Enteric anendocrinosis attributable to a novel Neurogenin-3 variant

Congenital diarrhea and enteropathies (CODEs) are a group of monogenic disorders that often present with severe diarrhea in the first weeks of life. Enteric anendocrinosis (EA), an extremely rare cause of CODE, is characterized by a marked reduction of intestinal enteroendocrine cells (EC). EA is associated with recessively inherited variants in Neurogenin-3 (NEUROG3) gene. Here we investigate a case of a male infant who presented with mysterious severe malabsorptive diarrhea since birth. Thorough clinical assessments and laboratory tests were successful to exclude the majority of differential diagnosis categories. However, the patient's diagnosis was not established until the genetic test using whole-exome sequencing (WES) was performed. We identified a novel homozygous missense disease-causing variant (DCV) in NEUROG3 (c.413C>G, p.Thr138Arg). Moreover, molecular dynamic simulation analysis showed that (p.Thr138Arg) led to a global change of the NEUROG3 orientation affecting its DNA binding capacity. To the best of our knowledge, this is the first time to apply WES to reach a differential diagnosis of patients with CODEs. Our study not only expands our knowledge about NEUROG3 variants and their clinical consequences but also proves that WES is a very effective tool for the diagnosis of CODEs. This might be of value in early diagnosis of diseases and prenatal CODEs detection.     

电针对沙鼠急性脑缺血再灌注后神经原损伤的保护作用

本实验利用沙鼠急性脑缺血再灌注模型，研究电针对脑缺血及再灌注各期脑电活动的影响及组织病理学的改变。结果表明：缺血１０ｍｌｎ，脑电幅度受到严重抑制，甚至变平坦，总功率大大下降，再灌注后总功率难以恢复，在１２０ｍｉｎ时仅恢复到缺血前的２７．３９±１１．３１％，以后即不再进一步恢复，电针组动物缺血１０ｍｉｎ再灌注后，脑电的恢复明显比对照组快，１２０ｍｉｎ时恢复至缺血前的７１．４５±１６．４６％（Ｐ＜０．０１），２４０ｍｉｎ时继续恢复至缺血前的７５．２７±１８．４３％。同时电针能明显减轻缺血１０ｍｉｎ后再灌注２４小时的神经原缺血性损伤。结果提示：电针对急性脑缺血引起的神经原损伤具有保护作用，并能促进脑功能的恢复。     

The instability of membrane markers expressed by human monocytes and macrophages in culture

Surface markers were tested on freshly isolated human monocytes and following their in vitro maturation to macrophages. The markers tested were HLA-DR antigens, receptors for the Fc of IgG and complement as well as membrane markers defined by monoclonal antibodies. The results revealed a dynamic expression of some of the markers on monocytes which was influenced by several variables. The expression of the markers was modulated by the presence of different sera, by treatment with lymphokines and interferon and following the in vitro maturation of monocytes to macrophages. The most unstable marker was found to be the HLA-DR, which was modulated by all these variables. The 63D3 was affected by different sera and culture supernatant, as well as following the maturation of monocytes to macrophages, but not by lymphokines and interferon. One of the markers, the Mac 120, was found to be relatively stable and did not change significantly following the maturation of monocytes to macrophages. The Fc and complement receptors were also stable in their expression under these conditions, but were probably partially blocked in the presence of human serum. These results indicated that at least some of the heterogeneity related to the monocyte population was probably not due to the occurrence of stable subsets of cells, but rather to reversible changes in marker expression.     

β Chain deficiency in three patients with dysfunctional C8 molecules

Structural and functional studies were performed on a dysfunctional C8 molecule present in the serum of two siblings and an unrelated individual. The C8 in these three sera exhibited a pattern of partial immunologic identity with C8 in normal serum but was devoid of functional activity. The C8 was immunoprecipitated from the three sera and from a control serum with an antihuman C8 antiserum and analyzed by SDS-PAGE using highly purified human C8 as a reference. A selective absence of a band of 62,000 mol. wt was observed in the immunoprecipitates from the sera containing dysfunctional C8. Experiments performed with the purified α-γ and γ subunits showed that the hemolytic activity of the C8 deficient sera could be reconstituted by the addition of the β chain but not the α-γ dimer. Binding of the dysfunctional C8 to C$\text{567}$ was excluded by the following observations: (1) EAC 1–7 treated with the C8 deficient sera and then washed could not be lysed after the addition of the β subunit and C9; and (2) the abnormal molecules did not interfere with the consumption of normal C8 by the soluble complex SC5b-7.     

