小剂量顺铂动脉化疗联合放疗对中晚期宫颈癌的临床疗效

目的:探讨小剂量顺铂用于子宫动脉化疗联合放疗治疗中晚期宫颈癌的临床疗效。方法:选择2010年8月~2012年8月我院收治的中晚期宫颈癌患者75例,根据不同治疗方案将其分为单纯放疗组25例(单纯采用放疗治疗)、小剂量动脉化疗组25例(同时放化疗,顺铂周疗的剂量控制在20 mg·m-2)及标准剂量静脉化疗组25例(同时放化疗,顺铂周疗的剂量控制在40 mg·m-2)。观察并比较三组患者的临床疗效、两年生存率及毒性反应发生情况等。结果:小剂量动脉化疗组与标准剂量静脉化疗组的总有效率及两年生存率显著高于单纯放疗组(P0.05),小剂量动脉化疗组的总有效率和两年生存率高于标准剂量静脉组,差异具有统计学意义(P0.05)。单纯放疗组及小剂量动脉化疗组的毒性反应发生率显著低于标准剂量静脉组(P0.05);单纯放疗组与小剂量动脉化疗组患者的毒性反应发生率对比无统计学差异(P0.05)。结论:小剂量顺铂动脉化疗可以有效降低中晚期宫颈癌患者的急性毒性反应,值得临床进一步推广应用。     

替吉奥联合伊立替康治疗晚期结肠癌的临床研究

目的:比较替吉奥联合伊立替康与替吉奥单药治疗晚期结肠癌的临床疗效。方法:选取2011年3月~2012年3月我院收治的晚期结肠癌患者90例,按照随机数字表法将患者分为研究组和对照组,每组45例,研究组给予替吉奥联合伊立替康,对照组给予替吉奥单药治疗,比较两组近期疗效、远期疗效和不良反应。结果:研究组的总有效率51.1%(23/45)显著高于对照组的26.7%(12/45),两组比较差异具有统计学意义(X2=13.281,P=0.017);研究组中位进展时间和中位生存时间均显著长于对照组,两组比较差异具有统计学意义(t=9.029,10.412,P=0.021,0.019);两组中性粒细胞减少和腹泻比较差异具有统计学意义(X2=11.517,12.041;P=0.023,0.019)。结论:替吉奥联合伊立替康治疗晚期结肠癌较单用替吉奥具有更好的治疗效果,值得临床推广应用。     

术前调强放疗联合替吉奥化疗对局部晚期直肠癌患者的疗效回顾分析

目的:探讨术前调强放疗联合替吉奥化疗对局部晚期直肠癌患者的疗效。方法:回顾性分析2012年12月至2014年12月我院收治的局部晚期直肠癌患者90例进行研究,根据治疗方法分为三组:A组(n=30)给予术前调强放疗联合替吉奥化疗治疗,B组(n=30)仅给予术前调强放疗治疗,C组(n=30)给予替吉奥化疗治疗。比较三组患者的总有效率,血清TPS、CYFRA21-1水平变化情况,1年、2年、3年复发、转移、生存率,保肛率及不良反应发生情况。结果:A组总有效率86.68%显著高于对照B组的46.67%和C组的50.00%,差异显著(P0.05);治疗前,三组TPS、CYFRA21-1水平无显著差异(P0.05);治疗后,三组TPS、CYFRA21-1水平均显著下降,且A组低于B组和C组(P0.05);三组患者1年、2年复发、转移情况无显著差异;A组3年复发、转移情况均显著低于B组和C组(P0.05);三组患者1年、2年生存率无显著差异;A组3年生存率均显著高于B组和C组(P0.05);三组患者发生恶心呕吐、白细胞减少等并发症发生情况无显著差异;A组保肛率均显著高于B组和C组(P0.05)。结论:采用术前调强放疗联合替吉奥化疗治疗局部晚期直肠癌疗效好于术前放疗。     

