口腔科医生全程干预对头颈部恶性肿瘤放疗并发症影响的临床研究

目的 减少头颈部恶性肿瘤患者放疗并发症.方法 对247例治疗组头颈恶性肿瘤放疗患者实施口腔科医生全程干预并与213例对照组患者进行比较.结果 治疗组与对照组均有不同程度的黏膜反应及口干、味觉减退,但在远期并发症发生率及患者对痛苦感受度方面明显低于对照组.结论 口腔科医生全程干预可有效减少头颈部放疗并发症,提高患者生存质量.     

TNF-α在慢性根尖周炎骨破坏中的机制探讨

目的:探讨牙髓卟啉单胞菌(Porphyromonas endodontalis,P.e)脂多糖(lipopolysaccharide,LPS)是否诱导成骨细胞产生肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)及TNF-α是否通过核因子κB(nuclear factor-κB,NF-κB)信号通路上调巨噬细胞集落刺激因子(macrophage colony stimulating factor,M-CSF)的产生.方法:以不同浓度P.e-LPS (0～50 mg/L)刺激MC3T3-E1细胞和以10 mg/L P.e-LPS作用细胞不同时间(0～24 h)后,采用反转录-聚合酶链式反应(RT-PCR)检测TNF-α mRNA的表达;以不同浓度TNF-α(0～ 10 ng/L)刺激MC3T3-E1细胞后,采用RT-PCR和酶联免疫吸附试验(ELISA)检测M-CSF mRNA和蛋白的表达;再以ELISA方法检测BAY 11-7082对TNF-α刺激MC3T3-E1细胞后M-CSF蛋白表达的影响.采用SPSS 13.0软件包对结果进行单因素方差分析和Dunnett t检验.结果:不同质量浓度的P.e-LPS (0～50 mg/L)刺激MC3T3-E1细胞后,TNF-α mRNA的表达具有剂量依赖性;10 mg/L P.e-LPS作用MC3T3-E1细胞6h时,TNF-α mRNA的表达量最大.随着作用时间的延长,TNF-α mRNA的表达量逐渐下降;不同质量浓度TNF-α(0～10 ng/L)刺激MC3T3-E1细胞后,M-CSF mRNA和蛋白的表达具有剂量依赖性,蛋白表达量从(37±2) ng/L(空白对照组)增加到(301±8) ng/L(10 ng/L组);10 mol/L BAY 11-7082预处理1h可以降低TNF-α诱导成骨细胞M-CSF蛋白的表达水平,蛋白表达量从(253±14) ng/L(TNF-α组)下降到(154±2)ng/L(BAY+TNF-α组),而单独使用BAY 11-7082组与空白对照组相比差异无显著性.结论:P.e-LPS诱导成骨细胞产生TNF-α,而TNF-α上调M-CSF可能通过NF-κB信号通路,这意味着TNF-α可能在P.e-LPS致慢性根尖周炎骨破坏中对成骨细胞发挥自分泌作用.     

B7-1、B7-2在牙龈卟啉单胞菌脂多糖诱导的T淋巴细胞反应中的作用

目的：研究B7?1、B7?2分子对牙龈卟啉单胞菌（ Porphyromonas gingivalis,P． g）脂多糖诱导的T淋巴细胞反应的影响。方法：分别从基因敲除小鼠（ B7?1 KO组、B7?2 KO组、B7?1／2 KO组）和野生小鼠（ WT组）骨髓培养获得原代树突状细胞（ dendritic cell,DCs）并经P． g脂多糖刺激后,与T细胞混合培养。 CCK8试剂盒评价T细胞增殖,ELISA检测培养液中IFN?γ、IL?4及IL?17的水平,荧光定量PCR检测T细胞IFN?γ、IL?4、IL?17、GATA?3、T?bet及RORγt的转录水平。结果：CCK8检测显示各组T细胞增殖水平无差异。 ELISA及荧光定量PCR显示与WT组比较,B7?1 KO组IFN?γ降低,IL?4升高,IL?17无变化,T?bet降低,GATA?3升高,RORγt无变化;B7?2 KO组IFN?γ升高,IL?4降低,IL?17降低,T?bet升高,GATA?3降低,RORγt降低;B7?1／2 KO组各因子变化趋势介于B7?1 KO组和B7?2 KO组之间。结论：B7?1及B7?2分子对P． g脂多糖刺激的T细胞增殖无明显影响。但B7?1分子可促进T细胞向Th1型分化,抑制Th2型分化,与Th17型分化相关性不大;而B7?2分子抑制T细胞向Th1型分化,促进Th2型及Th17型分化。     

Interleukin-37 gene polymorphism and susceptibility to pulmonary tuberculosis among Iraqi patients

