目的 构建和评估腹腔镜前列腺根治性切除术(RP)后切缘阳性的列线图模型,为筛选出术后切缘阳性(PSM)高危人群提供预测工具.方法 回顾性分析350例接受腹腔镜RP患者的临床病理资料.根据术后病理结果分为切缘阳性组(124例)和切缘阴性组(226例).采用二元多因素Logistic回归分析筛选RP术后PSM的独立危险因素,并构建列线图,绘制受试者工作特征(ROC)曲线及校准曲线对模型的区分度和准确性进行评估,采用Bootstrap resampling法对列线图诊断效能进行内部验证.根据预测模型将患者分为高切缘阳性风险组和低切缘阳性风险组,采用Kaplan-Meier法比较两组无生化复发(BCR)时间的差异.结果 穿刺神经侵犯、穿刺阳性针数百分比、吸烟史及术中出血量是术后PSM的独立危险因素(均P<0.05).构建列线图,ROC曲线下面积(AUC)为0.845(95%CI:0.801~0.888),校准曲线显示预测曲线与实际曲线有较高的一致性.高切缘阳性风险组与低切缘阳性风险组BCR时间差异有统计学意义(P<0.05).结论 本研究构建的列线图有较高的预测效能,有助于术前评估患者RP术后PSM的风险,为个体化诊疗提供依据.
N6-methyladenosine (m 6 A) is a key area in Epigenetics and has been increasingly focused these years. In the m 6 A process, readers recognize the m 6 A modification on mRNAs or noncoding RNAs and mediate different downstream events. Emerging studies have shown that YTHDC1, an important m 6 A reader, plays a key role in many biological functions and disease progression, especially cancers. Here we summarized the current mechanisms of YTHDC1 in biological functions and diseases and offered guidance for future researches to provide potential strategy for clinical diagnose and therapy.
Purpose. To access the incidence and predictors of Gleason grade group upgrading from cognitive MR-targeted fusion prostate biopsy to radical prostatectomy in a Chinese cohort. Materials and Methods. We included 199 patients in our institution between January 2016 and June 2021. Multivariable logistic regression model and nomograms were utilized to analyze the collected data. Results. The concordance rate of biopsy Gleason grade group and radical prostatectomy was 50.3% (100 in 199). Upgrading occurred in 80 (40.2%) patients and 37 (68.5%) patients have an upgrading Gleason grade group when the biopsy Gleason grade group was 1. Multivariable logistic regression models were established to analyze the incidence and predictors of Gleason grade group upgrading from cognitive MR-targeted fusion prostate biopsy to radical prostatectomy. Biopsy Gleason grade group, prostate volume, and patient year were confirmed to be individual predictors of upgrading. Based on the logistic regression models, nomograms for predicting probability of prostate Gleason grade group upgrading were generated. Conclusions. We established a logistic regression model to predict the accuracy of prostate biopsy GG and provide the probability of upgrading. Clinicians should be more cautious when deciding the treatment strategy especially for prostate cancer biopsy GG1 patients. Future studies should expand the sample size and include more variables to improve the accuracy of predicting upgrading and prostate cancer early screening program is urgently needed in our city in China.
Objective This investigation devoted to lncRNA FGF14 antisense RNA 2 (FGF14-AS2) in prostate carcinoma progression. Methods The levels of lncRNA FGF14-AS2, miR-96-5p, and Adherens junction-associated protein-1 (AJAP1) in prostate carcinoma were tested by Western blot and qRT-PCR. How these two genes interacted was confirmed by RNA immunoprecipitation and dualluciferase gene methods. The effect of FGF14-AS2/miR-96-5p/AJAP1 axis in prostate carcinoma progression was determined by MTT, Transwell, and nude mice tumor model. Results FGF14-AS2 was a downregulated lncRNA in prostate carcinoma tissue and cells. FGF14-AS2 could restrain miR-96-5p expression while miR-96-5p hampered AJAP1. FGF14-AS2 could effectively decrease the biological behaviors of prostate carcinoma cells, while knock-down of FGF14-AS2 triggered opposite results. Moreover, miR-96-5p mimic presented a cancer promoter role in prostate carcinoma cells. AJAP1 expression level could affect levels of proteins related to epithelial-mesenchymal transition. In vivo experiment suggested that overexpressing FGF14-AS2 could reverse the promotion of silenced AJAP1 on prostate carcinoma cell metastasis, thus to inhibit tumor growth. Conclusion lncRNA FGF14-AS2 was a downregulated lncRNA in prostate carcinoma and influenced cell proliferation and metastasis. The influence relied on modulating miR-96-5p and its target gene AJAP1.
