MTDH基因和ATG7基因在结直肠癌中的表达及临床意义

目的探讨异黏蛋白(MTDH)基因和自噬相关基因7 (ATG7)在结直肠癌(CRC)中的表达及临床意义。方法选取66例CRC患者的CRC组织及癌旁组织,比较CRC组织及癌旁组织中的MTDH mRNA和ATG7mRNA的相对表达量;比较不同临床特征CRC患者的CRC组织/癌旁组织MTDH mRNA、ATG7 mRNA的相对表达量;采用受试者工作特征(ROC)曲线分析CRC组织/癌旁组织中MTODH mRNA和ATG7 mRNA对结直肠癌的诊断价值,并分析MTDH mRNA与ATG7 mRNA的相关性。结果 CRC组织中MTDH mRNA和ATG7 mRNA相对表达量显著高于癌旁组织(P <0.01);TNM分期为Ⅲ~Ⅳ和有肝转移的CRC患者中,CRC组织/癌旁组织中的MTDH mRNA和ATG7 mRNA相对表达量均显著高于Ⅰ~Ⅱ期和无肝转移的CRC患者,低分化程度的CRC患者中CRC组织/癌旁组织中的MTDH mRNA和ATG7 mRNA相对表达量最高(P <0.01)。ROC曲线分析结果 CRC组织/癌旁组织中MTDH mRNA、ATG7 mRNA的AUC面积分别是0.934、0.900,诊断敏感度分别为90.91%、89.39%,特异度分别为86.37%、84.35%。Pearson分析结果表明CRC中MTDH的表达与ATG7的表达呈正相关(r=0.372,P=0.002)。结论 CRC组织中MTDH mRNA、ATG7 mRNA的表达高于癌旁组织。CRC组织中MTDH mRNA、ATG7 mRNA与TNM分期、分化程度、伴肝转移相关。CRC组织中MTDH mRNA、ATG7 mRNA具有诊断价值且两者具有正相关。     

High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer

Recent studies have reported that tumor‐infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine‐based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine‐based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM‐activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell‐related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine‐based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.     

基于网络药理学和分子对接技术探讨生脉注射液抗新型冠状病毒肺炎的作用机制

目的采用网络药理学与分子对接技术探讨生脉注射液的活性成分和治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制。方法利用TCMSP及BATMAN-TCM数据库筛选生脉注射液的活性化合物,通过TCMSP及Targetnet在线数据库预测作用靶点,通过Cytoscape3.7.1构建活性成分-作用靶点网络图;在GeneCards及OMIM数据库中以"coronavirus pneumonia"为关键词搜索冠状病毒肺炎相关疾病靶点,与生脉注射液化合物靶点进行交集筛选出共同靶点作为研究靶点,将共同靶点导入STRING数据库获取数据后在Cytoscape 3.7.1软件中构建蛋白质-蛋白质相互作用网络图;利用R语言进行GO(gene ontology)功能、KEGG(Kyoto encyclopedia of genes and genomes)通路富集分析,预测其作用机制,并构建"成分-靶点-通路"网络图;通过DiscoveryStudio 2.5软件对关键靶点进行分子对接分析。结果生脉注射液筛选得到22个活性化合物,分别为邻苯二甲酸二辛酯、β-谷甾醇、当归酰基戈米辛O、戈米辛A、戈米辛R、五味子丙素、内南五味子酯乙、长南酸、南五味子内酯、香蒲木脂素B、新杜松烷酸A、新杜松烷酸B、新杜松烷酸C、新南五味子木脂宁、五味子内酯A、五味子内酯E、五味子酸、尿苷、薯蓣皂苷元、鸟嘌呤核苷、N-反式阿魏酰酪胺、豆甾醇。相应作用靶点224个,与COVID-19的共同靶点16个,分别为CASP3、CASP8、PTGS2、BCL2、BAX、PRKCA、PTGS1、PIK3CG、F10、NOS3、DPP4、NOS2、TLR9、ACE、ICAM1、PRKCE,关键靶点涉及CASP3、PTGS2、NOS2、NOS3、ICAM1。GO功能富集分析得到生物过程(BP)条目771个,细胞组成(CC)条目11个,分子功能(MF)条目79个。KEGG通路富集分析筛选得到67条(P0.05)信号通路,主要涉及糖尿病并发症AGE-RAGE信号通路、凋亡通路、P53信号通路、小细胞肺癌通路等。分子对接结果显示与关键靶点对接较好的成分有五味子内酯E、豆甾醇、N-反式阿魏酰酪胺。结论生脉注射液中的活性化合物五味子内酯E、豆甾醇、N-反式阿魏酰酪胺等能作用于CASP3、PTGS2、NOS2、NOS3等靶点调节多条信号通路发挥抗炎、免疫调节、抗休克、增加血氧饱和度等作用,从而可能发挥对COVID-19的治疗作用。     

CML Case Studies: Impact of Comorbidities

Clinicians have the choice of five approved tyrosine kinase inhibitors (TKI) to select from for chronic phase CML patients. The best frontline drug for each patient and decisions about if and when to change to another TKI or to stop therapy need to be considered in the context of the comorbidities present. These issues are explored in three illustrative cases. The predominant toxicity issue for all of the TKIs except imatinib is vascular occlusive events, so a systematic approach to assessing

Discussion

The excellent long-term outcomes achieved in most CML patients has led to a revision of the goals of therapy.¹³ While preventing progression to blast crisis remains an important goal, avoiding organ toxicity may be equally important, since deaths from causes other than CML are much more common than CML-related deaths. Patients most at risk of organ toxicity are those patients with comorbidities, particularly those patients with comorbidities that increase their risk of vascular events.

