Background Aberrant activation of androgen receptor (AR) signaling plays a crucial role in the progression of prostate adenocarcinoma (PRAD) and contributes significantly to the development of enzalutamide resistance. In this study, we aimed to identify a novel AR-driven signature that can predict prognosis and endows potentially reveal novel therapeutic targets for PRAD. Methods The Seurat package was used to preprocess the single-cell RNA sequencing (scRNA-seq). Differentially expressed genes were visualized using limma and pheamap packages. LASSO and multi-variate Cox regression models were established using glmnet package. The package “Consensus Cluster Plus” was utilized to perform the consensus clustering analysis. The biological roles of origin recognition complex subunit 1 (ORC1) in PRAD were determined by gain- and loss-of-function studies in vitro and in vivo. Result We characterized the scRNA-seq data from GSE99795 and identified 10 AR-associated genes (ARGs). The ARGs model was trained and validated in internal and external cohorts. The ARGs were identified as an independent hazard factor in PRAD and correlated with clinical risk characteristics. In addition, the ARGs were found to be correlated with somatic tumor mutation burden (TMB) levels. Two groups that have distinct prognostic and molecular features were identified through consensus clustering analysis. ORC1 was identified as a critical target among these ARGs, and it ORC1 promoted proliferation and stem-like properties of PRAD cells. Chromatin immunoprecipitation (ChIP)-qPCR assay confirmed that AR could directly bind the promoter of ORC1. Activated AR/ORC1 axis contributed to enzalutamide resistance, and targeting ORC1 rendered PRAD cells more susceptible to enzalutamide. Conclusions This study defines an AR-driven signature that AR activates ORC1 expressions to promote PRAD progression and enzalutamide resistance, which may provide novel targets for PRAD treatment.

In this research, polyethylenimine-functionalized gold nanoclusters (PEI-AuNCs) were synthesized for the delivery of plasmid CMTM5 (pCMTM5) to prostate cancer (PCa) cells, with the objective of elucidating the mechanism underlying its anticancer efficacy. The PEI-AuNCs loaded with pCMTM5 (PEI-AuNCs@pCMTM5) tumor-targeting drug delivery system was established. Subsequently, both the obtained PEI-AuNCs and PEI-AuNCs@pCMTM5 underwent characterization through a transmission electron microscope (TEM) and dynamic light scattering (DLS). Employing RT-qPCR, western blot, flow cytometry, immunofluorescence, and co-immunoprecipitation (co-IP) assays, the consequences of CMTM5 overexpression on the expression of EGFR were investigated. Moreover, the influence of PEI-AuNCs@pCMTM5 on PC-3 cells was assessed through CCK-8, wound healing assay, and Transwell experiments. As a result, the PEI-AuNCs and PEI-AuNCs@pCMTM5 were presented as uniformly dispersed spherical with stable particle sizes and positive charges, showcasing favorable dispersion within the solution. In comparison to Lip2000, the PEI-AuNCs demonstrated superior transfection efficiency and lower cellular toxicity. Following the overexpression of CMTM5, the proliferative capacity of PC-3 cells was markedly suppressed, while both migratory and invasive abilities exhibited noteworthy reduction, with the efficacy of PEI-AuNCs@pCMTM5 consistently outperforming that of free pCMTM5. Subsequent mechanistic investigations unveiled that CMTM5 does not directly inhibit the synthesis of EGFR or facilitate its degradation, but rather influences the endocytic process of EGFR. In conclusion, the PEI-AuNCs nano-delivery system exhibits good biocompatibility and efficaciously conveys pCMTM5 to PCa cells. Crucially, pCMTM5 does not directly interact with EGFR, and CMTM5 governs the malignant progression of PC3 cells by promoting EGFR endocytosis.

