Abstract Objectives: This study aims to analyze the expression and prognostic significance of chromobox (CBX) family genes in pan cancer and to associate their roles with immune subtypes, tumor microenvironment and drug sensitivity. Methods: TCGA +GTEX method was used to analyze five members of the CBX2/4/6/7/8, Using 11,093 samples from 33 tumor types in TCGA database，to multidimensional analysis of five members of the CBX family, CBX2, CBX4, CBX6, CBX7, CBX8.including the differential expression of the CBX family in pan cancer, as well as the correlation between immune subtypes, tumor purity and stemness.Finally, the correlation data of CellMiner database was used to analyze the relationship between CBXs and drug sensitivity. Then, GO plot was performed, and GSEA analysis and weighted gene co-expression network analysis were generated. CellMiner database was used to analyze the correlation and mechanism of CBX family genes with drug sensitivity. Results: CBX 2/4/8 were highly expressed in pan-cancers. The expression level of CBX6 was heterogeneous among different tumor types, while that of CBX7 was low. The results show that CBX2, CBX4, and CBX8 are highly expressed in pan-cancer,and CBX6 is heterogeneous among different tumor types, while CBX7 is lowly expressed in almost tumor types.The expression of CBXs was correlated with the overall survival of patients, but the correlation direction depended on the cancer type. CBXs were significantly correlated with immune infiltration subtypes (P< 0.001). The expression of CBX2/CBX7s had differences in stromal cell score and RNAss stemness score. High expression of CBX82 was correlated with the high purity of most types of cancers, while CBX7 was contrary to this pattern. Rich analysis indicated that CBXs may affect the occurrence and progression of tumors by regulating RNA splicing and transcription coactivator activity. The core genes of hsa-mir-181a and EGR1 were identified in the established mRNA-TF-miRNA WGCNA network. Finally, our study revealed that CBX2 gene may be associated with sensitivity to Acrichine, Curcumin, Nelarabine, Ixabepilone, Ifosfamide, tfdu and Tamoxifen.The high expression of CBX7 was positively correlated with the drug resistance of cells to Aminoflavone, AFP464 and Lificguat.Conclusion: The CBX family showed different expression in different tumor types. CBX2 acted as an oncogene and might be overexpressed in a variety of human cancers, and CBX7 acted as a tumor suppressor gene and might become a promising therapeutic target. This study revealed multiple expression patterns of CBXs in pan cancer, providing new insights for cancer treatment, but further laboratory validation is needed.

目的 筛选喉鳞状细胞癌(laryngeal squamous cell carcinoma,LSCC)预后相关免疫核心基因并构建预后风险评分模型.方法 利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中LSCC转录组测序信息,筛选差异表达基因,并与已知免疫相关基因取交集,筛选LSCC中预后相关免疫核心基因.利用单因素Cox回归构建风险评分模型并采用Kaplan-Meier法验证风险评分模型与LSCC患者预后的关系,同时绘制受试者工作特征(receiver operating characteristic,ROC)曲线验证该模型准确度.结果 LSCC组织和癌旁组织中共有6800个差异表达基因,通过单因素Cox分析并与已知免疫相关基因取交集,从差异表达基因中筛选出34个预后枢纽基因.基于免疫核心基因构建风险评分模型,高危险组患者总生存期短于低危险组患者(P<0.01),风险评分模型预测LSCC患者预后的ROC曲线下面积为0.930.结合临床病理学参数分析发现,患者性别是LSCC预后的保护因素,N分期晚期和高风险评分为LSCC预后的危险因素(均P<0.05),而患者年龄和T分期与LSCC预后无关(均P>0.05).结论 LSCC中存在多个免疫核心基因异常表达,且与患者预后相关,基于其构建的风险评分模型可较好预测患者预后.

目的 基于网络药理学、分子对接技术结合体外实验,探讨益气解毒方及其活性成分槲皮素抑制鼻咽癌增殖的可能机制.方法 运用TCMSP、BATMAN-TCM、GEO、GeneCards、OMIM、TTD、PharmGkb等数据库检索益气解毒方的化学活性成分及鼻咽癌的作用靶点;STRING数据库构建可视化PPI网络;关键作用靶点进行GO和KEGG富集分析;采用分子对接验证槲皮素的可能靶点TP53、MYC、MDM2和AKT1;采用CCK-8法和RTCA法检测益气解毒方及主要活性成分槲皮素抑制鼻咽癌细胞CNE-2增殖的效应;采用Western blot检测药物对细胞增殖及PI3K/Akt信号通路关键蛋白表达的影响.结果 筛选得到益气解毒方有效化学成分197种,得到潜在共同作用靶点173个,核心基因为TP53、JUN、MAPK3、MYC等;KEGG分析主要富集在PI3K/Akt、MAPK等信号通路;分子对接结果示槲皮素与TP53、AKT1、MDM2、MYC均具有良好的结合位点;体外实验证实益气解毒方及槲皮素能抑制细胞增殖;药物能下调增殖相关蛋白XIAP、PCNA、Survivin及PI3K/Akt信号通路蛋白PI3K、AKT1、p-AKT1、mTOR的表达水平;激活PI3K/Akt信号通路后,槲皮素抑制细胞增殖的效应被削弱.结论 益气解毒方及主要活性成分槲皮素可能通过下调PI3K/Akt信号通路抑制鼻咽癌细胞增殖.

