1,25-Dihydroxyvitamin D3 pretreatment enhances the efficacy of allergen immunotherapy in a mouse allergic asthma model

Background  Allergen-specific immunotherapy can induce immune tolerance to specific allergens by regulating immune status of individuals. However, its clinical application is limited due to individual differences in efficacy among patients and un-confirmed safety. 1,25 Dihydroxyvitamin D₃ (1,25(OH)₂D₃) has been shown to be involved in a variety of physiological processes, including immune response regulation. In the present study we explored the role of 1,25(OH)₂D₃ pretreatment for immunotherapy.

Methods  Seventy-five BALB/c mice were randomly divided into five groups (15 mice per group). The mouse allergic asthma model was established by intra-peritoneal injection of ovalbumin (OVA, 10 μg) and aluminium hydroxide (2 mg) as an adjuvant. Intra-peritoneal injection of 50 ng of 1,25(OH)₂D₃ served as a pretreatment, subcutaneous injection of OVA (100 μg) as an immunotherapy, and 1% OVA inhalation as a challenge. Histopathological analysis was performed on four mice per group. The number of cells and their classification in bronchoalvolar lavage (BAL) fluid were assayed. Levels of serum OVA-specific immunoglobulin E (sIgE) and IFN-γ, IL-4, IL-5 and IL-10 in BAL fluid were measured by ELISA.

Results  After 1,25(OH)₂D₃ pretreatment, immunotherapy could significantly inhibit the infiltration of inflammatory cells into lung tissues and BAL fluid of mice with allergic asthma when compared with un-treated animals (eosinophils: (7.46±1.34)×10⁴/ml vs. (13.41±1.67)×10⁴/ml, P <0.05). In addition, levels of IL-4 ((36.91±7.87) pg/ml vs. (43.70±6.42) pg/ml, P >0.05) and IL-5 ((41.97±7.93) pg/ml vs. (60.14±8.35) pg/ml, P <0.05) in BAL fluid and serum sIgE ((0.42±0.05) vs. (0.75±0.06) OD units, P <0.05) were profoundly reduced. However, the IL-10 level in BAL fluid was significantly increased ((67.74±6.57) pg/ml vs. (44.62±8.81) pg/ml, P <0.05).

Conclusions  These results indicated that 1,25(OH)₂D₃ pretreatment enhanced the inhibitory effects of immunotherapy on allergic airway inflammation. In the treatment of allergic diseases, 1,25(OH)₂D₃ pretreatment may be beneficial for improving the efficacy of immunotherapy. 

     

1,25-二羟维生素D3处理的树突细胞在变应性气道炎症中的免疫调节作用

目的 探讨1,25-二羟维生素D,[1,25(OH)2D3]处理的树突细胞(DC)在变应性气道炎症中的免疫调节作用及其机制.方法 小鼠骨髓来源DC分2组,分别用1,25(OH):D,和磷酸盐缓冲液(PBS)处理,RT-PCR和蛋白质印迹法检测2组Dc Notch配体Mrna和蛋白表达.将2组DC和Notch配体中和抗体封闭的1,25(OH)2D3处理DC分别与小鼠脾脏来源CIM+T细胞共培养,流式细胞仪检测CD4+T细胞中CD4+CD25+Foxp3+T细胞百分比.将卵清蛋白(OVA)致敏小鼠分2组,每组5只,分别过继转移1,25(OH)2D3组DC[1,25(OH)2D3-DC组]和PBS组DC(PBS-DC组),以OVA激发气道炎症后行肺脏病理、支气管肺泡灌洗液(BALF)中自细胞介素4(IL-4)、IL-5、IL-13和干扰素γ(IFN-γ)水平以及脾脏CD4+T细胞中CD4+CD25+Foxp3+T细胞百分比检查.结果 1,25(OH)2D3组DC Notch配体Jaggedl和Jagged2 Mrna表达(0.376±0.029、0.564±0.018)和蛋白表达(0.786±0.034、0.632±0.026)均明显高于PBS组(分别为0.146±0.032、0.267±0.012和0.124±0.025、0.098±0.012,均P＜0.01).与CIM+T细胞共培养后,1,25(OH)2D3组CD4+T细胞中CD4+C1)25+Foxp3+T细胞百分比(22.49%±0.56%)明显高于PBS组(6.67%±0.60%,P＜0.01);经Jagged2中和抗体封闭组CIM4CD25+Foxp3+T细胞百分比(6.56%±1.89%)明显低于未封闭组(20.37%±1.64%,P＜0.01),1,25(OH)2D3-DC组小鼠气道炎症明显轻于PBS-DC组;BALF中IL-4、IL-5、IL-13和IFN-γ水平(pg/ml)分别为33±5、134±23、91±11和未检测到(＜12.5),均明显低于PBS-DC组(分别为55±7、332±49、152±19、23±6,均P＜0.01);脾脏CD4+T细胞中CIM+CD25+Foxp3+T细胞百分比(14.69%±1.14%)明显高于PBS-DC组(2.38%±0.14%,P＜0.01).结论 1,25(OH)2D3处理DC对变应性气道炎症有抑制作用,这种作用可能与1,25(OH)2D3处理DC通过Jaggect2介导的Notch信号途径诱导CD4+CD25+Foxp3+T细胞生成有关.     