肝动脉化疗栓塞联合射频消融对中晚期肝癌患者血清肿瘤活性因子、肝功能和预后的影响

目的:探讨肝动脉化疗栓塞(TACE)联合射频消融(RFA)对中晚期肝癌患者血清肿瘤活性因子、肝功能和预后的影响。方法:选取2012年2月～2016年6月期间我院收治的中晚期肝癌患者103例,根据随机数字表法将患者分为对照组(n=51)和研究组(n=52),对照组患者给予RFA治疗,研究组给予TACE联合RFA治疗,比较两组临床总有效率,比较两组治疗前后肝功能、血清肿瘤活性因子水平,统计两组患者并发症情况和预后。结果:治疗后研究组临床总有效率为53.85%(28/52),高于对照组患者的33.33%(17/51)(P0.05)。两组患者治疗后总胆红素(TBIL)、丙氨酸转氨酶(ALT)、氨基酸转氨酶(AST)较治疗前降低(P0.05),但两组治疗后TBIL、ALT、AST比较差异无统计学意义(P0.05)。两组患者治疗后甲胎蛋白(AFP)、糖类抗原199(CA199),基质金属蛋白酶(MMP)均较治疗前降低,且研究组低于对照组(P0.05)。两组患者并发症发生率比较无差异(P0.05)。研究组患者治疗后1年、2年复发率低于对照组,生存率高于对照组(P0.05)。结论:TACE联合RFA治疗中晚期肝癌,疗效确切,可有效降低血清肿瘤活性因子水平,未加重肝功能损伤,且可改善患者的预后。     

吉非替尼治疗EGFR突变型晚期肺腺癌的近期疗效、毒副反应及疗效的影响因素分析

摘要 目的：探讨吉非替尼治疗表皮生长因子受体（EGFR）突变型晚期肺腺癌的近期疗效、毒副反应及疗效的影响因素。方法：选取2018年4月~2019年6月期间我院收治的EGFR突变型晚期肺腺癌患者97例。所有患者均给予吉非替尼治疗,观察其近期疗效及毒副反应情况。采用单因素和多因素 Logistic回归分析疗效的影响因素。结果：97例患者全部如期完成治疗,近期疗效评价：完全缓解（CR）、部分缓解（PR）、病情稳定（SD）、病情进展（PD）率分别为9.28%（9/97）、24.74%（24/97）、31.96%（31/97）、34.02%（33/97）。根据近期疗效结果将患者分为有效组（CR+PR,n=33）和无效组（SD+PD,n=64）。本研究中患者的毒副反应多为 I、Ⅱ度非血液学毒性,最常见的是皮肤毒性,如皮疹等;其他毒副反应如胃部不适、腹泻等,经对症治疗后均能缓解。单因素分析结果显示,吉非替尼治疗EGFR突变型晚期肺腺癌的疗效与性别、肿瘤临床分期、骨转移、肿瘤直径有关（P<0.05）,而与年龄、肾上腺转移、脑转移、吸烟史无关（P>0.05）。多因素Logistic回归分析结果显示,性别为男性、肿瘤分期Ⅳ期是影响吉非替尼治疗EGFR突变型晚期肺腺癌疗效的危险因素（OR=1.473、2.042,P<0.05）。结论：吉非替尼治疗EGFR突变型晚期肺腺癌具有不错的近期疗效,不良反应较少,性别为男性、肿瘤分期Ⅳ期是影响吉非替尼治疗EGFR突变型晚期肺腺癌疗效的危险因素。     