References

• 1.Saußele S, Krauß MP, Hehlmann R, Lauseker M, Proetel U et al, Impact of comorbidities on overall survival in patients with chronic myeloid leukemia: results of the randomized CML Study IV. Blood. 2015;126:42-49.
• 2.Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim D-W et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016; 30:1044–1054.
• 3.Castagnetti F, Gugliotta G, Breccia M,

     

Fine particulate matter and incidence of metabolic syndrome in non-CVD patients: A nationwide population-based cohort study

Background

It has been reported that particulate matter (PM) is associated with cardiovascular diseases (CVD) while metabolic syndrome is also an important risk factor for CVD. However, few studies have investigated the epidemiological association between PM and metabolic syndrome.

中药酊剂临床外用技术规范(草案)

基于对中药酊剂外用技术的数据挖掘,结合临床实际应用研究,经外治学会专家多次论证,形成中药酊剂临床外用技术规范(草案),包括临床适用范围、操作步骤以及外用酊剂的方法、剂量、频率、时间、注意事项、不良反应及护理要点。以期规范中药外用酊剂的临床应用,提高其疗效并减少不良反应。     

Characteristics and risk factors of bortezomib induced peripheral neuropathy: A systematic review of phase III trials

Bortezomib-induced peripheral neuropathy (BIPN) is a common toxicity associated with the treatment of multiple myeloma (MM), typically requiring dose reduction, delay, or cessation of treatment protocol. This systematic review aimed to investigate risk factors, trends, and variability associated with the development of BIPN. Searches were undertaken using Medline, PubMed, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Web of Science. Additional studies were identified by investigating authors' bibliographic references cited by original and review articles. Articles that reported on neuropathy in phase III randomised control trials involving bortezomib in any treatment arm for the treatment of MM were included in this review. A total of 43 full text articles met criteria, which examined 23 phase III trials (N = 8218). Overall incidence of neuropathy ranged from 8.4% to 80.5% (median = 37.8%) and severe neuropathy (grade 3-4) ranged from 1% to 33.2% (median = 8%). Similar reports of neuropathy of any grade and severe neuropathy were observed between the newly diagnosed and relapsed cohort. Bortezomib regimens with reduced dose intensity were associated with reduced neuropathy incidence. Increased cumulative dosing levels, intravenous compared with subcutaneous administration and combination therapy with thalidomide were associated with higher rates of BIPN. This analysis revealed that BIPN is a significant toxicity. More sensitive measures are required to capture the incidence and severity of BIPN. Better understanding of risk factors and reversibility profiles will minimise the number of cancer survivors living with residual treatment side effects.     

连续性肾脏替代治疗联合中药灌肠对急性肾损伤患者尿KIM-1、NGAL水平的影响

目的:探讨连续性肾脏替代治疗(CRRT)联合中药灌肠对重症急性肾损伤患者尿肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平和预后的影响。方法:回顾性分析89例重症急性肾损伤患者临床资料,依据不同治疗方式分为对照组43例和研究组46例,对照组采用CRRT治疗,研究组采用CRRT联合中药灌肠治疗。比较两组尿量恢复时间、重症医学科(ICU)住院时间、治疗前后肾功能、尿KIM-1、NGAL水平,序贯器官衰竭估计评分(SOFA)、急性生理与慢性健康评分表(APACHEⅡ)评分和预后情况。结果:研究组尿量恢复时间、ICU住院时间均少于对照组(P<0.05)。治疗前,两组肾功能、尿KIM-1、NGAL水平,SOFA、APACHEⅡ评分比较,差异无统计学意义(P>0.05); 治疗后,两组肾功能指标、尿KIM-1、NGAL水平,SOFA、APACHEⅡ评分均较治疗前下降,研究组低于对照组,差异有统计学意义(P<0.05)。研究组死亡率较对照组低(P<0.05)。结论:CRRT联合中药灌肠能够促进重症急性肾损伤患者肾功能的恢复,降低尿KIM-1、NGAL水平,改善预后。     

急诊治疗重症心力衰竭的方案及疗效探析

目的探讨急诊治疗重症心力衰竭的方案及疗效。方法选择本院80例2016年2月-2019年2月重症心力衰竭患者。随机分组,常规治疗组采取常规方法治疗,急诊治疗组则采取全面急诊治疗。比较两组重症心力衰竭疗效;重症心力衰竭症状改善的时间、心功能改善两级的时间;治疗前后患者舒张压、平均心率以及左心射血分数;不良反应。结果急诊治疗组重症心力衰竭疗效、重症心力衰竭症状改善的时间、心功能改善两级的时间、舒张压、平均心率以及左心射血分数相比较常规治疗组更好,P<0.05。两组未见严重不良反应,P>0.05。结论全面急诊治疗重症心力衰竭可获得较好预后,可有效改善患者的心功能,缓解症状,且安全性高,无明显不良反应。     

支原体肺炎患儿免疫功能变化的检测价值

目的分析免疫功能变化在支原体肺炎感染患儿中的检测价值。方法在2016年8月-2018年8月在医院接受诊治的114例支原体肺炎患儿与114例健康体检者作为本次研究。按根据是否属于支原体肺炎划分为试验组与常规组。试验组与常规组均接受免疫功能变化检测,总结并对比两组补体、免疫球蛋白水平、红细胞免疫水平以及T淋巴细胞亚群水平。结果试验组患儿的各项补体、免疫球蛋白水平相对于常规组而言均有明显数据差异(P<0.05);试验组患儿的各项细胞免疫水平相对于常规组而言均有明显数据差异(P<0.05);试验组患儿的各项T淋巴细胞亚群水平相对于常规组而言均有明显数据差异(P<0.05)。结论免疫功能变化在支原体肺炎感染患儿中的检测价值突出,可以作为患儿症状的检测与症状严重程度的判断依据。