Hp感染与血清前列腺素E变化的关系

目的研究人体感染幽门螺杆菌（helicobacter pylori,Hp）后血清前列腺素E（prostaglandin E,PGE）的变化。方法用14C-呼吸试验和快速尿素酶试验检测HP阳性患者,对50例HP阳性的浅表性胃炎患者用放免法查治疗前后血浆前列腺素E的水平。结果HP阳性患者血清PGE浓度为（51.12±18.1）pg/ml,明显高于HP阴性患者血清PGE的浓度。而HP阳性患者根治后血清PGE水平由（51.12±18.1）pg/ml降为（17.98±8.15）pg/ml,接近HP阴性患者的水平。结论HP感染可以使胃黏膜保护因子PGE的生成增加。其在胃黏膜损伤中的机制需要进一步研究。     

Intermittent hypercalcaemia and vitamin D sensitivity in Hodgkin's disease

A patient with Hodgkin's disease spontaneously developed steroid-responsive hypercalcaemia during two consecutive summers. Administration of 3000 U/day of vitamin D, while he was normocalcaemic, caused a sharp increase in serum 1,25(OH)2D3 (from 59 pg/ml to 142 pg/ml) and subsequently hypercalcaemia while serum 25(OH)D3 rose moderately within the normal range (from 2.8 ng/ml to 10 ng/ml). During a spontaneous episode of hypercalcaemia which was accompanied by increased circulating 1,25(OH)2D3 concentrations, administration of hydrocortisone decreased serum 1,25(OH)2D3 rapidly (from 115 pg/ml to 62 pg/ml) and eventually led to normocalcaemia while serum 25(OH)D3 remained unchanged. Thus the disturbances of mineral metabolism found in this patient with Hodgkin's disease are very similar to those previously described in sarcoidosis.     

Effects of heme oxygenase-1 gene modulated mesenchymal stem cells on vasculogenesis in ischemic swine hearts

Background  Mesenchymal stem cells (MSCs) transplantation may partially restore heart function in the treatment of acute myocardial infarction (AMI). The aim of this study was to explore the beneficial effects of MSCs modified with heme xygenase-1 (HO-1) on post-infarct swine hearts to determine whether the induction of therapeutic angiogenesis is modified by the angiogenic cytokines released from the implanted cells.

Methods  In vitro, MSCs were divided into four groups: (1) non-transfected MSCs (MSCs group), (2) MSCs transfected with the pcDNA3.1-Lacz plasmid (Lacz-MSCs group), (3) MSCs transfected with pcDNA3.1-hHO-1 (HO-1-MSCs group), and (4) MSCs transfected with pcDNA3.1-hHO-1 and pretreatment with an HO inhibitor, tin protoporphyrin (SnPP) (HO-1-MSCs+SnPP group). Cells were cultured in an airtight incubation bottle for 24 hours, in which the oxygen concentration was maintained at <1%, followed by 12 hours of reoxygenation. After hypoxia/reoxygen treatment, ELISA was used to measure transforming growth factor (TGF-β) and fibroblast growth factor (FGF-2) in the supernatant. In vivo, 28 Chinese mini-pigs were randomly allocated to the following treatment groups: (1) control group (saline), (2) Lacz-MSCs group, (3) HO-1-MSCs group, and (4) HO-1-MSCs + SnPP group. About 1×10⁷ of autologous stem cells or an identical volume of saline was injected intracoronary into porcine hearts 1 hour after MI. Magnetic resonance imaging (MRI) assay and postmortem analysis were assessed four weeks after stem cell transplantation.

