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Combined Analysis of the Transcriptome, Proteome and Metabolome in Human Cryopreserved Sperm. 人类冷冻精子转录组、蛋白质组和代谢组的综合分析
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2024-01-02 DOI: 10.5534/wjmh.230091
Longlong Fu, Fang Fang, Ying Guo, Jing Ma, Shusong Wang, Yiqun Gu, Xiangming Yan, Wenhong Lu, Ying Liu

Purpose: This study aimed to identify the altered pathways and genes associated with freezing damage in human sperm during cryopreservation by multiomics analysis.

Materials and methods: Fifteen fresh human semen samples were collected for transcriptomic analysis, and another 5 fresh human semen samples were obtained for metabolomic analysis. For each semen sample, 1 mL was cryopreserved, and another 1 mL was left untreated for paired design. The results were then combined with previously published proteomic results to identify key genes/pathways.

Results: Cryopreservation significantly reduced sperm motility and mitochondrial structure. Transcriptomic analysis revealed altered mitochondrial function, including changes in tRNA-methyltransferase activity and adenosine tri-phosphate/adenosine di-phosphate transmembrane transporter activity. Metabolomic analysis showed that the citrate cycle in mitochondria was significantly altered. Combining transcriptomic, proteomic, and metabolomic analyses revealed 346 genes that were altered in at least two omics analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that metabolic pathways were significantly altered and strongly associated with mitochondria. Five genes were altered in all three omics analyses: COL11A1, COL18A1, LPCAT3, NME1, and NNT.

Conclusions: Five genes were identified by multiomics analysis in human cryopreserved sperm. These genes might have specific functions in cryopreservation. Explorations of the functions of these genes will be helpful for sperm cryopreservation and sperm motility improvement or even for reproduction in the future.

目的:本研究旨在通过多组学分析确定人类精子在冷冻保存过程中与冷冻损伤相关的通路和基因的改变:收集 15 份新鲜人类精液样本用于转录组分析,另外 5 份新鲜人类精液样本用于代谢组分析。每个精液样本冷冻保存 1 毫升,另 1 毫升不做处理,进行配对设计。然后将结果与之前公布的蛋白质组学结果相结合,以确定关键基因/通路:结果:低温保存明显降低了精子活力和线粒体结构。转录组分析显示线粒体功能发生了改变,包括 tRNA-甲基转移酶活性和三磷酸腺苷/二磷酸腺苷跨膜转运体活性的变化。代谢组分析表明,线粒体中的柠檬酸循环发生了显著变化。结合转录组学、蛋白质组学和代谢组学分析发现,有 346 个基因在至少两项全局分析中发生了改变。京都基因和基因组百科全书(KEGG)分析表明,代谢途径发生了重大改变,并与线粒体密切相关。在所有三项全局分析中,有五个基因发生了改变:COL11A1、COL18A1、LPCAT3、NME1 和 NNT:结论:多组学分析发现了人类冷冻精子中的五个基因。结论:通过多组学分析,在人类冷冻精子中发现了五个基因,这些基因在冷冻保存中可能具有特殊功能。探索这些基因的功能将有助于精子的冷冻保存和精子活力的提高,甚至有助于未来的生殖。
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引用次数: 0
Novel Therapeutic Approach for Late-Onset Hypogonadism. 治疗晚发型性腺功能减退症的新方法
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2024-03-12 DOI: 10.5534/wjmh.240011
Sung Chul Kam, Yu Seob Shin
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引用次数: 0
MicroRNA-145 Gene Modification Enhances the Retention of Bone Marrow-Derived Mesenchymal Stem Cells within Corpus Cavernosum by Targeting Krüppel-Like Factor 4. MicroRNA-145基因修饰通过靶向Krüppel-Like因子4提高骨髓间充质干细胞在海绵体内的存留率
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2024-01-02 DOI: 10.5534/wjmh.230149
Daoyuan Hu, Yunlong Ge, Yuhang Xi, Jialiang Chen, Hua Wang, Chi Zhang, Yubin Cui, Lizhao He, Ying Su, Jun Chen, Cheng Hu, Hengjun Xiao

Purpose: The poor retention and ambiguous differentiation of stem cells (SCs) within corpus cavernosum (CC) limit the cell application in erectile dysfunction (ED). Herein, the effects and mechanism of microRNA-145 (miR-145) gene modification on modulating the traits and fate of bone marrow-derived mesenchymal stem cells (BMSCs) were investigated.