BACKGROUND:Cisplatin is a key therapeutic agent for bladder cancer, yet the emergence of cisplatin resistance presents a significant clinical challenge. OBJECTIVE:This study aims to investigate the potential and mechanisms of cyclanoline (Cyc) in overcoming cisplatin resistance. METHODS:Cisplatin-resistant T24 and BIU-87 cell models (T24/DR and BIU-87/DR) were established by increasing gradual concentration. Western Blot (WB) assessed the phosphorylation of STAT3, JAK2, and JAK3. T24/DR and BIU-87/DR cell lines were treated with selective STAT3 phosphorylation modulators, and cell viability was evaluated by CCK-8. Cells were subjected to cisplatin, Cyc, or their combination. Immunofluorescence (IHC) examined p-STAT3 expression. Protein and mRNA levels of apoptosis-related and cell cycle-related factors were measured. Changes in proliferation, invasion, migration, apoptosis, and cell cycle were monitored. In vivo, subcutaneous tumor transplantation models in nude mice were established, assessing tumor volume and weight. Changes in bladder cancer tissues were observed through HE staining, and the p-STAT3 was assessed via WB and IHC. RESULTS:Cisplatin-resistant cell lines were successfully established, demonstrating increased phosphorylation of STAT3, JAK2, and JAK3. Cisplatin or Cyc treatment decreased p-STAT3, inhibited invasion and migration, and induced apoptosis and cell cycle arrest in the G0/G1 phase in vitro. In vivo, tumor growth was significantly suppressed, with extensive tumor cell death. IHC and WB consistently showed a substantial downregulation of STAT3 phosphorylation. These changes were more pronounced when cisplatin and Cyc were administered in combination. CONCLUSION:Cyc reverses cisplatin resistance via JAK/STAT3 inhibition in bladder cancer, offering a potential clinical strategy to enhance cisplatin efficacy in treating bladder cancer.

Background Partial nephrectomy (PN) is one of the most preferred nephron-sparing treatments for clinical T1 (cT1) renal cancer, while radiofrequency ablation (RFA) is usually used for patients who are poor surgical candidates. The long-term oncologic outcome of RFA vs. PN for cT1 renal cancer remains undetermined. This meta-analysis aims to compare the treatment efficacy and safety of RFA and PN for patients with cT1 renal cancer with long-term follow-up of at least 5 years. Method This meta-analysis was performed following the PRISMA reporting guidelines. Literature studies that had data on the comparison of the efficacy or safety of RFA vs. PN in treating cT1 renal cancer were searched in databases including PubMed, Embase, Web of Science, and the Cochrane Library from 1 January2000 to 1 May 2022. Only long-term studies with a median or mean follow-up of at least 5 years were included. The following measures of effect were pooled: odds ratio (OR) for recurrence and major complications; hazard ratio (HR) for progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Additional analyses, including sensitivity analysis, subgroup analysis, and publication bias analysis, were also performed. Results A total of seven studies with 1,635 patients were finally included. The treatment efficacy of RFA was not different with PN in terms of cancer recurrence (OR = 1.22, 95% CI, 0.45–3.28), PFS (HR = 1.26, 95% CI, 0.75–2.11), and CSS (HR = 1.27, 95% CI, 0.41–3.95) as well as major complications (OR = 1.31, 95% CI, 0.55–3.14) ( P > 0.05 for all). RFA was a potential significant risk factor for OS (HR = 1.76, 95% CI, 1.32–2.34, P < 0.001). No significant heterogeneity and publication bias were observed. Conclusion This is the first meta-analysis that focuses on the long-term oncological outcomes of cT1 renal cancer, and the results suggest that RFA has comparable therapeutic efficacy with PN. RFA is a nephron-sparing technique with favorable oncologic efficacy and safety and a good treatment alternative for cT1 renal cancer.