Results  Post hypoxia/reoxygenation in vitro, TGF-β in the supernatant was significantly increased in the HO-1-MSCs ((874.88±68.23) pg/ml) compared with Lacz-MSCs ((687.81±57.64) pg/ml, P <0.001). FGF-2 was also significantly increased in the HO-1-MSCs ((1106.48±107.06) pg/ml) compared with the Lacz-MSCs ((853.85±74.44) pg/ml, P <0.001). In vivo, at four weeks after transplantation, HO-1 gene transfer increased the capillary density in the peri-infarct area compared with the Lacz-MSCs group (14.24±1.66/HPFs vs. 11.51±1.34/HPFs, P <0.001). Arteriolar density was also significantly higher in HO-1-MSCs group than in the Lacz-MSCs group (7.86±2.00/HPFs vs. 6.45±1.74/HPFs, P=0.001). At the same time, the cardiac function was significantly improved in the HO-1-MSCs group compared with the Lacz-MSCs group ((53.17±3.55)% vs. (48.82±2.98)%, P <0.05). However, all these effects were significantly abrogated by SnPP.

Conclusion  MSCs provided a beneficial effect on cardiac function after ischemia/reperfusion by the induction of therapeutic angiogenesis, and this effect was amplified by HO-1 overexpression.

     

Microinflammation is involved in the dysfunction of arteriovenous fistula in patients with maintenance hemodialysis

Background Vascular access （VA） dysfunction is a major clinical complication in the hemodialysis population and has a direct effect on dialysis outcome. This study was conducted to explore the role of microinflammation in the VA dysfunction in maintenance hemodialysis patients.
Methods Forty-seven patients （male 35 and female 12） receiving maintenance hemodialysis were included for this study. They were divided into three groups： group 1 （n=15）, patients with initial hemodialysis and new arteriovenous fistula （AVF）; group 2 （n=18）, patients treated with hemodialysis for long term with well-functional VA; group 3 （n=14）, maintenance hemodialysis patients with VA dysfunction. Biochemical parameters and serum tumor necrosis factor-α （TNF-α）, interleukin 6 （IL-6） and monocyte chemoattractant protein-1 （MCP-1） were determined. High-sensitivity C-reactive protein （hs-CRP） was determined by latex-enhanced immuno-nephelometric method. Tissues of radial artery were taken from group 1 and group 3 for the histological study. Expression of CD68 and MCP-1 in the radial artery was determined by immunohistochemistry.
Results Serum hs-CRP in group 3 was significantly higher than those in group 1 and group 2 （（7.40±2.42） mg/L vs （4.21±1.62） mg/L and （5.04±3.65） mg/L, P 〈0.01 and P 〈0.05, respectively）. Serum TNF-α in group 3 was significantly higher than those in group 1 and group 2 （（64.03±9.29） pg/ml vs （54.69±12.39） pg/ml and （54.05±7.68） pg/ml, P 〈0.05 and P 〈0.01, respectively）. Serum IL-6 in group 3 was also significantly higher than those in group 1 and group 2 （（70.09±14.53） pg/ml vs （56.43±10.11） pg/ml and （60.77±9.70） pg/ml, P 〈0.01 and P 〈0.05, respectively）. Patients in group 3 had a thicker internal layer of vessels than in group 1 （（0.356±0.056） mm vs （0.111±0.021） mm, P 〈0.01）. Expression of CD68 and MCP-1 in the fistula vessel walls in group 3 were much higher than those in group 1     

绝经后妇女骨密度与血清1，25-（OH）2D3，25-OHD3浓度关系的研究

目的：研究绝经后妇女无优势手臂骨密度与血清1,25-（OH）2D3,25-OHD3含量的关系。方法：采用定量超声骨量分析系统（QUS）测量82例绝经后妇女无优势前臂远端骨密度（BMD）以诊断骨质疏松,采用放射免疫法（RIA）和ELISA检测骨质疏松组和骨量正常组妇女血清中1,25-（OH）2D3,25-OHD3水平。结果：绝经后骨质疏松组妇女血清1,25-（OH）2D3,25-OHD3含量分别为（26.97±6.78）pg/ml和（34.75±12.62）nmol/L,骨量正常组分别为（34.75±12.62）pg/ml和（42.03±12.63）nmol/L,骨质疏松妇女血清1,25-（OH）2D3、25-OHD3含量明显低于骨量正常组（P〈0.01）。绝经后妇女无优势前臂骨密度与血清1,25-（OH）2D3含量存在明显相关性（r=0.387,P=0.001）,25-OHD3含量与前臂骨密度也存在相关性。结论：血清1,25-（OH）2D3水平与无优势前臂骨密度明显相关,是绝经后妇女骨量降低的重要原因之一。     

