Background The rising burden of urolithiasis in Southeast Asia and the lack of efficient risk-screening tools for low-resource primary care, such as those in Laos, motivated the development and external validation of a pragmatic nomogram integrating accessible environmental, behavioral, and clinical factors for in-hospital urolithiasis risk stratification, with long-term goal of application in grassroots screening. Methods A retrospective study was conducted with 665 consecutive inpatients (≥18 years, local residence ≥6 months) at a Lao Military Hospital (March 2024–February 2025). Data were collected using standardized questionnaires and electronic medical records. Least Absolute Shrinkage and Selection Operator (LASSO) regression selected predictors; nomogram performance was assessed by discrimination (area under the curve (AUC)), calibration (Brier score and Hosmer–Lemeshow test), and clinical utility (decision curve analysis (DCA)). Results Urolithiasis prevalence was 23.0% (153/665). Independent predictors included age (30–59 years, OR = 1.54; ≥60 years, OR = 1.13), sex (OR = 0.59), rural residence (OR = 0.52), high water intake (>1,500 mL/day, OR = 0.02), high sodium consumption (>10 g/day, OR = 21.90), and elevated blood calcium (OR = 9.12). The nomogram presented stable predictive performance, with an AUC of 0.882–0.907, Brier score of 0.086–0.111 (acceptable calibration, Hosmer–Lemeshow p = 0.198–0.892), and optimal clinical threshold at 0.20. Conclusions This externally validated nomogram uses six accessible environmental, behavioral, and clinical factors to stratify urolithiasis risk in Laos. At present, it helps guide targeted referral and optimize s resource allocation for hospitalized patients in resource—limited settings, while its application in primary care and among broader Southeast Asian populations remains to be prospectively evaluated.

BACKGROUND:As the only approved oral medication for premature ejaculation (PE), dapoxetine faces a high discontinuation rate, primarily due to lower than expected efficacy. The impact of serum metabolites on PE treatment remains undetermined; therefore, we aimed to identify metabolites associated with dapoxetine efficacy. METHODS:Clinical data and blood samples were collected from 116 patients with lifelong PE before 8 weeks of dapoxetine treatment. Serum was analyzed by untargeted metabolomics profiling. Efficacy was assessed with the Clinical Global Impression of Change (CGIC) scale: scores ≥ 1 were classified as the effective group and ≤ 0 as the ineffective group. Differential serum metabolites between the two groups were identified using the Mann-Whitney U test. Enrichment analysis determined metabolic pathways significantly associated with efficacy. RESULTS:Compared to the ineffective group, indoleacrylic acid and (-)-riboflavin were significantly upregulated in the effective group, while 15-keto-13,14-dihydroprostaglandin A2, dienestrol, hippuric acid, and PC (16:0/16:0) were downregulated. The six metabolites showed a discriminatory ability of 0.646, 0.667, 0.633, 0.645, 0.651, and 0.635, respectively. Incorporating them significantly improved the accuracy of the model predicting efficacy (0.892 vs. 0.738, p = 0.001), suggesting that modulating these specific metabolites may be a novel strategy for PE treatment. Moreover, differential metabolic ions between the two groups were mostly enriched in the arachidonic acid metabolism pathway, indicating that this pathway may represent an additional route associated with dapoxetine response. CONCLUSIONS:This study revealed serum metabolites correlated with dapoxetine efficacy, paving the way for future research into novel therapeutic targets and personalized treatment strategies.

