Prostatitis

前列腺炎
  • 文章类型: Journal Article
    背景:尽管认为前列腺炎或良性前列腺增生(BPH)与前列腺癌(PCa)有关,这些疾病的潜在因果效应尚不清楚.
    方法:我们使用双样本孟德尔随机化(MR)方法评估了前列腺炎或BPH与PCa之间的因果关系。本研究中使用的数据来自全基因组关联研究。使用逆方差加权和MREgger回归技术确定前列腺炎或BPH和PCa患者队列的遗传变异的关联。使用具有全基因组显著性(P<5×10-6)的独立遗传变异确定机会方向。使用敏感性分析证实了结果的准确性。
    结果:MR分析显示BPH对PCa有显著的因果效应(几率=1.209,95%置信区间:0.098~0.281,P=5.079×10-5),而前列腺炎对PCa无显著因果效应(P>0.05)。此外,多效性试验和留一分析显示,双样本MR分析有效可靠.
    结论:这项MR研究支持BPH对PCa有积极的因果关系,而遗传预测的前列腺炎对PCa没有因果关系。尽管如此,进一步的研究应该探索预防这些疾病的潜在生化机制和潜在的治疗靶点。
    BACKGROUND: Although it is thought that prostatitis or benign prostatic hyperplasia (BPH) is related to prostate cancer (PCa), the underlying causal effects of these diseases are unclear.
    METHODS: We assessed the causal relationship between prostatitis or BPH and PCa using a two-sample Mendelian randomization (MR) approach. The data utilized in this study were sourced from genome-wide association study. The association of genetic variants from cohorts of prostatitis or BPH and PCa patients was determined using inverse-variance weighted and MR Egger regression techniques. The direction of chance was determined using independent genetic variants with genome-wide significance (P < 5 × 10-6). The accuracy of the results was confirmed using sensitivity analyses.
    RESULTS: MR analysis showed that BPH had a significant causal effect on PCa (Odds Ratio = 1.209, 95% Confidence Interval: 0.098-0.281, P = 5.079 × 10- 5) while prostatitis had no significant causal effect on PCa (P > 0.05). Additionally, the pleiotropic test and leave-one-out analysis showed the two-sample MR analyses were valid and reliable.
    CONCLUSIONS: This MR study supports that BPH has a positive causal effect on PCa, while genetically predicted prostatitis has no causal effect on PCa. Nonetheless, further studies should explore the underlying biochemical mechanism and potential therapeutic targets for the prevention of these diseases.
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  • 文章类型: Journal Article
    目的:慢性前列腺炎/慢性盆腔疼痛综合征III型(CP/CPPS)的治疗一直被认为是复杂的,原因是该疾病的多种生物心理学因素。在这项临床研究中,我们的目的是评估棕榈酰乙醇胺治疗的疗效,CP/CPPSIII患者的Epilobium和金盏花提取物。
    方法:从2023年6月至2023年7月,我们在三个不同的机构中招募了45名受CP/CPPSIII型影响的连续患者。我们纳入了年龄在18至75岁之间的患者,在研究前出现3个月或更长时间的盆腔疼痛症状,美国国立卫生研究院慢性前列腺炎症状指数(NIH-CPSI)评分≥12分,诊断为NIHIII类,根据4玻璃测试Meares-Stamey测试。然后患者被分配接受PEA直肠栓剂,海马和金盏花,1栓剂/模具1个月。为了评估尿白细胞(U-WBC),所有患者都接受了标准尿液分析的测试。研究的主要终点是降低NIHCPSI。次要结果是峰值流量的变化,后空隙残留物(PVR),IIEF-5VAS评分,PSA和U-WBC的减少。
    结果:共有45名患者完成了研究方案。在基线,纳入队列的所有患者的中位年龄为49岁,PSA中位数为2.81ng/ml,NIH-CPSI中位数为18.55,IIEF-5中位数为18.27,U-WBC中位数为485.3/mmc,VAS评分中位数为6.49分,PVR中位数为26.5ml,流量峰值中位数为16.3ml/s.治疗1个月后,我们观察到NIH-CPSI有统计学意义的改善,U-WBC,PSA,IIEF-5峰值流量,PVR和VAS。
    结论:在这项观察性研究中,我们显示了PEA治疗的临床疗效,海马和金盏花,1栓剂/模具1个月,CP/CPPSIII患者。这种治疗的益处可能与尿液中炎性细胞的减少有关,这可能意味着炎性细胞因子的减少。这些结果应在更大样本量的进一步研究中得到证实。
    OBJECTIVE: The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underlying the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Palmitoylethanolamide, Epilobium and Calendula extract in patients with CP/CPPS III.
