱导毒性产物,包括晚期糖基化终末产物(advanced glycation end products,AGEs)和5-羟甲基糠醛(5-hydroxymethylfurfural,5-HMF)。食源性AGEs在体内的积累和循环与糖尿病并发症的发生有关,同时可能诱发氧化应激、炎症和动脉粥样硬化。5-HMF的代谢物5-磺基氧甲基糠醛(5-sulfooxymethylfurfural,5-SMF)有潜在基因毒性和致癌性。如何控制热加工食品中这些危害物的形成已成为食品行业的关注焦点。本文从美拉德反应和焦糖化反应两条途径探究了AGEs和5-HMF的形成机理,并对近5年二者的检测方法进行了综述,阐述了各类方法的优缺点,以期为建立二者的通用检测方法奠定基础。在此基础上,从削减前体物质的供给、阻断中间体的转化,以及去除已经生成的AGEs和5-HMF这3个方面着手,综述了近年来相应所采用的抑制策略,以期为AGEs和5-HMF在食品中的控制及热加工食品质量与安全管理提供理论依据。展开更多
文摘5α-reductase inhibitors (5α-RIs), including finasteride and dutasteride, are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many studies reported that preoperative 5α-RI had impact on intraoperative haemorrhage during surgery for BPH, but it was still in controversial. So, we conducted a systematic review of the effects and mechanisms of 5α-RIs on intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail Register of Controlled Trials and the reference lists of retrieved studies were searched in the analysis. Sixteen publications involving 15 different randomized controlled trials (RCTs) and a total of 1156 patients were used in the analysis, including 10 RCTs for finasteride and five RCTs for dutasteride. We found that preoperative finasteride treatment decreases microvessel density (MVD) in resected prostate specimens. Total blood loss, blood loss per gram of resected prostate tissue and decreases in haemoglobin were all greatly reduced in the finasteride group as compared to controls. Dutasteride appeared to have no effect on bleeding. This meta-analysis shows that preoperative finasteride treatment could decrease intraoperative haemorrhage during surgery for BPH. Preoperative dutasteride had no effect on intraoperative haemorrhage, but further high-qualitv prospective studies are still needed to confirm this observation.
基金This study was financially supported by the Program of Shanghai Municipal Commission of Health and Family Planning(ZY(2018-2020)-CCCX-5002).
文摘Benign prostatic hyperplasia(BPH)is a common disease in men,and is known to be related to 5α-reductase,which can affect steroid metabolism.Under the promotion of 5α-reductase,testosterone can be converted into dihydrotestosterone(DHT),and excessive DHT will cause related diseases.Since BPH seriously affects the quality of life of patients,it is essential to discover effective 5α-reductase inhibitors.In this study,the simple analytical method of high performance thin layer chromatography(HPTLC)was used to screen active compounds,and seven compounds with strong activity were screened out.This research will provide a reference for studying the material basis of drugs for the treatment of BPH.
基金This study was supported by the State Family Planning Committee
文摘Objectives To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organsMethods The expression level of 5α-reductase type 2 gene inhuman testis, epididymis and vas deferens tissues was determined by in situ hybridization using Digoxin labeled 5α-reductase type 2 cRNA probe.Results The brown granules of hybridizing signals distributed in the cytoplasm of Sertoli and Leydig cells of the testis, the principle cells of epididymis and the epithelial cells of vas deferens, but there was no positive signal in the nuclei of above-mentioned cells. No positive signal was observed in germ cells, basement of the testis, interstium of epididymis and basement, as well as smooth muscle of vas deferens. Conclusion This study confirmed that the 5α-reductase type 2 gene expressed in Sertoli , Leydig cells of the testis, and the principle cells of epididymis. The expression pattern of the gene in these cells in human was similar to that of rat and monkey. The presence of 5α-reductase type 2 gene in epithelial cells of the vas deferens suggested it might possess an important physiological role in human reproduction.
文摘Aim: To identify the genotype of two Indians with male pseudohermaphroditism. Methods: Standard radioimmunoassay procedure was used for estimating hormonal levels. Conventional cytogenetic analysis was carded out for diagnosing the genetic sex in these subjects with genital ambiguity. Molecular analysis was carried out by standard polymerase chain reaction procedure using different sets of primers and reaction conditions specific for the 5α- reductase type 2 gene (SRDSA2) gene. Direct sequencing was carried out using the ABI Prism dye terminator sequencing kit and the ABI 310 sequencing apparatus. Results: We found an SRDSA2 gene mutation in exon 5, where arginine is substituted with glutamine (R246Q), in two males with pseudohermaphroditism and ambiguous genitalia from unrelated families. This is the first time this mutation has been reported in individuals from India. Conclusion: Identification of the R246Q mutation of the SRDSA2 gene from two unrelated Indian families possibly extends the founder gene effect.
