Abstract Background: High mobility group box1 (HMGB1)is a chromatin-binding protein that especially regulates inflammatory signaling cascades. Several reports have demonstrated the anti-inflammatory effect of hesperidin. Whether hesperidin attenuates radiation-induced brain injury via inhibiting HMGB1-mediated neuroinflammation remains unclear. Methods: Morris water maze test and the step-down passive avoidance test were applied to evaluate whether hesperidin could relieve the irradiation-induced cognitive dysfunction. Nissl staining, western blotting and immunofluorescence were performed to uncover the mechanisms. Results: In this study, we found that radiation reduced the neuronal number and increased the content of the proinflammatory cytokines in the hippocampus, and hesperidin significantly reversed these changes. More importantly, hesperidin significantly improved the learning and memory abilities of X-ray-stimulated mice. We also found that radiation markedly increased Iba-1 expression in the hippocampus and resulted in substantial translocation of HMGB1 from the nucleus to the cytoplasm in the hippocampus and BV-2 cell, and hesperidin reversed the radiation-induced upregulation of Iba-1 and the cytoplasmic translocation of HMGB1. Moreover, hesperidin rescued the radiation-induced the upregulations in the phosphorylation levels of ERK, p38 and p65 in the hippocampus. Conclusions: This study demonstrated that hesperidin alleviated the radiation-induced cognitive dysfunction via inhibiting HMGB-mediated neuroinflammation, and indicated that hesperidin could be a promising candidate for treatment of radiation- induced brain injury.

Abstract Background: High mobility group box1 (HMGB1)is a chromatin-binding protein that especially regulates inflammatory signaling cascades. Several reports have demonstrated the anti-inflammatory effect of hesperidin. Whether hesperidin attenuates radiation-induced brain injury via inhibiting HMGB1-mediated neuroinflammation remains unclear. Methods: Morris water maze test and the step-down passive avoidance test were applied to evaluate whether hesperidin could relieve the irradiation-induced cognitive dysfunction. Nissl staining, western blotting and immunofluorescence were performed to uncover the mechanisms. Results: In this study, we found that radiation reduced the neuronal number and increased the content of the proinflammatory cytokines in the hippocampus, and hesperidin significantly reversed these changes. More importantly, hesperidin significantly improved the learning and memory abilities of X-ray-stimulated mice. We also found that radiation markedly increased Iba-1 expression in the hippocampus and resulted in substantial translocation of HMGB1 from the nucleus to the cytoplasm in the hippocampus and BV-2 cell, and hesperidin reversed the radiation-induced upregulation of Iba-1 and the cytoplasmic translocation of HMGB1. Moreover, hesperidin rescued the radiation-induced the upregulations in the phosphorylation levels of ERK, p38 and p65 in the hippocampus. Conclusions: This study demonstrated that hesperidin alleviated the radiation-induced cognitive dysfunction via inhibiting HMGB-mediated neuroinflammation, and indicated that hesperidin could be a promising candidate for treatment of radiation- induced brain injury.

目的:探讨直肠癌新辅助治疗中盆腔骨髓保护调强放疗与病理反应的相关性.方法:回顾性分析2017年01月至2020年12月于我院接受新辅助放化疗及根治性手术的192例Ⅱ、Ⅲ期直肠癌患者的临床病理资料,其中95例为接受盆腔骨髓保护调强放疗的患者(淋巴细胞保护组),余97例患者来源于本单位回顾性数据库(对照组).比较两组患者淋巴细胞绝对计数最低值、淋巴细胞下降程度及肿瘤病理反应率差异,分析直肠癌新辅助治疗中盆腔骨髓保护调强放疗与病理反应的相关性.结果:淋巴细胞保护组患者放化疗期间最低淋巴细胞计数、放化疗后淋巴细胞计数及病理反应率均高于对照组,差异有统计学意义.淋巴细胞保护组3-4级淋巴细胞减少症发生率为38.9％,低于对照组的56.8％(P=0.034).多因素Logistic回归分析结果显示3-4级淋巴细胞减少症、淋巴细胞保护、临床分期及等待手术期间化疗是肿瘤病理反应状态的独立影响因素.结论:直肠癌患者新辅助放化疗期间3-4级淋巴细胞减少症与治疗后肿瘤病理反应状态密切相关,通过盆腔骨髓保护调强放疗可有效保护患者的淋巴细胞,减轻3-4级淋巴细胞减少症发生率,提高肿瘤病理反应.

分别从肿瘤缺氧微环境理论、肿瘤"血瘀证"机制与肿瘤缺氧微环境的关系及活血化瘀中药改善肿瘤缺氧微环境方面对肿瘤缺氧微环境研究的状况进行分析,认为缺氧微环境与肿瘤血管生成、肿瘤进展转移、能量代谢异常、放化疗抵抗等都密切相关.属中医血瘀证,活血化瘀药物对于改善肿瘤缺氧微环境具有重要意义.

