低剂量辐射诱导适应性反应的分子机制研究现状

低剂量辐射(low dose radiation,LDR)可以增强细胞对随后进行的攻击性剂量(challenge dose)照射的抵抗能力,从而降低攻击性照射引起的染色体畸变和DNA损伤。人们把LDR的这种效应称之为"低剂量辐射诱导的适应性反应"。低剂量辐射诱导适应性反应的分子机制主要涉及细胞信号转导、ROS(活性氧物质)的作用和DNA修复兴奋效应等方面。     

内脏脂肪与2型糖尿病血管并发症的关系研究进展

2型糖尿病(T2DM)血管并发症包括大血管并发症和微血管并发症,其发病率的升高往往伴随着高肥胖发生率。肥胖是T2DM的独立危险因素。研究显示,体脂分布而不是体脂总量与肥胖患者的代谢及心血管风险相关。体重指数(BMI)和腰围(WC)不能准确地反映肥胖患者的体脂分布情况,因此,内脏脂肪越来越受重视,并可能成为T2DM血管并发症的预测指标。本文就内脏脂肪与T2DM血管并发症的相关性及其作用机制研究进展进行综述,以期为内脏脂肪的深入研究和临床检查提供参考。     

低剂量辐射的细胞遗传适应性反应机理研究现状

很多学者对LDR(低剂量辐射)可以在体内及体外培养的细胞中诱导出适应性反应的机理进行了深入的研究,发现适应性反应的诱导与很多因素有关,这些因素包括LDR诱导的DNA修复系统的激活、LDR诱导的基因和蛋白的作用、抗氧化物酶的作用、细胞信号转导以及与p53蛋白有关的细胞周期阻滞的影响等。     

低剂量辐射诱导适应性反应的分子机制研究现状

低剂量辐射(low dose radiation，LDR)可以增强细胞对随后进行的攻击性剂量(challenge dose)照射的抵抗能力，从而降低攻击性照射引起的染色体畸变和DNA损伤。人们把LDR的这种效应称之为“低剂量辐射诱导的适应性反应”。低剂量辐射诱导适应性反应的分子机制主要涉及细胞信号转导、ROS(活性氧物质)的作用和DNA修复兴奋效应等方面。     

低剂量辐射诱导蛋白对正常人外周血淋巴细胞亚群的刺激效应

目的 探讨低剂量辐射(LDR)诱导蛋白对淋巴细胞亚群功能的影响。方法 观察LDR诱导蛋白对单克隆抗体铺皿法—直接法分离出的淋巴细胞亚群CD4、CD8、CDl9细胞转化功能的影响。结果 经LDR诱导蛋白作用后，亚群细胞14C—TdR掺入值增高，分别为对照组的118．23％、115．18％和121．62％。结论 LDR诱导蛋白能不同程度地刺激CD4、CD8、CDl9细胞DNA合成。     

低剂量电离辐射对高剂量辐射致癌的影响

低剂量辐射 (LDR)免疫增强效应及其诱导的适应性反应已得到大量实验研究和人体观察资料证实 ,其生物学意义引起许多学者的关注[1 5 ]。免疫系统是机体防御系统的重要组成部分 ,特别是免疫监视作用在肿瘤发生、发展和转归上起着十分重要的作用。因此LDR免疫增强效应及其诱导的适应性反应对机体抗肿瘤能力影响的研究具有重要的理论和临床意义。本研究较系统地探讨了LDR对高剂量辐射诱发小鼠胸腺淋巴瘤 (TL)的影响及其免疫学机理 ,其结果对评价LDR对机体健康影响及在临床上的应用具有重要的意义。一、材料和方法1 动物 :雌性C57BL 6J纯…     

宫颈癌的高剂量率后装内照射治疗简介

本文结合宫颈癌高剂量率后装内照射的临床实践,对内照射剂量率、剂量率效应机制、HDR及LDR内照射的放射生物学效应差异、HDR及LDR内照射放射生物剂量等方案的选择和等效方案换算以及HDR的适当分割次数等问题作了讨论,部分情况附以举例。并介绍了26个组6161例宫颈癌HDR内照射治疗的实施方案和并发症率的临床资料。     