Materials and methods: The effects of miR-145 on cell apoptosis, proliferation, migration, and differentiation were determined by flow cytometry, cell counting kit-8, transwell assays and myogenic induction. Then, the age-related ED rats were recruited to four groups including phosphate buffer saline, BMSC, vector-BMSC, overexpressed-miR-145-BMSC groups. After cell transplantation, the CC were harvested and prepared to demonstrate the retention and differentiation of BMSCs by immunofluorescent staining. Then, the target of miR-145 was verified by quantitative real-time polymerase chain reaction and immunohistochemical. After that, APTO-253, as an inducer of Krüppel-like factor 4 (KLF4), was introduced for rescue experiments in corpus cavernosum smooth muscle cells (CCSMCs) under the co-culture system.

Results: In vitro, miR-145 inhibited the migration and apoptosis of BMSCs and promoted the differentiation of BMSCs into smooth muscle-like cells with stronger contractility. In vivo, the amount of 5-ethynyl-2'-deoxyuridine (EdU)+cells within CC was significantly enhanced and maintained in the miR-145 gene modified BMSC group. The EdU/CD31 co-staning was detected, however, no co-staining of EdU/α-actin was observed. Furthermore, miR-145, which secreted from the gene modified BMSCs, dampened the expression of KLF4. However, the effects of miR-145 on CCSMCs could be rescued by APTO-253.

Conclusions: Overall, miR-145 modification prolongs the retention of the transplanted BMSCs within the CC, and this effect might be attributed to the modulation of the miR-145/KLF4 axis. Consequently, our findings offer a promising and innovative strategy to enhance the local stem cell-based treatments.

目的:干细胞(SCs)在海绵体(CC)内的存留性差和分化不明确限制了细胞在勃起功能障碍(ED)中的应用。本文研究了microRNA-145(miR-145)基因修饰对骨髓间充质干细胞(BMSCs)性状和命运的影响及机制:通过流式细胞仪、细胞计数试剂盒-8、Transwell试验和成肌诱导法测定miR-145对细胞凋亡、增殖、迁移和分化的影响。然后,将年龄相关性 ED 大鼠分为四组,包括磷酸盐缓冲液组、BMSC 组、载体-BMSC 组、过表达-miR-145-BMSC 组。细胞移植后,收获并制备CC,通过免疫荧光染色显示BMSCs的保留和分化。然后,通过实时定量聚合酶链反应和免疫组化验证了 miR-145 的靶点。随后,在共培养系统下,引入作为克鲁珀尔样因子 4(KLF4)诱导剂的 APTO-253 对海绵体平滑肌细胞(CCSMCs)进行拯救实验:结果:在体外,miR-145能抑制BMSCs的迁移和凋亡,并促进BMSCs分化为收缩力更强的平滑肌样细胞。在体内,miR-145基因修饰的BMSC组CC内5-乙炔基-2'-脱氧尿苷(EdU)+细胞的数量明显增加并保持不变。检测到EdU/CD31共染色,但未观察到EdU/α-肌动蛋白共染色。此外,从基因修饰的 BMSCs 中分泌的 miR-145 抑制了 KLF4 的表达。然而,miR-145对CCSMCs的影响可以被APTO-253所挽救:总之,miR-145修饰可延长移植的BMSCs在CC内的存留时间,这种效应可能归因于miR-145/KLF4轴的调节。因此,我们的研究结果为加强基于局部干细胞的治疗提供了一种前景广阔的创新策略。
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引用次数: 0
Serenoa repens for the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Enlargement: An Updated Cochrane Review. Serenoa repens 用于治疗良性前列腺增生引起的下尿路症状:最新 Cochrane 综述。
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2024-01-02 DOI: 10.5534/wjmh.230222
Juan Víctor Ariel Franco, Leonel Fabrizio Trivisonno, Nadia Sgarbossa, Gustavo Ariel Alvez, Cecilia Fieiras, Camila Micaela Escobar Liquitay, Jae Hung Jung

