急性脑梗死患者血浆氧化型低密度脂蛋白、超敏C反应蛋白水平与颈动脉狭窄的关系

目的探讨急性脑梗死(ACI)患者血浆氧化型低密度脂蛋白(ox-LDL)、超敏C反应蛋白(hs-CRP)水平与颈动脉狭窄(CAS)的关系及二指标之间的相互联系。方法选择经颈部血管彩超证实有CAS的ACI患者66例,与同期健康体检者30例对照,测定血浆ox-LDL、hs-CRP值。ACI患者根据颈动脉狭窄程度和神经功能缺损程度评分进行分组,比较ox-LDL、hs-CRP与CAS、神经功能缺损程度的关系。结果 ACI患者各颈动脉狭窄组血浆ox-LDL、hs-CRP水平均明显高于正常对照组,重度狭窄组患者ox-LDL、hs-CRP水平均显著高于中度狭窄组和轻度狭窄组,中度狭窄组显著高于轻度狭窄组,各组之间比较差异均有统计学意义(P<0.05)。重型神经功能缺损组的ACI患者ox-LDL、hs-CRP水平均显著高于中型组和轻型组,中型组显著高于轻型组,各组之间比较差异均有统计学意义(P<0.05)。ACI患者ox-LDL、hs-CRP水平呈显著正相关(r=0.426,P<0.05)。结论血浆ox-LDL、hs-CRP水平与ACI患者CAS程度及神经功能缺损的严重程度相关,ox-LDL、hs-CRP在ACI患者CAS的发生、发展过程可能起着协同作用。     

Molecular mechanisms of the secretion of cytokines and chemokines from human monocytes activated by pneumococcal surface protein A (PspA): Roles of mitogen-activated protein kinases and NF-kappaB

Pneumococcal surface protein A (PspA) plays a key role in the pathogenesis of invasive pneumococcal infection. PspA might modulate specific immune responses in human population. Circulating monocytes are essential for the innate responses and subsequent acquired immune responses to Streptococcus pneumoniae. In this study, we investigated the effects of PspA on cytokine and chemokine secretion from human peripheral blood monocytes and the underlying intracellular signaling mechanisms. Stimulation of monocytes with purified PspA protein induced the significant release of inflammatory cytokine IL-6 and chemokines including CXCL8, CCL2, CCL4 and CCL5. Products from PspA-deficient mutant pneumococcus that did not express PspA induced significantly less secretion of these mediators than those from wild type pneumococcus. Further investigations showed that PspA activated the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways in human monocytes. Moreover, inhibition of these pathways using selective inhibitors could significantly reduce the cytokine and chemokine secretion induced by PspA. Taken together, our findings provide insight for PspA-mediated activation of human monocytes via NF-κB and MAPKs signaling cascades in the pathogenesis of invasive pneumococcal infection.     

CNI induced Th17/Treg imbalance and susceptibility to renal dysfunction in renal transplantation

Calcineurin inhibitors (CNI) prevent graft rejection by blocking interleukin-2 (IL-2), which was required for development and function of Foxp3⁺CD4⁺CD25⁺ regulatory T cells (Treg). Recently, IL-2 was reported to play a part in the inhibition of Th17 cells. The renal transplantation recipient who used CNI regularly might have Th17/Treg imbalance with increased Th17 cells and decreased Treg cells, which would cause renal dysfunction even rejection. To assess the effect of CNI on Th17 cells and Treg cells, we included 123 renal transplantation recipients (101 in a stable stage and 22 with renal dysfunction) and 27 healthy volunteers. Among all the recipients, 103 recipients used CNI and 20 recipients used sirolimus without CNI. The recipients who used CNI were further classified into four groups according to the blood levels of CNI: Of all these subjects, Th17 and Treg frequencies in the peripheral blood were analyzed by flow cytometry (FCM). Serums IL-17, IL-23, IL-6, IFN-r, and TGF-β were analyzed by ELISA. The results demonstrated that the transplantation recipient treated by CNI revealed an obvious increase in peripheral Th17 frequencies and a significant decrease in Treg frequencies when compared with the sirolimus group and healthy people (P < 0.05). Even more, the transplantation recipient with renal dysfunction had the highest level of Th17 cells (P < 0.05) while the lowest Treg cells compared with stable recipient and healthy control, with increased serums IL-6 and IL-17. Our results indicated that CNI was associated with Th17/Treg imbalance in peripheral blood, which supported the followed generation of renal dysfunction after transplantation.     

