异丙酚对脂多糖诱导大鼠腹腔巨噬细胞Toll样受体-4 mRNA表达的影响

目的 观察异丙酚对脂多糖（LPS）诱导大鼠腹腔巨噬细胞Toll样受体-4（TLR-4）mRNA表达的影响，探讨异丙酚抑制LPS诱导白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF—α）产生的机制。方法 雄性Wistar大鼠32只，处死后分离腹腔巨噬细胞，随机分为4组（n=8）：A组（阴性对照组）；B组LPS（终浓度为1μg／ml）／加入巨噬细胞中；C组LPS（终浓度为1μg／ml）＋异丙酚（终浓度为1μg／ml）加入巨噬细胞中；D组LPS（终浓度为1μg／ml）＋异丙酚（终浓度为5μg／ml）加入巨噬细胞中。细胞培养12h后。用ELISA方法检测培养上清液中IL-6、TNF-α的浓度，用RT-PCR方法检测TLR-4mRNA的表达水平。结果 与A组相比，B组IL-6、TNF-α和TLR-4m RNA水平均增加，C组IL-6、TLR-4m RNA水平升高（P〈0．01）；与B组相比，C组、D组IL-6、TNF-α和TLR-4m RNA水平降低（P〈0．05或〈0．01）。结论 异丙酚通过下调TLR-4m RNA的表达水平，从而一定程度上抑制了LPS诱导大鼠腹腔巨噬细胞，TNF-α和IL-6的产生。     

淫羊藿苷治疗骨性关节炎的研究进展

骨性关节炎是一种好发于负重较大的膝关节、髋关节及脊柱等部位的慢性关节疾病,其病因复杂,至今尚未阐明。随着我国人口老龄化的加剧,骨关节炎的发病率不断增高,2015年统计数据发现我国大陆地区骨性关节炎的发病率约为13%。目前临床上针对骨性关节炎有保守及手术等疗法,如膝关节骨性关节炎可保守治疗也可行单髁置换、胫骨高位截骨及双间室置换等手术疗法,手术治疗创伤大,费用高,远期效果并非一劳永逸。而现有的保守疗法远期效果并不显著,所以寻找新的有效的治疗药物显得更为迫切。近年来研究发现淫羊藿苷在治疗骨关节炎方面有着显著的作用,它可促进骨髓间充质干细胞成软骨分化及促进软骨细胞增殖,有效修复骨性关节炎所致的软骨病损;可抑制软骨细胞外基质的降解,延缓骨关节炎所致的软骨组织破坏;可促进成骨细胞增殖,在骨性关节炎早期促进成骨及解除矿化障碍,阻止软骨下骨的进一步病变;可抑制破骨细胞的破骨作用,达到保护软骨下骨的目的;还可抑制炎症因子所致的滑膜炎症反应,缓解关节炎所致疼痛等症状。总之,淫羊藿苷可有效治疗骨性关节炎,尤以早期为著。目前的研究仅局限于组织细胞及动物实验,为明确淫羊藿苷治疗骨性关节炎的有效性及安全性,尚需更多的临床型研究予以证实,这也是今后的研究方向。     

Effects of WNK3 kinase on regulation of large-conductance calcium-activated potassium channels and its mechanisms

Objective To investigate the effects of WNK3 kinase on the regulation of large-conductance calcium-activated potassium channels (Maxi K channels) on African green monkey kidney fibroblast-like cells (Cos-7 cells) and its mechanisms. Methods (1) Cos-7 cells were transfected with 0, 0.6, 1.2, 1.8 μg WNK3 plasmid+0.5 μg Maxi K plasmid. The total protein expression of Maxi K channel and the phosphorylation of mitogen-activated protein kinase (MAPK) extracellular regulated kinase-1 and-2 (ERK1/2) were detected by Western blotting. (2) Cos-7 cells were divided into the control group (2.5 μg Maxi K plasmid) and the experimental group (2.5 μg WNK3 plasmid+2.5 μg Maxi K plasmid). Cell surface biotinylation was used to investigate the cell surface protein expression of Maxi K channel in Cos-7 cells. Immunoprecipitation and Western blotting were used to detect the ubiquitination of Maxi K channel protein. (3) WNK3 kinase was knocked down by WNK3 siRNA. The lysosomal degradation pathway was blocked by the proton pump inhibitor (Baf-A1). Cos-7 cells were divided into Maxi K+negative control siRNA group, Maxi K+WNK3 siRNA group and Maxi K+WNK3 siRNA+Baf-A1 group. The protein expression of Maxi K channel protein was detected by Western blotting. Results (1) Compared with those in 0 μg WNK3 plasmid groups, in 0.6, 1.2, 1.8 μg WNK3 plasmid groups the total protein expression of the Maxi K channel increased and the phosphorylation level of MAPK ERK1/2 reduced on a dose-dependent manner (all P＜0.01). (2) Compared with those in the control group, the total protein expression and cell surface membrane protein expression of the Maxi K channel increased in the experimental group (P＜0.01), while the ubiquitination of the Maxi K channel protein reduced (P＜0.01). (3) Compared with the Maxi K+negative control siRNA group, the expression of Maxi K protein reduced in the Maxi K+WNK3 siRNA group (P＜0.01), but did not change in the Maxi K+WNK3 siRNA+Baf-A1 group (P＞0.05). The expression of Maxi K protein in Maxi K+WNK3 siRNA+Baf-A1 group was higher than that in Maxi K+WNK3 siRNA group (P＜0.01). Conclusions WNK3 kinase inhibits the lysosomal degradation pathway of Maxi K channel protein by reducing the ubiquitination of Maxi K channel, and promotes the expression of Maxi K channel protein in cells and on cell membrane. These effects may be achieved by suppressing MAPK ERK1/2 signal transduction pathway.     