基金The study was supported by the Chinese State Family Planning Commission
文摘To study the expression pattern of 5α-reductase type 2 gene in human male reproductive organs. Methods: The expression level of 5ct-reductase type 2 gene in human testis, epididymis and vas deferens tissues was determined by in situ hybridization using a digoxin-labeled 5α-reductase type 2 cRNA probe. Results: The brown granules of hybridizing signals distributed in the cytoplasm of the Sertoli and Leydig cells of the testis, the principle cells of epididymis and the epithelial cells of vas deferens, but there was no positive signal in the nuclei of these cells. No positive signal was observed in the germ cells, basement of the testis, interstium of the epididymis and basement and the smooth muscle cells of vas deferens. Conclusion: This study confirmed that the 5a-reductase type 2 gene expressed in the Sertoli and Leydig cells of the testis and the principle cells of the epididymis. The expression pattem of the gene in these cells in the human was similar to that in the rat and monkey. The presence of 5α-reductase type 2 gene in the epithelial cells of the vas deferens suggests that it may play a physiological role in human reproduction. [Reprod Contracep (in English) 2002; 13: 67]
文摘The changes in 5α-reductase (type 2 ) gene expression in the epi-didymis of puberty diabetic rats were studied by the Northern blot and Dotblot method. Rats were divided into 3 groups: the control group (C), thediabetic group (D), and the diabetic group with insulin treatment (DI).Results: The Northern blot intensity of the caput epididymis in Group D is
文摘Dihydrotestosterone (DHT) is implicated in the development of benign prostate hyperplasia (BPH). We investigated if Uromedic? pumpkin (variety of Cucurbita pepo L. convar. citrullinina GREB. var. styriaca GREB) seed soft extract (active ingredients of GRANUFINK? Prosta forte 500 mg), seed oil and isolated Δ7-sterols could inhibit the conversion of [1,2,6,7-3H(N)]-testosterone to DHT by 5α-reductases. Also, we tested competition with [3H]-DHT for binding to the androgen receptor (AR). Pumpkin seed oil and pumpkin seed soft extract were identified as moderately active inhibitors of 5α-R1 and 5α-R2, with almost similar inhibitory capacities (IC50 5 mg/ml for 5α-R1 and about IC50 = 6 mg/ml for 5α-R2). The isolated Δ7-sterols were more active inhibitors (IC50 = 0.3 mg/ml for 5α-R1, IC50 = 1.0 mg/ml for 5α-R2). All three test compounds bound to the AR dose-dependently, with strong binding by Δ7-sterols (IC50 = 0.2 mg/ml) and weaker binding by pumpkin seed oil (IC50 = 0.4 mg/ml) and pumpkin seed soft extract (IC50 = 1.1 mg/ml). We propose that inhibition of 5α-reductases and competitive binding to the AR are mechanisms of action, by which the Uromedic? pumpkin seed derived test compounds, most specifically Δ7-sterols, counteract DHT and thereby exert clinically positive effects on the prostate, as well as bladder-strengthening effects.
基金The study was supported by the Foundation of the Paediatric Medical Coordinated Development Center of Beijing Hospitals Authority(XTYB201808)Jin Lei Paediatric Endocrinology Growth Research Fund for Young Physicians(PEGRF+1 种基金No.PEGRF202011034)Beijing Municipal Science and Technology Commission(No.Z201100005520061).
文摘5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone,which causes abnormal urogenital sinus development.The aim of this study was to analyze the relationship between genotype–phenotype,surgical selections,and postoperative complications of 5α-reductase 2-deficient patients with hypospadias.We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children’s Hospital,Capital Medical University(Beijing,China),from April 2007 to December 2021.A total of 69 patients were included in this study;the mean age at surgery was 34.1 months,and the average follow-up time was 54.1 months.Sixty children were treated with preoperative hormone stimulation(PHS)to promote penile growth.The average penis length and glans width were increased by 1.46 cm and 0.62 cm,respectively.The most frequent mutations were p.R227Q(39.1%,54/138),p.Q6^(*)(15.2%,21/138),p.G203S(12.3%,17/138),and p.R246Q(11.6%,16/138).In 64 patients who were followed up,43 had a one-stage operation and 21 had a staged operation,and there were significant differences in external masculinization score(EMS)(P=0.008)and the average number of operation required to cure(P<0.001)between one-stage and staged operations.PHS had a positive effect(P<0.001)on penile development.The p.R227Q mutation was associated with higher EMS and less severe hypospadias.One-stage surgery can be selected if conditions permit.The growth and development of children are acceptable in the long term,but penis growth remains unsatisfactory.Longterm complications of hypospadias should be considered during puberty.
基金Acknowledgment This study was support by Natural Science Foundation of Shanghai, China (No. 06ZR14137).
文摘Aim: To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone (T) undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T (FT) and dihydrotestosterone (DHT) were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score (VESS) was computed. Results: Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups (P 〈 0.01); DHT concentrations of group D rats were significantly decreased (P 〈 0.01 ) when compared with those of groups A and C. Rats in groups B and D rats (with low androgen levels) had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion: These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.