Purpose: To assess the effects of Serenoa repens in the treatment of men with lower urinary tract symptoms (LUTS) consistent with benign prostatic hyperplasia (BPH).

Materials and methods: We performed a comprehensive search using multiple databases up to September 2022 with no language or publication status restrictions. We included parallel-group randomized controlled trials of participants with BPH who were treated with Serenoa repens or placebo/no treatment. We used standard Cochrane methods, including a GRADE assessment of the certainty of the evidence (CoE).

Results: We included 27 studies involving a total of 4,656 participants. Serenoa repens results in little to no difference in urologic symptoms at short-term follow-up (International Prostate Symptom Score [IPSS]: mean difference [MD] -0.90, 95% confidence interval [CI] -1.74 to -0.07; I²=68%; 9 studies, 1,681 participants; high CoE). Serenoa repens results in little to no difference in the quality of life at short-term follow-up (high CoE). Serenoa repens probably results in little to no difference in adverse events (moderate CoE). Different phytotherapeutic agents that include Serenoa repens may result in little to no difference in urologic symptoms compared to placebo at short-term follow-up (IPSS: MD -2.41, 95% CI -4.54 to -0.29; I²=67%; 4 studies, 460 participants; low CoE). We are very uncertain about the effects of these agents on quality of life (very low CoE). These agents may result in little to no difference in the occurrence of adverse events (low CoE).

Conclusions: Serenoa repens alone provides little to no benefits for men with LUTS due to benign prostatic enlargement. There is more uncertainty about the role of Serenoa repens in combination with other phytotherapeutic agents.

目的:评估Serenoa repens治疗下尿路症状(LUTS)与良性前列腺增生症(BPH)一致的男性的效果:我们利用截至 2022 年 9 月的多个数据库进行了全面检索,没有语言或出版状况限制。我们纳入了对患有良性前列腺增生症的患者进行的平行分组随机对照试验,这些患者接受了Serenoa repens治疗或安慰剂/无治疗。我们采用了标准的 Cochrane 方法,包括对证据的确定性(CoE)进行 GRADE 评估:我们纳入了 27 项研究,共有 4,656 人参与。在短期随访中,Serenoa repens对泌尿系统症状几乎没有影响(国际前列腺症状评分[IPSS]:平均差[MD]-0.90,95%置信区间[CI]-1.74至-0.07;I²=68%;9项研究,1681名参与者;高CoE)。在短期随访中,Serenoa repens 对生活质量的影响几乎没有差异(高 CoE)。在不良反应方面,Serenoa repens 可能几乎没有差别(中度 CoE)。在短期随访中,含有Serenoa repens的不同植物治疗剂可能会导致泌尿系统症状与安慰剂相比几乎没有差异(IPSS:MD -2.41,95% CI -4.54 至 -0.29;I²=67%;4 项研究,460 名参与者;低 CoE)。我们还不能确定这些药物对生活质量的影响(CoE 很低)。这些药物可能对不良事件的发生几乎没有影响(低 CoE):结论:对于因良性前列腺增生导致尿失禁的男性而言,单独使用蛇床子碱几乎没有任何益处。结论:单独使用蛇床子素对良性前列腺增生导致的尿失禁男性患者没有什么益处,而蛇床子素与其他植物治疗药物联合使用的作用则存在更多不确定性。
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引用次数: 0
Management of Male Infertility with Coexisting Sexual Dysfunction: A Consensus Statement and Clinical Recommendations from the Asia-Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA). 同时存在性功能障碍的男性不育的治疗:亚太性医学学会(APSSM)和亚洲男性健康与老龄化学会(ASMHA)的共识声明和临床建议。
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2023-10-16 DOI: 10.5534/wjmh.230180
Eric Chung, Jiang Hui, Zhong Cheng Xin, Sae Woong Kim, Du Geon Moon, Yiming Yuan, Koichi Nagao, Lukman Hakim, Hong-Chiang Chang, Siu King Mak, Gede Wirya Kusuma Duarsa, Yutian Dai, Bing Yao, Hwancheol Son, William Huang, Haocheng Lin, Quang Nguyen, Dung Ba Tien Mai, Kwangsung Park, Joe Lee, Kavirach Tantiwongse, Yoshikazu Sato, Bang-Ping Jiann, Christopher Ho, Hyun Jun Park

Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients' factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men's Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: "low libido", "erectile dysfunction", "ejaculatory dysfunction", "premature ejaculation", "retrograde ejaculation", "delayed ejaculation", "anejaculation", and "orgasmic dysfunction" between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socio-economic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient's individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.

由于各种相互作用的因素,如性心理、社会文化和关系动态,男性不育(MI)和男性性功能障碍(MSD)通常可以共存。每种形式的默沙东的存在都会对男性生殖产生不利影响,治疗策略需要根据患者的因素、当地专业知识和地理社会经济地位进行个性化。亚太性医学学会(APSSM)和亚洲男性健康与老龄化学会(ASMHA)旨在根据当前证据提供一份共识声明和一套实用的临床建议,以指导亚太地区临床医生管理MI和MSD。对文献进行了全面的叙述性综述,以确定各种形式的MSD及其与MI的关系。在MEDLINE和EMBASE数据库中搜索了以下英文文章:“性欲低下”、“勃起功能障碍”、“射精功能障碍”、,2001年1月至2022年6月期间,“性交”和“性高潮功能障碍”,重点是各组织认可的已发布指南。该APSSM共识委员会小组使用小组修改的德尔菲方法评估并提供了MI和临床相关MSD领域的循证建议,并特别强调了与AP地区相关的地方社会经济文化问题。尽管由于地理专业知识、地方资源和社会文化因素,管理MI和MSD的治疗策略存在差异,但专家组一致认为,建议对每个MSD领域采用多学科管理方法进行综合生育率评估。重要的是要解决个体MI问题,重点是改善精子发生和促进生殖途径,同时通过循证治疗来管理各种MSD状况。所有治疗方案都应根据患者的个人需求、信念和偏好进行讨论和实施,同时结合当地专业知识和可用资源。
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引用次数: 0
Advances in Male Contraception: When Will the Novel Male Contraception be Available? 男性避孕的进展:新型男性避孕药何时上市?
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2024-01-02 DOI: 10.5534/wjmh.230118
Jongwon Kim, Byeongchan So, Yongki Heo, Hongyun So, Jung Ki Jo

Many contraceptive methods have been developed over the years due to high demand. However, female contraceptive pills and devices do not work for all females due to health conditions and side effects. Also, the number of males who want to actively participate in family planning is gradually increasing. However, the only contraceptive options currently available to males are condoms and vasectomy. Therefore, many male contraceptive methods, including medication (hormonal and non-hormonal therapy) and mechanical methods, are under development. Reversibility, safety, persistence, degree of invasion, promptness, and the suppression of anti-sperm antibody formation are essential factors in the development of male contraceptive methods. In this paper, male contraceptive methods under development are reviewed according to those essential factors. Furthermore, the timeline for the availability of a new male contraception is discussed.