    METHODS: From June 2023 to July 2023, we enrolled 45 consecutive patients affected by CP/CPPS type III in three different institution. We included patients aged between 18 and 75 years with symptoms of pelvic pain for 3 months or more before the study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 12 point and diagnosed with NIH category III, according to 4-glass test Meares-Stamey test. Patients were then allocated to receive rectal suppositories of PEA, Epilobium and Calendula, 1 suppository/ die for 1 month. All patients have been tested with standard urinalysis in order to assess urinary leukocytes (U-WBC). The primary endpoint of the study was the reduction of NIHCPSI. The secondary outcomes were the change of peak flow, post-void residual (PVR), IIEF-5, VAS score, PSA and decrease of U-WBC.
    RESULTS: A total of 45 patients concluded the study protocol. At baseline, the median age of all the patients included in the cohort was 49 years, the median PSA was 2.81 ng/ml, the median NIH-CPSI was 18.55, the median IIEF-5 was 18.27, the median U-WBC was 485.3/mmc, the median VAS score was 6.49, the median PVR was 26.5 ml and the median peak flow was 16.3 ml/s. After 1 month of therapy we observed a statistically significant improvement of NIH-CPSI, U-WBC, PSA, IIEF-5, peak flow, PVR and VAS.
    CONCLUSIONS: In this observational study, we showed the clinical efficacy of the treatment with PEA, Epilobium and Calendula, 1 suppository/die for 1 month, in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cells in the urine that could imply a reduction of inflammatory cytokines. These results should be confirmed in further studies with greater sample size.
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  • 文章类型: Journal Article
    背景技术泌尿生殖系统细菌感染在人类中具有高发病率。泌尿生殖道感染的最常见原因是革兰氏阴性细菌。抗生素在治疗传染病方面非常有效,但它们伴有健康并发症。益生菌是活的微生物,其被认为在以足量食用时对人类健康具有有益作用。这项研究旨在比较897例泌尿生殖道感染患者使用和不使用益生菌的抗生素治疗结果。包括膀胱炎,尿道炎,前列腺炎,和外阴阴道炎.材料与方法本研究共纳入897例患者,年龄在18至55岁之间。将患者分为干预组,其中包括460名患者(254名妇女,206名男性)和包括437名患者(240名女性,197名男子)。患者接受的益生菌是ProBalans®的胶囊。膀胱炎的诊断,尿道炎,前列腺炎,外阴阴道炎,性传播感染是用几个测试来完成的,抗生素用于治疗。使用卡方或Fisher精确检验分析定性数据。结果我们发现干预组和对照组患者治疗后改善的印象存在显着差异。结论益生菌联合抗菌药物治疗泌尿生殖道感染有助于降低抗菌药物的不良反应。提高抗生素治疗的效率,减少细菌对抗生素的耐药性。然而,需要进一步的研究来证实这些潜在的健康益处.
