急性1,2-二氯乙烷中毒性脑病临床特征及护理对策研究

目的:总结急性1,2-二氯乙烷中毒性脑病的临床特征,提出有效的护理对策。方法:回顾性分析2003年1月至2013年6月收治的急性1,2-二氯乙烷中毒性脑病患者69例的临床护理资料。结果:急性1,2-二氯乙烷中毒性脑病的主要病变为脑水肿,临床特征主要是潜伏期短,有头晕、头痛、烦躁不安,意识模糊,伴胃肠症状,病情可突然恶化,头颅CT表现为两侧大脑半球皮质下白质、基底节区、小脑齿状核见对称性低密度影,头颅MRI显示双侧对称性病变。护理对策是密切观察病情,注意脑水肿变化的临床指标和及时给予足量激素、加强脱水、高压氧舱等。结论:急性1,2-二氯乙烷中毒脑病以脑水肿为主,出现头晕、头痛、烦躁不安,意识模糊甚至昏迷;加强基础护理、积极防治脑水肿、及时进行康复治疗是护理关键。     

Therapeutic Effects of Adipose Stem Cells from Diabetic Mice for the Treatment of Type 2 Diabetes

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Mesenchymal stem cells protect from acute liver injury by attenuating hepatotoxicity of liver natural killer T cells in an inducible nitric oxide synthase‐ and indoleamine 2,3‐dioxygenase‐dependent manner

The effects of mesenchymal stem cells (MSCs) on the phenotype and function of natural killer T (NKT) cells is not understood. We used concanavalin A (Con A) and α‐galactosylceramide (α‐GalCer)‐induced liver injury to evaluate the effects of MSCs on NKT‐dependent hepatotoxicity. Mouse MSCs (mMSCs) significantly reduced Con A‐ and α‐GalCer‐mediated hepatitis in C57Bl/6 mice, as demonstrated by histopathological and biochemical analysis, attenuated the influx of inflammatory [T‐bet⁺, tumour necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ)‐producing and GATA3⁺, interleukin‐4 (IL‐4)‐producing] liver NKT cells and downregulated TNF‐α, IFN‐γ and IL‐4 levels in the sera. The liver NKT cells cultured in vitro with mMSCs produced lower amounts of inflammatory cytokines (TNF‐α, IFN‐γ, IL‐4) and higher amounts of immunosuppressive IL‐10 upon α‐GalCer stimulation. mMSC treatment attenuated expression of apoptosis‐inducing ligands on liver NKT cells and suppressed the expression of pro‐apoptotic genes in the livers of α‐GalCer‐treated mice. mMSCs reduced the cytotoxicity of liver NKT cells against hepatocytes in vitro. The presence of 1‐methyl‐dl ‐tryptophan, a specific inhibitor of indoleamine 2,3‐dioxygenase (IDO), or l ‐N^G‐monomethyl arginine citrate, a specific inhibitor of inducible nitric oxide synthase (iNOS), in mMSC‐conditioned medium injected into α‐GalCer‐treated mice, counteracted the hepatoprotective effect of mMSCs in vivo and restored pro‐inflammatory cytokine production and cytotoxicity of NKT cells in vitro. Human MSCs attenuated the production of inflammatory cytokines in α‐GalCer‐stimulated human peripheral blood mononuclear cells in an iNOS‐ and IDO‐dependent manner and reduced their cytotoxicity against HepG2 cells. In conclusion, MSCs protect from acute liver injury by attenuating the cytotoxicity and capacity of liver NKT cells to produce inflammatory cytokines in an iNOS‐ and IDO‐dependent manner.     

2-甲氧基雌二醇上调Bax/BCL-2比例诱导淋巴瘤Raji细胞凋亡的研究

目的:研究2-甲氧基雌二醇(2-ME2)对淋巴瘤Raji细胞的作用及其作用机制.方法:用不同浓度2-ME2作用于淋巴瘤Raji细胞,CCK8法检测2-ME2对Raji细胞增殖的影响;流式细胞仪FITC/PI双标法检测细胞早期的凋亡;蛋白印迹法检测2-ME2对Raji细胞BCL-2、Bax、Caspase-3、C-myc...     

