骨折早期调节RANKL表达对骨折愈合影响的实验研究

目的通过对大鼠股骨骨折早期局部应用重组人骨保护素Fc融合蛋白(OPG-Fc),研究调节骨保护素(OPG)和核因子-κB受体活化因子配体(RANKL)的表达变化对骨折早期的影响,探讨其表达调节方式及作用机制。方法 48只雌性SD大鼠随机分成实验组和对照组,每组24只。建立大鼠股骨骨折模型,于术后第7天、第14天、第21天、第28天4个时间节段分批处死模型,标本切片后通过HE染色观察骨折愈合情况,免疫组织化学染色研究破骨细胞数量变化。结果 HE染色示单纯骨折组呈典型骨折愈合过程,而骨折局部注射OPG组骨痂形成及改造提前,骨折愈合加速。免疫组织化学染色显示在第7天、第14天、第21天、第28天各个时间节段单纯骨折组破骨细胞计数值均高于骨折应用OPG组,差异有统计学意义(P0.05)。结论骨折早期调节RANKL表达,当RANKL/OPG比值减小时,骨折局部破骨细胞减少,骨痂形成增多,骨折愈合加速。     

Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.     

儿童呼吸道感染患者血清IP-10，MCP-1 平检测的临床意义

目的 研究皖南地区儿童呼吸道病原体感染的流行病学特点,探讨混合病原体感染患儿血清中干扰素诱生蛋白10(interferon-inducible protein-10,IP-10),单核细胞趋化蛋白-1( monogyte chemoattractant protein-1),MCP-1表达水平在急性呼吸道感染诊断中的应用价值。方法 收集2017年6月～2019年6月皖南医学院第一、二附属医院急性呼吸道感染患儿血标本,采用间接免疫荧光法检测呼吸道九项病原体IgM,分析不同年龄段呼吸道病原体感染的差异性。采用酶联免疫吸附试验检测混合感染患儿血清中IP-10,MCP-1的表达水平,分析炎症因子表达水平与疾病严重程度的相关性。结果 5 122例急性呼吸道感染患儿中,以肺炎支原体感染率最高,混合感染患儿共544例,以肺炎支原体联合呼吸道合胞病毒感染率最高。检测血清中的CRP,IP-10和MCP-1的表达水平相比较单独感染组,混合感染组升高更为明显,对比组之间的差异均具有统计学意义(F=1.045～4.889,均P<0.05)。相关性研究分析显示,混合感染组IP-10,MCP-1与CRP 表达水平呈正相关性(r = 0.612,P<0.001; r= 0.804,P<0.001)。结论 急性呼吸道感染患儿中,混合感染更易表现为咳嗽、鼻塞流涕及发热等症状,同时炎症反应增强,病情的严重程度增加,血清IP-10和MCP-1表达水平可作为急性呼吸道感染病情严重程度指标之一。     

以肺动脉高压为首发表现的先天性中枢性低通气综合征临床特征和基因分析

目的探讨先天性中枢性低通气综合征(CCHS)的临床和基因变异特征。方法分析1例首发表现为不明原因肺动脉高压的CCHS患儿的临床资料,并总结国内外文献中CCHS病例的临床特点、致病机制和基因变异情况。结果11月龄女婴,主要表现为浮肿、尿少、低血压、嗜睡、发绀、抽搐及颅内压增高。B型脑利钠肽、丙氨酸氨基转移酶升高,凝血酶原时间延长。颅脑磁共振示右侧额叶出血;超声心动图示中重度肺动脉高压。靶向捕获二代测序未发现可能的致病基因。采用Sanger法验证示患儿PHOX 2 B基因第3外显子存在多聚丙氨酸重复扩展变异,基因型为20/25。患儿入院后采用无创通气,睡眠时呼吸浅慢、微弱,伴血氧下降;血气分析提示二氧化碳潴留。随后改用夜间无创通气、降肺压药物治疗。复查肺动脉压力明显下降,生命体征稳定。随访至24月龄,夜间只需较低压力水平的无创通气,生长发育无异常。结论对于不明原因的肺动脉高压伴撤机困难患儿,需警惕CCHS。疑诊者应尽早针对CCHS相关基因进行靶向捕获二代测序及PHOX 2 B基因Sanger法验证。早期给予无创通气有望改善预后。     