Objective:This study is to investigate the predictive value of serum levels of TIMP-2 and insulin-like growth factor-binding protein 7(IGFBP7) in patients with DCD(donation after cardiac death) kidney transplantation.Methods:A prospective research design was used to select DCD kidney transplant patients admitted to the Li Huili Hospital of Ningbo University from January 2018 to October 2020.Inclusion criteria: ①Complete data; ②There were no serious complications affecting the function of the transplanted kidney in the early postoperative period.Exclusion criteria: ①Incomplete data; ②Patients were unable or unwilling to cooperate with the study; ③Severe complications affecting the function of the transplanted kidney occurred early after the operation.The ELASE method was used to quantitatively detect the serum TIMP-2 and IGFBP7 levels at 6, 12, 24, 48, 72 hours and 7 days after renal transplantation, and monitor the serum creatinine values during the same period and 21 days after the operation. According to the occurrence of DGF, the measured values of TIMP-2 and IGFBP7 at different time points and their product's ability to predict the occurrence of DGF after kidney transplantation were analyzed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of TIMP-2 and IGFBP7 for DGF.Results:A total of 33 patients were enrolled, 7 patients (21.2%) in the DGF group and 26 patients (78.8%) in the non-DGF group. Between the two groups, the donor glomerular filtration rate were [98.5(15.8-132.5)ml/(min·1.73m 2) and 79.1(60.6-102.5)ml/(min·1.73m 2)], recipient gender (male/female: 3/4 cases and 10/16 cases), recipient age [48(34-56) Years old and 45(23-61) years old], the recipient's preoperative creatinine [1114.0(731.4-1293.0)μmol/L and 858.4(657.6-1051.9)μmol/L], the recipient's preoperative urea nitrogen [15.0(13.2-19.6)mmol/L and 17.3(13.6-20.9)mmol/L], receptor preoperative albumin [43.5(38.5-45.3)mmol/L and 41.2(37.5-46.1) mmol/L], recipient dialysis method [hemodialysis/peritoneal dialysis: 3/4 cases and 9/17 cases], warm ischemia time [6(5-7) and 5(4-6) min, there was no statistically significant difference] ( P>0.05). The values of serum IGFBP7 and TIMP-2×IGFBP7 in the DGF group were higher than those in the non-DGF group at all time points ( F=15.753, P=0.040; F=13.000, P=0.024), while serum TIMP-2 was not significant between the two groups difference ( F=1.157, P=0.075). For the diagnostic value of DGF, the AUC of serum IGFBP7 at 48 h after surgery was 0.863 (95% CI 0.696-1.000, P=0.004). When 5.97 ng/ml was used as the cut-off value, the sensitivity was 85.7% and the specificity was 80.8 %. The AUC of TIMP-2×IGFBP7 at 48 hours after surgery was 0.819 (95% CI 0.641-0.996, P=0.011). When 62.06(ng/ml) 2 was used as the cutoff value, the sensitivity was 71.4% and the specificity was 80.8%.There was no statistical difference in the area under the curve between the two ( P>0.05). There were differences in the dynamic trend of serum IGFBP7 and creatinine in the DGF group. Serum IGFBP7 at 7 days after surgery was positively correlated with creatinine at 21 days after surgery. Conclusion:Serum IGFBP7 and TIMP-2×IGFBP7 could predict the occurrence of DGF after DCD donor kidney surgery. The predictive value changes with time. Among them, 48h and 7d after surgery are the most valuable. However, serum TIMP-2 has not been found to have predictive value in this study.