BACKGROUND:Despite being the only approved oral therapy for premature ejaculation (PE), dapoxetine faces high discontinuation rates because of its suboptimal efficacy. Given that the role of gut microbiota in PE treatment has remained unexplored, we aim to investigate gut microbiota that may reflect the efficacy of dapoxetine. METHODS:Clinical data and fecal samples were collected from patients with lifelong PE before treatment. Gut microbiota was profiled via 16S rDNA sequencing, and differential microbiota between effective and ineffective groups were identified with the LEfSe method. To explore potential links between gut dysbiosis and efficacy, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway functional predictions were performed with the PICRUSt2 method. Efficacy was assessed using the Clinical Global Impression of Change (CGIC) scale, with scores ≥1 defined as the effective group. RESULTS:In the effective group, Erysipelotrichaceae_UCG_003, Parabacteroides_distasonis, and Prevotella_7_unclassified were significantly more prevalent, while Collinsella aerofaciens was less abundant. Their abundance was significantly correlated with CGIC scores, with correlation coefficients of 0.331, 0.250, 0.288, and ‒0.345, respectively. The discriminatory abilities of the four differential microbiota were 0.654, 0.669, 0.701, and 0.615, respectively. Incorporating them significantly improved the accuracy of the model predicting efficacy (0.796 vs. 0.738), which further suggests that modulating microbiota could be a novel strategy for PE treatment. The predicted gene abundance in the arachidonic acid metabolism pathway was significantly elevated in the effective group, indicating that dapoxetine's mechanism may also involve modulating this pathway. CONCLUSIONS:This study identified gut microbiota associated with the efficacy of dapoxetine for the first time. Targeted modulation of specific gut microbiota may provide a novel strategy for PE treatment.

BACKGROUND:Although a nomogram for predicting the efficacy of dapoxetine (DapE-Nomo) has already been developed, its reliability is limited due to only 4 weeks of follow-up and a lack of external validation. Several patients with premature ejaculation (PE) achieve satisfactory therapeutic effects after longer periods of treatment clinically, we therefore aimed to develop and validate an 8-week DapE-Nomo. METHODS:The training cohort included 243 patients with lifelong PE from Xijing Hospital and Northwest Women's and Children's Hospital (Jan 2019-Jul 2020), while the validation cohort comprised 397 patients from Xijing Hospital and Xi'an Daxing Hospital (Aug 2020-Jan 2022). Efficacy was measured using the Clinical Global Impression of Change (CGIC) scale, with a CGIC score ≥ 1 indicating an improvement (iCGI). LASSO regression was utilized to identify the most valuable predictors (MVPs) of iCGI. The DapE-Nomo was developed utilizing logistic regression coefficients of MVPs and validated across both cohorts. RESULTS:After 8 weeks of medication, 47.7% of patients in the training cohort and 47.6% in the validation cohort achieved iCGI. MVPs of iCGI included intravaginal ejaculation latency time, difficulty delaying ejaculation, and education level. The DapE-Nomo showed discriminatory abilities of 0.722 and 0.709 in internal and external validations, respectively, with satisfactory calibration and clinical utility in both. The optimal cutoff value of the DapE-Nomo was identified as 153.4 in both cohorts. Individuals with scores ≥153.4 exhibited a 3.833-fold and 4.137-fold chance of achieving iCGI, respectively, compared with those with scores < 153.4. CONCLUSION:We constructed and validated the inaugural 8-week DapE-Nomo. In outpatient settings, it will enable andrologists to more accurately evaluate the efficacy and promptly adjust treatment plans for patients with scores below 153.4. Moreover, It will help patients who've taken dapoxetine for 4 weeks with poor results decide whether to stop.

Patient Health Questionnaire-9 (PHQ-9) is the most widely used tool for screening for major depressive disorder (MDD). Although its reliability and validity have been proven, missed or misjudged cases during MDD screening are often encountered. A nomogram that considers the weights of depressive symptoms was developed using data from premature ejaculation patients to improve screening accuracy. During a 33-month prospective study, a training cohort comprising 605 participants from Xijing Hospital was used to develop and internally validate the nomogram. A validation cohort comprising 461 patients from Xi'an Daxing Hospital was also used to externally test the nomogram. The nomogram was established by integrating the LASSO regression-based optimal predictors of MDD according to their coefficients in a multivariate logistic regression model. The nomogram was well-calibrated during internal and external validations. Moreover, it showed a better discriminatory capacity and yielded more net benefits in both validations than PHQ-9. With better performance, the nomogram may help reduce the number of missed or misjudged cases during MDD screening. This study is the first to weigh the direct indicators of MDD under the DSM-5 criteria, presenting a fresh concept that can be applied to other populations to enhance screening accuracy.

