Background The improvement efficacy of consolidation chemotherapy after definitive concurrent chemotherapy and radio-therapy (CCRT) on the prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In addition, there is a lack of nutritional risk screening tools which can consistently and accurately predict the survival of patients with esophageal cancer. Objective To investigate the effect of consolidation chemotherapy on the prognosis of patients with locally advanced ESCC receiving definitive CCRT. Methods A total of 223 patients with ESCC who received definitive CCRT in the department of radiotherapy, the Fourth Hospital of Hebei Medical University from January 2013 to December 2018 were selected as the research objects and divided into the simple CCRT group (n=87) and combined consolidation chemotherapy group (n=136) according to chemoradiotherapy regimen adopted by the patients. General data, ECOG score, tumor site, tumor length, TNM stage, radiotherapy dose, irradiation mode and chemotherapy regimen of the included patients were collected by electronic medical record system. Nutritional Risk Screening 2002 (NRS 2002) was used to score the nutritional status of the patients before chemoradiotherapy. Efficacy evaluation was performed within 1 month after CCRT, including complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Patients were followed up by telephone (completed by the follow-up center) and outpatient review until 2022-09-30, with overall survival (OS), local relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) collected. Survival curves of OS, LRRFS and DMFS were plotted by Kaplan-Meier method and compared by Log-rank test. Univariate and multivariate Cox risk regression models were used to explore the influencing factors of patient prognosis. Results There was no significant difference in baseline data between the simple CCRT group and combined consolidation chemotherapy group (P>0.05). There was no significant difference in the rates of OS, LRRFS and DMFS between the two groups (χ2=1.942, 0.743, 1.272; P=0.163, 0.389, 0.259). There were significant differences in the rates of OS, LRRFS and DMFS between patients with NRS 2002 score <3 (n=172) and patients with NRS 2002 score≥3 (n=51) before treatment (χ2=6.585, 4.858, 7.814; P=0.010, 0.028, 0.005). Multivariate Cox proportional hazard regression analysis showed that TNM stage and NRS 2002 score were influencing factors of OS and DMFS (P<0.05), irradiation mode was an influencing factor of LRRFS and DMFS (P<0.05), and clinical efficacy was an influencing factors of OS, LRRFS and DMFS (P<0.05). Stratified analysis showed that in patients with TNM stage Ⅱ and clinical efficacy of CR, the OS rates in the combined consolidation chemotherapy group (n=74, n=33) were significantly higher than those in the simple CCRT group (n=43, n=28), with statistically significant differences (χ2=4.811, 3.932; P=0.028, 0.047) . Conclusion Consolidation chemotherapy did not improve the prognosis of stageⅡ-Ⅲ ESCC patients after definitive CCRT, but may bring survival benefits for patients with early clinical stage, good response and nutritional status. As a nutritional risk screening tool, NRS 2002 has significant predictive value for the long-term survival of patients with locally advanced ESCC after chemoradiotherapy.