血清AGEs、sRAGE水平与急性脑梗死后出血性转化的相关性

摘要 目的：探讨血清晚期糖基化终末产物（AGEs）及可溶性期糖基化终末产物受体（sRAGE）与急性脑梗死后出血性转化（hemorrhagic transformation,HT）的相关性。方法：将2017年1月至2019年12月于我院诊治的131例急性脑梗死患者纳入研究对象,根据患者是否出现出血性转化将其分为HT组及NHT组,比较两组患者AGEs、sRAGE等实验室指标,采用多因素Logistic回归模型对影响急性脑梗死出血性转化的因素进行分析,并采用Pearson相关模型对血清中AGEs水平与sRAGE水平的相关性进行分析。结果：HT组患者合并糖尿病史、心房颤动病史比例、脑栓塞比例、梗死面积、采用抗凝治疗比例及血清中IL-1β、TNF-α、AGEs水平明显高于NHT组（均P＜0.05）;多因素Logistic回归分析示大梗死面积、高IL-1β、TNF-α及AGEs水平是患者出现急性脑梗死后出血性转换的保护因素（OR=0.625, 0.832, 0.874, 0.708;均P＜0.05）,而无抗凝治疗、高sRAGE则是患者出现急性脑梗死后出血性转换的危险因素（OR=10.901, 1.004;均P＜0.05）;相关性分析示血清中sRAGE水平与AGEs、IL-1β及TNF-α水平呈明显负相关（ρ=-0.852,-0.828,-0.826;均P＜0.05）。结论：血清AGEs是急性脑梗死患者出现出血性转化的危险因素,而sRAGE则是保护因素,sRAGE可能通过抑制RAGE与AGEs结合,从而减少释放炎症介质,减轻血管损伤,降低HT发生风险。     

HMGB1 Protein Does Not Mediate the Inflammatory Response in Spontaneous Spinal Cord Regeneration: A HINT FOR CNS REGENERATION*

Uncontrolled, excessive inflammation contributes to the secondary tissue damage of traumatic spinal cord, and HMGB1 is highlighted for initiation of a vicious self-propagating inflammatory circle by release from necrotic cells or immune cells. Several regenerative-competent vertebrates have evolved to circumvent the second damages during the spontaneous spinal cord regeneration with an unknown HMGB1 regulatory mechanism. By genomic surveys, we have revealed that two paralogs of HMGB1 are broadly retained from fish in the phylogeny. However, their spatial-temporal expression and effects, as shown in lowest amniote gecko, were tightly controlled in order that limited inflammation was produced in spontaneous regeneration. Two paralogs from gecko HMGB1 (gHMGB1) yielded distinct injury and infectious responses, with gHMGB1b significantly up-regulated in the injured cord. The intracellular gHMGB1b induced less release of inflammatory cytokines than gHMGB1a in macrophages, and the effects could be shifted by exchanging one amino acid in the inflammatory domain. Both intracellular proteins were able to mediate neuronal programmed apoptosis, which has been indicated to produce negligible inflammatory responses. In vivo studies demonstrated that the extracellular proteins could not trigger a cascade of the inflammatory cytokines in the injured spinal cord. Signal transduction analysis found that gHMGB1 proteins could not bind with cell surface receptors TLR2 and TLR4 to activate inflammatory signaling pathway. However, they were able to interact with the receptor for advanced glycation end products to potentiate oligodendrocyte migration by activation of both NFκB and Rac1/Cdc42 signaling. Our results reveal that HMGB1 does not mediate the inflammatory response in spontaneous spinal cord regeneration, but it promotes CNS regeneration.     

COMP-Ang1 inhibits apoptosis as well as improves the attenuated osteogenic differentiation of mesenchymal stem cells induced by advanced glycation end products

Background

In the present study, we have investigated the possibility that cartilage oligomeric matrix protein angiopoietin1 (COMP-Ang1), important factor in angiogenesis, osteogenesis and the survival of mesenchymal stem cells (MSCs) through the Ang1/Tie2 pathway has beneficial effects on osteogenic differentiated cells (ODCs) from MSCs treated by advanced glycation end products (AGE), which are pathological factors of diabetes.