重症肺炎患者血清和肺泡灌洗液中IL-6和IL-10水平的变化及其与预后的相关性

目的：观察重症肺炎患者血清和肺泡灌洗液中白介素-6(IL-6)和白介素-10(IL-10)水平的变化,并探讨其与临床预后的关系,为临床治疗提供相关依据。方法选取我院重症医学科2014年10月至2015年12月收治的99例重症肺炎患者为研究对象,依据患者病程第10天的临床转归,将其分为好转组59例和恶化组40例。分别在患者病程第1、5、10天,检测其血清和肺泡灌洗液中IL-6、IL-10的水平,同时统计临床肺部感染评分(CPIS),并分析CPIS评分与IL-6、IL-10的水平的相关性。结果第5天和第10天时,好转组血清中IL-6水平分别为(43.18±16.79) pg/mL和(26.88±7.65) pg/mL,明显低于恶化组的(49.77±14.26) pg/mL和(39.73±8.12) pg/mL;好转组肺泡灌洗液中IL-6水平分别为(70.43±28.65) pg/mL和(35.17±9.81) pg/mL,明显低于恶化组的(81.52±20.14) pg/mL和(72.17±19.81) pg/mL,差异均具有统计学意义(P<0.05);组内比较,好转组和恶化组患者血清和肺泡灌洗液中IL-6水平均随着时间推移出现显著下降,差异均具有统计学意义(P<0.05)。第5天和第10天好转组患者血清中IL-10水平分别为(5.21±1.77) pg/mL和(3.63±1.54) pg/mL,明显低于恶化组的(9.76±3.11) pg/mL和(13.16±3.82) pg/mL,好转组肺泡灌洗液中IL-10水平分别为(7.75±1.8) pg/mL和(4.13±1.21) pg/mL,明显低于恶化组的(12.17±3.26) pg/mL和(15.82±4.88) pg/mL,差异均具有统计学意义(P<0.05);好转组患者血清IL-10随着时间推移逐渐降低,差异均具有统计学意义(P<0.05),而恶化组患者血清和肺泡灌洗液中IL-10的水平则持续性升高,差异均具有统计学意义(P<0.05)。相关性分析结果显示,CPIS评分与血清和肺泡灌洗液中IL-6、IL-10的水平均呈明显的正相关(95%CI=0.8118~0.9992,P=0.0018;95%CI=0.9539~0.9998,P=0.0002)。结论动态监测重症肺炎患者血清和肺泡灌洗液中IL-6、IL-l0的水平及变化趋势,能够反映患者预后情况,值得在临床中借鉴和推广。     

糖尿病肾病Vit D缺乏与颈动脉内中膜厚度及冠脉钙化相关关系研究

目的了解糖尿病肾病(DN)患者血清维生素D不足与缺乏的发生情况,探讨其与颈动脉内中膜厚度(IMT)、冠脉钙化之间的相关关系。方法采用放射免疫分析法检测151例DN患者空腹血清25-羟胆骨化醇〔25(OH)D3〕、1,25-二羟胆骨化醇〔1,25(OH)2D3〕、全段甲状旁腺激素(iPTH)浓度,根据25(OH)D3水平将DN患者分为维生素D缺乏组(Vit-D-D)、不足组(Vit-D-I)及正常组(Vit-D-N),比较各组间矿物质代谢、脂代谢、颈动脉内中膜厚度(IMT)、冠脉钙化等指标的差异。多元线性回归分析法分析IMT与25(OH)D3、1,25(OH)2D3、iPTH、脂代谢指标的相关性;logistic回归分析法分析冠脉钙化与25(OH)D3、1,25(OH)2D3、iPTH、脂代谢指标的相关性。结果 DN患者血清25(OH)D3水平为(28±18.1)ng/mL,四分位数间距16.92～35.45ng/mL,Vit-D-I组71例,占47.01%,Vit-D-D组28例,占18.54%。血清1,25(OH)2D3水平为(28.93±33.13)pg/mL,四分位数间距10.36～31.08pg/mL,Vit-D-I者117例,占77.5%。与Vit-D-N组相比,Vit-D-D组的体质量指数(BMI)、24h尿蛋白、胆固醇(CHO)和低密度脂蛋白(LDL)增高,差异有统计学意义(P<0.05)。多元线性回归分析,IMT与年龄、性别、血磷正相关,logistic回归分析,冠脉钙化与血清1,25(OH)2D3负相关。结论 DN患者中维生素D不足和缺乏发生率高,维生素D缺乏者具有较高的尿蛋白、CHO和LDL,冠脉钙化与血清1,25(OH)2D3呈负相关关系。     