由于需求量大,多年来已开发出许多避孕方法。然而,由于健康状况和副作用的原因,女性避孕药和避孕工具并不适用于所有女性。此外,希望积极参与计划生育的男性人数也在逐渐增加。然而,目前可供男性选择的避孕方法只有避孕套和输精管结扎术。因此,许多男性避孕方法,包括药物(激素和非激素疗法)和机械方法,都在开发之中。可逆性、安全性、持久性、侵袭程度、及时性和抑制抗精子抗体形成是开发男性避孕方法的基本要素。本文根据这些基本因素对正在开发的男性避孕方法进行了综述。此外,本文还讨论了新的男性避孕方法问世的时间表。
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引用次数: 0
Effects of Physical Activity on Fertility Parameters: A Meta-Analysis of Randomized Controlled Trials. 体育锻炼对生育参数的影响:随机对照试验的元分析》(Meta-Analysis of Randomized Controlled Trials)。
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2024-01-02 DOI: 10.5534/wjmh.230106
Arturo Lo Giudice, Maria Giovanna Asmundo, Sebastiano Cimino, Giuseppe Morgia, Andrea Cocci, Marco Falcone, Ioannis Sokolakis, Paolo Capogrosso, Afonso Morgado, Giorgio Ivan Russo

Purpose: Augmented adiposity may negatively impact sexual sphere through its metabolic effects and its detrimental impact on reproductive hormones. Moreover, a dysregulated metabolic pathway may promote apoptosis among spermatogenic cells. Based on these premises, a relation between weights loss and ameliorate semen parameters seems beneficial. To investigate if physical activity may affect semen parameters and fertility rate, a systematic literature search on major dataset has been performed.

Materials and methods: The search terms included: "Assisted reproduction therapies," "fertility," "semen parameters," "sperm parameters," and "physical activity." This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines and it was registered on PROSPERO (CRD42023384471). A total of 47 studies have been identified; 1 reference has been eliminated after duplication check. After preliminary screening 32 papers have been excluded. Considering the exclusion criteria, 15 full-text articles were evaluated for eligibility. After a full-text review, six studies published during a span of eight years (2014-2022) have been included in the meta-analysis. Semen parameters, pregnancy and birth rates were investigated. The revised Cochrane risk of bias tool (Rob2) has been used to check the risk of bias.

Results: The number of patients enrolled in studies ranges from 17 to 521; in the end, a total of 1,637 patients have been enrolled in the study. Fertility parameters investigated were semen quality parameters and pregnancy rates and live births. A statistically significant relationship between physical exercise and sperm concentration (p=0.02), total sperm motility (p<0.01), total sperm count (p<0.01), normal morphology (p<0.01) has been established. Moreover, the study registered a statistically significant association within physical activity and total pregnancy rate (p<0.01) and live birth rate (p<0.01).

Conclusions: We demonstrated that physical activity is significantly associated with amelioration of semen parameters and may be crucial in improving or even reverting male infertility.

