Predictors of response and survival in patients with unresectable hepatocellular carcinoma treated with nivolumab: real-world experience

Real-world predictors of the treatment efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC) are unknown. This retrospective study enrolled 87 consecutive patients with unresectable HCC from May 2017 to December 2019 at two hospitals. Of the 87 patients, 7, 9, 60, and 11 patients had Barcelona Clinic Liver Cancer stages A, B, C, and D, respectively, and 45, 30, and 10 patients were Child-Pugh class A, B, and C, respectively. The median injection numbers of nivolumab and treatment duration were 6 (3-8) and 2.53 (1.47-4.23) months, respectively, and 64.4% of patients received combination therapy. Radiological imaging was not assessed for 25 patients. Objective response (OR) and disease control rates were 19.5% and 39.1%, respectively. A single tumor (odds ratio: 9.542, P = .015) and ≥20% decline in serum α-fetoprotein protein (AFP) levels within the first 3 months of treatment (defined as AFP response, odds ratio: 5.997, P = .042) were predictors of OR. Lack of macrovascular invasion, combination therapy, and AFP response were predictors of progression-free survival. A Cancer of the Liver Italian Program (CLIP) score of 0-2 (hazard ratio [HR]: 3.717, P = .004) and grade 1-2 immune-related adverse events (irAEs, HR: 2.217, P = .049) were predictors of overall survival (OS) in the entire cohort, and a CLIP score of 0-2 (HR: 3.257, P = .009) was a predictor of OS in evaluable patients. IrAEs ≥ grade 3 were noted in 14 patients, and three died as a result. Having a single tumor and AFP response were predictors of OR, and CLIP score was a predictor of OS.     

Protective role of histone deacetylase 4 from ultraviolet radiation-induced DNA lesions

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.     

The Relationship between Food Security Status and Sleep Disturbance among Adults: A Cross-Sectional Study in an Indonesian Population

Background: The relationship between food insecurity and the experience of sleep disturbance has received little attention among researchers, although food insecurity is associated with poor physical and mental health globally. This study aimed to investigate the relationship between food security status and sleep disturbance among adults 20–64 years old. Methods: The study’s population-based sample included 20,212 Indonesian adults who participated in the fifth wave of the Indonesia Family Life Survey (IFLS5) in 2014. Dietary intake data, gathered using a food frequency questionnaire (FFQ), were used to assess the food security status. Sleep disturbance was assessed using the 10-item Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaire. We used multiple linear and logistic regression models to test the study hypothesis. Results: A higher likelihood of experiencing sleep disturbance was recorded in people aged older than 56 years (OR = 1.78, 95% CI: 1.17–2.72, p = 0.007), people with depressive symptoms (OR = 3.57, 95% CI: 2.77–4.61, p < 0.001), and food-insecure people (OR = 1.32, 95% CI: 1.02–1.70, p = 0.036). A lower likelihood of experiencing sleep disturbance was recorded in people with low educational attainment (OR = 0.41, 95% CI: 0.30–0.57, p < 0.001). Sleep disturbance was dependent on the food consumption groups and food security status among men (p = 0.004). Conclusions: Sleep disturbance may be affected by the food-insecure status of adults, and later, may lead to serious health outcomes.     

婴幼儿多发性大动脉炎14例临床特点分析

目的通过分析总结14例婴幼儿多发性大动脉炎(TA)的临床特点,并结合文献复习总结,以提高对该病的认识及诊疗水平。方法回顾性分析2016年7月至2019年5月在首都儿科研究所附属儿童医院住院的TA婴幼儿的临床资料及随访情况,并结合文献,分析总结该病的临床特点。结果14例患儿年龄为1个月23 d^28个月,男6例,女8例。临床表现中最常见的是发热[10例(71.4%)],高血压9例(64.3%),脉弱或无脉5例(35.7%)。按照病变血管部位的临床分型,广泛型11例(78.5%),头臂动脉型3例(21.4%),本组患儿无胸腹主动脉及单纯肺动脉型。14例TA患儿中,12例有颈总动脉、颈动脉、锁骨下动脉及冠状动脉及其分支(前降支、回旋支)受累(85.7%);11例肾动脉受累(78.6%);9例腋动脉受累(64.2%);8例腹主动脉受累(57.1%);6例降主动脉受累(42.9%);6例胸主动脉受累(42.9%);6例肠系膜上动脉受累(42.9%);5例股动脉受累(35.7%);5例肺动脉受累(35.7%);4例肱动脉受累(28.6%)。14例患儿中,误诊11例,诊断不清3例,误诊时间为18 d^2个月。误诊病例中,8例误诊为不典型川崎病。14例患儿中,7例治疗后大部分病变血管范围逐渐减少,受累较轻血管甚至可以完全恢复正常血管状态。4例患儿血管影像学检查较前无明显加重或好转。9例出现高血压患儿应用降压药血压能控制在正常范围,但不能停用降压药。5例查体发现脉弱或无脉患儿均未改善。14例患儿中7例生长发育同正常同龄儿,7例落后于正常同龄儿身高体质量第25百分位。14例患儿随访2~22个月,均规律治疗,未出现复发。结论3岁以内TA累及血管较多,病情严重,误诊率高,经过治疗病情很快能够控制,但容易遗留血管病变,部分患儿预后不佳。     