目的 评价颐和春口服液联合西医常规治疗ⅢA型前列腺炎(肾阳虚型)合并不育症的临床疗效.方法 选取2019年11月-2021年1月温州市人民医院就诊的120例患者为研究对象,按照1:1的比例,随机分为对照组及治疗组,对照组给予生精胶囊联合西医常规治疗,治疗组给予颐和春口服液联合西医常规治疗,疗程均为12周.观察两组的临床疗效,对比两组患者治疗前后的美国国立卫生院慢性前列腺炎症状指数(National Institutes of Health Chronic Prostatitis Symptoms index,NIH-CPSI)评分、中医证候评分、炎症指标、精液常规指标.结果 治疗后,治疗组总有效率为96.7％,显著高于对照组的总有效率86.7％(P＜0.05).治疗后,两组NIH-CPSI的疼痛或不适评分、排尿症状评分、生活质量评分、总评分及中医症状评分均显著低于治疗前,且治疗组上述评分显著低于对照组(P＜0.05).治疗后,两组前列腺液白细胞计数、C-反应蛋白、白细胞介素-2水平均显著低于治疗前,且治疗组前列腺液炎症指标水平显著低于对照组(P＜0.05).治疗后,两组精液量、精子密度、精子总数、精子活力、精子存活率均显著高于治疗前,且治疗组精液指标水平显著高于对照组(P＜0.05).两组不良反应情况无显著性差异.结论 颐和春口服液联合西医常规治疗ⅢA型前列腺炎(肾阳虚型)合并不育症患者临床疗效好、安全性高,值得临床推广.

Prostate cancer (PCa) endangers the life and health of older men. Most PCa cases develop into castration-resistant PCa (CRPC) within 2 years. At present, the molecular mechanisms of the occurrence and development of PCa and its transformation to CRPC remain unknown. The present study aimed to investigate the role of CKLF-like Marvel transmembrane domain containing family member 5 (CMTM5) in PCa and its molecular mechanism in vitro. PCa tissues and paired adjacent normal prostate tissues from 70 patients were collected to examine the expression levels of CMTM5 and EGFR via immunohistochemistry, reverse transcription-quantitative PCR and western blotting. Then, CMTM5-overexpressing DU145 cells were constructed, and CMTM5 expression in these transfected cells and vector control cells was examined via western blotting. Cell Counting Kit-8 and plate clone formation assays were used to evaluate the proliferation and colony number of CMTM5-overexpressing cells and vector control cells. Then, cell migration and invasion were assessed using wound healing assay, Transwell assay and immunofluorescence analysis with DAPI staining. The effect of CMTM5 on apoptosis and its underlying molecular mechanism were examined using western blotting and flow cytometry. The results demonstrated that CMTM5 expression in PCa tissues and cell lines was significantly downregulated, while EFGR expression was significantly upregulated. The proportion of high CMTM5 expression in PCa tissues was significantly lower compared with that in normal prostate tissues. By contrast, the proportion of high EGFR expression in PCa tissues was significantly increased compared with that in normal prostate tissues. Moreover, CMTM5 overexpression significantly inhibited cell proliferation, migration and invasion, and promoted cell apoptosis compared with vector control cells in vitro. Furthermore, the regulation of PCa by CMTM5 was associated with the downregulation of PI3K/AKT and its downstream Bcl-2 expression, as well as the upregulation of Bax expression. In conclusion, CMTM5 may be an effective tumor suppressor gene for PCa, especially for castration-resistant PCa, by downregulating EGFR and PI3K/AKT signaling pathway components.

目的:探讨早期小剂量激素对泌尿系感染性休克早期目标导向治疗(early goal directed therapy,EGDT)后急性肺损伤的预防及临床价值.方法:选择2019年1月—2020年10月在院治疗的诊断为泌尿系感染性休克患者84例,按患者入院顺序编号奇偶数法均分为对照组(EGDT及抗感染手术等综合治疗)、治疗组各42例(在抗感染手术等综合治疗+早期小剂量氢化可的松琥珀酸钠200 mg/d微泵持续维持,与EGDT同时开始),对两组患者在年龄、性别、入ICU前的SOFA评分和APACHE-Ⅱ评分、3 h EGDT达标例数、6 h EGDT达例数,入院第1、3、7、10天白细胞计数、降钙素原(PCT)值、C反应蛋白(CRP)值,ICU期间最差氧合指数并统计符合诊断的急性肺损伤发生例数,进展至ARDS呼吸衰竭气管插管例数、ICU 7 d、ICU 14 d转出例数、28 d死亡例数进行比较.结果:两组3 h达标例数、7 d转出例数比较差异有统计学意义(P＜0.05).治疗组在入院第3、7天白细胞值,第3天PCT值,第7天CRP值恢复更快.治疗组中急性肺损伤例数、气管插管例数小于对照组,两组气管插管例数比较差异有统计学意义(P＜0.05),两组28 d死亡率比较差异无统计学意义(P＞0.05).结论:早期小剂量激素能促进泌尿系感染性休克患者EGDT更快达标,缩短感染指标的恢复时间,降低EGDT后气管插管的发生,缩短ICU停留时间,减少费用支出,具有一定的临床价值.