BackgroundControl of tuberculosis (TB) depends on a balance between host's immune factors and bacterial evasion strategies. Interleukin-37 (IL-37) is among the immunomodulatory factors that have been proposed to influence susceptibility to tuberculosis.MethodsA case–control study was conducted on 105 patients with pulmonary TB (37 active, 41 multi-drug resistant and 27 relapse) and 79 healthy controls to determine serum levels and single nucleotide polymorphisms (SNPs) of IL-37. The IL-37 level was assessed with an enzyme-linked immunosorbent kit, while DNA-sequencing was used to detect SNPs in the promoter region of IL37 gene.Results: Median level of IL-37 was markedly increased in serum of TB patients compared to controls (325.0 vs. 169.1 pg/mL; p < 0.001). This increase was universally determined in subgroups of patients distributed according to gender, age groups, and clinical type of disease, while no significant differences were found between the subgroups in patients or controls. Analysis of receiver operating characteristic curve confirmed these findings and IL-37 occupied a very good area under the curve, which was 0.816 (95% CI = 0.744–0.888; p < 0.001). At a cut-off value of 185.6 pg/mL, the sensitivity and specificity of IL-37 were 81.0 and 82.3%, respectively. Of the nine detected SNPs (rs2466449 G/A, rs2466450 A/G, rs2723168 G/A, rs3811042 G/A, rs3811045 T/C, rs3811046 G/T, rs3811047 A/G, rs3811048 G/A and rs200782323 G/A), only rs3811048 showed a significant association with TB; the G allele showed a significantly decreased frequency in TB patients compared to controls (25.2 vs. 44.9%; OR = 0.41; p < 0.001). It was possible to assign five haplotypes, and three showed significant differences between patients and controls. Frequency of haplotype A-A-G-A-C-T-G-A-G (0.331 vs. 0.213; OR = 2.10; p = 0.015) was significantly increased in TB patients compared to controls. On the contrary, frequencies of haplotypes A-A-G-A-C-T-G-G-G (0.029 vs. 0.116; OR = 0.24; p = 0.01) and A-A-G-G-T-G-A-G-G (0.140 vs. 0.275; OR = 0.45; p = 0.015) were significantly decreased in patients.ConclusionsIL-37 was up-regulated in the serum of TB patients irrespective of their gender, age or clinical type of disease. SNPs in the promoter region of IL37 gene were proposed to be associated with susceptibility to TB.     

长链非编码RNA在结直肠癌中的研究进展

长链非编码RNA（LncRNA）是近十年来肿瘤领域分子机制研究的热点之一,被证实在生物体内对基因的表达具有调控作用,与肿瘤的发生与发展密切相关。结直肠癌是一种严重危害人类健康的恶性肿瘤,研究发现许多LncRNA在结直肠癌中表达失调。异常表达的LncRNA作为关键的调控因子,参与了多种生物学过程,影响肿瘤细胞的增殖和凋亡、侵袭转移及调节肿瘤耐药。研究LncRNA在肠癌中的作用机制可以为结直肠癌临床治疗提供一些新思路。此外,LncRNA还可作为一种潜在的生物标志物用于结直肠癌早期诊断及预后评估。     

Ultrasonic enhancement of gene transfection in murine melanoma tumors

The enhancement of gene transfection by ultrasound (US) was evaluated in vitro and in vivo using the B16 mouse melanoma model. Cultured cells were either exposed in suspensions in vitro or implanted subcutaneously in female C57BL/6 mice for 10–14 days and, subsequently exposed, in vivo. For comparison to results with a luciferase plasmid, a reporter plasmid for green fluorescent protein (GFP) was used to evaluate transfection efficiency. US was supplied by a system, similar to a Dornier HM-3 lithotripter, that produced shock waves (SW) of 24.4 MPa peak positive and 5.2 MPa peak negative pressure amplitudes at the focus. The plasmids were mixed with the suspensions to achieve 20 μL mL⁻¹, or were injected intratumorally to provide 0.2 mg DNA per mL of tumor. Acoustic cavitation was promoted by retaining 0.2 mL of air in the 1.2-mL exposure chambers in vitro and by injecting air at 10% of tumor volume in vivo. In vitro, cell counts declined to 5.3% of shams after 800 SW exposure, with 1.4% of the cells expressing GFP after 2 days of culture. In vivo, 2 days after 400 SW exposure, viable-cell recovery from excised tumors was reduced to 4.2% of shams and cell transfection was enhanced by a factor of about 8, reaching 2.5% of cell counts (p < 0.005 in t-test). These results show that strong tumor ablation induced by US shock wave treatment can be coupled with simultaneous enhancement of gene transfection.     

