干扰素β与丙种球蛋白治疗实验性周围神经病的机理研究

目的探讨干扰素β（IFN—β）和丙种球蛋白（IVIG）对空肠弯曲菌（CJ）脂多糖（LPS）诱导的免疫性周围神经病的治疗机理。方法健康Wister大鼠40只,体重205～230g,用CJ LPS成功诱导出免疫神经病后,随机分为IFN—β组、IVIG组、IFN—β联合IVIG组和正常对照组。IFN—β组：每隔1d,给予IFN—β1．3μg/kg皮下注射,共6周。IVIG组：每隔2周,静脉注射IVIG 400mg／（kg·d）,连续5d,共2次。IFN—β和IVIG联合组：IFN—β和IVIG的给药时间分别同IFN—β组和IVIG组。对照组：以PBS溶液（200μl/只）替代IFN-β或IVIG。分别于治疗前和治疗后第2、4、6周取血,用ELISA方法检测血清中抗GM1IgG、MMP-9和TNF—α滴度,第6周取坐骨神经进行病理学检查和免疫组化检测坐骨神经上特异性IgG结合。结果（1）3个治疗组治疗2周时,抗GM1IgG、MMP-9和TNF—α滴度与对照组比较差异无统计学意义（P〉0．05）。（2）3个治疗组治疗4周时,抗GM1IgG、MMP-9和TNF—α滴度明显低于对照组（P〈0．01）;3组之间抗GM1IgG滴度比较差异无统计学意义（P〉0．05）;联合治疗组MMP-9和TNF—α水平低于单一治疗组（P〈0．05）。（3）3个治疗组治疗6周时,抗GM1IgG、MMP-9和TNF—α滴度、神经原纤维病变率和神经上特异性IgG结合明显低于对照组（P〈0．01）;各指标联合治疗组明显低于单一治疗组（P〈0．01）。结论IFN—β和IVIG通过对特异性体液免疫和细胞免疫的同时抑制,达到对CJ LPS诱导的免疫性周围神经病的治疗作用;IFN—β和IVIG联合应用疗效更佳。     

大剂量免疫球蛋白对免疫性周围神经病治疗机理的实验研究

目的　探讨静脉注射免疫球蛋白 (IVIg)对空肠弯曲菌脂多糖 (CJLPS)诱导的免疫性周围神经病的治疗机理。方法　 ( 1)在CJLPS免疫大鼠后的不同时间 ,按 40 0mg/ (kg·d)注射IVIg。第3 5天取坐骨神经进行病理学检查 ,ELISA方法检测血清中抗CJLPS抗体滴度 ,免疫组化及原位杂交技术检测神经上特异性IgG及TNF αmRNA表达 ;( 2 )在CJLPS刺激下体外培养外周血单核细胞(PBMC) ,并分别在培养液中加入 1、2 5、5、10mg/mlIVIg。将上清分别注入同种大鼠的神经外膜下 ,7d后进行病理学检查 ;采用原位杂交技术检测培养PBMC的TNF αmRNA表达。结果　 ( 1)IVIg干预下 ,经CJLPS免疫大鼠神经原纤维病变率仅为 1 0 % ,未干预者达 15 0 % ,差异有显著性 (P <0 0 1)。未干预组血清中抗CJLPS特异性IgG滴度比干预组高 9倍。IVIg干预组神经上无明显特异性IgG及TNF αmRNA表达 ,而未用IVIg者表达强阳性 ;( 2 )CJLPS免疫的大鼠PBMC的TNF αmRNA ,IVIg干预组 ( 1 0 % )比IVIg未干预免疫组 ( 9 5% )减少 ;( 3 )CJLPS刺激下健康鼠PBMC体外培养 ,5mg/ml和 10mg/ml大剂量IVIg干预组的TNF αmRNA阳性表达率 ( 3 %和 2 % ) ,较 2 5mg/ml和 1mg/ml小剂量组阳性率 ( 13 %和 11 5% )为低 (P <0 0 1)。其上清液神经外膜下注射后 ,大剂量干     

肝素或生理盐水延长外周静脉短导管留置时间的系统评价和Meta分析

背景 新生儿或儿童选择生理盐水还是肝素溶液封管,在2021年《静脉输液护理实践指南》未做出明确推荐,在《儿童静脉输液治疗临床实践循证指南》则明确推荐用肝素溶液封管.目的 儿科使用含肝素溶液和0.9％的生理盐水溶液作为外周静脉短导管(PIVC)封管液的效果比较.研究设计基于RCT的系统评价/Meta分析.方法 住院留置P...     