目的 探讨双支架治疗未破裂椎动脉夹层动脉瘤的安全性和有效性.方法 回顾性分析2016年7月至2018年10月在复旦大学附属华山医院北院接受双支架(套叠式)植入治疗的32例未破裂椎动脉夹层动脉瘤患者临床资料.根据术后随访和DSA复查结果,评价双支架治疗未破裂椎动脉夹层动脉瘤的安全性和有效性.结果 32例患者双支架血流重建均获成功,支架释放成功率为100％.术中和术后均未发生瘤体破裂.术后随访1～24个月,平均12个月,结果显示19例患者(59.4％,19/32)为影像学治愈,3例(9.4％)为改善(动脉瘤体积缩小),5例(15.6％)为稳定,1例(3.1％)发生缺血事件(表现为肢体偏瘫),4例(12.5％)复发.结论 双支架治疗未破裂椎动脉夹层动脉瘤安全有效,但远期疗效有待进一步验证.

目的 通过网络药理学探讨黄连和黄芪治疗鼻咽癌的作用机制.方法 采用中药系统药理学分析平台(TCMSP)获取黄连和黄芪的活性成分和作用靶点.通过GeneCards数据库获取鼻咽癌相关靶点,应用R语言软件及Perl语言程序筛选出与黄连和黄芪的共同靶点.使用STRING数据库进行蛋白-蛋白相互作用(PPI)网络分析.应用Cytoscape 3.6.0软件构建成黄连和黄芪活性成分-鼻咽癌-靶点交集网络.通过R语言软件对共同靶点进行基因本体(GO)和基因功能(KEGG)富集分析.采用MTT法对活性成分抗增殖效应进行体外验证.结果 共获得黄连和黄芪中19个活性成分,183个候选靶点,鼻咽癌相关靶点768个,两者匹配映射得到共同靶点95个,出现频次较高的有丝氨酸/苏氨酸激酶1 (AKT1)、原癌基因(JUN)、丝裂原活化蛋白激酶(MAPK)1、RELA、白细胞介素(IL)-6等,主要涉及受体配体活性、细胞因子活性、蛋白激酶调节活性、DNA结合转录激活活性等生物过程,并主要富集在磷脂酰肌醇激酶(PI3K)/AKT信号通路、MAPK信号通路、IL-17信号通路、肿瘤坏死因子(TNF)信号通路等调控通路.MTT实验表明小檗碱和芒柄花黄素均能抑制人鼻咽癌CNE细胞增殖.结论 黄连和黄芪中的槲皮黄素、山柰酚、芒柄花黄素、小檗碱等多成分可能通过PI3K-AKT、MAPK等多个信号通路作用于鼻咽癌.

目的 总结重型颅脑损伤去骨瓣减压术中对侧迟发性血肿的手术经验.方法 回顾分析2011年1月～2018年10月收治的47例重型颅脑损伤的临床资料,去骨瓣减压术中出现急性脑膨出,CT发现对侧颅内血肿35例(CT组),术中超声发现对侧颅内血肿12例(超声组).结果 超声组手术时间[(4.98±0.60)h]较CT组[(7.11±1.54)h]明显缩短(P＜0.01).术后6个月,CT组GOS评分4～5分7例,3分6例,2分5例,1分17例;超声组GOS评分4～5分5例,3分3例,2分2例,1分2例.两组预后无统计学差异(P＞0.05).结论 CT、术中超声能及时准确发现颅内血肿,指导手术,但术中超声能缩短手术时间.