生存素,Fas,bcl-2和bax在急性髓系白血病病人骨髓细胞中的表达及其临床意义

为了研究抗凋亡基因生存素和bcl 2及促凋亡基因Fas和bax在急性髓系白血病 (AML)中的表达及其临床意义 ,采用RT PCR法分析生存素在 6 8例初治AML病人骨髓细胞中表达的阳性率 ,用流式细胞术检测Fas,bcl 2和bax在AML病人骨髓细胞中的表达和bcl 2 /bax比值。研究结果显示 :① 6 8例初治AML病人生存素mRNA阳性率为 70 .6 % (48/ 6 8) ,明显高于对照 (30 % ,6 / 2 0 ) (P <0 .0 0 5 ) ;②治疗前 ,AML病人骨髓细胞表达Fas和bcl 2明显高于对照 (P <0 .0 0 1) ,但bax表达与对照差异无显著性 (P >0 .0 5 ) ;③生存素阳性AML病人表达Fas明显低于生存素阴性AML病人 (P <0 .0 1) ,bcl 2明显高于生存素阴性AML病人 (P <0 .0 0 1) ,bax表达无差异 (P >0 .0 1) ;④生存素阳性AML病人的CR率明显低于阴性组 (31/ 4 8,6 4 .6 %vs 18/ 2 0 ,90 % ,P <0 .0 5 ) ;⑤生存素阳性AML病人CR组Fas和bcl 2较治疗前明显下降 (P <0 .0 0 1) ,bax变化无差异 (P >0 .0 5 ) ,而生存素阳性的NR组Fas较治疗前显著下降 (P <0 .0 0 1) ,bcl 2则上升 (P <0 .0 0 1) ,bax变化无差异 (P >0 .0 5 ) ,bcl 2 /bax比值NR组明显高于CR组 (P <0 .0 0 1)。结论 :①初治AML病人 70 .6 %表达生存素 ,生存素阳性者CR低 ;②生存素阳性AML病人Fas低于生存素阴     

pEGFP/A_2M(FP_6)转染神经干细胞海马移植治疗APP/PS1双转基因AD小鼠的实验观察

目的:携带pEGFP/A2M(FP6)的神经干细胞(NSCs)定向移植到APP/PS1双转基因AD小鼠海马内,观察移植细胞的分化、迁移,脑内Aβ沉积的变化,以及对AD小鼠学习记忆功能的影响。方法:APP/PS1转基因AD小鼠分为假手术(SO)组、人工脑脊液(ACSF)组、转染pEGFP的NSCs(pEGFP-NSCs)组及转染pEGFP/A2M(FP6)的NSCs(pEGFP/A2M(FP6)-NSCs)组,移植物小鼠海马CA1区定位注射,水迷宫实验检测小鼠认知功能,免疫组化观察小鼠脑内移植细胞的分化、迁移及Aβ病理变化。结果:pEGFP/A2M(FP6)-NSCs组和pEGFP-NSCs组转基因小鼠逃避潜伏期较SO组及ACSF组显著缩短(P<0.05);pEGFP/A2M(FP6)-NSCs组转基因小鼠逃避潜伏期较pEGFP-NSCs组缩短(P<0.05)。pEGFP/A2M(FP6)-NSCs组和pEGFP-NSCs组转基因小鼠海马及皮质内,部分Aβ染色阳性斑块周围可见表达EGFP的移植细胞。pEGFP/A2M(FP6)-NSCs组转基因小鼠额叶、海马区域,Aβ染色阳性斑块数量和平均面积均较其他3组显著减少(P<0.05)。移植的NSCs,部分细胞Nestin染色呈阳性,部分细胞GFAP染色呈阳性,少数细胞MAP-2染色呈阳性。结论:移植pEGFP/A2M(FP6)NSCs到APP/PS1双转基因AD小鼠海马,可减少AD小鼠脑内Aβ斑块沉积,部分移植的NSCs分化为神经元及星形胶质细胞,小鼠的学习记忆功能显著改善。     

髓白1号方联合化疗对急性髓系白血病患者骨髓中Th17细胞的调控作用研究

目的:探索髓白1号方联合化疗对AML患者骨髓液中Th17细胞的调控作用,为提高AML患者治疗效果与长期生存提供指导.方法:选取2017年4月-2019年8月在武威市人民医院血液科住院的AML患者70例,并以25名健康志愿者纳入对照组;然后AML患者根据治疗方案分为联合治疗组(髓白1号方联合化疗)和非联合治疗组(单纯化疗...     