成纤维细胞生长因子23与血液透析患者血磷和甲状旁腺激素浓度的关系

目的 观察维持性血液透析患者血中成纤维细胞生长因子23(fibroblast growth factor23,FGF23)浓度,探讨维持性血液透析(maintenance hemodialysis, MHD)患者FGF23的浓度及其与血磷、甲状旁腺激素(parathyroid hormone,PTH)浓度之间的关系。方法 选取稳定MHD患者50例,健康对照30人,透析患者根据PTH浓度分为A1组(PTH<300 pg/mL)、A2组(PTH为300~500 pg/mL)、A3组(PTH>500 pg/mL)。应用酶联免疫分析法测定血清FGF23和1,25-二羟活性维生素D₃［1,25-dihydroxy-cholecalciferol, 1,25-(OH)₂D₃］浓度,同时测定血清PTH、血钙(Ca²⁺)、磷(P^3－)、碱性磷酸酶(alkaline phosphatase,ALP)、白蛋白(albumin,ALB)等指标。结果 ①透析患者血清Log FGF23水平显著高于对照组,Log1,25-(OH)₂D₃水平显著低于对照组,差异有统计学意义。②Log FGF23水平在PTH>500 pg/mL组显著高于PTH<300 pg/mL组。③LogFGF23与Log PTH、血磷、Log ALP呈正相关,与Log 1,25-(OH)₂D₃呈负相关。④逐步多元线性回归分析显示,血磷、钙磷乘积、Log PTH是影响Log FGF23水平的独立影响因素。结论 维持性血液透析患者血清FGF23升高,且继发性甲状旁腺功能亢进者FGF23明显升高。     

3种血液净化方法对维持性血液透析患者血磷及甲状旁腺素的清除效果比较

目的探讨3种不同血液净化方法对维持性血液透析（maintenance hemodialysis,MHD）患者血磷及甲状旁腺素（parathyro idhor mone,PTH）的清除效果。方法选取我院39例维持性血液透析患者并随机分为3组：血液灌流联合血液透析（HD＋HP）组,血液透析滤过（HDF）组和血液透析（HD）组。比较3组治疗前、后血磷及血PTH清除率。结果HD组治疗后血PTH值下降,但无统计学差异（P〉0.05）;血磷治疗后下降且有显著性差异（P〈0.05）。HDF组治疗后血PTH值及血磷值均下降且有显著性差异（P〈0.05）。HD＋HP组治疗后血PTH下降有显著性差异（P〈0.05）,且差异显著高于HDF组（P〈0.05）;血磷值下降且有显著性差异（P〈0.05）。结论血液灌流串联血液透析及血液透析滤过均能有效清除血磷及PTH。血液透析可以有效清除血磷但不能有效清除PTH。     

幽门螺杆菌感染患者胃泌素、IL-8、IL-10水平变化

目的：研究幽门螺杆菌（HP）感染与白介素-8（IL-8）、白介素-10（IL-10）和胃泌素（GAS）的关系。方法：108例患者均经^13C-尿素呼气实验和血清学检测HP,并于晨起空腹在胃镜检查前后取静脉血2mL,3000rpm离心10分钟,分离血清,测定血清中GAS、IL-8、IL-10的含量。结果：HP阳性组血清IL-8、IL-10、GAS含量分别为51．49±9．41pg／mL、312．84±47．91pg／mL、10．34±7．24ng／mL。HP阴性组血清IL-8、IL-10、GAS含量分别为37．44±9．05pg／mL、356．39±51．89pg／mL和5．12±3．51ng／L。HP阳性组血清IL-8、GAS含量分别高于阴性组（P〈0．01）,IL-10含量低于HP阴性组（P〈0．01）。HP阳性组血清IL-8与GAS间呈正相关（r=0．382,P〈0．01）,IL-10与GAS间呈负相关（r=-0．202,P〈0．05）。结论：HP感染的慢性胃炎和消化性溃疡患者IL-8、IL-10、GAS含量变化与HP感染有关,HP感染胃肠黏膜产生的炎症损伤与IL-8有关,血清IL-10对炎症有抑制作用。     