    BACKGROUND Urogenital bacterial infections have a high incidence in humans. The most frequent cause of infections of the urogenital tract is gram-negative bacteria. Antibiotics are very effective in curing infectious diseases but they are accompanied by health complications. Probiotics are live microorganisms that are believed to confer a beneficial effect on human health when consumed in adequate amounts. This study aimed to compare outcomes from antibiotic treatment with and without the use of probiotics in 897 patients with lower urogenital tract infections, including cystitis, urethritis, prostatitis, and vulvovaginitis. MATERIAL AND METHODS A total of 897 patients aged 18 to 55 years were included in this research. Patients were divided into an intervention group including 460 patients (254 women, 206 men) and a comparison group including 437 patients (240 women, 197 men). The probiotics received by patients were capsules of ProBalans®. The diagnosis of cystitis, urethritis, prostatitis, vulvovaginitis, and sexually transmitted infection was done using several tests, and antibiotics were used for treatment. Qualitative data were analyzed using the chi-square or Fisher exact test. RESULTS We found a significant difference regarding patients\' impressions of improvement after therapy between patients in the intervention group and the comparison group. CONCLUSIONS Use of probiotics together with antibiotics in the treatment of urogenital tract infection can help to reduce the adverse effects of antibiotics, increase the efficiency of antibiotic therapy, and reduce bacterial resistance to antibiotics. However, further research is needed to confirm these potential health benefits.
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  • 文章类型: Journal Article
    已经报道了组织蛋白酶与前列腺癌(PCa)之间的关系。然而,缺乏对组织蛋白酶和良性前列腺疾病(BPDs)的研究。这项研究通过利用孟德尔随机化(MR)分析来确定是否存在因果关系,调查了组织蛋白酶和BPD之间的潜在遗传联系。
    从FinnGenBiobank获得了有关BPD的公开摘要统计数据。数据包括149,363个人,有30,066例BPH和119,297例对照,和123,057个人,有3,760例和119,297例前列腺炎对照。IEUOpenGWAS提供了10种组织蛋白酶的全基因组关联数据。为了评估BPDs和组织蛋白酶之间的因果关系,采用了五种不同的MR分析,主要方法是逆方差加权(IVW)方法。此外,我们进行了敏感性分析,以检查研究结果的水平多效性和异质性.
    IVWMR检查结果显示,组织蛋白酶O对BPH具有有益作用(IVWOR=0.94,95%CI0.89-0.98,P=0.0055),而组织蛋白酶X对前列腺炎有威胁(IVWOR=1.08,95%CI1.00-1.16,P=0.047)。通过反向MR分析,提示前列腺炎对组织蛋白酶V有不良影响(IVWOR=0.89,95%CI0.80-0.99,P=0.035),而在BPH和组织蛋白酶之间没有观察到有利的关联。从MR-Egger获得的结果,加权中位数,简单模式,和加权模式方法与IVW方法的结果一致。基于敏感性分析,异质性,水平多效性不太可能扭曲结果。
    这项研究提供了组织蛋白酶和BPD之间遗传因果联系的初步证据。我们的发现表明组织蛋白酶O对预防BPH有益,而组织蛋白酶X对前列腺炎有潜在威胁。此外,前列腺炎对组织蛋白酶V水平有负面影响。这三种组织蛋白酶可以作为BPDs诊断和治疗的靶点,这需要进一步的研究。
    UNASSIGNED: The relationship between cathepsins and prostate cancer (PCa) has been reported. However, there is a lack of research on cathepsins and benign prostate diseases (BPDs). This study investigated the potential genetic link between cathepsins and BPDs through the utilization of Mendelian randomization (MR) analysis to determine if a causal relationship exists.
    UNASSIGNED: Publicly accessible summary statistics on BPDs were obtained from FinnGen Biobank. The data comprised 149,363 individuals, with 30,066 cases and 119,297 controls for BPH, and 123,057 individuals, with 3,760 cases and 119,297 controls for prostatitis. The IEU OpenGWAS provided the Genome-wide association data on ten cathepsins. To evaluate the causal relationship between BPDs and cathepsins, five distinct MR analyses were employed, with the primary method being the inverse variance weighted (IVW) approach. Additionally, sensitivity analyses were conducted to examine the horizontal pleiotropy and heterogeneity of the findings.
