Fragile X mice: reduced long-term potentiation and N-Methyl-D-Aspartate receptor-mediated neurotransmission in dentate gyrus

Fragile X syndrome (FXS) is a monogenic mental retardation syndrome that frequently includes autism. The Fmr1-knockout (Fmr1-KO) mouse, like FXS-affected individuals, lacks the fragile X mental retardation protein (FMRP) and models autism as well as FXS. Limited human data and several mouse models have implicated the hippocampal dentate gyrus (DG) in autism. We therefore investigated whether the Fmr1-KO mouse exhibited functional changes in DG. We found diminished medial perforant path-granule cell long-term potentiation (LTP), complementing previous investigations of synaptic plasticity in Fmr1-KO demonstrating impaired LTP in CA1, neocortex, and amygdala and exaggerated long-term depression in CA1. We also found that peak amplitude of NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) was smaller in Fmr1-KO than control. AMPA receptor-mediated EPSCs were comparable in the two strains, yielding a lower NMDA/AMPA ratio in Fmr1-KO mice and suggesting one mechanism by which absent FMRP might contribute to diminished LTP. The clinical hallmarks of autism include both excessive adherence to patterns and impaired detection of socially important patterns. The DG has a putative role in pattern separation (for time, space, and features) that has been attributed to granule cell number, firing rates, adult neurogenesis, and even perforant path LTP. DG also contributes to pattern completion in CA3 via its mossy fiber efferents, whose terminals include abundant FMRP in "fragile X granules." Together with the present data, these observations suggest that DG is a candidate region for further investigation in autism and that the Fmr1-KO model may be particularly apt.     

Ubiquitin‐negative,eosinophilic neuronal cytoplasmic inclusions associated with stress granules and autophagy: An immunohistochemical investigation of two cases

Identification of the proteinaceous components of the pathological inclusions is an important step in understanding the associated disease mechanisms. We immunohistochemically examined two previously reported cases with eosinophilic neuronal cytoplasmic inclusions (NCIs) (case 1, Mori et al. Neuropathology 2010; 30: 648–53; case 2, Kojima et al. Acta Pathol Jpn 1990; 40: 785–91) using 67 antibodies against proteins related to cytoskeletal constituents, ubiquitin‐proteasome system, autophagy‐lysosome pathway and stress granule formation. Regional distribution pattern of eosinophilic NCIs in case 1 was substantially different from that in case 2. However, NCIs in both cases were immunonegative for ubiquitin and p62 and were immunopositive for stress granule markers as well as autophagy‐related proteins, including valosin‐containing protein. Considering that eukaryotic stress granules are cleared by autophagy and valosin‐containing protein function, our findings suggest that eosinophilic NCIs in the present two cases may represent the process of autophagic clearance of stress granules.     

Expression of reg protein in rat regenerating islets and its co-localization with insulin in the Beta cell secretory granules

Summary Regenerating islets can be induced by the administration of poly(ADP-ribose) synthetase inhibitors to 90% depancreatized rats. In screening a regenerating isletderived cDNA library, we previously isolated a novel gene, reg (regenerating gene), which encodes a 165-amino acid protein with a 21-amino acid signal sequence. In the present study, we have examined the expression and localization of reg protein in the regenerating islets by immunocytochemical techniques using a monoclonal antibody against a recombinant rat reg protein of 144 amino acids without the signal sequence. Light microscopy examination showed strong immunoreactivity for reg protein in the regenerating islets of the rats at two weeks and two months after the 90% pancreatectomy, whereas reg protein was almost undetectable in normal rat islets or in the islets of the rats one year after the pancreatectomy. Almost all the reg protein-positive cells were stained for insulin. By applying the immunogold technique at the ultrastructural level, it was demonstrated that both reg protein and insulin occur in the central granular core of the regenerating Beta cell secretory granules. These results suggest that reg protein is synthesized in and secreted from the regenerating Beta cells and that its expression is closely associated with Beta-cell regeneration.     