糖皮质激素治疗大肠杆菌致急性呼吸窘迫综合征的实验研究

目的研究糖皮质激素(GC)治疗感染性急性呼吸窘迫综合征(ARDS)的临床价值。方法大肠杆菌腹腔注射制备猪ARDS模型。健康雄性幼猪9头,按随机原则分为对照组(n=3)、早期治疗组(n=4)和中期治疗组(n=2);甲基泼尼松龙20mg(4mg·kg-1·d-1)静脉注射,12h1次;观察动物各项生理指标与生存时间;72h处死动物,常规方法检测肺组织湿/干重(W/D)比值,光镜下Smith评分法观察病理学改变。结果早、中期治疗组动物存活时间长于对照组,但差异均无显著性(P均>0.05);早期治疗组氧合指数(PaO2/FiO2)和平均动脉压(MAP)均较对照组改善明显(P均<0.05),中期治疗组自身对照PaO2/FiO2和MAP也明显改善(P<0.05或P<0.01);除早期治疗组总蛋白(TP)显著高于中期治疗组外,各组支气管肺泡灌洗液(BALF)中总磷脂(TPL)、饱和磷脂酰胆碱(DSPC)、白细胞计数以及肺表面张力、肺W/D比值差异均无显著性(P均>0.05);早、中期治疗组肺组织病理学改变较对照组均加重(P均<0.01)。结论GC能改善感染性ARDS低氧血症与休克,对终末期肺表面活性物质、表面张力和形态学改变无明显影响。     

Development of a checklist to aid in the assessment of ‘failure to return’ from approved leave by acute inpatients

Better assessment of consumer behaviour and intentions prior to the granting of approved leave may reduce failure to return from such episodes of leave. The aims of this study were (i) to gain consensus on the factors associated with failure to return, and (ii) use these factors to construct a checklist to aid in assessment of consumers prior to being granted leave. Following a review of the literature a pool of 36 factors was identified. These were then assessed for relevance to absconding from approved leave using a modified Delphi approach. After two Delphi rounds, 10 factors were retained and these were collapsed under 6 domains; history of absconding, current substance use, behaviour cues, verbal cues, lack of engagement, and changes in mental state. While staff reactions to the checklist were positive, further testing of its effectiveness in the clinical setting is required.     

片仔癀通过抑制TLR4/MAPK信号通路减轻LPS诱导的BV2小胶质细胞神经炎症损伤研究

目的:研究片仔癀(PZH)对脂多糖(LPS)诱导的BV2小胶质细胞神经炎症损伤的保护作用及机制。方法:将BV2小胶质细胞培养于含有10%胎牛血清和1%青霉素-链霉素的RPMI-1640完全培养基中,并置于5%CO2,37℃培养箱中常规培养。将BV2小胶质细胞以5×104个/mL的密度接种于96孔板,LPS(100 ng/mL)诱导BV2小胶质细胞炎症反应,同时分别用不同浓度PZH(0.05、0.10、0.15 mg/mL)干预12 h,加入MTT并于4 h后检测其490 nm处吸光度。将BV2小胶质细胞以5×104个/mL的浓密度接种于24孔板,LPS(100 ng/mL)诱导BV2小胶质细胞炎症反应,分别用不同浓度PZH(0.05、0.10和0.15 mg/mL)干预12 h,收集上清并使用ELISA法测定细胞上清中IL-6的水平。将BV2小胶质细胞以1.6×105个/mL的密度接种于6孔板,LPS(100 ng/mL)诱导BV2小胶质细胞炎症反应,同时分别用不同浓度PZH(0.05、0.10、0.15 mg/mL)干预12 h,使用TRIzol试剂提取总RNA,逆转录制备cDNA,然后采用RT-qPCR法检测BV2小胶质细胞中炎症因子IL-1β、IL-6和TNF-α转录水平。将BV2小胶质细胞以1.6×105个/mL的密度接种于6孔板,LPS(100 ng/mL)诱导BV2小胶质细胞炎症反应,同时分别用不同浓度PZH(0.05、0.10、0.15 mg/mL)干预12 h,加入RIPA蛋白裂解液提取蛋白质,然后采用Western blot法检测BV2小胶质细胞中TLR4、ERK1/2、p-ERK1/2、p38、p-p38、JNK、p-JNK、COX-2和iNOS蛋白表达水平。结果:①MTT实验结果显示,与正常对照组比较,不同浓度PZH和LPS各自单独干预或者两者共同干预对BV2小胶质细胞活力均无明显影响(P>0.05)。②ELISA结果显示,与正常对照组比较,模型组IL-6分泌水平明显上升(P<0.001);与模型组比较,不同浓度PZH可显著降低IL-6分泌水平(P<0.05,P<0.05,P<0.01)。③RT-qPCR结果显示,与正常对照组比较,模型组IL-1β(P<0.001)、IL-6(P<0.001)和TNF-α(P<0.01)转录水平明显上升;与模型组比较,不同浓度PZH可明显降低IL-1β(P<0.05,P<0.01,P<0.001)、IL-6(P>0.05,P<0.01,P<0.001)和TNF-α(P<0.01,P<0.01,P<0.001)转录水平。④Western blot结果显示,不同浓度PZH能显著抑制LPS诱导的TLR4/MAPK信号通路的激活,减少TLR4(P>0.05,P<0.05,P<0.05)、p-ERK1/2(P>0.05,P<0.05,P<0.01)、p-p38(P<0.05,P<0.01,P<0.01)、COX-2(P<0.01,P<0.01,P<0.001)和iNOS(P<0.01,P<0.01,P<0.01)蛋白表达水平,但对p-JNK蛋白表达无明显影响(P>0.05)。结论:片仔癀可明显改善LPS诱导的神经炎症损伤,其作用可能与抑制TLR4/MAPK信号通路激活相关。     

