不同剂量谷氨酸脱羧酶对非肥胖型糖尿病小鼠发生1型糖尿病的影响

目的不同剂量谷氨酸脱羧酶(GAD)对非肥胖型糖尿病小鼠(NOD)糖尿病免疫干预效果的影响。方法将3周龄40只体重(10.0±0.9)g雌性NOD小鼠分为4组分别腹腔注射GAD0.3mU和不完全弗氏佐剂(IFA)50μL、GAD3mU+IFA50μL、GAD0.03mU+IFA50μL、IFA50μL。8周龄时注射环磷酰胺200mg/kg加速糖尿病,定期检测血糖,眼内眦取血分离血清检测细胞因子白细胞介素(IL)4和干扰素(IFNγ)的变化,动态观察各组糖尿病发生发展的过程。28周时,全部处死,取脾、胸腺作淋巴细胞亚群测定,胰腺作病理组织学观察。结果GAD3mU+IFA50μL组小鼠无一只发生糖尿病,28周时血糖为(5.0+1.1)mmol/L;胰岛个数最多(8.2+2.3)个/张(P<0.01),胰岛炎评分最低(0.33+0.12)(P<0.01);血清中IL4的水平最高为(80+6)ng/L(P<0.01),IFNγ水平最低为(327±48)ng/L;CD8+/CD4+比值最大(P<0.01),在脾脏中为0.524±0.133,胸腺中为0.428±0.021。结论NOD小鼠在3周龄时腹腔注射CAD3mU+IFA50μL混合物比其他剂量组免疫调节效果好,较好地通过调节胸腺,脾淋巴细胞亚群分类,并通过淋巴细胞分泌Th1类因子和Th2类因子来调节Th0细胞的转化,从而抑制NOD小鼠胰岛炎,胰岛β细胞破坏减少,GAD3mU剂量组免疫干预NOD小鼠糖尿病的发生效果最好。     

补肾化痰中药对烟熏大鼠慢支模型血清IL-2 IL-8及免疫器官脏器系数的影响

目的:探讨补肾化痰中药对烟熏大鼠慢支模型血清IL-2、IL-8及免疫器官脏器系数的影响.方法:雄性Wistar大鼠72只,随机分为6组,即正常对照组、慢支模型组、气管炎咳嗽痰喘丸组、补肾化痰大剂量组、补肾化痰小剂量组及自然恢复组,采用香烟烟雾吸入法建立大鼠慢性支气管炎模型,采用放射免疫法测定各组大鼠血清IL-2、IL-8的含量,并计算胸腺及脾脏的脏器系数.结果:与正常对照组比较,慢支模型组和自然恢复组大鼠血清IL-2水平均显著降低(P<0.001),血清IL-8水平均显著升高(P<0.001),胸腺的脏器系数均明显降低(P<0.05);经用补肾化痰中药治疗后,血清IL-2水平显著升高(P<0.01或P<0.05),IL-8水平显著下降(P<0.01或P<0.05),胸腺的脏器系数明显升高(P<0.05),而脾脏的脏器系数各组之间无明显差异(P>0.05).结论:补肾化痰中药对烟熏大鼠慢支模型有免疫调节作用,而单纯戒烟在短期内并不能使已经严重失调的免疫功能得到明显改善.     

补肾化痰中药对烟熏大鼠慢支模型血清IL-2IL-8及免疫器官脏器系数的影响

目的：探讨补肾化痰中药对烟熏大鼠慢支模型血清IL-2、IL-8及免疫器官脏器系数的影响。方法：雄性Wistar大鼠72只，随机分为6组，即正常对照组、慢支模型组、气管炎咳嗽痰喘丸组、补肾化痰大剂量组、补肾化瘦小剂量组及自然恢复组，采用香烟烟雾吸入法建立大鼠慢性支气管炎模型，采用放射免疫法测定各组大鼠血清IL-2、IL-8的含量。并计算胸腺及脾脏的脏器系数。结果：与正常对照组比较．慢支模型组和自然恢复组大鼠血清IL-2水平均显著降低（P〈0．001）。血清IL-8水平均显著升高（P〈0．001），胸腺的脏器系数均明显降低（P〈0．05）；经用补肾化痰中药治疗后，血清IL-2水平显著升高（P〈0．01或P〈0．05），IL-8水平显著下降（P〈0．01或P〈0．05），胸腺的脏器系数明显升高（P〈0．05），而脾脏的脏器系数各组之间无明显差异（P〉0．05）。结论：补肾化痰中药对烟熏大鼠慢支模型有免疫调节作用，而单纯戒烟在短期内并不能使已经严重失调的免疫功能得到明显改善。     

Does perioperative biological therapy increase 30-day post-operative complication rates in inflammatory bowel disease patients undergoing intra-abdominal surgery? A systematic review