初诊2型糖尿病患者血清活性维生素D3水平的变化及其临床意义

目的：观察初诊2型糖尿病患者血清活性维生素D3水平的变化情况,为临床治疗和干预提供理论依据。方法选取2014年1月至2015年6月期间就诊于我院干部病科和内分泌科的200例2型糖尿病患者设为观察组,选取同期就诊于我院的100健康查体者作为对照组。比较两组受检者的年龄、病程、体质指数(BMI)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)及胰岛素分泌指数(HOMR-β)、胰岛素抵抗指数(HOMR-IR)、血清活性维生素D3水平,以及谷丙转氨酶(ALT)、谷草转氨酶(AST)、肌酐(CRE)、血钙、血磷水平。结果(1)两组受检者的血清TG、TC、ALT、AST、CRE、血钙、血磷水平比较差异均无统计学意义(P>0.05);(2)与对照组比较,观察组患者的FPG [(9.85±2.50) mmol/L vs (4.84±0.54) mmol/L]、2 hPG [(10.28±2.28) mmol/L vs (5.21±0.56) mmol/L]、HbA1c [(7.66±2.36)% vs (4.62±0.47)%]明显升高,FINS [(7.40±5.06)μU/ml vs (11.87±6.81)μU/ml ]、HOMR-β[(25.81±20.13) vs (254.33±102.14)]、1,25-(OH)D3[(15.57±3.58) ng/ml vs (51.72±8.96) ng/ml]水平明显降低,差异具有统计学意义(P<0.05),而HOMR-IR[(3.40±2.83) vs (2.32±0.63)]与对照组比较差异无统计学意义(P>0.05);(3)1,25-(OH)D3与HOMR-β呈正相关(r=0.72,P<0.05),与HOMR-IR无明显相关性(r=-0.11,P>0.05)。结论初诊2型糖尿病患者血清1,25-(OH)D3降低,低1,25-(OH)D3水平影响患者的胰岛素β细胞的分泌功能。     

沙利度胺联合化疗治疗白血病临床疗效研究

目的探讨研究沙利度胺联合化疗治疗急性白血病的临床疗效以及对血管内皮生长因子（VEGF）、血管内皮生长因子受体（VEGFR）、碱性成纤维细胞生长因子（bFGF）、骨髓微血管密度（MVD）的影响。方法将符合标准的45例急性白血病患者分成观察组（24例）和对照组（21例），每组均进行常规化疗，观察组同时口服沙利度胺100mg／d。取患者血浆，使用ELISA法测定治疗前后2组患者VEGF、VEGFR、bFGF以及MVD水平以及不良反应的发生情况，比较两种治疗方法的疗效。结果治疗后观察组患者VEGF、VEGFR与MVD分别为（212．8±36．2）pg／ml、（1765．4±338．1）pg／ml、（8．31±1．55）n／HP，与对照组的（289．0±31．7）pg,／ml、（1359．9±392．8）pg／ml、（14．21±2．74）n／HP相比差异有统计学意义（P〈0．05）。2组患者的bFGF分别为（2．10±0．19）pg／ml与（2．12±0．29）pg／ml，差异无统计学意义（P〉0．05）。观察组消化道反应与神经系统症状发生率显著性高于对照组（P〈0．05）。结论沙利度胺通过抑制患者体内VEGF的表达与减少MVD而达到治疗急性白血病的目的，值得临床推广并进一步深入研究。     

Role of cyclooxygenase-2 signaling pathway dysfunction in unexplained recurrent spontaneous abortion