Effect of intravenous immunoglobulin on inhibiting peripheral blood lymphocyte apoptosis in acute Kawasaki disease

This study aimed to explore the therapeutic mechanism of intravenous immunoglobulin (IVIG) for Kawasaki disease (KD). Peripheral blood lymphocytes (PBLs) obtained from 26 children with KD and 20 age-matched healthy children were stimulated with anti-CD3 monoclonal antibody (mAb), and the percentage of apoptotic cells and DNA fragmentation were assayed at 0, 12, 24, 48 and 72 h in vitro. The patients were divided into two groups: one treated with aspirin combined with IVIG (n = 16) and one treated with aspirin alone (n = 10). PBLs were stimulated by phytohaemagglutinin to evaluate the lymphocyte proliferative response. Compared with normal controls, the apoptotic cell percentage and the DNA fragmentation were markedly decreased (p < 0.001) and delayed in PBLs from KD patients. After IVIG treatment, the decreased percentage of apoptotic cell and delayed DNA fragmentation were restored to the state of the normal controls, accompanied by a fast clinical remission compared with the aspirin-alone group. The lymphocyte proliferative response was also decreased 3-5 d after IVIG therapy (p < 0.001). Conclusion: The results suggest that decreased PBL apoptosis may be involved in the pathogenesis of KD. The therapeutic mechanism of IVIG in KD may be partially due to the reversal of the inhibited lymphocyte apoptosis, and may have implications for other autoimmune diseases with inefficient lymphocyte apoptosis.     

静脉注射免疫球蛋白对急性川崎病患儿淋巴细胞凋亡的影响

通过观察静脉注射免疫球蛋白（ＩＶＩＧ）对川崎病（ＫＤ）患儿淋巴细胞凋亡（ＡＰＯ）的影响，进一步探讨ＩＶＩＧ对免疫性疾病的作用机理。对２６例川崎病患儿和２０名健康儿童外周血单个核细胞（ＰＢＭＣ）经抗－ＣＤ３单克隆抗体刺激培养不同时间（０，１２，２４，４８，７２小时）ＡＰＯ百分率和ＤＮＡ片断化分析，２６例患儿随机分为两组，阿司匹林＋ＩＶＩＧ治疗组（ｎ＝１６）和阿司匹林治疗组（ｎ＝１０），并对ＰＢＭＣ经植物血凝素（ＰＨＡ）刺激淋巴细胞增殖反应进行了观察。结果：ＫＤ患儿ＡＰＯ百分率和ＤＮＡ片断化较正常儿童明显降低（Ｐ＜０．００１）和延迟；ＩＶＩＧ治疗后，降低的ＡＰＯ百分率和延迟的ＤＮＡ片断化被逆转，同时与单用阿司匹林组比较，临床症状明显改善。淋巴细胞增殖反应下调（Ｐ＜０．００１）。外周血淋巴细胞ＡＰＯ下调可能参与了ＫＤ的发病。ＩＶＩＧ治疗ＫＤ的机理可能部分归于对被抑制的淋巴细胞ＡＰＯ的逆转。ＩＶＩＧ对其它淋巴细胞凋亡不足的自身免疫性疾病治疗可能存在同样机理。     

Challenges in pediatric transplantation: the impact of chronic kidney disease and cardiovascular risk factors on long-term outcomes and recommended management strategies

Barriers to successful outcomes following pediatric transplantation have shifted from ischemic reperfusion injury and rejection to more long-term complications. Of particular concern is the high prevalence of CKD owing to preexisting damage and nephrotoxicity, as well as other CV complications such as hypertension and cardiomyopathy. All of these contribute to graft loss and shortened life expectancy, thereby limiting the success story of solid-organ transplantation. Managing CKD and related CV morbidity should be integral to the care of pediatric transplant patients, and timely detection of any irregularities would increase the chances of restoring lost kidney function. GFR is still the widely accepted indicator of renal function, and nuclear medicine techniques are the gold standard measurement methods. These methods are limited by costs, radiation exposure and substrate injection, and current practice still uses the Schwartz estimate, despite its well-documented limitations. Newer endogenous markers of GFR, such as cystatin C clearance, give a more accurate measure of true GFR but have not been embraced in the management of pediatric transplant recipients. Furthermore, indirect markers (e.g., microalbuminuria and hypertension) could also aid early detection of renal damage. The effects of mainstay immunosuppressants on kidney and heart function are varied, with available data indicating favorable outcomes with tacrolimus compared with ciclosporin. There is a need for appropriately designed and powered randomized controlled trials to validate innovative concepts for tailored immunosuppression in the pediatric population. To date, very few studies have generated long-term data in pediatric renal transplant patients - results of 1-4-yr study favored tacrolimus over ciclosporin, but other immunosuppressive agents also need to be evaluated.