低剂量辐射的细胞遗传适应性反应机理研究现状

很多学对LDR（低剂量辐射）可以在体内及体外培养的细胞中诱导出适应性反应的机理进行了深入的研究，发现适应性反应的诱导与很多因素有关，这些因素包括LDR诱导的DNA修复系统的激活、LDR诱导的基因和蛋白的作用、抗氧化物酶的作用、细胞信号转导以及与p53蛋白有关的细胞周期阻滞的影响等。     

多次低剂量照射对雄性糖尿病大鼠脾细胞凋亡和免疫因子的影响

目的 观察多次低剂量辐射(LDR)对糖尿病(DM)大鼠脾细胞凋亡和免疫因子的影响。方法 大鼠随机分为对照组、DM组和DM+LDR组;剂量分别为25、50和75 mGy,共照射15次;照射后4周,采用流式细胞术检测脾细胞凋亡和TCRα β百分数的变化,酶联免疫吸附法(ELISA)检测血清和脾细胞培养上清IL-2含量的变化。结果 与对照组相比,DM和DM + LDR两组大鼠体重均下降,尤以DM组明显。DM+LDR组大鼠血糖水平虽明显高于对照组(t₂₅=23.321、 t₅₀=18.329、 t₇₅=9.23,P<0.01),但显著低于DM组(t₂₅=3.574、 t₅₀=4.593、 t₇₅=5.577,P< 0.01)。同时发现:与对照组相比,DM+LDR各组脾细胞凋亡增加,其中DM+50 mGy组增加明显(t₅₀=4.102,P<0.01)。血清IL-2含量也增加,但是差异均无统计学意义。脾细胞培养上清IL-2含量明显下降(t₂₅=7.778、 t₅₀=7.411、 t₇₅=8.325,P<0.01)。与DM组相比,DM+LDR各组脾细胞凋亡和TCRα β百分数均明显降低(凋亡:t₂₅=4.772、 t₅₀=3.346、 t₇₅=6.778;TCRα β:t₂₅=3.381、 t₅₀=5.807、 t₇₅=2.356,P<0.05～P<0.01)。血清IL-2含量呈下降趋势;脾细胞培养上清IL-2含量均有升高趋势。结论 多次LDR能够削弱糖尿病造成的大鼠体重减轻和血糖升高,降低糖尿病所致的脾细胞凋亡,并能调节脾脏免疫因子,改善其失衡状态。     

间充质干细胞对2型糖尿病小鼠糖尿病肾病进展的影响及其机制

目的 探讨脐带间充质干细胞(UC-MSCs)早期注射对2型糖尿病(T2DM)小鼠糖尿病肾病进展的影响及其可能机制。方法 选取20只5周龄雄性db/db小鼠构建T2DM小鼠模型，随机分为干细胞治疗组(MSCs组，n=10)和T2DM组(n=10)；另设置鼠龄匹配的db/m小鼠为正常对照组(NC组，n=10)。MSCs组小鼠行连续6周的人UCMSCs(1×10⁶/0.2 ml生理盐水)尾静脉输注治疗，NC组及T2DM组尾静脉输注等体积生理盐水，每周1次，连续输注6次。每周监测各组小鼠的血糖和体重。第6次治疗结束后，心脏灌流处死各组小鼠并采集血液、留取肾脏组织，行生化和组织病理学检查。采用Western blotting检测各组肾脏沉默信息调节因子1(SIRT1)蛋白以及紧密连接蛋白1(Claudin-1)的表达情况，并采用免疫组化检测SIRT1、Claudin-1、Ⅰ型胶原蛋白(Col Ⅰ)、Col Ⅳ的表达情况。电镜观察各组小鼠肾小球的形态。取对数生长期HK-2细胞，将细胞分为对照组、高糖诱导模型组(HG组)、高糖诱导siRNA组(HG+siRNA组)、MSCs组(...     