Background:Although erectile dysfunction (ED) often occurs simultaneously with depression, not all patients with ED suffer major depression (MD), with a PHQ-9 score ≥15 indicating MD. Because the PHQ-9 questionnaire includes phrases such as "I think I am a loser" and "I want to commit suicide," the psychological burdens of ED patients are likely to increase inevitably after using the PHQ-9, which, in turn, may affect ED therapeutic effects. Accordingly, we endeavored to develop a nomogram to predict individual risk of PHQ-9 score ≥15 in these patients.Methods:The data of 1,142 patients with ED diagnosed in Xijing Hospital and Northwest Women and Children's Hospital from January 2017 to May 2020 were analyzed. While the Least Absolute Shrinkage and Selection Operator regression was employed to screen PHQ-9 score ≥15 related risk factors, multivariate logistic regression analysis was performed to verify these factors and construct the nomogram. The training cohort and an independent cohort that comprised 877 prospectively enrolled patients were used to demonstrate the efficacy of the nomogram.Results:The IIEF-5 score, PEDT score, physical pain score, frequent urination, and feeling of endless urination were found to be independent factors of PHQ-9 score ≥15 in patients with ED. The nomogram developed by these five factors showed good calibration and discrimination in internal and external validation, with a predictive accuracy of 0.757 and 0.722, respectively. The sensitivity and specificity of the nomogram in the training cohort were 0.86 and 0.52, respectively. Besides, the sensitivity and specificity of the nomogram in the validation cohort were 0.73 and 0.62, respectively. Moreover, based on the nomogram, the sample was divided into low-risk and high-risk groups.Conclusion:This study established a nomogram to predict individual risk of PHQ-9 score ≥15 in patients with ED. It is deemed that the nomogram may be employed initially to avoid those with a low risk of MD completing questionnaires unnecessarily.

目的 观察经皮神经电刺激(TENS)对慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)的临床疗效.方法 选取空军军医大学第一附属医院泌尿外科就诊的CP/CPPS患者140例,随机分为治疗组和对照组,治疗组采用经皮神经电刺激联合药物治疗,对照组采取药物治疗,观察比较治疗前后两组患者慢性前列腺炎症状评分(NIH-CPSI)、国际前列腺症状评分(IPSS)、治疗有效率等指标的变化.结果 共122例患者完成了整个临床研究.治疗后,两组患者NIH-CPSI评分和IPSS评分较治疗前均显著降低(P<0.001),且两组患者间NIH-CPSI评分和IPSS评分有统计学差异(P<0.001).治疗组总体有效率(95.1％)高于对照组(90.2％),且治疗组显效率(70.5％)明显高于对照组(4.9％),差异均有统计学意义(P<0.001).与对照组相比,治疗组NIH-CPSI评分变化值(分)与年龄(岁)具有较强的正相关关系(r=0.477,P<0.001).结论 与单一药物治疗相比,TENS联合药物可明显改善CP/CPPS患者的临床症状,其治疗显效率明显高于单一药物治疗;与中青年患者相比,TENS疗法可能更适合中老年患者.

目的 根据射精潜伏期(EL)建立原发性早泄大鼠模型,并与根据射精频率(EF)建立模型的方法做对比,探究其可行性.方法 用雄性Wistar大鼠84只,同龄雌性Wistar大鼠50只,雌鼠去势后在交配实验前用激素诱导发情,雌雄大鼠1∶1合笼1 h,观察记录大鼠性行为学参数:骑跨潜伏期(ML)、插入潜伏期(IL)、射精潜伏期(EL)、骑跨频率(MF)、插入频率(IF)、射精频率(EF)、射精后间隔(PEI)以及插入比例(IR).分析发现EL和EF均呈正态分布N(μ,σ2).根据EF分布规律及10％原则,将大鼠分为快速射精组(EF＜3),正常射精组(3≤EF≤5)及迟缓射精组(EF＞5);根据EL的分布规律,将大鼠同样分为快速射精组(EL＜μ-a),正常射精组(μ-σ≤EL≤μ+σ)及迟缓射精组(EL＞μ+σ).结果 最终筛选出54只大鼠.两种建模方法都显示:3组大鼠(快速射精、正常射精及迟缓射精组)的EL明显递增,EF明显递减,而MF、ML、IL以及IR差异无统计学意义(P＞0.05).且根据EL建模的方法能显示出PEI和IF的差异性(P＜0.05),而用EF建模的方法未能显示出此差异(P＞0.05).结论 根据EL建立原发性早泄大鼠模型可以筛选出快速射精的大鼠,且与根据EF建模的方式相比能显示出更多的差异.