背景 颈胸上段食管鳞癌发病率相对较低，治疗难度较大，治疗模式存在争议，缺乏便捷、准确判断预后的生物标志物，总体预后欠佳。目的 探讨根治性同步放化疗模式下颈胸上段食管鳞癌患者的长期预后及其影响因素。方法 选取2013年1月—2017年12月于河北医科大学第四医院放疗科行根治性同步放化疗的颈胸上段食管鳞癌患者作为研究对象。通过电子病历系统收集患者一般资料、美国东部协作肿瘤组（ECOG）评分、肿瘤部位、肿瘤长度、TNM分期、放疗剂量、照射方式、化疗方案、毒副作用等，计算衍生中性粒细胞与淋巴细胞比例（d NLR）。依据患者d NLR，将患者分为d NLR＜2.15组（64例）和d NLR≥2.15组（42例）。对患者进行随访，放疗1年内每3个月复查1次，2～5年内每半年复查1次，5年后每1年复查1次，计算患者总生存期（OS）、无进展生存期（PFS）、无局部区域复发生存期（LRRFS）、无远转生存期（DMFS）。采用Kaplan-Meier法绘制患者OS、LRRFS、DMFS的生存曲线，OS、PFS、LRRFS、DMFS影响因素的单因素分析采用Log-rank检验。采用多因素Cox风险回归分析探讨患者OS、PFS、LRRFS、DMFS的影响因素。结果 截至末次随访，患者3、5、7年总生存率分别为55.7%、43.0%、37.8%，中位OS为47.5[95%CI（29.4,65.6）]个月；3、5、7年无进展生存率分别为45.3%、37.7%、31.1%，中位PFS为30.7[95%CI（21.1,40.3）]个月；3、5、7年无局部区域复发生存率50.9%、41.4%、33.5%，中位LRRFS为43.5[95%CI（21.6,65.4）]个月；3、5、7年无远转生存率49.1%、38.6%、34.4%，中位DMFS 34.7[95%CI（20.7,48.7）]个月。多因素Cox风险回归分析结果显示，TNM分期、照射方式为患者OS、PFS、LRRFS及DMFS的影响因素（P＜0.05），性别为LRRFS的影响因素（P＜0.05）,d NLR为PFS及DMFS的影响因素（P＜0.05）。患者发生≥2级急性放射性肺炎、放射性食管炎、白细胞减少、贫血、血小板减少者分别为10例、25例、32例、9例、11例。结论颈胸上段食管鳞癌患者行根治性同步放化疗长期预后较为满意，且耐受良好。局部复发为主要失败模式，选择性淋巴引流区照射显著改善患者预后，可予以临床推广，d NLR对患者长期生存有一定的预测作用。

Background:The systemic inflammation response index (SIRI) and prognostic nutritional index (PNI) have been shown to be correlated with the prognosis of various solid tumors. This study sought to investigate the prognostic value of the SIRI and the PNI individually and in combination in locally advanced elderly esophageal squamous cell carcinoma (ESCC) patients treated with radical radiotherapy.Methods:The data of 192 ESCC patients aged ≥65 years, who had been treated with definitive radiotherapy between 2013 and 2016, were retrospectively analyzed. The optimal cutoff values of SIRI and PNI were determined by receiver operating characteristic curves. Kaplan-Meier curves and Cox proportional hazards models were used to analyze the effect of the SIRI and PNI on overall survival (OS) and progression-free survival (PFS). The areas under the curve were measured to evaluate the predictive ability of the SIRI, PNI, and SIRI combined with PNI for OS.Results:The optimal cutoff values of the pretreatment SIRI and PNI were 1.03 and 49.60, respectively. The univariate and multivariate analyses demonstrated that T stage (P=0.021), TNM stage (P=0.022), synchronous chemotherapy (P=0.032), the SIRI (P=0.001), and the PNI (P=0.045) were independent prognostic factors for OS and N stage (P=0.004), synchronous chemotherapy (P=0.016) and the SIRI (P=0.004) were independent prognostic factors for PFS. The AUC of the combined SIRI and PNI (0.706; 0.612-0.801) was higher than those of the SIRI (0.648; 0.540-0.756) and the PNI (0.621; 0.523-0.720). Patients in the low-SIRI and high-PNI groups, especially those in clinical stage II or who received synchronous chemotherapy (P<0.001, P=0.002), had better OS and PFS than those in the other groups (P<0.001).Conclusions:The SIRI and PNI are simple and reliable biomarkers for predicting long-term survival in elderly patients with locally advanced ESCC after radical radiotherapy. A high SIRI and a low PNI indicated poor prognosis, and the combination of the SIRI and PNI improved the accuracy of prognosis prediction and could be used to guide individualized treatment of patients.