丙烯酰胺对大鼠神经行为和黑质纹状体多巴胺及其代谢产物含量的影响

目的初步探讨丙烯酰胺(ACR)对大鼠神经行为的影响,并通过测定黑质纹状体多巴胺(DA)及其代谢产物二羟苯乙酸(DOPAC)、高香草酸(HVA)含量阐明其可能机制。方法将健康成年雄性SD大鼠随机分成对照组和ACR组,每组7只。ACR组以40mg/kg的ACR灌胃染毒,对照组灌胃等容量的生理盐水,连续12天。第0、3、6、9和12天分别评定步态分值、后肢撑力及甩尾时间。末次给药后24小时,断头处死,于冰盘上迅速分离纹状体,HPLC荧光检测法检测DA及其代谢产物的含量。结果与对照组相比,ACR组大鼠的步态评分、后肢撑力指数显著性升高(P<0.01),甩尾时间显著降低(P<0.01)。纹状体内DA含量与对照组相比,约降低了65.64%,差异有显著性(P<0.01)。结论 ACR能引起大鼠神经行为功能的改变,同时能降低纹状体内DA含量,黑质纹状体DA系统可能参与了ACR的神经毒性作用。     

珠蛋白生成障碍性贫血基因携带者红细胞生成与铁调素的相关性研究

目的 通过检测珠蛋白生成障碍性贫血基因携带者血液红细胞生成相关生化指标的改变,分析其与血清铁调素的相关性.方法 通过对34例珠蛋白生成障碍性贫血基因携带者(携带组)和40例健康者(对照组)进行血细胞分析和血清铁、铁蛋白(Fer)、铁调素测定,比较其红细胞铁代谢相关参数与血清铁调素的相关性,并对结果进行统计学分析.结果 携带组红细胞(RBC)、血红蛋白(Hb)、Fer、血清铁及铁调素与对照组比较,差异均有统计学意义(P<0.05).携带组血清铁调素与RBC、Hb呈正相关[RBC(男r=0.781 5,P<0.01,女r=0.714 2,P=0.002)、Hb(男r=0.569 7,P<0.01,女r=0.549 2,P<0.05)],与Fer无关[(男r=0.130 6,P=0.50,女r=0.425 0,P＝0.10)].结论 珠蛋白生成障碍性贫血基因携带者血清铁调素含量降低,与红细胞生成呈正相关,红细胞生成是珠蛋白生成障碍性贫血基因携带者血清铁调素水平的重要调控因素.     

关于小儿急性呼吸窘迫综合征的临床研究

目的总结无创持续气道正压通气治疗小儿急性呼吸窘迫综合征的效果。方法 25例患儿皆选择持续无创持续气道正压通气（CPAP）治疗,所选择为Bubble CPAP婴儿呼吸机。连接方式主要为鼻塞,同时需调整相关的参数,其中,流量可调节（4~15LPM）,一般选择6~8LPM,不超过10LPM,,氧浓度可调（21%~100%）,一般〈45%,不超过60%,CPAP压力靠刻度管调节（3~10cmH2O）,一般在4~8cmH2O,气体可以选择进行温化与湿化,湿度0.8~1.0,温度30~35℃,严格监测患儿的血压、意识状态、末梢循环情况、呼吸、经皮血氧饱和度以及心率等。对比患儿治疗前与治疗后2h、24h的氧合指数PaO2/FiO2,血氧饱和度、呼吸频率以及心率等。结果 25例患儿在给予无创持续气道正压通气（CPAP）治疗后,其相关症状均出现明显的改善,其中,与治疗前相比,治疗后2h及治疗后24h患儿氧合指数PaO2/FiO2〉200,血氧饱和度明显上升,治疗前、后差异有统计学意义（P〈0.01）;与治疗前相比,治疗后2h及治疗后24h患儿呼吸频率与心率明显下降,治疗前、后差异有统计学意义（P〈0.01）。结论无创气道正压通气治疗小儿急性呼吸窘迫综合征,可以有效地改善相关的症状,使氧合指数PaO2/FiO计上升,患儿的经皮血氧饱和度逐渐上升,同时可以降低患者的呼吸频率与心率,对患儿疾病治疗有着至关重要的作用,值得在临床医学中推广使用。     