Warburg effect is a pivotal hallmark of cancers and appears prevalently in renal cell carcinoma (RCC). FBP1 plays a negative role in Warburg effect as a rate-limiting enzyme in gluconeogenesis, yet its mechanism in RCC remains to be further characterized. Herein, we revealed that FBP1 was downregulated in RCC tissue samples and was related to the poor survival rate of RCC. Strikingly, miR-24-1 whose DNA locus is overlapped with enhancer region chr9:95084940-95087024 was closely linked with the depletion of FBP1 in RCC. Of note, miRNAs like miR-24-1 whose DNA loci are enriched with H3K27ac and H3K4me1 modifications are belonging to nuclear activating miRNAs (NamiRNAs), which surprisingly upregulate target genes in RCC through enhancer beyond the conventional role of repressing target gene expression. Moreover, miR-24-1 reactivated the expression of FBP1 to suppress Warburg effect in RCC cells, and subsequently inhibited proliferation and metastasis of RCC cells. In mechanism, the activating role of miR-24-1 was dependent on enhancer integrity by dual luciferase reporter assay and CRISPR/Cas9 system. Ultimately, animal assay in vivo validated the suppressive function of FBP1 on 786-O and ACHN cells. Collectively, the current study highlighted that activation of FBP1 by enhancer-overlapped miR-24-1 is capable of contributing to Warburg effect repression through which RCC progression is robustly blocked, providing an alternative mechanism for RCC development and as well implying a potential clue for RCC treatment strategy.

Purpose PLND (pelvic lymph node dissection)-validated nomograms are widely accepted clinical tools to determine the necessity of PLND by predicting the metastasis of lymph nodes (LNMs) in pelvic region. However, these nomograms are in lacking of a threshold to predict the metastasis of extrareolar lymph nodes beyond pelvic region, which is not suitable for PLND. The aim of this study is to evaluate a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases beyond pelvic region in high-risk prostate cancer patients, by using 68Ga-PSMA PET/CT as a reference to determine LN metastases (LNMs). Experimental Design We performed a retrospective analysis of 57 high-risk treatment-naïve PC patients in a large tertiary care hospital in China who underwent 68Ga-PSMA-617 PET/CT imaging. LNMs was detected by 68Ga-PSMA-617 PET/CT and further determined by imaging follow-up after anti-androgen therapy. The pattern of LN metastatic spread of PC patients were evaluated and analyzed. The impact of 68Ga-PSMA PET/CT on clinical decisions based on three clinical PLND-validated nomograms (Briganti, Memorial Sloan Kettering Cancer Center, Winter) were evaluated by a multidisciplinary prostate cancer therapy team. The diagnostic performance and the threshold of these nomograms in predicting extrareolar LNMs metastasis were evaluated via receiver operating characteristic (ROC) curve analysis. Results LNMs were observed in 49.1% of the patients by 68Ga-PSMA PET/CT, among which 65.5% of LNMs were pelvic-regional and 34.5% of LNMs were observed in extrareolar sites (52.1% of these were located above the diaphragm). The Briganti, MSKCC and Winter nomograms showed that 70.2%-71.9% of the patients in this study need to receive ePLND according to the EAU and NCCN guidelines. The LN staging information obtained from 68Ga-PSMA PET/CT would have led to changes of planned management in 70.2% of these patients, including therapy modality changes in 21.1% of the patients, which were mainly due to newly detected non-regional LNMs. The thresholds of nomograms to predict non-regional LNMs were between 64% and 75%. The PC patients with a score >64% in Briganti nomogram, a score >75% in MSKCC nomogram and a score >67% in Winter nomogram were more likely to have non-regional LNMs. The AUCs (Area under curves) of the clinical nomograms (Briganti, MSKCC and Winter) in predicting non-regional LNMs were 0.816, 0.830 and 0.793, respectively. Conclusions By using 68Ga-PSMA PET/CT as reference of LNM, the PLND-validated clinical nomograms can not only predict regional LNMs, but also predict non-regional LNMs. The additional information from 68Ga-PSMA PET/CT may provide added benefit to nomograms-based clinical decision-making in more than two-thirds of patients for reducing unnecessary PLND. We focused on that a threshold can be set for current clinical PLND-validated nomograms to predict extrareolar LN metastases with an AUC accuracy of about 80% after optimizing the simple nomograms which may help to improve the efficiency for PC therapy significantly in clinical practice.