针刀与电针对照治疗神经根型颈椎病疗效观察

目的：验证针刀治疗神经根型颈椎病疗效并分析治疗机理。方法：选择病程半月以上的神经根型颈椎病160例,随机分为针刀组80例,对照组80例。针刀组针对颈椎问盘退变、椎间孔狭窄、斜角肌慢性损伤等不同病理,采用针刀治疗;对照组采用电针治疗作对照,2周后统计疗效。结果：针刀纽80例,痊愈7例,显效22例,好转42例,无效9例,总有效率88．75％。针灸对照组80例,痊愈4例,显效5例,好转49例,无效22例,总有效率72．50％。在相同疗程内,针刀组疗效显著优于针刺对照组（P〈0．01）。结论：治疗神经根型颈椎病,针刀组相对于针灸对照组,针对性强、疗程短、疗效更佳。     

一种改进的遗传算法及其在喜树碱和三唑醇类化合物的QSAR研究中的应用

目的 :考察改进的遗传算法 (GA)在QSAR中的变量优选能力。方法 :用自编程的改进的GA选择变量 ,PLS方法拟合模型 ,对 7,9,10 ,11取代的喜树碱衍生物和取代苯环双三氮唑醇类抗真菌化合物两个数据组进行QSAR研究。结果 :对两个数据组分别得到了一批较常规QSAR分析结果更优的方程。结论 :GA作为一种启发式搜索算法以其高效快速、并行性的特点尤其适合于QSAR研究 ,但因其仅以统计指标为进化依据 ,故需对其实施必要的预处理及结果检查     

合欢皮皂苷物质的分离、纯化及其抗血管活性的研究

目的 分离合欢皮中的皂苷物质,并评价其对人脐静脉内皮细胞(EA.hy926)增殖的影响.方法 以细胞活性为指标,依次采用D101大孔树脂、硅胶柱、反相C18色谱柱从合欢皮正丁醇相中分离得到活性组分H5;采用UPLC-TOF-MS分析,确定此组分中所含的主要成分.结果 组分H5中主要皂苷类物质为julibroside J5、julibroside J8、isomer of J5和isomer of J8,总含量为79.15％,且对EA.hy926细胞的增殖具有抑制作用(IC50=7.82 ±1.59 μg·mL-1).结论 成功分离得到了具有抗血管新生作用的合欢皮皂苷物质.     

电针“丰隆”穴对高脂血症大鼠的调控及其作用机制

目的:探讨电针“丰隆”穴治疗高脂血症的作用机制.方法:将40只健康SD大鼠随机分为正常对照组、高脂饲料组、高脂饲料治疗组、高脂+普通饲料组及高脂+普通饲料治疗组,每组8只.两治疗组电针“丰隆”穴,每日1次.治疗30 d后,检测各组大鼠血脂水平,即总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇( LDL-C)、高密度脂蛋白胆固醇(HDL-C)含量,实时定量聚合酶链反应( RT-PCR)及免疫印迹法(Western Blotting)检测各组大鼠肝脏组织中ATP结合盒转运子A1(ABCA1)、过氧化体增殖物激活型受体α(PPARα)、肝X受体α(LXR-α)和视黄酸X受体α( RXR-α)基因表达的变化.结果:高脂饲料组大鼠血浆TC、LDL-C较正常对照组明显上升(均P＜0.01);高脂+普通饲料组大鼠血浆TC、LDL-C与高脂饲料组比较明显下降(均P＜0.01),较正常对照组仍升高明显(均P＜0.01);电针“丰隆”穴治疗后,大鼠血浆TC、LDL-C明显下降(均P＜0.01);TG、HDL-C变化不明显(均P＞0.05).与正常对照组比较,高脂饲料组大鼠肝脏ABCA1、PPARα、LXR-α及RXR-α的mRNA和蛋白含量均显著降低(均P＜0.01);高脂+普通饲料组大鼠肝脏ABCA1、PPARα、LXR-α及RXR-α的mRNA和蛋白含量与高脂饲料组比较有所上升,较正常对照组仍降低明显(均P＜0.01);电针治疗后,大鼠肝脏组织中ABCA1、PPARα、LXR-α及RXR-α的mRNA和蛋白含量均显著升高(均P＜0.05).结论:电针“丰隆”穴能够明显下调高脂血症大鼠血脂中TC、LDL-C水平,上调肝脏ABCA1、PPARα、LXR-α、RXR-α的基因表达,从而促进由其介导的胆固醇逆转运,对高脂血症具有一定的治疗作用.     