    UNASSIGNED: The examination of IVW MR findings showed that cathepsin O had a beneficial effect on BPH (IVW OR=0.94, 95% CI 0.89-0.98, P=0.0055), while cathepsin X posed a threat to prostatitis (IVW OR=1.08, 95% CI 1.00-1.16, P=0.047). Through reverse MR analysis, it was revealed that prostatitis had an adverse impact on cathepsin V (IVW OR=0.89, 95% CI 0.80-0.99, P=0.035), while no favorable association was observed between BPH and cathepsins. The results obtained from MR-Egger, weighted median, simple mode, and weighted mode methods were consistent with the findings of the IVW approach. Based on sensitivity analyses, heterogeneity, and horizontal pleiotropy are unlikely to distort the results.
    UNASSIGNED: This study offers the initial evidence of a genetic causal link between cathepsins and BPDs. Our findings revealed that cathepsin O was beneficial in preventing BPH, whereas cathepsin X posed a potential threat to prostatitis. Additionally, prostatitis negatively affected cathepsin V level. These three cathepsins could be targets of diagnosis and treatment for BPDs, which need further research.
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  • 文章类型: Journal Article
    男性尿路感染(mUTIs)在初级保健中很少见。mUTI的定义因国家而异。法国mUTIs的治疗管理是基于14天的氟喹诺酮类药物疗程,尽管抗微生物药物耐药性风险很高。
    这项定性研究的目的是探索全科医生(全科医生)在mUTI的诊断和治疗管理方面的经验和行为。
    全科医生是在法国上诺曼底(HauteNormandie)通过便利抽样招募的,并与半结构化指南进行了单独采访。使用解释性现象学方法记录和分析了全科医生的经验和行为。
    从2021年3月到2022年5月,20名全科医生被纳入研究。定义mUTI被认为是一种诊断挑战。仅基于临床证据的诊断是不够的,需要补充测试。对于全科医生:“男性膀胱炎不存在”。mUTI被认为是一种不寻常的疾病,可以揭示潜在的疾病。全科医生认为氟喹诺酮类药物是“有效的”抗生素,并以相同的14天疗程治疗所有患者。全科医生实施了抗生素管理的改进策略,并使用计算机决策支持系统遵循了指南。
    由于初级保健中的低暴露和可变的临床表现,mUTI的全科医生经验有限,代表诊断和治疗挑战。为了改变全科医生的抗生素处方行为,将需要提出准则的范式转变。关键信息定义男性尿路感染代表了全科医生的诊断挑战。仅基于临床证据的诊断是不够的,需要补充测试。男性尿路感染是初级保健中的一种不寻常疾病,表明是更严重的潜在疾病。
    UNASSIGNED: Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based on a 14-day course of fluoroquinolones despite a high risk of antimicrobial resistance.
    UNASSIGNED: The objective of this qualitative study was to explore general practitioners\' (GPs) experiences and behaviours regarding the diagnostic and therapeutic management of mUTIs.
    UNASSIGNED: GPs were recruited by convenience sampling in Haute Normandie (France) and interviewed individually with semi-structured guides. GPs\' experiences and behaviours were recorded and analysed using an interpretive phenomenological approach.
    UNASSIGNED: From March 2021 to May 2022, 20 GPs were included in the study. Defining a mUTI was perceived as a diagnostic challenge. A diagnosis based on clinical evidence alone was insufficient and complementary tests were required. For GPs: \'male cystitis does not exist\'. A mUTI was considered an unusual disease that could reveal an underlying condition. GPs considered fluoroquinolones to be \'potent\' antibiotics and treated all patients with the same 14-day course. GPs implemented improvement strategies for antibiotic stewardship and followed the guidelines using a computerised decision support system.
    UNASSIGNED: GPs\' experiences of mUTIs are limited due to low exposure and variable clinical presentations in primary care, representing a diagnostic and therapeutic challenge. In order to modify GPs\' antibiotic prescribing behaviours, a paradigm shift in the guidelines will need to be proposed.KEY MESSAGESDefining a male urinary tract infection represents a diagnostic challenge for GPs.A diagnosis based on clinical evidence alone is insufficient and complementary tests are required.A male urinary tract infection is an unusual disease in primary care and suggests a more serious underlying condition.