Background: Renal cell carcinoma (RCC) is the most common malignancy in the urinary system. Despite substantial improvements in available treatment options, the survival outcome of advanced RCC is unsatisfactory. Identifying novel biomarkers to assist in early diagnosis and to screen patients who are sensitive to immunotherapy would be beneficial. CD248 is a promising candidate that deserves to be investigated.Methods: The Cancer Genome Atlas (TCGA) data set and clinical specimens were adopted to analyze the expression of CD248 between normal and tumor tissues. Univariate and multivariate Cox regression analyses were employed to identify independent prognostic factors and construct a CD248-based prognostic signature. The correlation among the present signature, tumor-infiltrating immune cells (TIICs), the tumor mutation burden (TMB), and immunomodulatory molecules was evaluated. The weighted gene co-expression network analysis (WGCNA), the enrichment analysis, and the miRNA correlation analysis were performed to explore the underlying mechanism of CD248 in the progression of RCC.Results: The overexpression of CD248 in RCC was related to a poor prognosis, and a CD248-based prognostic signature could precisely stratify patients with RCC with different survival outcomes regardless of the training or testing cohort. The present signature could reflect the immunosuppressive landscape of RCC (i.e., increased infiltration of regulatory T cells and upregulated immune checkpoints), accompanied by deteriorated clinicopathologic indexes. The TMB and immunostimulatory molecules expression also increased with the risk score generated from the present signature. CD248 co-expressed gene sets were identified through the WGCNA algorithm, and several immunosuppressive Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were significantly enriched. The result of CD248-correlated miRNA further emphasized the importance of CD248 in RCC.Conclusion: CD248 is a valuable biomarker to improve the diagnostic and therapeutic efficiency of RCC. The immunosuppressive effect of CD248 co-expressed genes may provide insight for the present study, and miRNA would help to reveal the mechanism of the expressive regulation of CD248.

恶性肿瘤引起的输尿管梗阻(malignant ureteral obstruction,MUO)通常由盆腔恶性肿瘤局部侵犯或压迫输尿管导致,大多数病例来自妇科、消化道及腹膜后肿瘤,且肿瘤的放化疗导致输尿管周围纤维化会加重梗阻的程度,此类患者如不进行治疗,将很快出现上尿路功能损害,甚至器官功能衰竭.上尿路减压和维持输尿管通畅为首选的治疗方案,治疗的目标是解除输尿管梗阻,避免泌尿系统的并发症,为患者提供继续治疗原发肿瘤的机会.随着技术进步及新材料的开发,各种输尿管支架包括聚合物输尿管支架、金属输尿管支架被应用于临床治疗MUO,为泌尿外科医师提供了更多的选择,同时有助于提高患者生活质量.

Ethnopharmacological relevance: Sini decoction (SND) is a famous Traditional Chinese Medicine (TCM) formula composed of Acontium carmichaeli, Zingiber officinale and Glycyrrhiza uralensis, which is considered as an efficient formula against doxorubicin (DOX)-induced heart failure. But the compatibility mechanism of SND remains unclear. Aim of the study: The present study aimed to investigate the compatibility mechanism of SND against DOX-induced heart failure in rats. Materials and methods: Mass spectrometry-based serum metabolomics were performed. The relative distance values (RDVs) of SND, A. carmichaeli-free decoction (ACFD), Z. officinale-free decoction (ZOFD) and G. uralensis-free decoction (GUFD) treated groups from the control/DOX groups in multidimensional space were calculated to provide a measure of compatibility effect of SND. SND, ACFD, ZOFD, GUFD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of SND by computational systems analysis. Real-time quantitative PCR was further employed to validate the key metabolic pathways at the level of the gene. Results: The RDVs combined with the hemodynamic and biochemical analysis showed that the protection effects were sorted as SND > GUFD > ZOFD > ACFD. It revealed that DOX-induced heart failure perturbed 16 metabolic pathways, and SND, GUFD, ZOFD and ACFD-treated groups could significantly reversed 12, 10, 7 and 6 metabolic pathways of these 16 metabolic pathways, respectively. Metabolic pathway and RT-PCR analysis indicated that both SND and GUFD could protect DOX-induced heart failure mainly by regulating PLA2-COX pathway and PLA2-CYP pathway. Conclusion: It can be concluded that A. carmichaeli played an essential role in attenuation of DOX-induced heart failure among the three herb constituents of SND and the constituent herbs mutually reinforced each other. This work demonstrated that metabolomics combined with computational systems analysis was a promising tool for uncovering the compatibility effects of TCM.