自噬是一种将细胞质成分在溶酶体内降解并将产生的大分子成分回收循环利用的细胞过程.放射治疗是治疗多种癌症以杀死或控制恶性肿瘤细胞的重要手段,而肿瘤放疗抵抗限制了放疗的疗效,开发新的药物以提高放射敏感性是亟待解决的重要难题.一些中药成分可通过干预自噬达到放疗增敏的效果,但目前的研究局限于细胞层面.

Nasopharyngeal carcinoma (NPC) is the subclass of head and neck cancer with the highest incidence among otolaryngology malignancies. A growing amount of evidence has proven that circular RNAs (circRNAs) play key roles in the progression of multiple cancers. It has been reported that circ-NOTCH1 is a novel circRNA and functions as an oncogene in gastric cancer, while the regulatory mechanism of circ-NOTCH1 in NPC remains unknown. In the present research, our findings revealed that circ-NOTCH1 was overexpressed in NPC tissues and cells. Circ-NOTCH1 knockdown suppressed NPC cell proliferation, invasion, and migration. Subsequently, we discovered that c-Myc can activate circ-NOTCH1 by binding to the NOTCH1 promoter. c-Myc functioned as a tumor promoter in NPC cells. Mechanistically, circ-NOTCH1 served as a competitive endogenous RNA to modulate c-Myc expression by sponging miR-34c-5p. Additionally, overexpression of c-Myc reversed the circ-NOTCH1 knockdown-mediated inhibition of NPC cellular progression. Overall, this study suggested that c-Myc-induced circ-NOTCH1 promoted malignant phenotypes of NPC cells by regulating the miR-34c-5p/c-Myc axis.

Background To evaluate the value of pretreatment inflammatory-nutritional biomarkers in predicting responses to neoadjuvant chemoradiotherapy (nCRT) and survival in patients with locally advanced rectal cancer (LARC). Methods Patients with LARC who underwent nCRT and subsequent surgery between October 2012 and December 2019 were considered for inclusion. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), and prognostic nutritional index (PNI) were calculated from according to routine laboratory data within 1 week prior to nCRT. The correlations between baseline inflammatory-nutritional biomarkers and responses were analyzed using Chi-square test or Fisher’s exact test, and multivariate logistic regression analysis was performed to identify the independent predictors of pathological responses to nCRT. Univariate and multivariate Cox proportional hazard models were used to assess the correlations of predictors with disease-free survival (DFS) and overall survival (OS). Results A total of 273 patients with LARC were enrolled in this study. Higher LMR and PNI were observed in the good-response group, meanwhile higher NLR and PLR were observed in the poor-response group. Multivariate logistic regression analysis results revealed that PLR and PNI independently predicted responses to nCRT. Multivariable Cox regression analysis determined that PNI was an independent predictor of DFS and OS in patients with LARC. The value of pretreatment PNI in predicting responses and survival was continuously superior to those of NLR, PLR, and LMR. The optimal cutoff value of the PNI was approximate 45. Subgroup analyses indicated that the pathological responses and survival in the high PNI group (≥ 45) were significantly better than those in the low PNI group (< 45), especially in patients with clinical stage III rectal cancer. Conclusion The pretreatment PNI can serve as a promising predictor of response to nCRT and survival in patients with LACR, which is superior to NLR, PLR, and LMR, and the patients with clinical stage III rectal cancer who have a higher PNI are more likely to benefit from nCRT.

目的:分析不同的炎症及营养相关指标与直肠癌新辅助放化疗后肿瘤病理反应状态及患者预后的相关性,探讨其临床应用价值.方法:回顾性分析2012年10月至2019年2月在南京中医药大学附属医院接受新辅助放化疗及根治性手术的211例Ⅱ、Ⅲ期直肠癌患者的临床病理资料,依据患者放化疗前1周内血常规和肝肾功能检查结果,计算基线中性粒细胞/淋巴细胞之值(NLR)、血小板/淋巴细胞之值(PLR)、淋巴细胞/单核细胞之值(LMR)及预后营养指数(PNI).根据患者术后病理结果,基于肿瘤消退分级(TRG)标准评价肿瘤病理反应状态.采用Logistic模型、Kaplan-Meier法、Cox回归模型分析各炎症及营养相关指标与直肠癌新辅助放化疗肿瘤病理反应状态及患者预后的相关性.结果:新辅助放化疗后病理反应(TRG 0～1级)患者共135例(64.0％),非病理反应(TRG 2～3级)患者76例(36.0％).多因素Logistic回归分析结果显示,基线PNI(OR=1.245,95％CI 1.123～1.380,P<0.001)及癌胚抗原(OR=0.500,95％CI 0.255～0.979,P=0.043)是病理反应状态的独立影响因素.多因素预后分析显示性别、淋巴(ypN)分期、基线NLR及PNI是无病生存期(DFS)的独立影响因素;性别、ypN分期及基线PNI是总生存期(OS)的独立影响因素.分层分析显示ypN阳性患者中高PNI组(PNI>45)5年DFS和OS显著长于低PNI组(无病生存率63.6％vs.48.0％,P=0.002;总生存率69.2％vs.51.9％,P=0.005),而ypN阴性患者中高PNI组与低PNI组预后差异无统计学意义(无病生存率83.2％vs.79.5％,P=0.252;总生存率89.2％vs.85.1％,P=0.299).结论:基线PNI水平与Ⅱ、Ⅲ期直肠癌新辅助放化疗后肿瘤病理反应状态及患者预后相关,其疗效预测价值优于NLR、PLR及LMR.PNI简单无创、经济有效,可作为临床预后预测指标的补充,值得进一步研究.