目的 探讨那不勒斯预后评分(NPS)对临床Ⅲ期食管癌患者生存预后的预测价值.方法 回顾性分析行根治性放疗的163例临床Ⅲ期食管癌患者.根据放疗前血常规及生化结果计算每例患者NPS,然后依据NPS分值分为低危组(0分)、中危组(1～2分)以及高危组(3～4分)并比较3组生存预后差异.应用Kaplan-Meier法及Cox比例风险模型进行单因素和多因素预后分析,绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC),比较NPS与预后营养指数(PNI)、中性粒细胞/淋巴细胞比值(NLR)、淋巴细胞/单核细胞比值(LMR)等其他营养及炎症指标对生存预后的预测价值.结果 依据放疗前NPS结果,将163例患者分为低危组38例、中危组71例及高危组54例.对低、中、高危组生存状况的分析显示,1年总生存率分别为89.7％、78.3％、66.9％,3年总生存率分别为60.1％、40.7％、26.6％,5年总生存率分别为48.1％、25.2％、17.1％(Log-rankχ2=16.398,P<0.01);1年无进展生存率分别为76.7％、52.7％、50.8％;3年无进展生存率分别为50.1％、25.3％、19.4％,5年无进展生存率分别为42.0％、21.1％、12.9％(Log-rankχ2=16.852,P<0.01).多因素分析显示,NPS中、高危组和同期未化疗为影响患者总生存及无进展生存的独立危险因素.NPS预测生存的AUC值(0.658)优于PNI(0.581)、NLR(0.561)、LMR(0.578),差异有统计学意义(Z分别为1.938、2.016、1.950,P<0.05).结论 放疗前NPS是接受根治性放疗的临床Ⅲ期食管癌患者预后的独立影响因素,其对生存预后的预测价值优于其他营养及炎症指标,NPS较高的患者预后相对较差.

Background: Acute ischemic stroke (AIS) is a severe neurological disease with complex pathophysiology, resulting in the disability and death. The goal of this study is to explore the underlying molecular mechanisms of AIS and search for new potential biomarkers and therapeutic targets.Methods: Integrative analysis of mRNA and miRNA profiles downloaded from Gene Expression Omnibus (GEO) was performed. We explored differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMirs) after AIS. Target mRNAs of DEMirs and target miRNAs of DEGs were predicted with target prediction tools, and the intersections between DEGs and target genes were determined. Subsequently, Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses, Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), competitive endogenous RNA (ceRNA) (lncRNA-miRNA-mRNA) network, protein–protein interaction (PPI) network, and gene transcription factors (TFs) network analyses were performed to identify hub genes and associated pathways. Furthermore, we obtained AIS samples with evaluation of immune cell infiltration and used CIBERSORT to determine the relationship between the expression of hub genes and infiltrating immune cells. Finally, we used the Genomics of Drug Sensitivity in Cancer (GDSC) database to predict the effect of the identified targets on drug sensitivity.Result: We identified 293 DEGs and 26 DEMirs associated with AIS. DEGs were found to be mainly enriched in inflammation and immune-related signaling pathways through enrichment analysis. The ceRNA network included nine lncRNAs, 13 miRNAs, and 21 mRNAs. We used the criterion AUC >0.8, to screen a 3-gene signature (FBL, RPS3, and RPS15) and the aberrantly expressed miRNAs (hsa-miR-125a-5p, hsa-miR-125b-5p, hsa-miR-148b-3p, and hsa-miR-143-3p) in AIS, which were verified by a method of quantitative PCR (qPCR) in HT22 cells. T cells CD8, B cells naïve, and activated NK cells had statistical increased in number compared with the acute cerebral infarction group. By predicting the IC50 of the patient to the drug, AZD0530, Z.LLNle.CHO and NSC-87877 with significant differences between the groups were screened out. AIS demonstrated heterogeneity in immune infiltrates that correlated with the occurrence and development of diseases.Conclusion: These findings may contribute to a better understanding of the molecular mechanisms of AIS and provide the basis for the development of novel treatment targets in AIS.