肝内外胆管结石腹腔镜、内镜联合微创手术方案研究

目的:研究肝内外胆管结石腹腔镜、十二指肠镜、胆道镜联合微创治疗方案。方法:回顾分析2000年10月至2009年10月为671例患者微创治疗肝内外胆管结石的临床资料。采用一镜Ⅰ方案治疗321例,一镜Ⅱ方案治疗12例;二镜Ⅰ方案治疗216例,二镜Ⅱ方案治疗67例,二镜Ⅲ方案治疗5例;三镜Ⅰ方案治疗46例,三镜Ⅱ方案治疗31例。结果:用内镜、腹腔镜联合微创治疗方案治疗肝内外胆管结石成功657例,总成功率97.9%(657/671),术后无严重并发症发生及死亡病例。结论:肝内外胆管结石临床表现多样,采用相应的内镜、腹腔镜联合微创治疗方案,拓宽了微创治疗范围,疗效满意。     

一氧化氮抑制兔关节软骨细胞II型胶原的合成

一氧化氮（NO）在骨关节炎和关节软骨代谢中具有重要的病理生理作用。为研究NO与关节软骨II型胶原的关系,我们在培养的兔关节软骨细胞中以药物刺激产生NO后,分别用ELISA及RT-PCR法测定II型胶原及前II型胶原α1链（COL2A1）mRNA表达量的变化。结果表明,0.2mM的硝普钠（SNP）可释放出大量NO,使软骨细胞II型胶原的含量减低,同时,RT-PCR法证实前II型胶原mRNA表达量也减少。100u/ml白细胞介素-1（IL-1）可刺激软骨细胞释放NO并使II型胶原量降低,其COL2A1mRNA表达量也减少。加用1mg/ml精氨酸甲酯（NAME,NO合酶抑制剂）后,则抑制了IL-1的作用,使NO产量下降,II型胶原含量部分恢复,COL2A1完全恢复。本试验证实了NO作为IL-1的下游分子抑制II型胶原的合成;其抑制作用是通过减少前II型胶原α1链mRNA表达量完成的。这在软骨细胞反分化过程中具有重要意义。     

Exploration of the association between serum uric acid and testosterone in adult males: NHANES 2011–2016

BackgroundPrevious studies have suggested that the possible relationship between serum uric acid (SUA) and testosterone. However, the results of previous studies are controversial and there is limited evidence examining the relationship between SUA and testosterone in a general US population of men. The objective of this study is to explore the correlation of SUA and testosterone among adult males from the US.MethodsData from the National Health and Nutrition Examination Survey 2011–2016 were used, including a total of 7,796 male participants aged 18 years or older and excluding those lacking serum testosterone and uric acid data. Clinical characteristics of the participants among different SUA groups and testosterone groups are compared. Univariate and multivariate linear regression analyses were applied to evaluate the association between SUA and testosterone.ResultsWe found an inverse association between SUA and testosterone after fully adjusted the potential confounding factors in general US adult males. In the multivariate linear regression analysis, we found that increasing age (estimate testosterone percent difference: −0.20% per year, P<0.01), uric acid (estimate testosterone percent difference: −4.40% per md/dL, P<0.01) and BMI (estimate testosterone percent difference: −2.86% per kg/m2, P<0.01) were associated with declining serum testosterone. This association remained significant in sensitivity analysis, while in the stratified analysis, above association was not significant in men with diabetes or aged 65 and over.ConclusionsSUA levels might be negatively associated with serum testosterone in adult males.     