目的:肥胖症可能会对新陈代谢产生影响,并对生殖激素产生不利影响,从而对性功能产生负面影响。此外,代谢途径失调可能会促进生精细胞凋亡。基于这些前提,减肥与改善精液参数之间的关系似乎是有益的。为了研究体育锻炼是否会影响精液参数和受孕率,我们对主要数据集进行了系统的文献检索:检索词包括"辅助生殖疗法"、"生育能力"、"精液参数"、"精子参数 "和 "体育锻炼"。本分析根据《系统综述和元分析首选报告项目》指南进行,并在 PROSPERO(CRD42023384471)上进行了注册。共确定了 47 项研究;1 项参考文献在重复检查后被剔除。经过初步筛选,32 篇论文被排除在外。考虑到排除标准,对 15 篇全文进行了资格评估。经过全文审查,6 篇发表于 8 年内(2014-2022 年)的研究被纳入荟萃分析。对精液参数、怀孕率和出生率进行了调查。修订后的 Cochrane 偏倚风险工具(Rob2)用于检查偏倚风险:参与研究的患者人数从17人到521人不等;最终,共有1637名患者参与了研究。研究的生育参数包括精液质量参数、怀孕率和活产率。体育锻炼与精子浓度(p=0.02)、精子总活力(pConclusions:我们的研究表明,体育锻炼与精液参数的改善密切相关,可能对改善甚至逆转男性不育症至关重要。
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引用次数: 0
The Need of Systematic Biopsies for the Appropriate Management of Localized Prostate Cancer. 对局部前列腺癌进行适当治疗需要系统的活组织检查。
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2024-03-29 DOI: 10.5534/wjmh.230331
Juan Morote, Nahuel Paesano, Violeta Catalá
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引用次数: 0
Active Surveillance for Taiwanese Men with Localized Prostate Cancer: Intermediate-Term Outcomes and Predictive Factors. 台湾男性癌症局部前列腺癌的主动监测:中期结果和预测因素。
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2023-09-26 DOI: 10.5534/wjmh.230107
Jian-Hua Hong, Ming-Chieh Kuo, Yung-Ting Cheng, Yu-Chuan Lu, Chao-Yuan Huang, Shih-Ping Liu, Po-Ming Chow, Kuo-How Huang, Shih-Chieh Jeff Chueh, Chung-Hsin Chen, Yeong-Shiau Pu

Purpose: Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS.

Materials and methods: This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model.

Results: A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL² predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17-2.88) and conversion (HR 1.56, 95% CI 1.05-2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years).

Conclusions: AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.