Objective:To investigate the relationship between systemic immune-inflammation index (SII) and the prognosis of esophageal cancer patients treated with radical radiotherapy and to predict the prognosis of the patients using the SII combined with clinical staging.Methods:A retrospective analysis was conducted for 248 patients with esophageal cancer who were admitted to the Department of Radiotherapy in the Fourth Hospital of Hebei Medical University between 2014 and 2016. These patients included 146 males and 102 females, with a median age of 67 years. Among them, 134 patients received concurrent chemotherapy and 114 patients received radiotherapy alone. The SII before radiotherapy was defined as platelet count × neutrophil count/lymphocyte count. The patients were divided into a low-SII group and a high-SII group according to the optimal cutoff value of pretreatment SII determined by the receiver operating characteristics (ROC) curve. Survival analysis was calculated using the Kaplan-Meier method, and the Cox proportional hazards model was used for multivariate analysis. For these patients, the prognosis effects and the predictive value for survival of different SII levels combined with TNM staging were compared.Results:According to the ROC curves, the optimal cutoff value of SII before radiotherapy was 740.80. Based on this number, the patients were divided into a low-SII group (< 740.80, 150 cases) and a high-SII group (≥ 740.80, 98 cases). The objective response rate of the low-SII group was significantly higher than that of the high-SII group (86.0% vs 75.5%, χ2=4.39, P=0.036). The 1-, 3-, and 5-year overall survival (OS) rates of the low-SII group were 78.6%, 45.6%, and 32.3%, respectively. These rates were significantly higher than the corresponding rates of the high-SII group, which were 71.0%, 28.3%, and 16.4% ( χ2=11.22, P=0.001), respectively. Moreover, the 1-, 3- and 5-year progression-free survival (PFS) rates of the low-SII group were 67.0%, 36.9%, and 32.0%, respectively. Again, these rates were significantly higher than those of the high-SII group, which were 45.5%, 17.5%, and 12.5% ( χ2=15.38, P < 0.001), respectively. Multivariate analysis showed that TNM staging, treatment method, and SII were independent prognostic factors for OS and PFS ( HR=1.39-1.60, P<0.05). Patients with low SII and early clinical staging had a better prognosis than other subgroups ( χ2=13.68, 13.43, P=0.001). The area under curve (AUC) of SII combined with TNM staging (0.70) was higher than that of SII (0.63) and TNM staging (0.62) ( Z=2.48, 2.57, P < 0.05). Conclusions:Pretreatment SII has a high predictive value for the prognosis of esophageal cancer after radiotherapy, and higher SII indicates a worse prognosis. Thus, combining SII with TNM staging can improve the prediction accuracy of the prognosis of esophageal cancer patients.

目的 探讨预后营养指数(PNI)对接受根治性放疗或放化疗的老年食管癌患者长期生存的预测价值.方法 对接受根治性放疗或放化疗且符合入组条件的188例老年食管癌患者进行回顾性分析.计算每例患者放疗前PNI值[PNI=血清白蛋白值(g/L)+5×外周血淋巴细胞总数(×109/L)],运用受试者工作特征(ROC)曲线确定其预测患者长期生存的最佳临界值,分为高PNI组及低PNI组,并比较2组患者生存预后及急性不良反应.结果 全组患者1、3、5年总生存率分别为74.5％、33.5％、24.9％.依据ROC曲线计算得出放疗前PNI最佳临界值为48.65,测量曲线下面积为0.649,敏感度为60.2％,特异度为70.1％.高PNI组(≥48.65)的86例和低PNI组(<48.65)的102例患者1、3、5年总生存率分别为83.7％、43.0％、32.5％和66.7％、24.5％、15.7％(Log-rankχ2=11.719,P<0.01).TNM分期为Ⅲ期和放疗前PNI<48.65为影响患者生存率的独立危险因素(P<0.05).另外,高PNI组≥3级急性放射性食管炎发生率低于低PNI组(χ2=4.438,P<0.05).结论 PNI对于老年食管癌接受根治性放疗后的长期生存具有较高的预测价值,PNI较高的患者具有相对良好的预后.