小儿止哮平喘颗粒对动物模型止咳化痰平喘作用的实验研究

目的观察小儿止哮平喘颗粒对动物模型的止咳化痰平喘作用。方法以咳嗽、喘憋潜伏期,酚红排泌为指标,观察小儿止哮平喘颗粒对小鼠氨水引咳模型及气管段酚红法、豚鼠整体动物药物引喘模型的影响。结果西药对照组、中浓度组、高浓度组引喘时间及跌倒时间与对照组比较差异均有统计学意义（P＜0．05）;对照组、低及中浓度组酚红浓度与高浓度组比较差异均有统计学意义（P＜0．05）。结论小儿止哮平喘颗粒对动物模型小鼠具有止咳化痰平喘作用。     

The clinical significance of eosinophils in the amniotic fluid in preterm labor

Objective.?White blood cells are not traditionally considered to be normally present in amniotic fluid. This study was conducted after the observation that a patient with preterm labor and intact membranes had eosinophils as a predominant cell in the amniotic fluid, and had an episode of asthma during the index pregnancy. The goal of this study was to determine whether women presenting with preterm labor with eosinophils in the amniotic fluid had a different outcome than those without eosinophils as the predominant white blood cell in the amniotic cavity.

Methods.?This retrospective case–control study included women who presented with preterm labor and intact membranes between 24 and 34 weeks of gestation. Patients underwent an amniocentesis shortly after admission for the assessment of the microbiologic status of the amniotic cavity and/or fetal lung maturity. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Cytologic studies included amniotic fluid white blood cell count and differential, which was performed on cytocentrifuged specimens. Patients with microbial invasion of the amniotic cavity and/or an amniotic fluid white blood cell count >20 cells/mm³ were excluded from the study. Cases were defined as women in whom the differential contained >20% of eosinophils. Controls were selected among women with an amniotic fluid eosinophil count ≤20% and matched for gestational age at amniocentesis. The analysis was conducted with non-parametric statistics.

Results.?The study population consisted of 10 cases and 50 controls. Gestational age and cervical dilatation at admission were similar in both groups. Cases had a lower gestational age at delivery than controls [34.6 weeks, inter-quartile range (IQR) 32–37.3 weeks vs. 38.0 weeks, IQR 35–40 weeks, respectively; p?=?0.018]. The prevalence of preterm delivery ≤35 weeks was higher among patients who had >20% eosinophils than in the control group [50% (5/10) vs. 18% (9/50), respectively; p?=?0.029]. Similar results were observed for delivery at <37 weeks [cases: 70% (7/10) vs. controls: 36% (18/50); p?=?0.046].

Conclusions.?Women with preterm labor and intact membranes who have a large proportion of eosinophils in the amniotic fluid are at an increased risk for spontaneous preterm delivery. These patients may have had an episode of preterm labor related to a type I hypersensitivity reaction.     

影响移植后的脂肪颗粒活性因素

目的观察碱性成纤维细胞生长因子（bFGF）、血管内皮细胞生长因子（VEGF）、表皮细胞生长因子（EGF）、胰岛素及自体真皮颗粒对培养及移植的脂肪颗粒活性的影响因素。方法通过对培养中的幼鼠脂肪细胞,分别添加bFGF、VEGF、EGF、胰岛素及自体真皮颗粒,四甲基偶氮唑盐（MTT）法测定各组脂肪细胞活性,分析其作用效果;通过对移植体的大体观察、质量测定、HE染色、微血管数量及免疫组织化学染色等,比较各组添加物对脂肪组织活性的影响。结果除真皮颗粒组及对照组外,各实验组在不同时间点的最佳脂肪细胞活性浓度基本一致,且其细胞活性均高于对照组（P〈0．05）。动物实验中对照组可见较大区域坏死灶、囊样脂肪池。实验组脂肪细胞大小不一,存在大量的小体积脂肪细胞;除胰岛素组外,各实验组移植物残余质量及各组微血管密度均明显高于对照组,但随移植时间的延长差异逐渐缩小。结论bFGF、VEGF、EGF及胰岛素均能不同程度提高脂肪细胞活性,bFGF、VEGF、EGF及自体真皮颗粒均能不同程度地提高脂肪颗粒移植后的移植物质量,改善脂肪组织的血运重建。     