Objective: In the studies of locally advanced cervical carcinoma (LACC), the efficacy of adjuvant chemotherapy (ACT) after curative concurrent chemoradiotherapy (CCRT) has not been clearly investigated. This paper aimed to evaluate the impact of CCRT followed by ACT compared with the impact of CCRT alone in the treatment of LACC. Data sources, methods of study selection: The Web of Science, Cochrane Library, EM BASE, and PubMed were systematically reviewed to find eligible studies up to 28 February 2020. The pooled analysis was conducted through random- or fixed-effect models. Clinical endpoints such as overall survival (OS), progression-free survival (PFS), local failure rate (LFR), distant metastasis (DM), as well as adverse events (AEs) were examined as evaluation indexes. Tabulation, integration and results: Three retrospective studies and two randomized trials were enrolled in this meta-analysis comprising 1172 patients (CCRT arm: 588; CCRT + ACT arm: 584). No significant differences were discovered in OS (hazard ratio [HR] = 0.94, 95% confidence interval [CI]: 0.46,1.94, p = 0.88) and PFS (HR = 0.91, 95% CI: 0.50,1.67, p = 0.76) between CCRT followed by ACT and CCRT alone. The pooled RRs for LFR (RR = 0.64, 95% CI: 0.44, 0.92, p = 0.02) and DM (RR = 0.50, 95% CI: 0.35, 0.71, p < 0.05) showed that the application of CCRT followed by ACT decreased LFR and DM compared with CCRT alone. However, CCRT followed by ACT arm had more acute hematologic toxicities (anemia, neutropenia, thrombocytopenia) and grade 3-4 proctitis (all p < 0.05), than CCRT arm; no statistic differences were found in late toxicities (cystitis and proctitis) between the two arms (p > 0.05). Conclusion: This study suggested that CCRT followed by ACT did not prolong OS and PFS. It decreased LFR and DM compared with CC RT alone. CCRT followed by ACT raised the incidence of acute hematologic toxicities and proctitis but did not increase late toxicities. Further study is needed in CCRT followed ACT for LACC.

目的 探讨采用MRI识别盆腔内造血活性骨髓,优化老年直肠癌患者调强放疗(IMRT)计划的临床价值.方法 对Ⅱ、Ⅲ期接受新辅助放化疗的老年直肠癌患者分别采用依据MRI识别盆腔活性骨髓法(MRI法)及CT图像骨窗下勾画骨髓腔法(CT法)两种方法勾画盆腔骨髓,并设计MRI-IMRT及CT-IMRT两种治疗计划.比较两种方法定义的骨髓体积及IMRT计划的骨髓及靶区、其他危及器官(小肠、膀胱及股骨头)的剂量学参数差异.结果 MRI法勾画的盆腔骨髓平均体积为(374.42±138.58)cm3,CT法为(1142.56±118.72)cm3,MRI法勾画的盆腔骨髓平均体积明显小于CT法,两组间差异有统计学意义(P<0.05).MRI-IMRT计划的盆腔骨髓各剂量体积受量均低于CT-IMRT计划,两种计划间盆腔骨髓V5、V10及V20差异有统计学意义(P<0.05).两种IMRT计划的靶区覆盖率及其他危及器官各剂量学参数差异均无统计学意义(P>0.05).结论 在Ⅱ、Ⅲ期老年直肠癌新辅助IMRT中,采用MRI能较清晰的识别盆腔造血活性骨髓范围,相较于传统的CT图像勾画骨髓腔方式,可明显缩小骨髓体积,利于IMRT计划实施.MRI-IMRT计划在保证靶区覆盖率,且不增加周围危及器官受量的前提下,可有效降低盆腔活性骨髓低剂量辐射剂量体积(V5、V10及V20).