Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy

The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients.In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic ^99mTc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (T_max), and time for peak activity to decrease by 50% (T_1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of T_max for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed.Quantitative ^99mTc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of T_max for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, T_max) were statistically significantly associated with the conventional liver function parameters.Quantitative ^99mTc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and T_max values obtained from dynamic HBS show good correlation with conventional liver function parameters.     

Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf^V600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr^CreERT2/+; Braf^{LSL‐V600E/+}; Pten^flox/flox) to Sirt5^?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5^?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf^V600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.     

ArcCHECK系统在食管癌螺旋断层放疗计划验证中的应用

目的 探讨ArcCHECK系统在食管癌断层治疗旋转照射和固定野照射计划验证中的应用,总结相关经验。方法 对32例不同部位食管癌分别制作Helical旋转照射和Direct固定野照射验证计划,并通过ArcCHECK测量、分析,对比验证结果通过率。分析靶体积与计划验证通过率的相关性。将靶体积较小的治疗验证计划分别放在ArcCHECK模体中心和外周探测点处,分析验证通过率差异。结果 Helical计划验证通过率高于Direct计划(P<0.01),其靶体积与验证通过率的相关系数分别为-0.364和-0.042,P值分别为0.041和0.819。Helical计划采用3%/2mm标准时,高剂量区放在模体中心和外周探测点处测得的通过率不同(P=0.005),后者通过率更高;采用3%/3mm标准时与Direct计划的3%/3m、3%/2mm标准的相近(P均>0.05)。结论 Helical计划验证通过率普遍高于Direct计划,原因可能与ArcCHECK探测器的角度响应以及因更多参考点受到低剂量辐射而未参与计算有关,另外还可能跟Direct计划对断层治疗剂量控制系统要求更高有关。在Helical验证计划中,当采用3%/3mm标准时,靶体积越大,验证时出现较低通过率的可能性增加,但相关系数较低。验证计划的高剂量区位于模体中心或者探测点处都可以实现计划验证,综合考量建议放在模体等中心处。     

microRNA-613调控CDK14来抑制老年胶质瘤患者瘤细胞的增殖和侵袭作用

目的 探讨microRNA-613调控细胞周期蛋白依赖性激酶14(CDK14)通路来抑制老年胶质瘤患者瘤细胞增殖和侵袭的机制。方法 购自上海北诺生物科技有限公司的人脑胶质瘤细胞株U251共24株,分为shNC组、shmicroRNA-613组、Vector组、microRNA-613组,每组各6株; Western Blotting法和qRT-PCR法检测敲减microRNA-613和过表达microRNA-613后的人脑胶质瘤细胞株U251中CDK14蛋白表达水平,CCK-8细胞增殖实验、Transwell小室实验验证敲除microRNA-613和过表达microRNA-613后U251细胞的增殖、侵袭能力。结果 人胶质瘤细胞株U251敲减microRNA-613后CDK14蛋白表达增加(P<0.05); 人胶质瘤细胞株U251过表达microRNA-613后CDK14蛋白表达减少(P<0.05); 转染第24、36、48 h microRNA-613组U251细胞增殖率P<0.05); microRNA-613组U251细胞侵袭能力>Vector组,shNC组>shmicroRNA-613组(P<0.05)。结论 microRNA-613可通过调控CDK14信号转导通路来抑制人脑胶质瘤细胞U251增殖、转移。     

The prognostic role of tumour‐infiltrating lymphocytes in oral squamous cell carcinoma: A meta‐analysis

It has been suggested that tumour‐infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta‐analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta‐analysis. Our pooled meta‐analysis showed that high infiltration of CD8⁺ TILs, CD45RO⁺ TILs and CD57⁺ TILs favoured better overall survival (OS). However, high infiltration of CD68⁺ macrophages and CD163⁺ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8⁺ TILs, CD45RO⁺ TILs, CD57⁺ TILs, CD68⁺ macrophages and CD163⁺ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.     

Prevalence of hereditary breast and ovarian cancer (HBOC) predisposition gene mutations among 882 HBOC high‐risk Chinese individuals

Identification of deleterious variants in hereditary breast and ovarian cancer (HBOC) susceptibility genes allows for increased clinical surveillance and early detection, and could predict the response to poly (ADP‐ribose) polymerase (PARP) inhibitor in patients with advanced ovarian carcinomas. To determine the prevalence and clinical prediction factors for HBOC syndrome, 882 selected individuals underwent multigene panel testing for HBOC risk assessment during the period from January 2015 to March 2018. Overall, 176 deleterious mutations were observed in 19.50% (n = 172) of individuals. Twenty‐six of 176 mutations could not be retrieved in related public databases and were considered to be novel. Among patients with ovarian cancer, 115 deleterious mutations were identified in 429 patients (48.6%) with significant enrichment for a family history of breast or ovarian cancer syndrome (P < .05). In the breast cancer subgroup, 31 deleterious mutations were identified in 261 patients. Besides BRCA1 (8; 25.8%) and BRCA2 (11; 35.5%), the most frequently occurring genes, an additional 12 deleterious mutations (38.7%) were found in seven other susceptibility genes. Higher mutation incidence (57.9%) was observed in subjects with histories of breast and ovarian cancer. Our results highlighted the genetic heterogeneity of HBOC and the efficiency of a multigene panel in carrying out risk assessment.     

皮肤再生医疗技术治疗糖尿病足溃疡疗效分析

目的:分析、总结、探讨皮肤再生医疗技术在临床上治疗糖尿病足溃疡的可行性与有效性。方法:对32例糖尿病足溃疡住院病人采用皮肤再生医疗技术为主、必要时配合植皮的治疗方法进行局部创面修复。结果:32例糖尿病足溃疡应用皮肤再生医疗技术获得修复9例(占28.1％),皮肤再生医疗技术 皮片移植12例(占37．5％),皮肤再生医疗技术 皮瓣修复5例(占15．6％),进行截肢6例(占18．8％)。结论:及时就诊、及时采用皮肤再生医疗技术为主的治疗方法能有效修复溃疡创面、降低糖尿病足截肢率。