Role of inflammatory response in liver diseases: Therapeutic strategies

Inflammation and tumorigenesis are tightly linked pathways impacting cancer development. Inflammasomes are key signalling platforms that detect pathogenic microorganisms, including hepatitis C virus(HCV) infection, and sterile stressors(oxidative stress, insulin resistance, lipotoxicity) able to activate pro-inflammatory cytokines interleukin-1β and IL-18. Most of the inflammasome complexes that have been described to date contain a NOD-like receptor sensor molecule. Redox state and autophagy can regulate inflammasome complex and, depending on the conditions, can be either pro-or antiapoptotic. Acute and chronic liver diseases are cytokinedriven diseases as several proinflammatory cytokines(IL-1α, IL-1β, tumor necrosis factor-alpha, and IL-6) are critically involved in inflammation, steatosis, fibrosis, and cancer development. NLRP3 inflammasome gain of function aggravates liver disease, resulting in severe liver fibrosis and highlighting this pathway in the pathogenesis of non-alcoholic fatty liver disease. On the other hand, HCV infection is the primary catalyst for progressive liver disease and development of liver cancer. It is well established that HCV-induced IL-1β production by hepatic macrophages plays a critical and central process that promotes liver inflammation and disease. In this review, we aim to clarify the role of the inflammasome in the aggravation of liver disease, and how selective blockade of this main pathway may be a useful strategy to delay fibrosis progression in liver diseases.     

熊去氧胆酸联合维生素D治疗PBC患者疗效和外周血T淋巴细胞亚群的变化

目的 研究应用维生素D辅助熊去氧胆酸（UDCA）治疗原发性胆汁性肝硬化（PBC）患者的疗效及其对血清25-羟基维生素D3（25-（OH）2-D3）和外周血T淋巴细胞亚群的影响。方法 2013年4月~2016年4月收治的70例PBC患者,采用随机数字表法分为观察组35例和对照组35例,分别给予UDCA或UDCA联合骨化三醇胶丸治疗。采用全自动电化学发光免疫分析法检测血清25-（OH）2-D3,使用流式细胞仪检测外周血T淋巴细胞亚群。结果 在治疗1年末,观察组血清25-（OH)2-D3水平为（24.5±4.2） ng/ml,外周血CD8⁺细胞百分比为（29.0±5.2）%,显著高于对照组的（20.2±3.6）ng/ml和（26.3±4.8） %（P<0.05）,CD4⁺细胞百分比和CD4⁺/CD8⁺比值分别为（31.8±5.9）%和（1.1±0.2）,显著低于对照组的[（36.2±6.4） %和（1.4±0.3）,P<0.05];应用巴塞罗那标准考核,观察组对UDCA应答率为85.7%,显著高于对照组的62.9%（P<0.05）;观察组血清二胺氧化酶（DAO）、D-乳酸、谷草转氨酶（AST）和碱性磷酸酶（ALP）水平分别为（3.5±0.6） U/ml、（8.2±1.5） μg/ml、（62.3±11.2） U/L和（317.5±57.3） U/L,显著低于对照组的[（3.9±0.7） U/ml、（9.4±1.7） μg/ml、（76.9±13.9） U/L和（355.4±64.2） U/L,P<0.05]。结论 应用维生素D辅助治疗PBC患者可以提高对UDCA的应答率,纠正免疫功能紊乱,保护肠道屏障功能,促进肝功能恢复。     

血管收缩剂对大鼠肿瘤血流动力学改变的研究

目的：研究血管收缩剂对肿瘤血流动力学的改变,探讨其对占位性病变的诊断作用。方法：Ｗｉｓｔａｒ大鼠８只,腋下种植Ｗａｒｋｅｒ－２５６癌肉瘤。皮下注射阿拉明０．０５ｍｇ,注射前后彩色多普勒超声对照检查肿瘤内血管长短、多少、粗细,血管连续性及血管血流动力学改变。血流动力学指标行ｔ检验。结果：注药后,瘤内彩色血流明显较前增多,流道增粗、增长,血流呈连续性,注药前后动脉收缩期峰值流速各为０．０６～０．２０ｍ／ｓ;０．１３～０．４３ｍ／ｓ（Ｐ＝０．０９）,舒张期末流速各为０．００～０．０７ｍ／ｓ;０．０３～０．１０ｍ／ｓ（Ｐ＝０．０２）,阻力指数各为０．６０～１;０．５２～０．８５（Ｐ＝０．０４）,静脉易检出,流速增快。结论：血管收缩剂引起肿瘤血供增加,血液流速增快,阻力指数降低,可用于肿瘤的血流动力学研究     

急性胰腺炎发病过程中肿瘤坏死因子作用的实验研究

目的　探讨肿瘤坏死因子 (TNF -α)在急性胰腺炎 (AP)发病过程中的作用。方法　采用放射免疫学法检测TNF-α水平 ,并分析其与急性胰腺炎病变严重程度 (以病理切片确定 )的相关性。结果　胰腺炎组B(2 15± 90pg/ml)、胰腺炎加重组C(2 41± 75pg/ml)、胰腺炎拮抗组D(175± 2 6 8pg/ml)的血清TNF -α水平都比对照组A(2 4 1± 8 2pg/ml)明显增高 (P <0 0 5 )。结论　TNF -α在急性胰腺炎的发病过程中起重要的介导作用 ,并反映急性胰腺炎的病变程度 ,阻断TNF -α能减轻急性胰腺炎的病理损害作用。