Bladder cancer (BCa) is a common urinary tract malignancy with frequent recurrences after initial resection. Submucosal injection of gemcitabine prior to transurethral resection of bladder tumor (TURBT) may prevent recurrence of urothelial cancer. However, the underlying mechanism remains unknown. In the present study, ultra-performance liquid chromatography Q-Exactive mass spectrometry was used to profile tissue metabolites from 12 BCa patients. The 48 samples included pre- and post-gemcitabine treatment BCa tissues, as well as adjacent normal tissues. Principal component analysis (PCA) revealed that the metabolic profiles of pre-gemcitabine BCa tissues differed significantly from those of pre-gemcitabine normal tissues. A total of 34 significantly altered metabolites were further analyzed. Pathway analysis using MetaboAnalyst identified three metabolic pathways closely associated with BCa, including glutathione, purine and thiamine metabolism, while gluta-thione metabolism was also identified by the enrichment analysis using MetaboAnalyst. In search of the possible targets of gemcitabine, metabolite profiles were compared between the pre-gemcitabine normal and post-gemcitabine BCa tissues. Among the 34 metabolites associated with BCa, the levels of bilirubin and retinal recovered in BCa tissues treated with gemcitabine. When comparing normal bladder tissues with and without gemcitabine treatment, among the 34 metabolites associated with BCa, it was observed that histamine change may be associated with the prevention of relapse, whereas thiamine change may be involved in possible side effects. Therefore, by employing a hypothesis-free tissue-based metabolomics study, the present study investigated the metabolic signatures of BCa and found that bilirubin and retinal may be involved in the mechanism underlying the biomolecular action of submucosal injection of gemcitabine in urothelial BCa.
Glycolysis, through anaerobic respiration, can supply energy for human sperm motility. MicroRNAs (miRNAs) could participate in the glycolytic pathway through regulating target genes. To investigate the potential role of glycolysis-related miRNAs in asthenozoospermia, TaqMan Low Density Array (TLDA) was used to screen potentially functional miRNAs, and seven glycolysis-related miRNAs were isolated to be related to asthenozoospermia. After qRT-PCR validation, only one seminal plasma miRNA, let-7b-5p, was found significantly decreased in severe asthenozoospermia cases compared with healthy controls. To further understand whether let-7b-5p is involved in asthenozoospermia by regulating the glycolytic pathway, we carried out gain-and-loss function study of let-7b-5p in GC-2 cells and detected the glycolytic activities. Our results showed that knocking down let-7b-5p could inhibit glycolytic activities. Besides, we also found overexpressed Aurkb (a target gene of let-7b-5p) could recapitulate the effects of knocking down let-7b-5p. Our findings indicated that low expression of let-7b-5p could repress glycolysis in asthenozoospermia by targeting AURKB.
microRNAs (miRNAs) are a class of small RNAs that regulate gene expression. It has been demonstrated that aberrant miRNA expression is associated with cancer development and carcinogenesis. Altered miRNA expression has been suggested to occur in bladder cancer. In other cancer systems, studies have indicated that miR-143, as a tumor suppressor gene, plays essential roles in cancer progression. However, its role in bladder cancer has yet to be elucidated. In the present study, we observed that miR-143 expression was downregulated in human bladder cancer tissues and cells, and that its levels were negatively correlated with bladder cancer clinical stages. We further demonstrated that insulin-like growth factor-1 receptor (IGF-1R) is a functional target of miR-143. Their expression levels were inversely correlated in bladder cancer samples. Overexpression of miR-143 inhibited cell proliferation and promoted chemosensitivity of bladder cancer 5637 cells to gemcitabine. Consistently, small interfering RNA-mediated knockdown of IGF-1R phenocopied miR-143 overexpression. Notably, the expression of IGF-1R is a predictor of patient prognosis. Collectively, our findings indicate that miR-143 is a valuable biomarker for bladder cancer. The miR-143/IGF-1R axis is associated with bladder cancer drug resistance and patient survival.