基金Beijing Municipal Science&Technology Commission(No.Z201100005520061)Jinlei Pediatric Endocrinology Growth Research Fund for Young Physicians(PEGRF)(No.PEGRF201809006)。
文摘Importance:Children with 5-alpha-reductase deficiency(5α-RD)and hypospadias present with micropenis,which makes it difficult to obtain sufficient tissue for urethral reconstruction.Objective:We investigated the therapeutic effects of oral testosterone undecanoate and established a standard androgen treatment protocol for patients with 5α-RD with micropenis.Methods:Patients with 5α-RD were treated with oral testosterone undecanoate for 3 months as a course.All patients were treated with no more than 3 courses.If the penile length(PL)reached 2.5 cm(the minimum criterion for surgery)or greater than or equal to−2.5 standard deviations(SDs)(lower limit of normal),testosterone undecanoate was considered to be effective.Results:The median age of 90 patients with 5α-RD was 1.7 years(0.9,3.1 years).The baseline PL was 1.9±0.6 cm before treatment.At the end of the first course,the PL of 63 patients(70%)reached 2.5 cm,and 49 patients(54%)reached greater than or equal to−2.5 SDs.After two treatment courses,the PL of 81 patients(90%)reached 2.5 cm,and 90 patients(100%)reached greater than or equal to−2.5 SDs.After three courses,the PL of all patients reached 2.5 cm,and all patients reached a PL greater than or equal to−2.5 SDs.No abnormal increase was observed in height-SD score,weight-SD score,or ratio of bone age to chronological age during the 1-3-year follow-up.Interpretation:After 3-9 months of treatment,PL increased to the target length.No severe adverse reactions were observed during follow-up.Testosterone undecanoate was safe and effective in children with 5α-RD with micropenis.
文摘目的:研究溶质载体家族6成员9(solute carrier family 6 member 9,SLC6A9)表达对结直肠癌细胞增殖、迁移和5-氟尿嘧啶(5-fluorouracil,5-FU)药物敏感性的影响。方法:TCGA数据库分析、实时荧光定量PCR和Western blot分析检测SLC6A9在结肠癌组织、正常结肠细胞系(NCM460)和结直肠癌细胞系(SW620、HCT116、HT29、Lovo和SW480)中的表达。将SCL6A9过表达质粒及阴性对照(SLC6A9 OE、Vector)转染HT29细胞,将SCL6A9小干扰RNA及阴性对照(SLC6A9 siRNA1#、siRNA2#和Scramble)转染SW620细胞。划痕愈合实验和Transwell实验检测各组细胞的迁移、侵袭能力。Western blot和细胞免疫荧光检测EMT相关蛋白E-cadherin、Vimentin的表达水平。利用CCK-8法和构建裸鼠移植瘤模型检测SLC6A9过表达对结直肠癌细胞5-FU药物敏感性的影响。结果:与正常结肠组织和NCM460细胞相比,SLC6A9在结肠癌组织和结直肠癌细胞系中低表达(均P<0.05)。SLC6A9过表达引起E-cadherin蛋白表达增加,Vimentin蛋白水平降低,抑制结直肠癌细胞的迁移、侵袭(P<0.05)。SLC6A9低表达引起E-cadherin蛋白表达降低,Vimentin蛋白水平增加,促进结直肠癌细胞的迁移、侵袭能力(P<0.05)。SLC6A9过表达提高了5-FU的药物敏感性,并使肿瘤生长缓慢,质量减轻(P<0.05)。而SLC6A9低表达降低了5-FU的药物敏感性(P<0.05)。结论:SLC6A9过表达能够抑制结直肠癌细胞的迁移、侵袭和EMT进程,并增强5-FU对结直肠癌细胞的药物敏感性。
文摘食品加工过程中的美拉德反应有助于形成一些热诱导毒性产物,包括晚期糖基化终末产物(advanced glycation end products,AGEs)和5-羟甲基糠醛(5-hydroxymethylfurfural,5-HMF)。食源性AGEs在体内的积累和循环与糖尿病并发症的发生有关,同时可能诱发氧化应激、炎症和动脉粥样硬化。5-HMF的代谢物5-磺基氧甲基糠醛(5-sulfooxymethylfurfural,5-SMF)有潜在基因毒性和致癌性。如何控制热加工食品中这些危害物的形成已成为食品行业的关注焦点。本文从美拉德反应和焦糖化反应两条途径探究了AGEs和5-HMF的形成机理,并对近5年二者的检测方法进行了综述,阐述了各类方法的优缺点,以期为建立二者的通用检测方法奠定基础。在此基础上,从削减前体物质的供给、阻断中间体的转化,以及去除已经生成的AGEs和5-HMF这3个方面着手,综述了近年来相应所采用的抑制策略,以期为AGEs和5-HMF在食品中的控制及热加工食品质量与安全管理提供理论依据。