参地颗粒对慢性肾炎脾肾亏虚证患者血清 VEGF、尿 EGF 的干预作用

目的：观察慢性肾小球肾炎（ CGN）脾肾亏虚证患者血清血管内皮生长因子（ VEGF）和尿表皮生长因子（EGF）的变化及参地颗粒的干预作用。方法：64例 CGN 脾肾亏虚证患者随机分为对照组和治疗组各32例,实际完成61例（对照组31例,治疗组30例）,并设正常组20例。治疗组口服参地颗粒,对照组口服氯沙坦钾片,疗程均为8周,观察治疗前后临床疗效、24 h 尿蛋白定量、尿红细胞计数、血清 VEGF 和尿 EGF 水平变化,并与正常组比较。结果：治疗组临床疾病总有效率和中医证候疗效总有效率均为86．67%,优于对照组的61．30%（P 〈0．05）;治疗组治疗后24 h 尿蛋白定量、尿红细胞计数均较治疗前降低（P 〈0．05）,而对照组治疗后24 h 尿蛋白定量较治疗前降低（P 〈0．05）,但尿红细胞计数降低不明显（P 〉0．05）;两组患者治疗前血清 VEGF 和尿 EGF 水平明显高于正常组（P 〈0．01）,治疗后两组血清 VEGF 和尿 EGF 水平均下降（P 〈0．05）,且治疗组优于对照组（P 〈0．05）。结论：CGN 脾肾亏虚证患者血清 VEGF、尿 EGF 水平上升,参地颗粒可显著降低患者血清 VEGF、尿 EGF 水平,降低中医证候积分,改善临床症状,其机制之一可能与其降低患者血清 VEGF、尿 EGF 水平有关。     

自体颗粒脂肪移植矫治颜面部凹陷

目的:探讨自体颗粒脂肪移植治疗颜面部凹陷的疗效。方法:肿胀麻醉下,利用注射器抽吸脂肪颗粒。过滤纯化后用脂肪抽吸针将脂肪颗粒注射在面部凹陷部位。结果:采用自体脂肪颗粒移植治疗颜面部凹陷20例,17例手术一次成功,另3例补充注射1次,效果均满意。结论:利用自体颗粒脂肪移植治疗颜面部凹陷,手术易行,创伤小,效果较好,值得推广。     

泽黄颗粒对糖尿病大鼠肾脏和尿液AQP2表达的调节效应

目的：探讨肾脏和尿液AQP2的表达与糖尿病肾病（DN）大鼠水液代谢异常关系及泽黄颗粒防治DN效应机制。方法：用高脂高糖饲料加小剂量STZ诱导DM大鼠模型,随机分为糖尿病模型组（DM组）、泽黄颗粒治疗组（Z组）和格列吡嗪对照组（G组）,正常对照组（N组）。于实验第12周末检测BG、HbA1c、Ccr、UAER及血液流变学指标;观察肾组织病理改变;运用Western-Blot、Real-Time PCR法检测肾脏AQP2蛋白及mRNA表达变化,并检测尿液内AQP2浓度的变化。结果：与DM组相比,Z组大鼠BG、HbA1c、UAER、全血黏度、血浆黏度、肾脏AQP2蛋白、AQP2 mRNA表达和尿液内AQP2浓度均明显下降（P〈0.05）,Ccr明显升高（P〈0.01）。与G组相比,Z组大鼠全血黏度、TG、TC水平明显降低（P〈0.05）。结论：泽黄颗粒可下调糖尿病大鼠肾脏和尿液AQP2的表达,这可能是其调节水液代谢的机制和防治DN的基础。     

葛根芩连汤配方颗粒与传统汤剂治疗2型糖尿病疗效比较

 目的 观察2型糖尿病患者应用葛根芩连汤配方颗粒与传统汤剂的疗效。方法 选取2017-01至2017-09入住唐山市中医医院的2型糖尿病160例,随机分为对照组(80例)、治疗组(80例)。两组均以盐酸二甲双胍缓释片为基础治疗,对照组配合使用葛根芩连汤,治疗组配合使用葛根芩连汤配方颗粒。治疗2个月后比较两组患者治疗前后临床症状和各指标的变化。结果 对照组和治疗组临床总有效率分别为86.25%和90.00%,治疗后,对照组和治疗组的空腹血糖、餐后2 h血糖、糖化血红蛋白及餐后C肽均显著降低(P<0.05),组间比较,空腹血糖和餐后2 h血糖差异有统计学意义(P<0.05)。结论 葛根芩连汤配方颗粒与传统汤剂均可以对2型糖尿病患者达到较好治疗效果,但葛根芩连汤配方颗粒在降低空腹血糖和餐后2 h血糖方面要优于传统汤剂,值得临床推广。