Low-dose radiation induces renal SOD1 expression and activity in type 1 diabetic mice

Abstract

Purpose: Oxidative stress plays a critical role in the pathogenesis of diabetic nephropathy (DN). As an antioxidant, superoxide dismutase (SOD)-1 deficiency exacerbates but SOD1 supplementation prevents diabetes-induced renal damage. Previously, we have demonstrated that repetitive exposure to low-dose radiation (LDR) at 25 mGy significantly prevents DN. Whether this prevention is related to SOD1 expression and activity remains unknown. The aim of the present study was to explore the effects of different methods of LDR treatment on SOD1 expression and activity in the kidneys of diabetic mice.

Materials and methods: C57BL/6J mice were induced with type 1 diabetes using streptozotocin (STZ). Diabetic mice were irradiated with whole-body X-rays at either a single dose of 25 mGy or 75 mGy, or three doses of 25 mGy and then sacrificed at different times. Body weight, blood glucose level, and renal SOD1 expression and activity were measured.

Results: LDR had no impact on the body weights or blood glucose levels of the mice in either the normal or diabetic groups. A single exposure of LDR at 25 mGy did not preserve renal SOD1 expression and activity in diabetic mice, but a single exposure of LDR at 75 mGy or three exposures of LDR at 25 mGy could preserve them.

Conclusion: The stimulation of renal SOD1 expression and activity by a single or cumulative LDR of 75 mGy may be one of the preventive mechanisms of DN observed in the previous study.     

2型糖尿病慢性并发症120例分析

目的分析住院2型糖尿病患者慢性并发症情况,为防治2型糖尿病并发症提供依据。方法以2008年1月—2010年12月在第四军医大学唐都医院住院的2型糖尿病患者120例作为研究对象,设计统一调查表,按病历记录顺序,分别收集住院患者姓名、性别、病程、年龄、糖化血红蛋白、血糖、血脂和相关检查及病史等。结果与健康对照组比较,2型糖尿病患者血中总胆固醇(TC)、三酰甘油(TG)和低密度脂蛋白胆固醇(LDL-C)明显升高(P<0.05或0.01),而高密度脂蛋白胆固醇(HDL-C)无显明改变(P>0.05)。在120例糖尿病中,微血管并发症发生率为24.2%(29/120),大血管并发症发生率为5.8%(7/120),合并症中以高血压、高脂血症和脂肪肝所占为多,感染的发生率也相对较高,为23.3%(28/120)。此外,2型糖尿病微血管并发症以糖尿病视网膜病变为多,该并发症与病程、三酰甘油呈正相关(P<0.05)。结论对2型糖尿病患者进行并发症筛查,做到早发现早治疗,这对控制2型糖尿病并发症发展具有重要临床意义。     

Exercise training and experimental diabetes modulate heat shock protein response in brain

In diabetes, defense systems against cellular stress are impaired. Heat shock proteins (HSPs) function primarily as molecular chaperones. Factors that raise tissue HSP levels may slow progression of diabetes and improve diabetic complications that also affect brain tissue. This study tested the effect of an 8-week exercise training on brain HSP response in rats with or without streptozotocin-induced diabetes (SID). In untrained animals, the HSP levels were not different between SID and non-diabetic groups. Endurance training, however, increased HSP72 and HSP90 protein in non-diabetic rats, whereas SID significantly decreased the effect of training on these HSPs. At the mRNA level, HSP60, HSP90 and GRP75 were increased due to training, whereas HSP72 mRNA was only increased in exercise-trained diabetic animals. Training or diabetes had no effect on protein carbonyl content, a marker of oxidative damage. Altogether, our findings suggest that endurance training increases HSP expression in the brain, and that experimental diabetes is associated with an incomplete HSP response at the protein level.     