壳聚糖水凝胶与星形胶质细胞体外生物相容性评价的实验研究

研究壳聚糖水凝胶材料与星形胶质细胞的体外生物相容性,初步探讨壳聚糖水凝胶作为神经组织工程支架材料的可行性。利用氯化壳聚糖、β-甘油磷酸钠和羟乙基纤维素制备壳聚糖水凝胶,MTT法评价其细胞毒性;体外培养鉴定新生Wistar大鼠脑皮层星形胶质细胞;壳聚糖水凝胶与星形胶质细胞体外共培养,观察星形胶质细胞在材料上的生长;MTT法检测接种后1、35、、7d的细胞增殖度。体外成功制备壳聚糖水凝胶,该材料无细胞毒性;体外分离、培养得到状态良好的星形胶质细胞;体外星形胶质细胞在材料上培养呈星形,生长良好,有分支状突起形成;MTT结果表明,材料-细胞共培养组中的细胞增殖度明显高于单纯细胞组（P〈0.001）。壳聚糖水凝胶与星形胶质细胞在体外具有良好的生物相容性,有望作为神经组织工程支架材料。     

轻型胃肠炎伴惊厥32例临床分析

目的分析轻型胃肠炎伴惊厥(CwG)临床特点及随访预后。方法对2007年10月—2010年3月我科确诊的32例轻型胃肠炎伴惊厥患儿临床资料回顾性分析和出院后≥1年的随访。结果 32例中男14例,女18例,年龄最小7个月,最大29个月,发病季节以秋冬季为主。临床主要表现为腹泻、呕吐,伴或不伴轻度脱水,伴无热惊厥。惊厥多发于病程1～5d,其中23例为全身强直阵挛性发作,9例为部分性发作泛化为全身性发作。惊厥持续时间<10min。其中7例一次病程中发作2次,发作间期EEG正常,脑影像学、血生化、脑脊液检查正常。惊厥发作易控制,出院后随访32例,随访≥1年,2例出现复发,复发间隔时间分别为3个月、4.5个月。32例本次惊厥发作前均无热性惊厥史,1例发作后随访到7个月时出现1次热性惊厥发作。全部病例无癫和热性惊厥家族史,精神运动发育正常。结论婴幼儿轻型胃肠炎可以伴有无热惊厥,易于控制,预后良好,不必进行抗癫治疗。     

AMP kinase-related kinase NUAK2 affects tumor growth, migration, and clinical outcome of human melanoma

The identification of genes that participate in melanomagenesis should suggest strategies for developing therapeutic modalities. We used a public array comparative genomic hybridization (CGH) database and real-time quantitative PCR (qPCR) analyses to identify the AMP kinase (AMPK)-related kinase NUAK2 as a candidate gene for melanomagenesis, and we analyzed its functions in melanoma cells. Our analyses had identified a locus at 1q32 where genomic gain is strongly associated with tumor thickness, and we used real-time qPCR analyses and regression analyses to identify NUAK2 as a candidate gene at that locus. Associations of relapse-free survival and overall survival of 92 primary melanoma patients with NUAK2 expression measured using immunohistochemistry were investigated using Kaplan-Meier curves, log rank tests, and Cox regression models. Knockdown of NUAK2 induces senescence and reduces S-phase, decreases migration, and down-regulates expression of mammalian target of rapamycin (mTOR). In vivo analysis demonstrated that knockdown of NUAK2 suppresses melanoma tumor growth in mice. Survival analysis showed that the risk of relapse is greater in acral melanoma patients with high levels of NUAK2 expression than in acral melanoma patients with low levels of NUAK2 expression (hazard ratio = 3.88; 95% confidence interval = 1.44-10.50; P = 0.0075). These data demonstrate that NUAK2 expression is significantly associated with the oncogenic features of melanoma cells and with the survival of acral melanoma patients. NUAK2 may provide a drug target to suppress melanoma progression. This study further supports the importance of NUAK2 in cancer development and tumor progression, while AMPK has antioncogenic properties.