Methods

Primary culture of MSCs was used. For comparison analysis of AGE and COMP-Ang1 effects, we performed cell viability assay with each treated variety concentration for 24 h. Apoptosis rate and Caspase-3 activity were measured by each ELISA assay. To make sure with Ang1/Tie2 pathway, we performed small interfering RNA transfected to MSCs. Real-time RT-PCR was performed to identify ODCs marker genes. Immunoblotting was used to evaluate the expression of Tie2, AKT, p38 and ERK.

Results

Our results clearly demonstrate that COMP-Ang1 upregulates the phosphorylation of AKT and p38 by activating the Ang1/Tie2 signaling pathway, indicating that COMP-Ang1 affects both AGE-induced apoptosis and the attenuated osteogenic differentiation of MSCs through the p38/MAPK and PI3K/AKT pathways.

Conclusions

COMP-Ang1 improves cell viability and differentiation function of ODCs against AGE via Ang/Tie2 signaling pathway.

General significance

Our results suggest the potential importance of COMP-Ang1 as a new therapy for impaired bone formation that is associated with diabetes and advanced age.     

Methylglyoxal-induced modification of arginine residues decreases the activity of NADPH-generating enzymes

Inadequate control of plasma and cellular glucose and ketone levels in diabetes is associated with increased generation of reactive aldehydes, including methylglyoxal (MGO). These aldehydes react with protein side chains to form advanced glycation end-products (AGEs). Arg residues are particularly susceptible to MGO glycation and are essential for binding NADP⁺ in several enzymes that generate NADPH, a coenzyme for many critical metabolic and antioxidant enzymes. In most animal cells, NADPH is produced predominantly by glucose-6-phosphate dehydrogenase (G6PD) in the oxidative phase of the pentose phosphate pathway and, to a lesser extent, by isocitrate dehydrogenase (IDH) and malic enzyme (ME). In this study, the activities of isolated G6PD, IDH, and ME were inhibited by MGO (0–2.5 mM, 2–3 h, 37 °C), in a dose- and time-dependent manner, with G6PD and IDH more sensitive to modification than ME. Significant inhibition of these two enzymes occurred with MGO levels ≥500 μM. Incubation with radiolabeled MGO (0–500 µM, 0–3 h, 37 °C) demonstrated dose- and time-dependent adduction to G6PD and IDH. HPLC analysis provided evidence for AGE formation and particularly the hydroimidazolones MG-H1 and MG-H2 from Arg residues, with corresponding loss of parent Arg residues. Peptide mass mapping studies confirmed hydroimidazolone formation on multiple peptides in G6PD and IDH, including those critical for NADP⁺ binding, and substrate binding, in the case of IDH. These results suggest that modification of NADPH-producing enzymes by reactive aldehydes may result in alterations to the cellular redox environment, potentially predisposing cells to further damage by oxidants and reactive aldehydes.     

基于Te-OnAdvanced的肺癌细胞15-脂氧化酶-2基因表达载体的构建与表达

目的：构建肺癌细胞15-脂氧化酶-2（15-Lox-2）的可诱导性真核表达载体pTRE-Tight-15-Lox-2,并在肺癌细胞中检测其是否可受强力霉素（DOX）诱导表达。方法：pcDNA3-15-LOX-2载体经＆0RI和XbaI双酶切线性化,回收15-LOX-2cDNA片段,将其克隆入pTRE-Tight载体的EcoRI和XbaI位点;采用脂质体法将pTet-0n-Ad-vanced与构建的pTRE-Tight-15-Lox-2共转染肺腺癌A549细胞,DOX诱导表达后,Western印迹检测15-Lox-2的表达水平。结果：构建了pTRE-Tight-15-Lox-2诱导表达载体;Western印迹检测表明,该载体能在肺癌细胞内表达,且其表达受DOX调控。结论：Tet-OnAdvanced系统能严密高效地调控15-LOX-2在肺癌细胞中的表达,为进一步研究15-LOX-2在肺癌中的作用奠定了基础。