miR-192负性调控人肝癌细胞株HepG2中RB1基因的表达

目的 探讨miR-192对人肝癌细胞株HepG2中RB1基因表达的调节作用.方法 运用生物信息学方法对miR-192进行靶基因预测并分析其潜在靶基因RB1;将含有miR-192结合位点的RB1 mRNA 3′端非编码区(3′UTR)片段和在miR-192结合位点进行突变的RB1 3′UTR突变片段克隆至报告基因载体pMIR-Report luciferase vector,重组质粒分别命名为pMIR-RB1和pMIR-RB1-mut;将重组质粒、Beta-gal内参质粒和microRNA共转染HepG2细胞,双荧光素酶报告基因系统检测各实验组中细胞荧光素酶的表达;SYBR Green荧光定量PCR和Western blot分别在mRNA和蛋白水平检测miR-192对内源性RB1表达的调节作用.结果 生物信息学分析筛选出89个miR-192的潜在靶基因,RB1基因是其中之一;测序验证重组质粒pMIR-RB1和pMIR-RB1-mut构建成功;过表达miR-192时,共转染pMIR-RB1质粒的细胞相对荧光素酶活性(4.80±0.36)较相应过表达miR-NC组(7.90±0.91)明显降低(P＜0.05),而共转染pMIR-Luc或pMIR-RB1-mut质粒的细胞相对荧光素酶活性[pMIR-Luc:(7.68±1.04);pMIR-RB1-mut:(7.56±0.99)]较相应过表达miR-NC组[pMIR-Luc:(7.86±0.73);pMIR-RB1-mut:(7.82±1.05)]无显著差异;上调miR-192水平显著降低HepG2细胞中内源性RB1 mRNA[(0.56±0.10)vs (1.05±0.13)]和蛋白(47% vs 100%)的表达.结论 RB1基因是miR-192的一个靶基因,在HepG2细胞中,miR-192通过直接结合RB1 mRNA 3′UTR而负性调控RB1基因表达.     

原发性卵巢类癌病例报告及文献复习

目的:探讨原发性卵巢类癌组织起源,临床病理特点、治疗及预后.方法:报道2例原发性卵巢类癌,并进行临床病理分析.结果:病例1中患者为40岁女性,病例2中患者为33岁女性,2例患者临床症状均有下腹疼痛,2例患者均接受手术治疗.组织病理学类型为:岛状型.临床病理分期病例1为Ⅰ a期,手术后无其他治疗已无瘤生存9年;病例2为Ⅲ...     

Prognostic impact of carcinoembryonic antigen (CEA) on patients with metastatic pancreatic cancer: A retrospective cohort study

BackgroundCarcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30–60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC.MethodsWe conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed.ResultsMedian overall survival (OS) was significantly shorter for patients with high CEA (>5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p < 0.001). After adjustment, CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45–2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71–1.40).ConclusionsThe present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA.     

Impact of Multiparametric MRI and PSA Density on the Initial Indication or the Maintaining in Active Surveillance During Follow-Up in low-Risk Prostate Cancer

IntroductionA greater selection of candidates for active surveillance (AS) of prostate cancer (PCa) may decrease the rate of delayed treatment. We aimed to study: 1) the impact of MRI and PSA density (PSAd) at baseline on the final status, and 2) the impact of bio-clinical features during the follow-up on pursuing AS.Materials and MethodsThis retrospective, monocentric study between June 2013 and July 2020, included 99 patients in AS (median follow-up: 19 months [18-92]). All MRI were reviewed by a single radiologist. Lost to follow-up were 17 patients and 6 patients chose treatment by themselves. Treatment was proposed in case of upgrading (≥ GG2) or increasing PCa volume.ResultsImpact of MRI and PSAd at baseline:  Combining PSAd ≤ 0.15 and PIRADS ≤ 3, the probability to remain in AS was 72%. This rate reached 83% when PSAd ≤ 0.10 was associated to normal MRI.  During follow-up:  One hundred fifty-seven prostatic biopsies (PBx) were performed and 38 (24%) found PCa upgrading. The association between negative MRI and PSAd ≤ 0.10, during follow-up, had an excellent NPV to predict treatment (95%). This combination concerned 25% (37/151) of surveillance biopsies that could have been avoided at the cost of delaying upgrading in 3% (1/37). In multivariate analysis, only PIRADS ≥ 4 before PBx was associated to a risk of treatment during follow-up (OR, 10.4 [95% CI, 4.2-25.8]; P < .0001).ConclusionUsing PSAd and MRI at baseline to select patients showed excellent performances to predict the maintenance in AS. During follow-up, MRI PIRADS ≥ 4 was associated to an increased risk of treatment.     