In vitro and in vivo antibacterial activity of nitrofurantoin against clinical isolates of E. coli in Japan and evaluation of biological cost of nitrofurantoin resistant strains using a mouse urinary tract infection model

IntroductionNitrofurantoin is a well-established antibiotic, and is an important first-line oral treatment for uncomplicated urinary tract infections. However, little information is available with respect to its antibacterial activity in Japan, in vivo efficacy, or the in vivo biological cost of resistant strains.MethodsWe compared the susceptibility of six representative antibacterial agents—nitrofurantoin, sulfamethoxazole/trimethoprim, fosfomycin, mecillinam, ciprofloxacin, and cefdinir—against E. coli clinically isolated in Japan during 2017. We evaluated the in vivo efficacy of nitrofurantoin using a model of mouse urinary tract infection caused by ciprofloxacin resistant E. coli. We obtained nitrofurantoin resistant isolates through tests generating spontaneous mutations, and assessed the in vivo fitness of nitrofurantoin resistant isolates.ResultsThe MIC₉₀ of nitrofurantoin was 16 μg/mL, and was the lowest among the drugs tested. It was found that, in the mouse urinary tract infection model, 30 mg/kg and 100 mg/kg of nitrofurantoin reduced the count of viable bacterial cells in the kidney, while 100 mg/kg of ciprofloxacin did not. All spontaneous bacterial mutants resistant to nitrofurantoin had deletions in the nfsA gene, and we found that the resistant strain had lower growth in the mouse urinary tract infection model than in the parent strain.ConclusionsWe demonstrated promising in vitro and in vivo activity of nitrofurantoin against E. coli clinical isolates in Japan, and lower in vivo fitness of the resistant strain of nitrofurantoin.     

Optimization of Whole-Body Positron Emission Tomography Imaging by Using Delayed 2-Deoxy-2-[F-18]fluoro-d-glucose Injection Following I.V. Insulin in Diabetic Patients

Purpose High blood glucose levels may decrease the sensitivity of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET). The goal of this study was to assess whether intravenous (i.v.) insulin followed by FDG injection 60 minutes later could decrease the blood glucose level of hyperglycemic patients without altering muscular, liver, or lung FDG uptake.Methods We evaluated 53 diabetic patients with a fasting glycemia higher than 7.0 mmol/l. The control group consisted of 53 nondiabetic patients with a normal fasting glycemia. Sixty minutes before FDG injection, all diabetic patients received up to two intravenous bolus of insulin. Regions of interest were drawn over the lungs, heart, liver, skeletal muscles, and over the most active lung nodule, if present, to calculate a standardized uptake value (SUV) normalized to the lean body weight.Results After one or two boluses of insulin (mean 3.4 units), 39 diabetic patients decreased their blood glucose level from 9.4 ± 1.8 to 6.1 ± 1.3 mmol/l. In 14 patients, two doses of insulin (mean 4.5 ± 2.3 units) were not sufficient, but managed to decrease the blood glucose level from 10.6 ± 2.1 to 9.1 ± 2.1 mmol/l. There was no significant difference for the SUV calculated on the lung, liver, heart, and skeletal muscles. No differences were noted in lung tumor uptake in patients who received insulin compared to the control group.Conclusions With a sufficient waiting period between the insulin and FDG injections, an i.v. bolus of insulin makes it possible to effectively decrease glycemia of diabetic patients without increasing muscular FDG uptake.     

Identification of HLA-A2-restricted CD8(+) cytotoxic T cell responses in primary biliary cirrhosis: T cell activation is augmented by immune complexes cross-presented by dendritic cells.