BackgroundBiopharmaceuticals revolutionised inflammatory bowel disease (IBD) treatment. However, it is postulated they compromise immunity, collagen production and angiogenesis resulting in infective post-operative complications and altered wound/anastomotic healing. Research has failed to agree on risks associated with perioperative biologics therefore it was anticipated that a systematic review may provide a consensus and contribute recommendations for clinical practice.MethodsA systematic review conducted as per PRISMA guidelines included a methodical search of PubMed, Google Scholar, EMBASE/Ovid and Cochrane Library using MeSH and/or keywords for papers published between 01/01/1998 and 04/02/2019.The population analysed included adult ulcerative colitis, Crohn's disease, Indeterminate Colitis or IBD unclassified patients. The intervention was intra-abdominal surgery in patients treated with biological therapy in the preceding 12 weeks compared to patients who had intra-abdominal surgery without biological therapy within the defined timeframe. The primary outcome was surgical site infection (SSI) with secondary outcomes including wound dehiscence, intra-abdominal sepsis/abscess, systemic infection and anastomotic breakdown within 30 days post-procedure. Papers were evaluated by two independent reviewers and those included were assessed for quality/bias using the Newcastle–Ottowa scale.Results2064 UC, Crohn's and IC patients were analysed across 8 included studies. Several studies' multivariate analyses demonstrated corticosteroids to be independent predictors of morbidity. There are no increased complications associated with anti-TNFα exposure while vedolizumab increased SSI and small bowel obstruction.ConclusionProspective studies and randomised control trials are required to clarify study outcomes and recommendations published to date. Presently, biologics should continue to be used and considered beneficial in this population.     

Primed neutrophil infiltrations into multiple organs in child physical abuse cases: A preliminary study

Physical abuse of the elderly induces a massive primed neutrophil infiltration into the lung and liver through chemotaxis by interleukin (IL)-8, similar to cases of traumatic or hemorrhagic shock. Here, we used immunohistochemical analyses to investigate this infiltration in cases of physically abused children. In addition, we examined the expression of neutrophil elastase (NE) as the inflammatory mediator and α1-antitrypsin (AAT) as the elastase inhibitor. The number of neutrophils in the abuse cases was increased significantly in the heart, lung, liver, and kidney, compared with that of control cases. IL-8-positive cells and NE-positive cells in all organs of abuse cases were significantly greater than those in control cases. Large quantities of oxidized AAT, which fails to inactivate NE and results in tissue damage, was detected in the liver of abuse cases. Neutrophil infiltration showed positive correlation with the degree of systemic accumulation of non-fatal injuries caused by repetitive abusive behavior. Although further investigation using more autopsy samples is necessary, results of our preliminary study indicate that massive neutrophil infiltration induced by IL-8 in multiple organs is a new complementary diagnostic indicator of physical abuse in children. Moreover, the demonstration of NE-positive cells and oxidized AAT provides firm evidence of tissue damage.     

Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.     

芒针对脊髓损伤大鼠运动功能和炎症水平的影响

目的探究芒针深刺秩边穴对大鼠脊髓损伤后运动功能的影响及可能作用机制。方法选择健康雄性Wister大鼠81只,随机分为正常组、模型组和芒针组(正常组9只,其余两组各36只),采用改良Allen's造模法制备大鼠脊髓中度损伤模型,模型组不做特殊处理,芒针组采用芒针深刺秩边穴,每日1次,每次30 min。分别于术后1 d、3 d、5 d、7 d行BBB(Basso-Beattie-Bresnahan)运动功能评分;术后1 d、3 d、5 d、7 d取受损段脊髓组织行酶联免疫吸附测定(ELISA)、实时荧光定量PCR(RT-qPCR)和苏木素-伊红染色(HE染色)。结果术后5 d和7 d,芒针组大鼠BBB评分高于模型组,差异有统计学意义(P<0.01);脊髓损伤后,模型组和芒针组大鼠脊髓组织中高迁移率族蛋白B1(HMGB1)、核转录因子kB(NF-kB)、白介素-6(IL-6)含量及HMGB1mRNA、NF-kBmRNA、IL-6mRNA水平显著升高(P<0.05);受损的脊髓组织松散,灰质中有许多空洞形成,伴有炎性细胞浸润。芒针治疗后,芒针组大鼠脊髓组织中HMGB1、NF-kB、IL-6含量及HMGB1mRNA、NF-kBmRNA、IL-6mRNA水平较模型组降低,且在3 d、5 d、7 d差异有统计学意义(P<0.05);受损部位的空洞及炎性细胞逐渐减少。结论脊髓损伤后,炎症因子的大量聚集引起级联性炎症反应,影响大鼠运动功能的恢复。芒针的抗炎机制可能包括抑制HMGB1的表达,降低NF-kB信号通路的传导,下调促炎因子IL-6的分泌。