Given the relatively poor understanding of the expression and functional effects of the N6-methyladenosine (m6A) RNA methylation on colorectal cancer (CRC), we attempted to measure its prognostic value and clinical significance. We comprehensively screened 37 m6A-related prognostic long non-coding RNAs (lncRNAs) with significant differences in expression based on 21 acknowledged regulators of m6A modification and data on 473 colorectal cancer tissues and 41 para-cancer tissues obtained from the TCGA database. Accordingly, we classified 473 CRC patients into two clusters by consensus clustering on the basis of significantly different survival outcomes. We also found a potential correlation between m6A-related prognostic lncRNAs and BRAF-KRAS expression, as well as immune cell infiltration. Then, we established a prognostic model by selecting 16 m6A-related prognostic lncRNAs via LASSO Cox analysis and grouped the CRC patients into low- and high-risk groups to calculate risk scores. Then, we performed stratified sampling to validate and confirm our model by categorising the 473 samples into a training group (N = 208) and a testing group (N = 205) in a 1:1 ratio. The survival curve showed a distinct clinical outcome in the low- and high-risk subgroups. We reconfirmed the reliability and independence of the prognostic model through various measures: risk curve, heat map and univariate and multivariate Cox analyses. To ensure that the outcomes were applicable to clinical settings, we performed stratified analyses on different clinical features, such as age, lymph node status and clinical stage. CRC patients with downregulated m6A-related gene expression, lower immune score, distant metastasis, lymph node metastasis or more advanced clinical staging had higher risk scores, indicating less-desirable outcomes. Moreover, we explored the immunology of colorectal cancer cells. The risk score showed positive correlations with eosinophils, M2 macrophages and neutrophils. In summary, our effort revealed the significance of m6A RNA methylation regulators in colorectal cancer, and the prognostic model we constructed may be used as an essential reference for predicting the outcome of CRC patients.

目的:在医学留学生临床实习中全面融入大数据时代下多元立体化带教模式的意义做探究.方法:在2019年9月至2021年8月时段,纳入在我院儿科实习的留学生15例,留学生存在语言、文化等因素差异情况,因此医院对留学生实施培养教育,因教师的英语水平存在局限,进而不能与留学生进行良好交流.需根据留学生的实际需求和临床特点,拟定针对性临床带教措施.分析大数据时代下多元立体化带教模式的应用价值.结果:在实行带教模式后,留学生对其满意度较高,得出此种带教模式可让留学生更好的掌握儿科相关知识.结论:大数据时代下多元立体化带教模式良好的应用在留学生临床实习中,可使留学生的自身思考、写作、学习能力等提升,为临床留学生带教工作提供足够参考.

BACKGROUND It is necessary to identify patients at risk of developing lymph node metastasis prior to papillary thyroid carcinoma (PTC) surgery. This can be challenging due to limiting factors, and an artificial intelligence algorithm may be a viable option. OBJECTIVE In this study, we aimed to evaluate whether combining an artificial intelligence algorithm (support vector machine and probabilistic neural network) and clinico-pathologic data can preoperatively predict lymph node metastasis of papillary thyroid carcinoma (PTC). METHODS We retrospectively examined 251 PTCs with lymph node metastasis and 194 PTCs without lymph node metastasis. The artificial intelligence algorithm included the support vector machine (SVM) and the probabilistic neural network (PNN). RESULTS The ACR TI-RADS (Thyroid Imaging, Reporting and Data System), number of tumours, no well-defined margin, lymph node status and rim calcification on ultrasonography (US), age, sex, tumour size, and presence of Hashimoto's thyroiditis were significantly more frequent among PTCs with central lymph node metastasis than those without metastasis (P<0.05). The PNN classifier revealed an F1 score of 0.88 on the central lymph node metastasis test set. The SVM classifier revealed an F1 score of 0.93 on the lateral lymph node metastasis test set. Our study demonstrates that combining artificial intelligence algorithms and clinico-pathologic data can effectively predict the lymph node metastasis of papillary thyroid carcinoma prior to surgery.