Objective To investigate the risk factors associated with post traumatic cerebral infarction (PTCI) after craniotomy hematoma evacuation for severe traumatic brain injury (sTBI) so as to provide clinical reference for the early prevention of postoperative PTCI.Methods A retrospective case control study was conducted to analyze the clinical data of 558 sTBI patients who received craniotomy hematoma evacuation admitted to Changsha Hospital of Traditional Chinese Medicine from October 2006 to June 2016.There were 340 males and 218 females,aged 15-71 years,with an average of 47.8 years.Among them,75 patients were at the age of less than 30 years,315 were at 30-50 years,and 168 were above 50 years.According to the Glasgow coma score (GCS),there were 127 patients with 3-4 points,124 with 5-6 points,and 307 with 7-8 points.The patients were divided into PTCI group (51 patients)and non-PTCI group (507 patients).The related indicators of the two groups of patients after admission were collected,including gender,age,injury cause,GCS,skull base fracture,traumatic subarachnoid hemorrhage (tSAH),cerebral hernia,hypotension,the time from injury to craniotomy,and whether decompressive craniectomy was performed.Univariate analysis was first performed for these factors,followed by multivariate logistic regression analysis.Results There were no significant differences in gender,age,injury cause,skull base fracture,and decompressive craniectomy between PTCI group and control group (P ＞ 0.05).In the PTCI group,there were 29 patients with GCS of 3-4 points,17 with 5-6 points,and five with 7-8 points;there were 48 patients with tSAH,37 patients with cerebral hernia,and 18 patients with hypotension.In terms of the time from injury to craniotomy,it took ＜ 3 hours in 30 patients,3-6 hours in 12,6-12 hours in five,and ＞ 12 hours in four.In the non-PTCI group,there were 98 patients with GCS of 3-4 points,107 with 5-6 points,and 302 with 7-8 points.There were 34 patients with tSAH,117 with cerebral hernia,and 35 with hypotension.In terms of the time from injury to craniotomy,it took ＜3 hours in 294 patients,3-6 hours in 130,6-12 hours in 68,and ＞ 12 hours in 15.The differences between the two groups were statistically significant (P ＜ 0.05).Multivariate logistic regression analysis indicated that GCS of 3-6 points,tSAH,cerebral hernia,time from injury to craniotomy,and hypotension were significantly associated with PTCI after operation for sTBI (P ＜ 0.01).Conclusions GCS of 3-6 points,tSAH,cerebral hernia,duration from injury to craniotomy,and hypotension time ＞ 3 hours are the high risk factors of PTCI in sTBI patients after craniotomy.For patients with these high risk factors,craniotomy should be performed in time,and the perioperative blood pressure and intracranial pressure stability should be maintained so as to relieve vasospasm.

目的:探讨气压泵联合穴位电刺激预防脑出血术后昏迷患者下肢深静脉血栓形成的作用.方法:2017年2月-2019年1月收治脑出血术后昏迷患者80例,随机分为两组各40例.观察组接受气压泵联合穴位电刺激治疗;对照组单独给予气压泵治疗.对比两组下肢深静脉血栓发生率及凝血指标、血流速度.结果:观察组患者下肢深静脉血栓发生率低于对照组,差异有统计学意义(P<0.05);观察组凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)高于对照组,D-二聚体低于对照组,差异有统计学意义(P<0.05);观察组股总静脉血流速度高于对照组,差异有统计学意义(P<0.05).结论:气压泵联合穴位电刺激能明显改善脑出血术后昏迷患者下肢血液流速,降低血栓形成风险,值得临床推广.

目的 探讨双侧平衡控制阶梯减压术治疗双侧外伤性颅内多发血肿的适应证及疗效.方法回顾性分析2014年1月至2017年12月手术治疗的52例幕上双侧外伤性颅内多发血肿的临床资料.术中采用双侧平衡减压,结合控制性阶梯减压技术,快速有效逐级减压,根据术中双侧情况决定下一步处理方法,以及是否去骨瓣;如果合并严重颅前窝底骨折,术中行颅底重建.结果术中发生脑膨出10例;去单侧骨瓣11例,去双侧骨瓣8例;术后复查CT,发现原有血肿增大或出现新血肿15例.随访6个月,按GOS评分:恢复良好22例,中残9例,重残9例,植物生存状态7例,死亡5例.结论双侧平衡控制阶梯减术可减少术中脑膨出及颅内再出血等发生率,是救治双侧外伤性颅内多发血肿有效方法.

目的 总结外伤性脑内血肿开颅清除术后术区再出血二次手术处理体会.方法 回顾性分析2006年10月至2016年2月收治的23例外伤性脑内血肿开颅清除术后术区再出血二次手术的临床资料.结果 根据GOS评分:11例恢复良好,6例重残,5例植物生存,2例死亡.再二次手术中未发生恶性脑膨出,第三次出血1例.结论 外伤性脑内血肿开颅清除术后术区再出血二次手术需采取正确的处理方法 ,避免术中恶性脑膨出,减少再出血机会,以提高生存率.