BACKGROUND:A predictive model for acquired premature ejaculation (APE) in PE patients has not yet been established.OBJECTIVES:This study was aimed at determining which factors were independently associated with the possibility of predicting APE in PE patients, and whether an effective pre-treatment nomogram for predicting their individual chances of being APE in PE patients can be developed.MATERIALS AND METHODS:We analyzed the medical histories of 915 PE patients diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) between May 2019 and May 2020. The diagnostic nomogram was developed using a multivariate logistic regression model by integrating selected significant variables determined through univariate analysis. Receiver operating characteristic curves were used to measure the predictive accuracy of the nomogram and its constituted variables, and calibrations were performed by making a comparison of nomogram-predicted probability with actual rate of APE.RESULTS:The independent predictors for APE that were identified include Age, Intra-vaginal Ejaculation Latency Time (IELT), Frequency of sexual desire (FSD), and Eysenck Personality Questionnaire-Revised Short Scale for Chinese (psychoticism) [EPQ-RSC(P)] scores. The predictive accuracy of the nomogram was 0.782 (95% CI: 0.723-0.841). Also, excellent agreement was demonstrated between the nomogram-predicted probability and the actual rate of APE.DISCUSSION AND CONCLUSION:We identified 4 independent predictors for APE and demonstrated the potential significant differences in psychoticism between LPE and APE patients. This was the first internally validated predictive APE nomogram where good discrimination and calibration were applied, and it offers a promising role in clinical practice. More studies are necessary for verification of its universal applicability.

ABSTRACT:Survival heterogeneity is observed among renal cell carcinoma (RCC) patients with metastases in different organs. Moreover, almost all previous prognostic nomograms based on data from metastatic RCC patients did not take competing events, such as death from cerebrovascular and heart diseases, into account. We aimed to construct novel prognostic nomograms for patients with lung metastatic clear cell RCC (LMCCRCC).Data of 712 non-Hispanic white LMCCRCC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Nomograms for predicting overall survival (OS) and disease-specific survival (DSS) were established using the Cox approach and Fine and Gray approach, respectively, and their performances were assessed using the concordance index (C-index), calibration plots, and an independent cohort comprising 181 Hispanic patients.Sex, tumor grade, T stage, N stage, presence or absence of bone metastases, and presence or absence of brain metastases were independent predictors for both OS and DSS. Additionally, presence or absence of liver metastases was an independent predictor only for DSS. Meanwhile, age at diagnosis was independently associated with OS. The C-indexes of the nomograms were 0.702 for OS and 0.723 for DSS in internal validation. In external validation, the C-indexes were 0.700 for OS and 0.708 for DSS. Both internal and external calibration plots showed excellent consistency between the prediction and the observation.The current study developed a novel nomogram for predicting individual OS in LMCCRCC patients. Moreover, we constructed an effective competing risk nomogram for predicting their individual DSS for the first time.

早泄(PE)是一种常见的男性性功能障碍,严重影响性生活质量.影像学技术作为科学研究的一种重要手段,在PE发生机制的研究中发挥着不可替代的作用.本文简述了PE的定义和分类及其发病的危险因素,重点从MRI、PET、脑电图、超声4种影像学技术的角度阐述PE发生机制的最新研究进展,并且提及了研究大脑功能代谢最新的fPET-FDG和一体化PET/MRI技术,以期为进一步的研究提供思路.

随着二代测序技术的出现,肿瘤基因组学的研究不断推进,二代测序联合液体活检技术在实体肿瘤中的应用研究不断深入.目前研究表明循环肿瘤DNA检测可能成为肾癌早期诊断、精准用药及病程监测的生物标志物.本文将对近几年循环肿瘤DNA在肾癌中的研究进展进行综述,探讨循环肿瘤DNA对肾癌的诊断、精准用药以及疾病监测等方面的临床价值,为后续循环肿瘤DNA在肾癌中的研究提供方向.