目的 探讨汉防己丙素(Cyc)干预亚硝基胺(BBN)致大鼠膀胱癌的作用及机制.方法 雄性SD大鼠随机分为对照组,模型组,Cyc低、高剂量(20、40 mg/kg)组,顺铂(5 mg/kg)组.大鼠ig 0.5 mL BBN (0.4 kg/L),2次倜,连续8周,建立膀胱癌模型.除对照组和模型组ip生理盐水外,其余各组ip设定剂量的药物,1次/d,连续8周.实验结束后,收集大鼠膀胱组织;通过HE染色观察大鼠膀胱组织病理变化;通过免疫组化法检测膀胱组织MMP9、Ki67的表达;通过免疫印迹法检测膀胱组织KLF4、p21、CyclinD1、E-cadherin、N-cadherin、Vimentin、Wnt、β-catenin蛋白的表达.结果 与模型组相比,Cyc可有效抑制膀胱炎细胞浸润、促进癌细胞出现不同程度退变、减少质比例;显著下调膀胱组织MMP9、Ki67的表达(P＜0.05、0.01);显著上调膀胱癌组织中KLF4、p21、E-cadherin的表达(P＜0.05、0.01);显著下调CyclinD1、Wnt、β-catenin、N-cadherin、Vimentin的表达(P＜0.05、0.01).结论 Cyc通过促进KLF4表达、阻断Wnt/β-catenin信号传导、抑制膀胱癌细胞上皮细胞-间充质转化进程,进而抑制膀胱癌细胞迁移与侵袭能力;同时通过上调KLF4水平,调控下游因子p21、CyclinD1表达,影响膀胱癌细胞的增殖能力,从而延缓BBN诱导的大鼠膀胱癌的病理进程.

Objective: It is to investigate the clinical effect of serum CEA, CA153, CYFRA21-1, CA125, NSE, and CA199 in the application of Myrian imaging rTo investigate the inhibition of resveratrol on the in vitro proliferation activity of human bladder cancer 5637 cells and its possible molecular mechanism. Methods: Human bladder cancer 5637 cells were cultured in vitro and divided into a blank control group and resveratrol groups (25 mu mol/l, 50 mu mol/l, 100 mu mol/l and 200 mu mol/l); then, the effect of resveratrol on the proliferation of 5637 cells was detected by conducting MTT tests. The effect of resveratrol (200 mu mol/l) on the apoptosis of 5637 cells was detected by flow cytometry. In the blank control group and resveratrol (25 mu mol/l, 50 mu mol/l, 100 mu mol/l and 200 mu mol/l) groups, total protein and mRNA were extracted. The effect of resveratrol on the expression of p-Akt and PTEN protein and mRNA were detected by Western blot and PCR. Results: Resveratrol significantly inhibited the in vitro proliferation activity of 5637 cells in a dose-dependent and time-depend-ent manner. The flow cytometry results showed that resveratrol induced apoptosis and arrested the cell cycle in G1 phase in 5637 cells. Resveratrol significantly inhibited the expression of p-Akt mRNA and protein and upregulated the expression level of PTEN mRNA and protein compared with the control (p < 0.05); these differences were statistically significant. Conclusion: Resveratrol can inhibit the proliferation of bladder cancer cells and induce apoptosis by the upregulation of PTEN expression.