Reperfusion after cerebral ischemia causes additional ischemic injuries due to sudden recovery of blood supply. It usually produces excessive reactive species, mitochondrial dysfunction, oxidative stress, and cell apoptosis. Our study is designed to examine the role of miR-421 antagomir in cerebral ischemia/reperfusion injuries, as well as its underlying mechanisms. Middle cerebral artery occlusion (MCAO) model was performed with male Sprague Dawley (SD) rats for the initiation of cerebral ischemia/reperfusion injuries. Malondialdehyde (oxidative stress marker) and superoxide dismutase (antioxidant enzyme) were measured as indicators for oxidative stress. Flow cytometry was utilized to evaluate the cell apoptosis effects from miR-421. miR-421 antagomir significantly decreased neurological deficits and infarction volumes. It also downregulated malondialdehyde contents, upregulated superoxide dismutase activities, promoted the expressions of myeloid cells leukemia-1 and B cells lymphoma-2, and downregulated the expressions of Bax in the ischemic cortex. In addition, miR-421targeted MCL1 to exert its biological functions. Our study indicated the neuroprotection effects of miR-421 antagomir on cerebral I/R injuries, which involved the suppression of cell apoptosis and oxidative stress. MiR-421 might provide a new therapeutic direction for ischemia/reperfusion injuries.

目的 探讨马德拉斯运动神经元病(MMND)的临床表现,以提高该病的诊断水平.方法 分析1例MMND患者的病史资料.结果 43岁男性患者以咀嚼肌无力起病,出现多发的脑神经(V、VII、IX、X、XI、XII)损害,颈部、背部、上肢肌肉萎缩、无力,结合电生理检查结果,诊断为MMND.结论 MMND是运动神经元病的一个少见亚型,主要表现为多发的脑神经损害,广泛的肢体萎缩、无力,上、下运动神经元均受累,肌电图提示广泛神经源性损害,呈进展性但相对良性病程.

目的 观察瑞舒伐他汀与氯吡格雷联合口服治疗急性脑梗死(ACI)的效果.方法 116例ACI患者随机分为两组各58例,观察组患者口服瑞舒伐他汀+氯吡格雷,对照组患者口服氯吡格雷,观察两组临床疗效,比较神经功能(NIHSS评分、Barthel指数)、血液流变学指标[全血低切黏度、全血高切黏度、纤维蛋白原(FIB)、血细胞比容]及血清脂蛋白相关磷脂酶A2(Lp-PLA2)、心型脂肪酸结合蛋白(H-FABP)、可溶性细胞间黏附分子1(sICAM-1)、可溶性血管细胞黏附分子1(sVCAM-1),并记录不良反应发生情况.结果 与对照组比较,观察组治疗总有效率高(P＜0.05).与同组治疗前比较,两组治疗后NIHSS评分减少,Barthel指数增加(P均＜0.05);与对照组比较,观察组治疗后NIHSS评分减少,Barthel指数增加(P均＜0.05).与同组治疗前比较,两组治疗后全血低切黏度、全血高切黏度、FIB、血细胞比容降低(P均＜0.05);与对照组比较,观察组治疗后全血低切黏度、全血高切黏度、FIB、血细胞比容降低(P均＜0.05).与同组治疗前比较,两组治疗后血清Lp-PLA2、H-FABP、sICAM-1、sVCAM-1水平降低(P均＜0.05);与对照组比较,观察组治疗后血清Lp-PLA2、H-FABP、sICAM-1、sVCAM-1水平降低(P均＜0.05).两组不良反应发生率比较,P ＞0.05.结论 瑞舒伐他汀与氯吡格雷联合口服治疗ACI患者效果较好,且能明显改善患者神经功能,降低血液黏度,降低血清Lp-PLA2、H-FABP、sICAM-1、sVCAM-1水平,减轻炎症反应,且不良反应发生率低.

Objective To investigate the changes of attentional compositions of subjects with hemispatial neglect(HSN).Method The electrical activities of the brain and respond time were recorded when one subject with HSN was carrying out the cue-target experimental paradigm. The attention related ERP (event-related potentials) components and behaviors data were analyzed.Results The respond time to the targets located in the left side was longer than ones in the right side; the main effect of cue types or the sides of targets was unremarkable to the amplitudes and lantency of 5 attention related ERP components ( antN1, postN1, LPD, P1, P2) . The P2 and post N1 in the left hemisphere indicated more obviously lateralization than in the right hemisphere.Conclusion Subjects with HSN show up lateralization in the left hemisphere when paying space-based or object-based attention.