目的:基于生物信息学探索肾细胞癌发病相关基因,并联合临床指标构建可预测肾癌患者总生存期(overall survival,OS)联合指标预后列线图,为肾癌临床预后评估提供了有效的新方法.方法:基于基因表达数据库(Gene Expression Omnibus,GEO)筛选差异表达基因并在TCGA数据库中进行验证并进行基于蛋白互作(protein-protein interaction,PPI)网络的模块建立.同时于TCGA数据库中利用Cox多因素分析筛选基因及肾癌预后相关性,采用Kaplan-Meier法计算OS,log-rank检验评价不同亚组生存差异的显著性;运用Cox单因素及多因素回归分析确定OS的独立预测因素,使用R软件整合所有具有独立预测意义的变量绘制可以个体化预测3年和5年OS的列线图,并采用Bootstrap法计算ROC曲线下面积(AUC)、绘制校准图对列线图进行内部验证.结果:通过GEO筛选出DEGs380个,在TCGA数据库汇中验证overlapping基因28个,与肾癌OS相关基因为SLC22A8及TNFAIP6(P＜0.05).病理等级≥G3、T3和M1期、SLC22A8基因表达值≥4.50、TNFAIP6基因表达值≥11.20是OS的独立危险因素.预测模型可准确预测患者预后,其预测3、5年OS的AUC分别为0.793和0.740,校准图显示列线图预测的3、5年OS分别与实际3、5年OS具有良好的一致性.结论:本研究通过大数据分析,发现了10个肾癌发病相关基因,并纳入预后评估的模型,建立了一种联合指标肾癌预后预测模型,为临床中肾癌患者的预后评估提供了一种有效的新方法.

目的 探讨非转移性膀胱小细胞癌(BSCC)的独立预后因素,并建立可以个体化预测患者癌症特异性生存率(CSS)的列线图.方法 回顾性分析SEER数据库中2004年至2016年确诊并登记的BSCC患者的临床病理资料,簇选后共纳入360例患者,应用Kapla n-Meier法计算患者的生存率并绘制生存曲线,Log-rank检验评价不同亚组生存差异的显著性,并根据Cox多因素分析结果,运用R软件绘制列线图.列线图的预测性能由校准图和ROC曲线下面积(AUC)进行内部验证.结果 年龄＞80岁、肿瘤最大径＞5.0 cm及T4期是CSS的独立危险因素;术中盆腔淋巴结清扫、(术前或术后)辅助化疗或联合放化疗是独立保护因素.所建列线图预测确诊后1、3、5年CSS的预测精准度分别为0.79、0.72和0.71.结论 基于SEER数据库,本研究确定了非转移性BSCC的独立预后因素,并建立了可以个体化预测非转移性BSCC患者预后的列线图,这将有助于设计临床试验和促进医患沟通.

A new drug, Caba-780, was synthesized by chemical coupling of the heptamethyl phthalocyanine near-infrared fluorescent (NIRF) dye IR-780 and the paclitaxel-based chemotherapeutic drug cabazitaxel. Then, the potential value of Caba-780 in the diagnosis and treatment of castration-resistant prostate cancer (CRPC) was evaluated. The CRPC cell lines DU145 and PC-3, as well as the normal human prostate stromal cell line WPMY-1, were used to evaluate the uptake of Caba-780 and its antitumor effect in vitro. The distribution, antitumor effect, and safety of Caba-780 were also evaluated in tumor-bearing mouse xenograft models. Our results showed that Caba-780 was efficiently absorbed by DU145 and PC-3 cells and that the cytotoxicity of Caba-780 was significantly stronger than that of IR-780 and cabazitaxel. In addition, Caba-780 inhibited the migration and invasion of DU145 and PC-3 cells and promoted apoptosis by prolonging the G2 phase of the cell cycle. Further analysis indicated that Caba-780 could be used to effectively image tumor xenografts. At the same time, this drug inhibited the growth of tumors in vivo. Therefore, the new synthetic drug Caba-780 has potential applications in the diagnosis and treatment of CRPC.