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  • 文章类型: Case Reports
    小细胞神经内分泌前列腺癌(SCNC)是一种罕见的侵袭性神经内分泌前列腺癌(NEPC),其特征是临床过程积极且对激素治疗缺乏反应。
    我们提供了一例60岁男性的病例报告,诊断为组织学证实的原发性转移(骨,淋巴结和内脏)SCNC,具有腺癌的小成分,其临床症状类似于急性前列腺炎。值得注意的是,基于血清的神经内分泌标志物(癌胚抗原,嗜铬粒蛋白A)阴性,患者前列腺特异性抗原(PSA)升高。肿瘤组织的基因检测显示乳腺癌基因2(BRCA2)拷贝数丢失和视网膜母细胞瘤基因(RB1)突变再次反映了该疾病的侵袭性。BRCA2拷贝数损失的种系测试并不显著。在6个周期的卡铂和依托泊苷联合雄激素剥夺治疗(ADT)后,东部肿瘤协作组(ECOG)的表现状态从3改善到0,此外,患者没有疼痛。根据临床改善,前列腺特异性膜抗原(PSMA)和氟脱氧葡萄糖正电子发射断层扫描-计算机断层扫描(FDGPET-CT)均显示转移负荷显著降低.目前,患者接受ADT+阿帕鲁胺治疗.
    我们首次证明了一例原发性转移性SCNC伴腺癌的病例,该病例通过以铂类为基础的化学疗法和激素疗法的组合成功治疗。此外,我们提供了有关SCNC治疗的文献综述,因为目前尚无针对该疾病的标准治疗方法.
    UNASSIGNED: Small cell neuroendocrine prostate cancer (SCNC) is a rare aggressive type of neuroendocrine prostate cancer (NEPC) characterized by aggressive clinical course and lack of response to hormone therapy.
    UNASSIGNED: We present a case report of a 60-year-old man diagnosed with a histologically confirmed primary metastatic (bone, lymph nodes and visceral) SCNC with small components of an adenocarcinoma with clinical symptoms mimicking an acute prostatitis. Of note, serum based neuroendocrine markers (carcinoembryonic antigen, chromogranin A) were negative and the patient had a prostate-specific antigen (PSA) elevation. Genetic testing of tumor tissue revealed breast cancer gene 2 (BRCA2) copy number loss and a retinoblastoma gene (RB1) mutation reflecting again the aggressiveness of the disease. Germline testing for the BRCA2 copy number loss was unremarkable. After 6 cycles of carboplatin and etoposide in combination with androgen deprivation therapy (ADT) the Eastern Cooperative Oncology Group (ECOG) performance status has improved from 3 to 0, in addition the patient was free of pain. In line with clinical improvement, both prostate-specific membrane antigen (PSMA) and fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) revealed a significant reduction of metastatic load. Currently, the patient is treated with ADT plus apalutamide.
    UNASSIGNED: We demonstrate for the first time a case of a primary metastatic SCNC with adenocarcinoma components successfully treated by the combination of platinum-based chemotherapy plus hormonal therapy. In addition, we provide a literature overview on management of SCNC as there is no standard treatment established for this disease.