Minimal Residual Disease Negativity Does Not Overcome Poor Prognosis in High-Risk Multiple Myeloma: A Single-Center Retrospective Study

BackgroundMinimal residual disease (MRD) is a standard measurement for response assessment in multiple myeloma (MM). Despite new treatments, high-risk MM patients continue to have poor prognosis. We evaluated the effect of MRD negativity in high-risk versus standard-risk patients.Patients and MethodsWe retrospectively evaluated all consecutive MM patients who underwent routine MRD testing by 1-tube 8-color advanced flow cytometry with 2,000,000 events and sensitivity level 10⁻⁵ at our center from 2015 to 2018 after initial therapy. Kaplan-Meier and log-rank test were used to assess survival estimates and differences between study groups.ResultsOne hundred thirty-six patients with MRD testing after initial therapy or autologous stem-cell transplantation were identified. At a median follow-up of 14 months (range, 1-36 months), progression-free survival and overall survival were significantly worse in high-risk versus standard-risk patients. During the study period, 50% of high-risk group had experienced disease progression (relapse and/or death) versus 20% in the standard-risk group (P = .0006). No patients with standard-risk died, but 4 (14%) in the high-risk group did (P = .0007). Regardless of MRD status, high-risk patients had statistically significant worse progression-free survival than standard-risk patients. At median follow-up, those with disease 10% standard-risk/MRD negative; 20% standard-risk/MRD positive; 40% high-risk/MRD negative; and 45% high-risk/MRD positive had either experienced relapse or died (P = .0041). MRD status did not significantly affect overall survival in either group (P = .0914); however, longer follow-up is needed to assess survival.ConclusionGenetic abnormalities remain a powerful prognostic indicator for MM, regardless of MRD status. For newly diagnosed MM patients treated with novel triple-drug initial therapy and frontline autologous stem-cell transplantation, MRD-negative status did not mitigate the poor-prognosis outcomes of high-risk MM patients.     

Infantile-onset ascending hereditary spastic paralysis: A case report and brief literature review

BackgroundInfantile-onset ascending hereditary spastic paralysis (IAHSP) is a rare, early-onset autosomal recessive motor neuron disease associated with mutations in ALS2.AimWe studied a 17-year-old boy who had features of IAHSP. We also reviewed the current literature on ALS2-related syndromes.MethodsClinical and neuroimaging studies were performed. Blood DNA analyses were combined with mRNA studies in cultured skin fibroblasts.ResultsLike previously described cases, the patient presented with severe spastic paraparesis and showed rapid progression of paresis to the upper limbs. He also developed bulbar involvement and severe scoliosis during childhood. In blood DNA we identified a novel splice-site homozygous mutation in ALS2 (c.3836+1G > T), producing exon skipping in fibroblast mRNA and predicting premature protein truncation.ConclusionsThis case adds to the allelic heterogeneity of IAHSP. Review of the pertinent literature indicates a fairly homogeneous clinical picture in IAHSP that should facilitate molecular confirmation and prevention of long-term complications.     

Artificial Intelligence in Cardiovascular Imaging: “Unexplainable” Legal and Ethical Challenges?

Nowhere is the influence of artificial intelligence (AI) likely to be more profoundly felt than in health care, from patient triage and diagnosis to surgery and follow-up. Over the medium-term, these effects will be more acute in the cardiovascular imaging context, in which AI models are already successfully performing at approximately human levels of accuracy and efficiency in certain applications. Yet, the adoption of unexplainable AI systems for cardiovascular imaging still raises significant legal and ethical challenges. We focus in particular on challenges posed by the unexplainable character of deep learning and other forms of sophisticated AI modelling used for cardiovascular imaging by briefly outlining the systems being developed in this space, describing how they work, and considering how they might generate outputs that are not reviewable by physicians or system programmers. We suggest that an unexplainable tendency presents 2 specific ethico-legal concerns: (1) difficulty for health regulators; and (2) confusion about the assignment of liability for error or fault in the use of AI systems. We suggest that addressing these concerns is critical for ensuring AI’s successful implementation in cardiovascular imaging.