目的 本研究的目的在于比较行腹腔镜根治性肾切除术(Laparoscopic radical nephrectomy,LRN)的老年局限性肾细胞癌(Local-ized renal cell carcinoma,LRCC)患者与中年患者的短期及长期结局.方法 2012年1月至2018年12月,共有58例年龄大于或等于70岁的LRCC患者(老年组)行LRN,这58例患者与同期因LRCC行LRN的109例中年患者(年龄在55～69岁之间,中年组)进行短期与长期结局的比较.结果 老年组的年龄、查尔森合并症指数及美国麻醉师协会评分高于中年组,其余的术前基线资料资料比较差异无统计学意义.老年组与中年组在手术时间、术中失血量、中转率、术后30天并发症发生率及严重程度、病理结果等短期结局方面比较差异无法统计学意义.长期随访结果表明,两组患者的肿瘤复发率类似.两组患者的总体生存率及无瘤生存率均类似.结论 LRN用于老年LRCC患者可取得与中年患者类似的短期及长期结局.

以泛在学习为代表的在线教育为未来远程教育开拓出新的学习领域.然而,多数泛在学习系统普遍存在学习者孤独感强烈、课程信息过载、学习控制功能不全、信任缺乏、学习迷航等问题.为准确实现个性化导学,结合泛在学习新特点,对传统教学环境重新优化改造,围绕重构数据采集方案、细化在线课程、优化设计学习资源和改进通信工具四个方面,建立个性化导学模型.该导学模型解决了学习者学习迷航问题,提升了学习者存在感,提高了学习效率.

Aim of Study: To further evaluate the influence of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null genotypes on bladder cancer risk, we conducted a meta-analysis in the Chinese population. Materials and Methods: PubMed and Chinese databases were electronically searched through April 2016. Results: Nine studies were included for our meta-analysis, involving 1646 bladder cancer cases and 1938 controls. In general, our findings indicated that a significant association existed between GSTM1-null genotype and the risk of bladder cancer in the studied Chinese population (odds ratio = 1.56, 95% confidence interval: 1.36u1.79). However, no significant association between GSTT1 polymorphism and bladder cancer was found. After stratification of the subgroup analyses by source of controls and geographical areas, a substantially elevated risk was revealed between GSTM1-null genotype and bladder cancer in the population-based studies and those conducted in South China and North China. Conclusion: Our meta-analysis suggested that GSTM1-null genotype is associated with an increased bladder cancer risk in the Chinese individuals.

Purpose: The purpose of this systematic review and meta-analysis was to evaluate the effects of massage on alleviating delayed onset of muscle soreness (DOMS) and muscle performance after strenuous exercise.Method: Seven databases consisting of PubMed, Embase, EBSCO, Cochrane Library, Web of Science, CNKI and Wanfang were searched up to December 2016. Randomized controlled trials (RCTs) were eligible and the outcomes of muscle soreness, performance (including muscle maximal isometric force (MIF) and peak torque) and creatine kinase (CK) were used to assess the effectiveness of massage intervention on DOMS.Results: Eleven articles with a total of 23 data points (involving 504 participants) satisfied the inclusion criteria and were pooled in the meta-analysis. The findings demonstrated that muscle soreness rating decreased significantly when the participants received massage intervention compared with no intervention at 24 h (SMD: –0.61, 95% CI: –1.17 to –0.05, P = 0.03), 48 h (SMD: –1.51, 95% CI: –2.24 to –0.77, P < 0.001), 72 h (SMD: –1.46, 95% CI: –2.59 to –0.33, P = 0.01) and in total (SMD: –1.16, 95% CI: –1.60 to –0.72, P < 0.001) after intense exercise. Additionally, massage therapy improved MIF (SMD: 0.56, 95% CI: 0.21–0.90, P = 0.002) and peak torque (SMD: 0.38, 95% CI: 0.04–0.71, P = 0.03) as total effects. Furthermore, the serum CK level was reduced when participants received massage intervention (SMD: –0.64, 95% CI: –1.04 to –0.25, P = 0.001).Conclusion: The current evidence suggests that massage therapy after strenuous exercise could be effective for alleviating DOMS and improving muscle performance.