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  • 文章类型: Journal Article
    目标:迄今为止,很少有研究考虑心理因素对慢性前列腺炎(PRO)模型的影响。这里,我们的目的是改进结合化学诱导前列腺炎和心理压力的鼠PRO模型。
    方法:将40只小鼠随机分为4组:正常对照组,PRO组,避水应激(WAS)组,和PRO+WAS组。将10只小鼠分配到每组:5只用于细胞图(CMG),5只用于vonFrey测试和组织学分析。PRO是通过前列腺注射10%多聚甲醛诱导的。将WAS小鼠置于中间平台上,每天1小时,连续10天。
    结果:vonFrey试验的结果表明,WAS和PRO均可诱导小鼠膀胱痛觉过敏,WAS+PRO组也有明显的盆腔疼痛症状。CMG结果表明,PRO小组,WAS组,PRO+WAS组均表现为膀胱过度活动,表现为排尿间隔缩短和阈值压力降低引起膀胱收缩。PRO组和PRO+WAS组的症状较WAS组严重。组织染色结果表明,WAS本身仅引起轻度前列腺炎症,但可明显加重化学诱导的前列腺炎症。以及肥大细胞的总数和活化肥大细胞的比例。
    结论:我们的精制鼠PRO模型可以表现出持续的膀胱过度活动,盆腔痛觉过敏和前列腺炎症。WAS可诱发轻度前列腺炎症,加重原发性前列腺炎症。
    OBJECTIVE: To date, few studies have considered the influence of psychological factors on chronic prostatitis (PRO) models. Here, we aimed to refine a murine PRO model combining chemically induced prostatitis with psychological stress.
    METHODS: A total of 40 mice were randomly divided into four groups: normal control (NC) group, PRO group, water avoidance stress (WAS) group, and PRO + WAS group. Ten mice were assigned to each group: five for cystometrograms (CMGs) and five for von Frey testing and histological analysis. PRO was induced through a prostatic injection of 10% paraformaldehyde. The WAS mice were placed on the middle platform for 1 h per day for 10 consecutive days.
    RESULTS: The results of the von Frey test demonstrated that both WAS and PRO induced bladder hyperalgesia in mice, and the WAS + PRO group showed significant pelvic pain symptoms either. The CMG results suggested that the PRO group, the WAS group, and the PRO + WAS group all exhibited bladder overactivity, presented as a shortened micturition interval and decreased threshold pressure evoking bladder contraction. The symptoms of the PRO group and the PRO + WAS group were more severe than those of the WAS group. The tissue staining results indicated that WAS itself caused only mild prostatic inflammation but could significantly aggravate chemical-induced prostatic inflammation, as well as the total number of mast cells and proportion of activated mast cells.
    CONCLUSIONS: Our refined murine PRO model could manifest persistent bladder overactivity, pelvic hyperalgesia and prostatic inflammation. WAS could induce mild prostatic inflammation and aggravate primary prostatic inflammation.
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  • 文章类型: Journal Article
    目的:慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)的患病率在男性人群中从8.4%到25%不等,并且与健康相关的生活质量下降有关。管理CP/CPPS仍然具有挑战性,并且由于复杂的疾病性质,没有任何通用的选择来有效治疗所有患者。本研究分析了体外冲击波疗法(eSWT)对疼痛缓解和幸福感的影响的当前可用数据。
    方法:我们遵守PRISMA2022指南,报告定量和定性数据合成。2023年3月,使用PubMed/Medline进行了文献检索,Scopus,谷歌学者。包括单独的eSWT或eSWT加常规药物治疗的随机前瞻性研究。使用RoB2.0估计偏倚风险。主要结果是自我报告的分数,包括NIH-CPSI问卷和VAS,在1个月或2、3和6个月随访。
    结果:与接受安慰剂或药物治疗的对照组相比,接受eSWT的CP/CPPS患者的疼痛缓解和其他主观NIH-CPSI评分改善更明显。eSWT的效果似乎是持久的,并在6个月的随访中得到证实(p<0.01)。
    结论:基于可访问研究的荟萃分析,我们获得了CP/CPPS治疗的等效eSWT适用性,并且由于其非侵入性,可以提供给患者,高水平的安全,和成功的临床结果证明在这个分析。
    OBJECTIVE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) prevalence varies from 8.4% to 25% of the male population and is associated with diminished health-related quality of life. Managing CP/CPPS remains challenging and there is not any common option to treat all patients effectively because of the complex disease nature. The currently available data for the extracorporeal shockwave therapy (eSWT) effect on pain relief and well-being were analyzed in the present study.