从形气神谈溃疡性结肠炎的中西医认识

溃疡性结肠炎(Ulcerative colitis,UC)是一种病情反复、迁延难愈的炎症肠病,已被世界卫生组织列为现代难治病之一[1]。本病病因及发病机制尚不明确,西药治疗效果欠佳。近年来中医药的介入,临床取得显著疗效。西医学认为疾病是机体在一定致病因素的作用下自稳调节紊乱,经过机体内损伤和抗损伤反应的相互斗争,表现出的一系列功能。     

泻浊化瘀汤联合血液透析治疗尿毒症临床效果及对TLR4、炎症细胞因子水平的影响

目的探讨泻浊化瘀汤联合血液透析治疗尿毒症患者的临床效果。方法选取2013年10月-2018年1月收治的107例尿毒症患者,采用随机数字表法分为试验组54例和对照组53例,两组患者均常规采用血液透析治疗,对照组透析治疗的过程中给予基础治疗,观察组给予基础治疗+泻浊化瘀汤,对比两组患者干预前后血液透析后的血肌酐(Scr)、尿素氮(BUN)、血钙、血磷、甲状旁腺激素(PTH)、血清C反应蛋白(CRP)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、Toll样受体4(TLR4)的水平。结果干预前,观察组和对照组的Scr、BUN、血钙、血磷、PTH、TNF-α水平差异无统计学意义(P>0.05);干预后,观察组的血磷、PTH、TNF-α水平均低于对照组(P<0.05),两组的Scr、BUN、血钙差异无统计学意义(P>0.05);干预前,观察组和对照组的血清IL-2、IL-6、TLR4和CRP水平差异无统计学意义(P>0.05);干预后,观察组的血清IL-2、IL-6、TLR4和CRP均低于对照组(P<0.05)。结论泻浊化瘀汤联合血液透析治疗尿毒症患者有利于降低血磷、降低患者的炎症反应程度及TLR4的水平,对于改善血透患者的治疗质量具有一定的作用。     

Ligustrazine inhibits high voltage-gated Ca~(2+) and TTX-resistant Na~+ channels of primary sensory neuron and thermal nociception in the rat:a study on peripheral mechanism

Objective Ligustrazine, also named as tetramethylpyrazine, is a compound purified from Ligusticum chuanxiong hort and has ever been testified to be a calcium antagonist. The present investigation was to determine the antinoci-ceptive effect of ligustrazine and, if any, the peripheral ionic mechanism involved. Methods Paw withdrawal Latency ( PWL) to noxious heating was measured in vivo and whole-cell patch recording was performed on small dorsal root ganglion (DRG) neurons. Results Intraplantar injection of ligustrazine (0.5 mg in 25μl) significantly prolonged the withdrawal latency of ipsilateral hindpaw to noxious heating in the rat. Ligustrazine not only reversibly inhibited high-voltage gated calcium current of dorsal root ganglion (DRG) neuron in dose-dependent manner with IC50 of 1.89 mmol/L, but also decreased tetrodotoxin (TTX) -resistant sodium current in relatively selective and dose-dependent manner with IC50 of 2.49 mmol/L. Conclusion The results suggested that ligustrazine could elevate the threshold of thermal nociception through inhibiting the high-voltage gated calcium current and TTX-resistant sodium current of DRG neuron in the rat.     

肝门胆管癌的动态增强CT诊断

目的评价螺旋CT对肝门胆管癌的诊断价值。方法13例肝门胆管癌行螺旋CT平扫及动态增强扫描,并与手术及病理对照分析。结果11例平扫表现为肝门区低密度软组织肿块;2例表现为肝门区胆管不规则增厚,管腔狭窄。增强扫描13例有延迟强化。结论螺旋CT扫描对肝门胆管癌的诊断具有重要意义。