目的:主动监测(AS)是低风险和中风险前列腺癌症(PC)患者的管理选择之一。然而,从大量纯亚洲人群中预测AS疾病重新分类和转为积极治疗的因素评估较少。本研究调查了接受AS的局限性PC患者的中期结果。材料和方法:本队列研究纳入了2012年6月至2023年1月期间在台湾诊断为局限性非高危PC的连续男性。研究终点是疾病重新分类(病理或放射学进展)和转为积极治疗。预测终点的因素使用Cox比例风险模型进行评估。结果:共有405名患者(中位年龄:67.2岁)连续入选,随访中位时间为64.6个月。根据国家癌症综合网络(NCCN)的风险分组,70名(17.3%)、164名(40.5%)、140名(34.6%)和31名(7.7%)患者分别被分为极低风险、低风险、有利的中间风险和不利的中间风险PC。5年再分类率分别为24.8%、27.0%、18.6%和25.3%。5年转化率分别为20.4%、28.8%、43.6%和37.8%。前列腺特异性抗原密度(PSAD)≥0.15 ng/mL²可预测再分类(危险比[HR]1.84,95%置信区间[CI]1.7-2.88)和转化率(HR 1.56,95%置信度1.05-2.31)。阳性核心中癌症的最大百分比(MPCPC)≥15%可预测转化率(15%的人得出结论:就重新分类和转换而言,AS是台湾非高危PC男性的可行选择。高PSAD预测重新分类,而高PSAD、MPCPC和GGG预测转换。
{"title":"Active Surveillance for Taiwanese Men with Localized Prostate Cancer: Intermediate-Term Outcomes and Predictive Factors.","authors":"Jian-Hua Hong, Ming-Chieh Kuo, Yung-Ting Cheng, Yu-Chuan Lu, Chao-Yuan Huang, Shih-Ping Liu, Po-Ming Chow, Kuo-How Huang, Shih-Chieh Jeff Chueh, Chung-Hsin Chen, Yeong-Shiau Pu","doi":"10.5534/wjmh.230107","DOIUrl":"10.5534/wjmh.230107","url":null,"abstract":"<p><strong>Purpose: </strong>Active surveillance (AS) is one of the management options for patients with low-risk and select intermediate-risk prostate cancer (PC). However, factors predicting disease reclassification and conversion to active treatment from a large population of pure Asian cohorts regarding AS are less evaluated. This study investigated the intermediate-term outcomes of patients with localized PC undergoing AS.</p><p><strong>Materials and methods: </strong>This cohort study enrolled consecutive men with localized non-high-risk PC diagnosed in Taiwan between June 2012 and Jan 2023. The study endpoints were disease reclassification (either pathological or radiographic progression) and conversion to active treatment. The factors predicting endpoints were evaluated using the Cox proportional hazards model.</p><p><strong>Results: </strong>A total of 405 patients (median age: 67.2 years) were consecutively enrolled and followed up with a median of 64.6 months. Based on the National Comprehensive Cancer Network (NCCN) risk grouping, 70 (17.3%), 164 (40.5%), 140 (34.6%), and 31 (7.7%) patients were classified as very low-risk, low-risk, favorable-intermediate risk, and unfavorable intermediate-risk PC, respectively. The 5-year reclassification rates were 24.8%, 27.0%, 18.6%, and 25.3%, respectively. The 5-year conversion rates were 20.4%, 28.8%, 43.6%, and 37.8%, respectively. A prostate-specific antigen density (PSAD) of ≥0.15 ng/mL² predicted reclassification (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.17-2.88) and conversion (HR 1.56, 95% CI 1.05-2.31). A maximal percentage of cancer in positive cores (MPCPC) of ≥15% predicted conversion (15% to <50%: HR 1.41, 95% CI 0.91-2.18; ≥50%: HR 1.97, 95% CI 1.1453-3.40) compared with that of <15%. A Gleason grade group (GGG) of 3 tumor also predicted conversion (HR 2.69, 95% CI 1.06-6.79; GGG 3 vs 1). One patient developed metastasis, but none died of PC during the study period (2,141 person-years).</p><p><strong>Conclusions: </strong>AS is a viable option for Taiwanese men with non-high-risk PC, in terms of reclassification and conversion. High PSAD predicted reclassification, whereas high PSAD, MPCPC, and GGG predicted conversion.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":"587-599"},"PeriodicalIF":4.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Role of Reactive Oxygen Species, Inflammation, and Endoplasmic Reticulum Stress Response in the Finasteride Protective Effect against Benign Prostate Hyperplasia. 活性氧、炎症和内质网应激反应在非那雄胺对良性前列腺增生的保护作用中的作用。
IF 4 3区 医学 Q1 ANDROLOGY Pub Date : 2024-07-01 Epub Date: 2023-10-16 DOI: 10.5534/wjmh.230122
Geum-Hwa Lee, Hwa-Young Lee, Luo Zhao, Mohammad Mamun Ur Rashid, Myung Ki Kim, Young Beom Jeong, Han-Jung Chae, Yu Seob Shin

Purpose: Benign prostate hyperplasia (BPH) is a common age-related chronic condition. Its pathogenesis involves androgen imbalance, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress. This study aims to assess the protective effect of finasteride, a 5α-reductase inhibitor, against testosterone propionate (TP)-induced BPH in rats and explore its potential mechanism of action.

Materials and methods: TP-induced BPH rats received either saline or finasteride (1 mg/kg) orally once a day for 7 weeks. Prior to sacrificing the animals, blood samples were collected. After sacrifice, prostate and tissue around the prostate were dissected from seminal vesical for further analysis. Body weight, prostate weight, dihydrotestosterone (DHT), 5α-reductase type 2 (5-AR2), and prostate-specific antigen (PSA) levels were measured. In addition, HIF-1α, VEGF, MMP-2 expressions in prostate, oxidative stress, inflammation, and ER stress responses were analyzed to understand the mechanism of action of finasteride.

Results: Finasteride administration inhibited prostate enlargement, DHT, 5-AR2, and PSA levels in BPH rats. Additionally, finasteride inhibited angiogenesis markers such as HIF-1α, VEGF, and MMP-2. Moreover, components of oxidative stress, inflammation, and ER stress responses were significantly regulated by finasteride treatment.