    METHODS: We adhered to PRISMA 2022 guidelines for reporting the quantitative and qualitative data synthesis. A literature search was conducted in March 2023 using PubMed/Medline, Scopus, and Google Scholar. Randomized prospective studies of eSWT alone or eSWT plus conventional medicinal treatment were included. The risk of bias was estimated using the RoB 2.0. Primary outcomes were self-reported scores, including the NIH-CPSI questionnaire and VAS, at 1 month or 2, 3, and 6, months follow-up.
    RESULTS: The CP/CPPS patients who receive eSWT have more pronounced pain relief and improvement of other subjective NIH-CPSI scores compared with control groups that received placebo or medication therapy. The effect of eSWT seems to be long-lasting and was confirmed in the 6-month follow-up (p < 0.01).
    CONCLUSIONS: Based on the meta-analysis of accessible studies, we receive the equivalence eSWT applicability for the CP/CPPS treatment and can be offered to patients because of its noninvasiveness, high level of safety, and successful clinical results demonstrated in this analysis.
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  • 文章类型: Journal Article
    本研究旨在通过网络药理学和实验研究,探讨褪黑素(MT)治疗慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)的潜在机制。MT的靶基因来自瑞士靶预测,SuperPred,SEA,和PharmMapper数据库,CP/CPPS目标是基于OMIM收集的,DisGeNet,和GeneCards数据库。分析了MT和CP/CPPS靶基因的交集。使用Cytoscape构建PPI网络以识别核心目标。通过使用R软件对共享靶标进行GO和KEGG富集分析。使用AutoDock和PyMOL进行MT与核心靶标的分子对接。使用GROMACS软件进行分子动力学模拟。并运用细胞实验验证了MT在CP/CPPS中的潜伏感化。网络药理学分析揭示了MT和CP/CPPS之间的284个共享目标,与AKT1,SRC,HSP90AA1,PTGS2,BCL2L1,ALB,CASS3,NFKB1,HIF1A,和ESR1被确定为关键目标。富集分析表明,MT通过各种生物过程影响CP/CPPS,通路分析强调PI3K-Akt的重要性,MAPK,拉斯,福克斯,HIF-1,EGFR,和凋亡途径。分子对接证实了MT和核心靶标之间的强结合。值得注意的是,分子动力学模拟结果表明,AKT1、PTGS2、ALB、HSP90AA1蛋白,MT分别为-26.15、-29.48、-18.59和-20.09千卡/摩尔,分别。这些结果表明,AKT1,PTGS2,ALB,HSP90AA1蛋白与MT强结合。细胞实验证明MT能抑制IL-1β的分泌,LPS诱导的RWPE-1细胞中的IL-6和TNF-α,缓解炎症,并抑制细胞凋亡和氧化应激。网络药理学,分子对接,分子动力学模拟,细胞实验表明,MT可以通过调节多个靶点和途径在CP/CPPS中发挥作用。这些发现为进一步探索MT在CP/CPPS治疗中的分子机制和临床应用提供了重要的科学依据,有望为新的治疗策略的发展提供新的思路和方向。
    This study is aimed at exploring the potential mechanisms of melatonin (MT) in treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using network pharmacology and experimental study. The target genes of MT were acquired from the Swiss Target Prediction, SuperPred, SEA, and PharmMapper databases, and the CP/CPPS targets were collected based on OMIM, DisGeNET, and GeneCards databases. The intersection of MT and CP/CPPS target genes was analyzed. A PPI network was constructed using Cytoscape to identify core targets. The shared targets underwent GO and KEGG enrichment analyses by Using R software. Molecular docking of MT with core targets was performed using AutoDock and PyMOL. GROMACS software was used for molecular dynamics simulation. And using cell experiments to verify the potential effect of MT in CP/CPPS. Network pharmacology analysis reveals 284 shared targets between MT and CP/CPPS, with AKT1, SRC, HSP90AA1, PTGS2, BCL2L1, ALB, CASP3, NFKB1, HIF1A, and ESR1 identified as key targets. Enrichment analysis indicates that MT affects CP/CPPS through various biological processes, and pathway analysis emphasizes the significance of PI3K-Akt, MAPK, Ras, FoxO, HIF-1, EGFR, and apoptosis pathways. Molecular docking confirms strong binding between MT and core