低剂量电离辐射对雄性糖尿病模型大鼠生殖损伤的影响

目的 探讨75 mGy照射对12周糖尿病(DM)大鼠睾丸生精细胞凋亡及抗氧化和性激素水平的影响。方法 随机将Wistar大鼠分为3组:健康对照组、75 mGy＋DM组及DM组,12周末记录其存活率和体重。采用流式细胞术和TUNEL染色法检测生精细胞凋亡率,应用试剂盒分别检测血清及睾丸抗氧化和激素水平的变化。结果 12周后,DM组大鼠存活率为25%,健康对照组为100%(χ²=15.938, P<0.01);75 mGy＋DM组大鼠存活率为56.25%,与DM组比较差异有统计学意义(χ²=4.00,P<0.05)。糖尿病大鼠生精细胞凋亡率较健康对照组明显增加,亦高于75 mGy+DM组(F＝5.496,P<0.05)。与健康对照组比较,糖尿病大鼠血清和睾丸组织中丙二醛(MDA)及NO含量不同程度增加,而75 mGy＋DM组大鼠血清和睾丸MDA含量显著低于单纯DM组,以睾丸组织中尤为明显(F=10.644,P<0.01);75 mGy照射显著降低了DM组大鼠血清NO含量(F=14.379, P<0.05),同时增加了DM组大鼠血清中的一氧化氮合酶(NOS)活性及睾丸酮(TS)和促滤泡激素(FSH)含量(F值分别为9.676、43.194和5.282,P<0.05或P<0.01)。结论 低剂量辐射显著降低睾丸组织及血清MDA和NO含量,增加抗氧化酶活性和TS及FSH含量,可能与其抑制糖尿病大鼠生精细胞凋亡增多所致生精障碍有关。     

Low-Dose-Rate versus High-Dose-Rate intracavitary brachytherapy in cervical cancer - Final Results of a Phase III randomized trial

PURPOSEIntracavitary brachytherapy using High-Dose-Rate (HDR) and Low-dose-rate (LDR) in cervical cancer has been utilized. We report the long-term final results of a large randomized trial in terms of toxicities and efficacy.METHODS AND MATERIALSBetween 1996 to 2005, 816 patients were randomized to LDR (n = 441 patients) or HDR brachytherapy (n = 369 patients) stratified by FIGO Stage grouping. Patients with Stage I-II received external irradiation of 40 Gy in 20 fractions (with midline block (MLB)) followed by either 2 LDR Intracavitary applications of 30 Gy to point A (2–3 weeks apart) or 5 HDR Intracavitary applications of 7 Gy to point A once weekly. Patients with Stage III received 50 Gy in 25 fractions (with MLB after 40 Gy) followed by either one application of LDR 30 Gy to point A or three applications of HDR 7 Gy to point A once weekly.RESULTSWith a median follow-up was 64 months (interquartile range [IQR]: 21 - 111), moderate to severe rectal and bladder complications were higher in LDR arm as compared to HDR arm (9.7% vs. 3.6%; p = 0.02) and (10.5% vs. 5.5%; p = 0.06) for Stage I-II. No difference in rectal or bladder complications for Stage III patients. Disease free and overall survivals were similar in both the arms for all stages.CONCLUSIONSHDR intracavitary brachytherapy with 7 Gy per fraction weekly is superior to LDR in terms of late rectal and bladder complications. Local control rates and survivals are similar irrespective of stages.     

糖尿病足治疗进展

糖尿病足是由于糖尿病患者合并周围神经病变及各种不同程度的下肢血管病变而引起的下肢组织破坏,是糖尿病患者的严重并发症之一,也是糖尿病患者致残、致死的主要原因之一。流行病学研究显示,截至2010年中国糖尿病足患者总数已超过1260万,约12%~25%的糖尿病患者一生中会罹患糖尿病足,严重影响了糖尿病患者的生存质量。因此,如何有效防治糖尿病足成为了临床治疗的重点及难点。为此,笔者在本文中将其治疗现状及进展予以综述,以期为糖尿病足的防治提供思路与帮助。     