Background Experimental evidence indicates that cyclooxygenase-2 （COX-2） plays a critical role in blastocyst implantation; however, little is known of the role of COX-2 in unexplained recurrent spontaneous abortion （URSA）. Methods We evaluated the expression level and potential signaling pathway of COX-2 in 30 cases of URSA who were excluded the abnormality of chromosomes, anatomy, endocrine, infectious, autoimmune diseases and in 30 normal pregnancies. Results The mRNA and the protein expression level of COX-2 in the URSA group （-0.238±0.848, 0.368±0.089, respectively） were significantly lower than that in the control group （1.943±3.845, 1.046±0.108, respectively） （both, P 〈0.01）. The expression of prostaglandins PGF2a, PGD2, PGE2, and PGI2, in the URSA group （（2326.0±295.6） pg/ml, （2164.0±240.5） pg/ml, （238.7±26.4） pg/ml, （2337.0±263.0） pg/ml, respectively） were significantly lower than that in the control group （（3450.0±421.7） pg/ml, （3174.0±415.6） pg/ml, （323.5±43.8） pg/ml, （3623.0±460.4） pg/ml, respectively） （P 〈0.05）. The mRNA expression level of PPARI3 and RXRa （0.859±0.653, -0.172±0.752, respectively） in URSA group was significantly lower than that in the control group （1.554±1.735, 0.777±2.482, respectively） （both P 〈0.05）. The mRNA and protein expression levels of vascular endothelial growth factor-A （VEGF-A） in the URSA group （2.010±1.522, 0.35±0.46） was significantly lower than that in the control group （4.569±2.430, 0.750±0.350） （both P 〈0.05）. Conclusions COX-2 and the COX-2-derived PGI2 signaling pathway possibly play an important role in successful embryo implantation, and their decreased expression may result in URSA. The decreased expression may influence the expression of VEGF-A which interferes with placental angiogenesis causing failure of embryo implantation, leading to spontaneous abortion.     

分泌型白细胞蛋白酶抑制因子在胸腔积液中的水平及意义

目的探讨各种疾病所致的胸腔积液中分泌型白细胞蛋白酶抑制因子的水平及其临床意义。方法收集85例胸腔积液及其同源外周血（分为四组,其中结核性胸腔积液组为29例,恶性胸腔积液组30例,细菌性胸腔积液组15例,漏出液组11例）。应用ELISA法测定胸水上清液和血清中分泌型白细胞蛋白酶抑制因子（SLPI）的浓度,并对结果及意义进行分析。结果（1）胸腔积液间：结核组浓度（211710±29130）pg／ml,分别与肿瘤组（99274±21807）pg／ml、细菌组（127980±34299）pr／ml及漏出液组（109360±21619）pg／ml相比,差异均有统计学意义（P〈0．05）;肿瘤组、细菌组及漏出液组三组之间相比差异均无统计学意义（P〉0．05）。（2）血清中：结核组（35116±4122．1）pg/ml及肿瘤组（25767±2054）pg／ml分别与漏出液组（51377±10190）pg／ml相比差异有统计学意义（P〈0．05）;漏出液组与细菌组（52396±8954．5）pg／ml比较差异无统计学意义,结核组、肿瘤组及细菌组之间差异亦无统计学意义（P〉0．05）。（3）胸腔积液与血清液间：结核组、肿瘤组与漏出液组之间差异有统计学意义（P〈0．05）;而在细菌组差异无统计学意义（P〉0．05）。（4）各组胸腔积液与同源外周血清之间无相关性（P〉0．05）。（5）受试者工作特征曲线（ROC曲线）结果显示：胸腔积液中SLPI浓度对结核性胸腔积液的最佳诊断阈值为236071pg／ml,相应灵敏度和特异度分别为43．33％和96．77％。结论白细胞蛋白酶抑制因子（SLPI）有可助于结核性与恶性、细菌性及漏出性胸腔积液的鉴别。SLPI浓度测定有可能成为结核性胸腔积液的新诊断方法。     

甲基丙二酸半胱氨酸在小儿早期VitB12缺乏症诊断中的作用

目的:探讨甲基丙二酸半胱氨酸在小儿早期VitB12缺乏症诊断中的作用.方法:维生素B12缺乏亚临床症状组50例、临床症状组50例及正常健康儿童50例,测定其红细胞平均体积(MCV),红细胞平均血红蛋白(MCH),血清维生素B12、尿中甲基丙二酸(MMA)及血清半胱氨酸(Hcy)浓度.结果:①临床症状组MCV(114.2...     

树脂吸附对慢性肾衰维持性血液透析患者血清甲状旁腺素的影响

目的观察树脂吸附对慢肾衰维持性血液透析患者血清甲状旁腺素水平的影响.方法60例慢肾衰维持性血液透析患者随机分为2组:血液吸附组(absorption AP)和血液透析组(hemodialysis HD),AP组接受HA型吸附器联合血液透析治疗,HD组接受血液透析治疗,检测治疗前后患者iPTH(imuno-parathroid hornone)的改变,同时观察皮肤搔痒症状改变.结果AP组患者血清iPTH从(291.69±237.48)pg/ml降至(122.19±114.50)pg/ml,前后比较有显著性差异(P＜0.05),平均单次清除率为48.60%,患者皮肤搔痒症状明显缓解,HD组患者血清iPTH从(297.68±211.3)pg/ml降至(248.11±105.53)pg/ml,前后比较无显著性差异(P＞0.05),单次清除率为13.14%.结论树脂吸附能有效地清除iPTH,缓解皮肤搔痒,而血液透析不能清除iPTH和缓解皮肤搔痒.     