腹腔镜保守手术联合药物防治输卵管妊娠后持续性异位妊娠的临床研究

目的:探讨米非司酮联合甲氨蝶呤用于防治输卵管妊娠腹腔镜保守手术后持续性异位妊娠(persistent ectopic pregnancy,PEP)的疗效。方法:为87例输卵管妊娠患者行腹腔镜保守手术,术前应用米非司酮50mg,2次/d,取出妊娠物后继续口服米非司酮50mg,2次/d,肌注甲氨蝶呤20mg,1次/d。结果:87例手术均获成功,术后无一例发生PEP。结论:术前用米非司酮,术后米非司酮联合甲氨蝶呤能预防输卵管妊娠腹腔镜保守手术后PEP的发生,患者痛苦少,无明显不良反应,具有临床应用价值。     

整形美容手术围术期的个性化护理

目的：讨论个性化护理在整形美容围术期护理中的必要性。方法：选取2012年4月以后于我院进行整形关容手术并接受个性化围术期护理的患者96例作为试验组,选取2012年4月前于我院进行整形美容手术并接受常规围术期护理的患者112例作为对照组,两组进行患者满意度和恢复时间的统计对比。结果：试验组满意率达92．71％,明显高于对照组的满意率75．89％。试验组平均恢复时间为（10．2±7．4）天,明显短于对照组平均恢复时间（18．9±8．2）天,两组数据均有显著性差异（p〈0．05）。结论：个性化的围术期护理可以提高整形美容手术护理质量,减少医疗纠纷的发生。     

儿童甲型流感合并川崎病的临床特征

目的分析儿童甲型流感合并川崎病（KD）的临床特征,增强对甲型流感合并川崎病的早期识别。 方法对首都医科大学附属北京地坛医院2018年1月1日至2019年12月31日收治的682例实验室确诊的甲型流感患儿资料进行回顾性分析,筛选甲型流感病毒感染合并川崎病儿童共14例（KD+甲流组）。选择同期就诊的符合纳入标准及排除标准的28例KD患儿为KD组,28例单纯甲型流感患儿为甲流组。比较KD+甲流组和KD组患儿临床表现、发热持续时间及冠状动脉病变发生率。比较KD+甲流组、KD组和甲流组患儿白细胞（WBC）、中性粒细胞百分比、淋巴细胞百分比、血小板、快速C-反应蛋白（CRP）、红细胞沉降率（ESR）、降钙素原（PCT）、血清淀粉样蛋白酶A（SSA）、白蛋白、转氨酶和心肌酶水平。 结果KD+甲流组患儿发热持续时间[（11.21 ± 3.36）d]较KD组[（6.29 ± 2.21）d]更长,差异有统计学意义（t = 5.81、P < 0.001）。KD+甲流组丙种球蛋白无反应型（IVIG）比例（42.9%）较KD组（14.3%）更高,差异有统计学意义（χ² = 4.1、P = 0.41）。KD+甲流组患儿WBC[（13.18 ± 4.39）× 10⁹/L]、ESR[（60.5 ± 15.82）mm/h]、CPR[55.5（17.56,61.0）g/L]、SSA[76.5（23.0,311.6）mg/L]和丙氨酸氨基转移酶（ALT）[49.5（23.1,78.0）U/L]均较KD组和甲流组升高,差异均有统计学意义（F = 27.92、P < 0.001,F = 47.97、P < 0.001,Z = 3.15、P = 0.007,Z = 4.36、P < 0.001,Z = 2.68、P = 0.027）。KD+甲流组较KD组患儿冠状动脉扩张发生概率更高（57.0% vs. 25.0%）,差异有统计学意义（χ² = 4.2、P = 0.041）。KD+甲流组患儿IVIG无反应型发生率较单纯KD组高（42.9% vs. 14.3%）,差异有统计学意义（χ² = 4.1、P = 0.041） 结论甲型流感合并KD患儿发热时间、明确诊断所需时间较长,其IVIG无反应型发生率更高,且血清SSA和ALT水平显著升高。     

心脾相关理论指导儿童神经精神类疾病的治疗

心主神藏脉,脾生营舍意。人体是有机的整体,在心神的统一调节下,脏腑经络、四肢百骸互调互用,共同完成人体正常的生命活动。水谷精气是维持基本生命活动的物质基础,作为生命活动的高级表现形式,神志活动必须依赖脾胃化生的气血濡养。现代医学研究发现肠道微生物能够诱发精神疾患,进一步佐证了心脾相关理论。小儿脾常不足,无论外感内伤、喂养不当皆损伤脾之运化,脾虚失运则化源不足,心失其濡养致神志不调;或脾胃失调,升降失司,湿聚成痰,痰浊随气机逆乱,上蒙清窍;或脾虚不健,痰湿内生,肝热内盛,痰为浊物,痰热互结,化风化热,随火上犯,易扰神明,蒙蔽清阳,扰乱神志。