超敏C反应蛋白与2型糖尿病大血管病变的关系

目的探讨超敏C反应蛋白（hsCRP）与2型糖尿病大血管病变的关系。方法收集122例2型糖尿病合并大血管病变患者（大血管病变组）、60例无大血管病变的2型糖尿病患者（2型糖尿病组）、35例健康人（对照组）的临床资料。比较3组hsCRP水平的差异,分析hsCRP的相关因素。采用Logistic回归分析探讨2型糖尿病患者大血管病变的相关因素。结果大血管病变组hsCRP水平高于2型糖尿病组及对照组（P〈0.05或P〈0.01）;2型糖尿病组hsCRP水平高于对照组（P〈0.05）。相关分析表明,hsCRP与糖尿病病程、高血压、体质量指数（BMI）、糖化血红蛋白（HbA1c）、空腹血糖（FPG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）呈正相关（P〈0.05或P〈0.01）,与高密度脂蛋白胆固醇（HDL-C）呈负相关（P〈0.05）。Logistic回归分析显示2型糖尿病大血管病变与HbA1c、hsCRP、糖尿病病程有关。结论 hsCRP是2型糖尿病大血管病变的重要相关因素,hsCRP可能是2型糖尿病大血管病变的独立预测因子,慢性炎症反应可能参与了2型糖尿病大血管病变的发生发展。     

Adjuvant high-dose-rate and low-dose-rate brachytherapy with external beam radiation in soft tissue sarcoma: a comparison of outcomes

PURPOSE: To compare outcomes of patients treated with low-dose-rate (LDR) adjuvant brachytherapy (BT) + external beam radiation therapy (EBRT) vs. high-dose-rate (HDR) adjuvant BT + EBRT. METHODS AND MATERIALS: Thirty-seven patients with soft tissue sarcoma (STS) were treated with pre- or postoperative external beam irradiation and postoperative LDR or HDR BT. RESULTS: There was no significant difference in the 2-year local control rates (90% with LDR boost vs. 94% for HDR). The rate of National Cancer Institute (NCI) grades 2-4 wound-healing complications was 40% in the LDR group vs. 18% in the HDR group (p = 0.14). On univariate analysis, only suboptimal geometry of the implant predicted for increasing complication rate in the LDR group. In the HDR group, BT dose per fraction, total BT dose, and total biologically equivalent dose (BED3) radiation dose were significant. CONCLUSIONS: HDR and LDR boost BT results in acceptable local control for STS. There is a suggestion that HDR may have lower incidence of severe (grade > or = 3) acute toxicity than LDR.     

From low-dose-rate to high-dose-rate brachytherapy in lip carcinoma: Equivalent results but fewer complications

PurposeTo compare the use of high-dose-rate (HDR) brachytherapy (BT) in patients with lip carcinoma with a former series previously treated with low-dose-rate (LDR) BT.Methods and MaterialsNinety-nine patients treated with LDR-BT were compared with 104 patients treated with HDR-BT. Distribution by stage was 53.5% T1, 15.1% T2, 3.1% T3, and 28.3% T4 for LDR and 52.9% T1, 32.7% T2, 0% T3, and 14.4% T4 for HDR. Some cases with positive or close margins received BT after surgery (34.3% with LDR vs. 16.3% with HDR). Parallel metallic needles were used in 100% of HDR cases and in 76% of LDR cases. Most HDR patients were treated with HDR-BT to a dose of 4.5–5 Gy per fraction prescribed to a 90% isodose, in nine fractions delivered twice daily for 5 days.ResultsMedian followup was 63 months for LDR-BT and 51 months for HDR-BT. Overall local control for LDR- vs. HDR-BT was 94.9% vs. 95.2%; and 100% vs. 100%, 86.6% vs. 94.1%, and 89.3% vs. 80%, for T1, T2, and T4 stage tumors, respectively. Disease-free survival for LDR vs. HDR was 95.9% vs. 94.2%. Soft tissue necrosis, bone necrosis, and fair-bad cosmesis for LDR vs. HDR was 15.1% vs. 0%, 1% vs. 0%, and 11.1% vs. 0%, respectively.ConclusionsTreatment with HDR-BT using rigid needles is a simple technique that provides good long-term results with minimal complications. LDR- and HDR-BT are regarded as equally effective in local control and disease-free survival, but fewer complications arise when using HDR-BT.