卒中后抑郁与抑郁症患者血清细胞因子及超敏C反应蛋白水平的对照研究

目的 比较卒中后抑郁与抑郁症患者多种血清细胞因子表达及超敏C反应蛋白水平,进一步探讨其发病机制.方法 采用酶联免疫吸附法（ELISA）检测30例卒中后抑郁病人（卒中后抑郁组）、30例卒中后非抑郁病人（卒中非抑郁组）、30例抑郁症病人（抑郁症组）、30例健康人（正常对照组）的血清白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平,同时采用散射比浊法测定4组患者的血清超敏C反应蛋白（hs-CRP）水平.结果 卒中后抑郁组、抑郁症组、卒中非抑郁组及正常对照组的血清IL-1β,IL-6,TNF-α和hs-CRP水平分别为：[（137.23±8.12）pg/ml,（34.12±3.12） pg/ml,（64.62±6.11） pg/ml,（6.70± 1.52） mg/L];[（133.21 ±7.56） pg/ml,（33.56±2.65） pg/ml,（62.95±5.66） pg/ml,（1.65±0.99） mg/L];[（43.25±6.23） pg/ml,（16.12±2.60） pg/ml,（32.23±7.12） pg/ml,（5.77± 1.21） mg/L];[（42.12±5.78） pg/ml,（15.32±3.23） pg/ml,（31.55±6.70） pg/ml,（0.66±0.74） mg/L].卒中后抑郁组和抑郁症组的血清IL-1β,IL-6,TNF-α水平明显高于卒中非抑郁组和正常对照组,差异有统计学意义（P＜0.01）;血清hs-CRP水平：卒中后抑郁组＞卒中非抑郁组＞抑郁症组＞正常对照组,差异有统计学意义（P＜0.05）.结论 卒中后抑郁和抑郁症可能具有相同的免疫机制.     

血浆脑利钠肽浓度与孕妇心衰发生的相关性研究

目的研究孕妇血浆脑利钠肽孕妇心衰发生的相关性。方法对苏州市立医院2011年9月至2013年9月间收治的孕妇重度子痫前期患者123例和双胎妊娠孕妇26例病例资料,并随机选择同期正常晚期妊娠孕妇78例作为对照。采用放射免疫方法测定孕妇血浆脑利钠肽（BNP）浓度,另根据孕妇血浆BNP水平,分为低水平组202例（BNP〈500 pg/ml）及高水平组（BNP〉500 pg/ml）,分析危险因素和妊娠结局。结果 （1）重度子痫前期组患者BNP浓度（252.51±375.95）pg/ml高于正常孕妇组（45.94±47.63）pg/ml差异有统计学意义（P〈0.05）;重度子痫前期组并发心衰组12例,其BNP浓度（1458.55±1341.77）pg/ml显著高于正常孕妇组（45.94±47.63）pg/ml,差异有统计学意义（P〈0.001）。（2）双胎组BNP浓度（356.73±415.57）pg/ml高于正常孕妇组（45.94±47.63）pg/ml,双胎并发心衰BNP的浓度（780.47±159.35）pg/ml,显著高于正常晚期妊娠孕妇（45.94±47.63）pg/ml,差异均有统计学意义（P〈0.05）。（3）BNP高水平组危险因素有血压的升高和双胎妊娠。（4）BNP高水平组胎盘早剥、心衰、产后出血及新生儿窒息发生率分别为15.4%、42.3%、23.1%及26.9%,均高于低水平组2.5%（P〈0.001）、6.9%（P〈0.001）、3.0%（P〈0.001）及12.4%（P〈0.05）,两组比较差异有统计学意义。结论重度子痫前期患者的血浆脑利钠肽浓度是反应子痫前期患者严重程度敏感指标,并能提前预测心衰的发生,同时双胎孕妇血浆脑利钠肽浓度明显升高。血压的升高和双胎妊娠是血BNP升高的危险因素;BNP水平高的妊娠不良结局升高。