Primary biliary cirrhosis (PBC) is characterized by an intense biliary inflammatory CD4(+) and CD8(+) T cell response. Very limited information on autoantigen-specific cytotoxic T lymphocyte (CTL) responses is available compared with autoreactive CD4(+) T cell responses. Using peripheral blood mononuclear cells (PBMCs) from PBC, we identified an HLA-A2-restricted CTL epitope of the E2 component of pyruvate dehydrogenase (PDC-E2), the immunodominant mitochondrial autoantigen. This peptide, amino acids 159-167 of PDC-E2, induces specific MHC class I-restricted CD8(+) CTL lines from 10/12 HLA-A2(+) PBC patients, but not controls, after in vitro stimulation with antigen-pulsed dendritic cells (DCs). PDC-E2-specific CTLs could also be generated by pulsing DCs with full-length recombinant PDC-E2 protein. Furthermore, using soluble PDC-E2 complexed with either PDC-E2-specific human monoclonal antibody or affinity-purified autoantibodies against PDC-E2, the generation of PDC-E2-specific CTLs, occurred at 100-fold and 10-fold less concentration, respectively, compared with soluble antigen alone. Collectively, these data demonstrate that autoantibody, helper, and CTL epitopes all contain a shared peptide sequence. The finding that autoantigen-immune complexes can not only cross-present but also that presentation of the autoantigen is of a higher relative efficiency, for the first time defines a unique role for autoantibodies in the pathogenesis of an autoimmune disease.     

Activation of protein breakdown and prostaglandin E2 production in rat skeletal muscle in fever is signaled by a macrophage product distinct from interleukin 1 or other known monokines.

During sepsis or after injection of endotoxin into rats, there is a large increase in muscle protein breakdown and prostaglandin E2 (PEG2) production. Prior studies showed that partially purified interleukin 1 (IL-1) from human monocytes can stimulate these processes when added to isolated rat muscles. The availability of pure recombinant IL-1 and other monokines has allowed us to investigate the identity of the active agent in this process. Incubation of muscles with recombinant human or murine IL-1 alpha or IL-1 beta or with IL-1 plus a phorbol ester did not stimulate muscle proteolysis or PGE2 production. Homogeneous natural porcine IL-1 ("catabolin") and mouse or human IL-1 beta were also not effective in vitro. In addition, a variety of other human cytokines, including tumor necrosis factor ("cachectin"), epidermal thymocyte-activating factor, eosinophil cytotoxicity-enhancing factor, interferon-alpha, beta, and gamma, platelet-derived growth factor, and transforming growth factor (TGF) beta, which are all released by activated macrophages, TGF-alpha, or mixtures of these polypeptides, also failed to activate proteolysis or PGE2 production. By contrast, a large increase in net protein breakdown could be induced in the rat soleus by polypeptides released from porcine monocytes or by the serum from febrile cattle which had been injected with Pasteurella haemolytica or bovine rhinotracheitis virus. Therefore, a still-unidentified product of activated monocytes appears to be responsible for the negative nitrogen balance that accompanies infectious illness.     

Glutamate and prostaglandin E2 in the trapezius muscle of female subjects with chronic muscle pain and controls determined by microdialysis.

Much is still unknown concerning the mechanisms underlying the development of chronic muscle pain. The presence and magnitude of inflammatory substances and neurotransmitters in chronic painful conditions is not clear. The aims of the present study were to determine, with the use of microdialysis, the interstitial concentrations and the equilibration times for PGE2 and glutamate in the trapezius muscles of nine female subjects with chronic muscle pain, and nine pain-free age-matched controls. A microdialysis probe was implanted in the upper part of the trapezius muscle and perfused with Ringer-acetate solution at a flow rate of 0.3 microL/min. Samples were obtained every 30 min, during a 4-h rest period. At equilibration, the mean concentrations (+/-SE) of PGE2 were 0.71 (+/-0.11) ng/mL for the pain-group and 0.97 (+/-0.35) ng/mL for the controls. For glutamate the mean concentrations for the pain-group were 66.3 (+/-13.3) micromol/L and 60.6 (+/-22.9) micromol/L for the controls. For the pain group and the control group, respectively, equilibration for PGE2 was reached at 180 and 150 min, and for glutamate at 150 and 120 min. The present study showed no differences between groups in the concentrations of PGE2 and glutamate in the trapezius muscle. Further, it revealed that when using the slow-flow method, a period of at least 2.0-2.5 h is needed, after probe insertion, to reach steady state for glutamate and PGE2.