4+4临床医学人才培养美国模式与交医模式的比较及思考

上海交通大学医学院借鉴北美医学院校的培养模式，从2002年起在国内率先开展临床医学专业"4+4"培养项目，招收优秀非医学应届本科毕业生攻读4年医学课程。经过20年的实践，交大医学院已积累了一系列具有中国特色且行之有效的办学经验，同时也面临问题和困惑。本研究对比分析交大医学院和美国一流医学院校哈佛医学院、斯坦福大学医学院的"4+4"人才培养模式，并从培养目标、招生方式与规模、课程设置、学位授予标准等方面展开深入探讨。研究表明，未来交大医学院还需通过凸显特色人才培养目标，完善招生标准与流程，优化课程体系，平衡临床和科研能力培养等举措加大教育教学改革力度，助力推进"4+4"临床医学人才培养模式从优秀迈向卓越。     

Industrial Production of Organophosphate Flame Retardants (OPFRs): Big Knowledge Gaps Need to Be Filled?

Bulletin of Environmental Contamination and Toxicology - Since the phase-out of traditional halogenated flame retardants (HFRs), interests of research are gradually being shifted to organophosphate...     

电针干预佐剂性关节炎大鼠踝关节滑膜细胞凋亡的MMP-3、MMP-9分子调节机制

目的观察电针干预对佐剂性关节炎大鼠踝关节滑膜细胞凋亡和相关蛋白基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶-9(MMP-9)表达的影响。方法32只雄性SD大鼠被随机分为生理盐水组、模型组、电针干预组和假电针干预组,每组8只。生理盐水组大鼠在双侧足垫部注射模拟造模,其余大鼠用弗氏完全佐剂在双侧足垫部注射造模。电针干预组大鼠予以电针干预。假电针干预组予以假电针刺激处理。HE染色观察模型大鼠踝关节炎症进展情况,Tunnel法检测模型大鼠踝关节滑膜细胞凋亡情况,RT-PCR检测踝关节滑膜的MMP-3、MMP-9的mRNA表达,Western blot检测踝关节滑膜的MMP-3、MMP-9的蛋白表达。结果HE染色显示,电针干预组大鼠的关节炎症显著轻于模型组。Tunnel法检测,电针干预可以促进关节炎大鼠的滑膜细胞凋亡。RT-PCR和Western blot检测结果显示,电针干预可以显著降低关节炎大鼠踝关节滑膜组织中的MMP-3、MMP-9 mRNA和蛋白表达水平(P<0.05)。结论电针干预可以显著减轻佐剂性关节炎大鼠的关节炎症和增殖的滑膜细胞数量,其分子机制可能和电针降低局部的MMP-3、MMP-9蛋白的表达有关。     

大体积肺癌IMRT初次及二次计划剂量学变化研究

目的 采用刚性配准和形变配准方法获得大体积非小细胞肺癌(NSCLC) IMRT中靶区和危及器官(OAR)的累加剂量,并与初次计划的剂量进行比较。方法 选择 30例采用IMRT的大体积NSCLC患者,每位患者分别在放疗前和放疗20分次时进行4DCT模拟定位,基于初次4DCT的平均密度投影CT1-avg制定放疗计划为Plan1,基于二次4DCT的平均密度投影CT2-avg修改放疗计划为Plan2,分别采用刚性配准和形变配准方法将两次计划进行剂量累加得到Plan刚性和Plan形变。比较初次定位和二次定位之间大体肿瘤体积(GTV,以吸气末时相图像CT50%上的勾画为准)和OAR (OAR,以平均密度投影图像CTavg上的勾画为准)的体积变化,以及Plan2、Plan刚性、Plan形变的剂量体积指标相比Plan1的差异。结果 二次定位和初次定位相比,GTV、心脏体积分别缩小44.2%、5.5%,患侧肺、健侧肺、全肺体积分别增大5.2%、6.2%、5.8%(P<0.05);对于内GTV (IGTV,10个4DCT时相的GTV融合而来)和计划靶体积(PTV)的D95%、D98%、V100%,Plan2与Plan1相近(P>0.05),Plan刚性、Plan形变较Plan1均略有下降(P<0.05);对于脊髓、心脏、患侧肺、双肺剂量,Plan2、Plan刚性、Plan形变较Plan1均降低(P<0.05),其中心 脏V30Gy和 Dmean分别降低27.3%、16.5%、15.3%和15.2%、6.6%、5.6%,双 肺V20Gy和 Dmean分别降低15.6%、4.5%、3.7%和15.7%、6.2%、5.1%;Plan形变的IGTV和PTV的D95%、D98%,心 脏V40Gy,患侧肺和全肺 的V20Gy、Dmean高于Plan刚性(P<0.05)。形变配准后OAR相似指数明显高于刚性配准(P<0.05)。结论 Plan2中OAR剂量体积指标相比Plan1差别很大,因此它们在预测OAR放射性损伤方面均有较大偏差,而形变配准得到的剂量体积指标可以提高预测精度。