Conclusions: This study suggests that finasteride prevents BPH-associated symptoms by regulating angiogenesis, reactive oxygen species, ER stress responses, and inflammation, another mechanism to explain the effect of the 5α-reductase against BPH.

目的:良性前列腺增生(BPH)是一种常见的与年龄相关的慢性疾病。其发病机制涉及雄激素失衡、炎症、氧化应激和内质网应激。本研究旨在评估5α-还原酶抑制剂非那雄胺对丙酸睾酮(TP)诱导的大鼠前列腺增生的保护作用,并探讨其潜在的作用机制。材料和方法:TP诱导的BPH大鼠口服生理盐水或非那雄胺(1mg/kg),每天1次,持续7周。在处死动物之前,采集了血样。牺牲后,从精囊中解剖前列腺和前列腺周围的组织进行进一步分析。测量体重、前列腺重量、二氢睾酮(DHT)、5α-还原酶2型(5-AR2)和前列腺特异性抗原(PSA)水平。此外,还分析了前列腺中HIF-1α、VEGF、MMP-2的表达、氧化应激、炎症和ER应激反应,以了解非那雄胺的作用机制。结果:非那雄胺给药可抑制BPH大鼠前列腺肥大、DHT、5-AR2和PSA水平。此外,非那雄胺抑制血管生成标志物,如HIF-1α、VEGF和MMP-2。此外,氧化应激、炎症和ER应激反应的成分受到非那雄胺治疗的显著调节。结论:本研究表明,非那雄胺通过调节血管生成、活性氧、ER应激反应和炎症来预防BPH相关症状,这是解释5α-还原酶对BPH作用的另一机制。
{"title":"The Role of Reactive Oxygen Species, Inflammation, and Endoplasmic Reticulum Stress Response in the Finasteride Protective Effect against Benign Prostate Hyperplasia.","authors":"Geum-Hwa Lee, Hwa-Young Lee, Luo Zhao, Mohammad Mamun Ur Rashid, Myung Ki Kim, Young Beom Jeong, Han-Jung Chae, Yu Seob Shin","doi":"10.5534/wjmh.230122","DOIUrl":"10.5534/wjmh.230122","url":null,"abstract":"<p><strong>Purpose: </strong>Benign prostate hyperplasia (BPH) is a common age-related chronic condition. Its pathogenesis involves androgen imbalance, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress. This study aims to assess the protective effect of finasteride, a 5α-reductase inhibitor, against testosterone propionate (TP)-induced BPH in rats and explore its potential mechanism of action.</p><p><strong>Materials and methods: </strong>TP-induced BPH rats received either saline or finasteride (1 mg/kg) orally once a day for 7 weeks. Prior to sacrificing the animals, blood samples were collected. After sacrifice, prostate and tissue around the prostate were dissected from seminal vesical for further analysis. Body weight, prostate weight, dihydrotestosterone (DHT), 5α-reductase type 2 (5-AR2), and prostate-specific antigen (PSA) levels were measured. In addition, HIF-1α, VEGF, MMP-2 expressions in prostate, oxidative stress, inflammation, and ER stress responses were analyzed to understand the mechanism of action of finasteride.</p><p><strong>Results: </strong>Finasteride administration inhibited prostate enlargement, DHT, 5-AR2, and PSA levels in BPH rats. Additionally, finasteride inhibited angiogenesis markers such as HIF-1α, VEGF, and MMP-2. Moreover, components of oxidative stress, inflammation, and ER stress responses were significantly regulated by finasteride treatment.</p><p><strong>Conclusions: </strong>This study suggests that finasteride prevents BPH-associated symptoms by regulating angiogenesis, reactive oxygen species, ER stress responses, and inflammation, another mechanism to explain the effect of the 5α-reductase against BPH.</p>","PeriodicalId":54261,"journal":{"name":"World Journal of Mens Health","volume":" ","pages":"600-609"},"PeriodicalIF":4.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11216955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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World Journal of Mens Health
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