PURPOSE:The main objective of the current research work was to investigate the antitumor effects of papaverine in PC-3 human prostate cancer cells along with testing its toxicity in the normal human fibroblast (NHF) cells.METHODS:The cytotoxic effects of papaverine were examined by the MTT cell viability assay. Flow cytometry using annexin V-FITC/PI was used to study the effects on apoptosis, including its quantification. Effects on cell cycle progression were analyzed by flow cytometry while as effects on apoptosis-related proteins, NF-kB and PI3K/Akt pathways were estimated by Western blot assay.RESULTS:The results indicated that papaverine could induce significant, highly selective and dose-dependent cytotoxic effects in PC-3 cells without causing too much toxicity in normal cells. Papaverine also led to induction of early and late apoptosis along with inducing sub-G1 cell cycle arrest in a dose-dependent manner. Papaverine induced a dose-dependent reduction in the expression levels of Blc-2 proteins and a dose-dependent increase in the expression levels of Bax protein. The expression levels of NF-kB were decreased markedly in comparison to the untreated control. Papaverine treatment also led to a dose-dependent downregulation of PI3K and phospho-Akt expression.CONCLUSION:Papaverine showed selective antitumor properties against PC-3 human prostate cancer cells by inducing early and late apoptosis, sub-G1 cell cycle arrest, modulation of apoptosis-related proteins like Bcl-2, Bax, Bid, XIAP and cytochrome C along with downregulation of NFkB, PI3K/Akt signalling pathway.

Background: Mitochondrial DNA (MtDNA) mutations affecting flagellar movement are often causes of sperm dysmotility. Among these mutations, mitochondrial transfer RNA (mt-tRNA) is the hot spot. However, the role of mt-tRNA mutations in male infertility remains heated debates. Purpose: To evaluate the roles of mt-tRNA mutations in male infertility. Methods: To address this problem, we reassessed 5 recent reported mutations: tRNAHis C12187A, tRNAThr G15928A, tRNAArg T10463C, tRNALys A8312G and tRNAAsp T7572C, in clinical expression of asthenozoospermia. We first performed database searches for these mutations; in addition, the phylogenetic approach was performed to determine the Conservation Index (CI) of these mutations between different species. We also used the bioinformatics tool to predict the secondary structure of mttRNAs with and without these mutations. In addition, the pathogenicity scoring system was used to assess the status of each mt-tRNA mutation. Results: We found that only tRNALys A8312G mutation could be regarded as "possibly pathogenic", whereas other mutations should be classified as "neutral polymorphisms". Conclusions: This is the first report dealing with the association between mt-tRNA mutations and male infertility, thus, our study provided novel insight into the molecular basis underlying mt-tRNA mutations in male infertility.

目的 分析肿瘤抑制基因CMTM5甲基化在肾癌表达,为临床诊断治疗提供参考.方法 检测肾癌细胞系和正常人肾细胞株中CMTM5的表达及甲基化水平.选取本院及部分苏大附一院肾癌患者为研究对象,检测患者血液、尿液中CMTM5的甲基化水平.征得患者同意后,肾癌患者手术治疗,留取标本,进行CMTM5的甲基化检测.结果 正常人肾细胞株CMTM5蛋白阳性率显著高于肾癌细胞株(χ2=3.2641,P<0.05),CMTM5甲基化阳性率显著低于肾癌细胞株(χ2=3.6944,P<0.05).肾癌组织中CMTM5蛋白阳性率(52.4%)显著低于正常肾组织(76.7%)(χ2=7.8889,P<0.05),CMTM5甲基化阳性率(73.0%)显著高于正常肾组织(48.3%)(χ2=7.8889,P<0.05),预后较差患者CMTM5表达较低.CMTM5甲基化表达与肾癌患者年龄、性别、病理分级无关,早期肾癌CMTM5甲基化表达显著低于Ⅲ期以后患者(χ2=6.3087,P<0.05).结论 CMTM5在肾癌组织中表达下调,且和其甲基化程度密切相关.肾癌患者的血液或尿液标本能检测到CMTM5的甲基化,可能为肾癌的早期诊断提供新的参考.