targets. It is worth noting that the molecular dynamics simulation showed that the average binding free energy of AKT1, PTGS2, ALB, HSP90AA1 proteins, and MT was - 26.15, - 29.48, - 18.59, and - 20.09 kcal/mol, respectively. These results indicated that AKT1, PTGS2, ALB, and HSP90AA1 proteins were strongly bound to MT. Cell experiments demonstrate that MT can inhibit the secretion of IL-1β, IL-6, and TNF-α in LPS-induced RWPE-1 cells, alleviate inflammation, and suppress cell apoptosis and oxidative stress. Network pharmacology, molecular docking, molecular dynamics simulation, and cell experiments showed that MT could play a role in CP/CPPS by regulating multiple targets and pathways. These findings provide an important scientific basis for further exploration of the molecular mechanism and clinical application of MT in CP/CPPS treatment and are expected to provide new ideas and directions for the development of novel therapeutic strategies.
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  • 文章类型: Journal Article
    前列腺炎代表男性泌尿生殖系统的常见疾病,显著影响男性患者的身心健康。虽然许多研究表明免疫细胞活性和前列腺炎之间存在潜在的联系,免疫细胞在前列腺炎中的确切因果作用仍不确定。本研究旨在使用双向孟德尔随机化方法探讨免疫细胞特征与前列腺炎之间的因果关系。本研究利用来自公共GWAS数据库的数据,并采用双向孟德尔随机化分析来研究免疫细胞与前列腺炎之间的因果关系。731免疫细胞特征与前列腺炎之间的因果关系主要通过方差逆加权(IVW)进行研究。辅以MR-Egger回归,一个简单的模型,加权中位数法,和加权模型。最终,结果进行了敏感性分析,以评估异质性,水平多效性,免疫细胞和前列腺炎中单核苷酸多态性(SNP)的稳定性。MR分析显示17个免疫细胞对前列腺炎表现出显著的因果效应。相比之下,反向MR的发现表明前列腺炎与13种免疫细胞之间存在显着因果关系。我们的研究利用双向孟德尔随机化建立特定免疫细胞表型和前列腺炎之间的因果关系,强调免疫系统行为和疾病之间的相互影响。我们的研究结果表明,有针对性的治疗方法以及纳入不同人群对更广泛的验证和个性化治疗策略的重要性。
    Prostatitis represents a common disease of the male genitourinary system, significantly impacting the physical and mental health of male patients. While numerous studies have suggested a potential link between immune cell activity and prostatitis, the exact causal role of immune cells in prostatitis remains uncertain. This study aims to explore the causal relationship between immune cell characteristics and prostatitis using a bidirectional Mendelian randomization approach. This study utilizes data from the public GWAS database and employs bidirectional Mendelian randomization analysis to investigate the causal relationship between immune cells and prostatitis. The causal relationship between 731 immune cell features and prostatitis was primarily investigated through inverse variance weighting (IVW), complemented by MR-Egger regression, a simple model, the weighted median method, and a weighted model. Ultimately, the results underwent sensitivity analysis to assess the heterogeneity, horizontal pleiotropy, and stability of Single Nucleotide Polymorphisms (SNPs) in immune cells and prostatitis. MR analysis revealed 17 immune cells exhibiting significant causal effects on prostatitis. In contrast, findings from reverse MR indicated a significant causal relationship between prostatitis and 13 immune cells. Our study utilizes bidirectional Mendelian Randomization to establish causal relationships between specific immune cell phenotypes and prostatitis, highlighting the reciprocal influence between immune system behavior and the disease. Our findings suggest targeted therapeutic approaches and the importance of including diverse populations for broader validation and personalized treatment strategies.
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