Functional evidence of decreased tumorigenicity associated with monochromosome transfer of chromosome 14 in esophageal cancer and the mapping of tumor-suppressive regions to 14q32

Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an approximately 2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer.     

Impact of Dissection after Drug-Coated Balloon Treatment of De Novo Coronary Lesions: Angiographic and Clinical Outcomes

PurposeDissection after plain balloon angioplasty is required to achieve adequate luminal area; however, it is associated with a high risk of vascular events. This study aimed to examine the relationship between non-flow limiting coronary dissections and subsequent lumen loss and long-term clinical outcomes following successful drug-coated balloon (DCB) treatment of de novo coronary lesions.Materials and MethodsA total of 227 patients with good distal flow (Thrombolysis in Myocardial Infarction flow grade 3) following DCB treatment were retrospectively enrolled and stratified according to the presence or absence of a non-flow limiting dissection. The primary endpoint was late lumen loss (LLL) at 6-month angiography, and the secondary endpoint was target vessel failure (TVF, a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization, and target vessel thrombosis).ResultsThe cohort consisted of 95 patients with and 132 patients without a dissection. There were no between-group differences in LLL (90.8%) returning for angiography at 6 months (0.05±0.19 mm in non-dissection and 0.05±0.30 mm in dissection group, p=0.886) or in TVF (6.8% in non-dissection and 8.4% in dissection group, p=0.799) at a median follow-up of 3.4 years. In a multivariate analysis, the presence of dissection and its severity were not associated with LLL or TVF. Almost dissections (93.9%) were completely healed, and there was no newly developed dissection at 6-month angiography.ConclusionThe presence of a dissection following successful DCB treatment of a de novo coronary lesion may not be associated with an increased risk of LLL or TVF (Impact of Drug-coated Balloon Treatment in de Novo Coronary Lesion; {"type":"clinical-trial","attrs":{"text":"NCT04619277","term_id":"NCT04619277"}}NCT04619277).     

皮下通道型胆囊肝胆管成形术治疗肝胆管结石 和胆管狭窄的临床研究

目的：总结皮下通道型胆囊肝胆管成形术的临床效果。方法：统计了1994年以来我院76例行STHG手术患者的适应症、临床效果及术后早期并发症。并选择同期实施的125 列行传统胆肠吻合（CJ）的患者进行对照。结果：STHG的手术适应症与传统胆肠吻合基本相同;STHG组患者的手术时间、住院时间、术中出血量明显少于CJ组,术后恢复良好,仅2例次并发症。结论;该术式既保存了胆囊及Oddi括约肌功能,又保证了胆汁的生理流向;防止了肠液的反,所以避免了消化功能紊乱,防止了反 流性胆管炎,对患者的影响小,是一种较为理想的治疗肝胆管结石和肝门胆管狭窄的术式。     

乙肝基因疫苗系列质粒的构建及其在真核细胞中的表达

目的 构建一系列乙肝病毒表面抗原大、中、小蛋白的真核细胞表达质粒,并研究其在真核细胞中的表达情况。方法 采用常规PCR法扩增S、前S2－S、前S1－前S2－S片断,利用重叠PCR法扩增出前S1－S片断后,分别插入Rc/CMV及pSG5UTPL/Flag载体质粒中,并在其ATG起始密码前加入KOZAK序列后转染SP2／0细胞,Western-Blot杂交检测所表达蛋白,并用核酸自动分析仪分析所插入片断的核酸序列。结果 插入片断的核苷酸序列与相应的大、中、小蛋白和前S1－S蛋白的编码基因一致,Western-Blot杂交检测出了相应的目的蛋白。结论 获得了8个能高效表达乙肝病毒表面抗原大、中、小蛋白和前S1－S蛋白的真核细胞表达质粒。     

Effects of diuretics on intradialytic hypotension in maintenance dialysis patients: a systematic review and meta-analysis

Purpose

Intradialytic hypotension (IDH) is a serious complication in dialysis patients. Diuretics might reduce the incidence of IDH by decreasing ultrafiltration. However, the effect of diuretics on IDH in maintenance dialysis patients is still unclear.

Methods

We searched Medline, Embase, the Cochrane Library, China National Knowledge Infrastructure and clinical trials registries from 1945 to May 2019. Randomized controlled trials (RCTs) or observational studies about IDH in maintenance dialysis with diuretics were included.

Results

Seven studies including 28,226 patients were included, of which 4 were RCTs involving mineralocorticoid receptor antagonists (MRAs) and 3 were observational studies involving loop diuretics. There was a trend that a lower incidence rate of IDH in maintenance dialysis patients who used loop diuretics than control, although the result was not statistically significant (OR 0.65, 95% CI 0.34–1.22, P?=?0.18). Similarly, lower incidence rate of all-cause mortality (OR 0.92, 95% CI 0.87–0.99; P?=?0.02) and cardiovascular (CV) mortality (OR 0.86, 95% CI 0.75–0.99, P?=?0.03) in dialysis patients who used loop diuretics than control. On the contrary, there were no significant difference in the incidence of IDH (OR 1.35, 95% CI 0.78–2.34, P?=?0.29) and all-cause mortality (OR 0.73, 95% CI 0.26–2.01; P?=?0.54) and CV mortality (OR 0.57, 95% CI 0.14–2.25; P?=?0.42) in maintenance dialysis patients who used MRAs compared with control.

Conclusion

Loop diuretics, but not MRAs, might have a potential benefit to reduce the incidence rate of IDH, all-cause mortality and CV mortality. More high-quality studies are needed to strengthen the arguments.

     

Culture bovine prospermatogonia with 2i medium

Germplasm cryopreservation and expansion of gonocytes/prospermatogonia or spermatogonial stem cells (SSCs) are important; however, it's difficult in cattle. Since inhibitors of Mek1/2 and Gsk3β (2i) can enhance pluripotency maintenance, effects of 2i-based medium on the cultivation of bovine prospermatogonia from the cryopreserved tissues were examined. The testicular tissues of newborn bulls were well cryopreserved. High mRNA levels of prospermatogonium/SSC markers (PLZF, GFRα-1) and pluripotency markers (Oct4/Pouf5, Sox2, Nanog) were detected and the PLZF⁺/GFRα-1⁺ prospermatogonia were consistently identified immunohistochemically in the seminiferous cords. Using differential plating and Percoll-based centrifugation, 41.59% prospermatogonia were enriched and they proliferated robustly in 2i medium. The 2i medium boosted mRNA abundances of Pouf5, Sox2, Nanog, GFRα-1, PLZF, anti-apoptosis gene Bcl2, LIF receptor gene LIFR and enhanced PLZF protein expression, but suppressed mRNA expressions of spermatogonial differentiation marker c-kit and pro-apoptotic gene Bax, in the cultured prospermatogonia. It also alleviated H₂O₂-induced apoptosis of the enriched cells and decreased histone H3 lysine (K9) trimethylation (H3K9me3) and its methylase Suv39h1/2 mRNA level in the cultured seminiferous cords. Overall, 2i medium improves the cultivation of bovine prospermatogonia isolated from the cryopreserved testes, by inhibiting Suv39h1/2-mediated H3K9me3 through Mek1/2 and Gsk3β signalling, evidencing successful cryopreservation and expansion of bovine germplasm.     

ASO Visual Abstract: Association of Obesity with Worse Operative and Oncologic Outcomes Among Patients Undergoing Gastric Cancer Resection

Annals of Surgical Oncology -     

Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.