化瘀祛痰方药对H2O2诱导人脐带静脉内皮细胞氧化应激保护作用的研究

目的探讨化瘀祛痰方药含药血清对H2O2诱导人脐带静脉内皮细胞（EA.hy926细胞）氧化应激的保护作用。方法体外培养EA.hy926细胞,随机分为5组。正常对照组：仅用DMEM完全培养基培养,不加任何药物;H2O2刺激组：培养液中加入终浓度为300μmol/L H2O2;含药血清低剂量组、含药血清中剂量组、含药血清高剂量组分别使用5%、10%、20%含药血清预处理24 h后加入终浓度为300μmol/L H2O2。各组细胞培养24 h后进行各项指标测定。采用MTT法检测细胞活性,黄嘌呤氧化酶法测定超氧化物歧化酶（SOD）活力,2,4-二硝基苯肼显色法检测乳酸脱氢酶（LDH）活性,硫代巴比妥酸法测定丙二醛（MDA）含量,硝酸还原酶法检测一氧化氮（NO）活性。采用细胞活性氧检测试剂盒,通过荧光显微镜观察细胞内活性氧水平的变化。结果与正常对照组相比,H2O2刺激后细胞活性明显下降,SOD、NO活性显著降低,而LDH活性、MDA含量则显著增加,活性氧水平明显升高。10%、20%化瘀祛痰方药含药血清可显著提高细胞存活率及SOD、NO活性,而显著降低LDH活性、MDA含量及活性氧水平。结论化瘀祛痰方药对H2O2诱导EA.hy926细胞氧化应激具有保护作用,这可能是其抗动脉粥样硬化的作用机制之一。     

早期电针干预对SAMP8小鼠学习记忆能力和海马磷酸化Tau蛋白水平的影响

目的:探讨早期电针"百会""大椎""肾俞"穴对快速老化小鼠(SAMP8小鼠)学习记忆能力和海马磷酸化Tau蛋白表达的影响,为临床电针治疗阿尔茨海默病(AD)时间点的选择提供参考。方法:将36只3月龄SAMP8小鼠随机分为模型组、3月龄电针组、9月龄电针组,每组12只;以12只同龄正常老化SAMR1小鼠作为空白对照组。3月龄电针组及9月龄电针组分别于小鼠3月龄及9月龄时予电针"百会""大椎""肾俞"穴治疗(连续波,2 Hz,1.5～2 mA),20 min/次,每日1次,8 d为一疗程,疗程间隔2 d,共治疗3个疗程。每组小鼠在水迷宫检测学习记忆能力结束后统一于10月龄取材;免疫组织化学法、免疫蛋白印迹法(Western blot)检测小鼠海马磷酸化Tau蛋白的表达,实时荧光定量PCR法检测小鼠海马Tau mRNA表达。结果:与空白对照组比较,模型组小鼠逃避潜伏期明显延长(P<0.01),原平台象限停留时间较短,跨越平台次数减少(P<0.01),海马磷酸化Tau蛋白及Tau mRNA表达较高(P<0.01);与模型组比较,3月龄电针组及9月龄电针组小鼠逃避潜伏期缩短(P...