芝麻素对大鼠骨质疏松症的作用研究

目的 在大鼠模型中探讨芝麻素对骨质结构改变的作用及对骨钙素和I型胶原表达的影响。方法 建立去卵巢(ovariectomized, OVX)大鼠模型,给予芝麻素(sesamin, 80 mg/kg)灌胃作为干预措施并同时建立对照组。应用显微计算机断层扫描(Micro-CT)对大鼠股骨进行分析,并应用免疫组化及免疫荧光检测大鼠股骨中的骨钙素(osteocalcin, OCN)水平以及I型胶原表达。结果 本实验研究条件下,与OVX组相比,OVX+S骨密度(bone mineral density, BMD)增加、小梁间距(trabecular spacing, Tb.Sp)降低,同时,干预组骨钙素和I型胶原表达显著增强(P<0.05)。结论 芝麻素可有效促进去卵巢大鼠骨结构重塑,对大鼠骨质疏松症有积极的治疗和预防作用。     

山茱萸新苷Ⅰ对成骨细胞的增殖及成骨分化的影响

目的基于Wnt信号通路及内质网应激研究山茱萸新苷Ⅰ对大鼠原代成骨细胞的增殖及成骨分化的影响。方法提取原代成骨细胞,CKK8实验检测在药物浓度下山茱萸新苷Ⅰ对成骨细胞增殖的影响;碱性磷酸酶(alkaline phosphatase,ALP)染色检测不同浓度山茱萸新苷Ⅰ干预下成骨细胞ALP的活性情况; Real-time PCR检测Wnt2、β-catenin、BMP2、OPG、NOX4、PERK基因mRNA的表达; Western blot检测Wnt2、β-catenin、PDI、CHOP和BIP蛋白表达量。结果 CKK8实验及ALP染色表明山茱萸新苷Ⅰ对成骨细胞增殖及分化有一定影响,不同浓度山茱萸新苷Ⅰ干预下成骨细胞出现不同程度的增殖;与空白对照组相比,山茱萸新苷Ⅰ组的Wnt2、BMP2、β-catenin、OPG、NOX4的mRNA表达水平显著升高(P0. 01),而PERK明显降低(P0. 01)。与空白对照组相比,山茱萸新苷Ⅰ组的成骨细胞Wnt2、β-catenin、PDI蛋白表达量显著升高(P0. 01),CHOP表达亦有轻微上升,但不明显(P0. 05),而BIP的蛋白表达水平明显降低(P0. 01)。结论山茱萸新苷Ⅰ浓度为1 mmol/mL时在促进成骨细胞的增殖分化的作用上表现最佳,其能显著升高成骨细胞Wnt2、BMP2、β-catenin、OPG和NOX4的mRNA表达水平,而降低PERK的mRNA表达水平,升高Wnt2、β-catenin、PDI的蛋白表达量,降低BIP的表达量,在山茱萸新苷Ⅰ的干预下,Wnt信号通路及内质网应激途径对成骨活动的发生发展起着重要作用。     

不同年龄段健康人群骨代谢指标Ⅰ型前胶原N末端前肽的特点分析

目的确定健康中国人群中Ⅰ型前胶原N末端前肽(type Ⅰ procollagen propeptide,PⅠNP)的年龄和性别特异性参考区间。方法采用骨密度测定法测定骨密度正常的中国人群599份血清,建立参考区间。年龄组分为20～29岁、30～39岁、40～49岁、50～59岁、≥60岁。结果在划分中国男性和女性人群的年龄组时,不同年龄组的总PINP存在显著差异。在男性人群中,PⅠNP水平随着年龄的增长而降低,然后在中年后保持稳定。在女性人群中,与男性人群相似的下降趋势与50～59岁年龄组的急剧增加相似。结论本研究初步建立了具有正常骨密度的中国男性和女性人群与年龄相关的PⅠNP参考区间。     

防己黄芪汤HPLC-UV/ELSD指纹图谱研究

目的建立防己黄芪汤(FHD)HPLC-UV/ELSD指纹图谱分析方法,归属和指认复方中主要特征峰。方法采用HPLC法,色谱柱为Venusil MP C18(250 mm×4.6 mm,5μm);流动相为乙腈-0.1%甲酸水溶液(梯度洗脱),紫外检测器:检测波长为254 nm,蒸发光散射检测器:漂移管温度为110℃,空气体积流量为3 L/min;进样量10μL;体积流量为1 m L/min。运用《中药色谱指纹图谱相似度评价系统(2008版)》对10批FHD指纹图谱进行相似度计算,并对共有峰进行药材归属及成分指认。结果建立了FHD指纹图谱;10批FHD指纹图谱相似度良好;在FHD HPLC-UV指纹图谱中标定了20个共有峰,其中3、6~8号峰来自防己,1、2、4、5、9、12、13、16、20号峰来自黄芪,10、11、13、14、15、17~19号峰来自甘草。在FHD HPLC-ELSD指纹图谱中标定了16个共有峰,其中1’~3’号峰来自防己,4’、7’、9’、11’、13’、15’、16’号峰来自黄芪,5’~8’、10’、12’、14’号峰来自甘草。通过进样对照品、复方以及在复方中加对照品的方式指认出复方中9个成分,分别为9/4’号峰(毛蕊异黄酮葡萄糖苷)、11/6’号峰(甘草苷)、13/7’号峰(芒柄花苷)、15号峰(甘草素)、16/9’号峰(毛蕊异黄酮)、20/15’号峰(芒柄花素),11’号峰(黄芪甲苷)、13’号峰(黄芪皂苷II)、16’号峰(黄芪皂苷I)。结论首次建立了FHD HPLC-UV/ELSD指纹图谱分析方法,该法操作简单、准确,精密度、重复性好,可用于表征FHD中化学成分信息,为FHD质量控制提供了可靠的科学依据。     

Stable impulsive zone model predictive control for type 1 diabetic patients based on a long-term model

In this work, the problem of regulating blood glucose (glycemia) in type I diabetic patients is studied by means of an impulsive zone model predictive control (iZMPC), which bases its predictions on a novel long-term glucose-insulin model. Taking advantage of the impulsive version of the model—which features real-life properties of diabetes patients that some other popular models do not—the given control guarantees the stability under moderate-to-severe plant-model mismatch and disturbances. Long-term scenarios—including meals and physiological parameter variations—are simulated and the results are satisfactory as every hyperglycemic and hypoglycemic episodes are suitably controlled.     

自体软骨细胞联合Ⅰ型胶原治疗剥脱性膝骨软骨炎

目的探讨自体软骨细胞联合Ⅰ型胶原蛋白三维支架治疗膝关节剥脱性骨软骨炎的疗效。 方法选取近5年来在青岛市黄岛区中心医院采用自体软骨细胞联合Ⅰ型胶原蛋白三维支架治疗膝关节剥脱性骨软骨炎的患者12例,用单因素方差分析评估术前与术后6个月、12个月国际膝关节文献委员会(IKDC)膝关节评估表、Lysholm膝关节功能评分。术后12个月磁共振成像(MRI)评估软骨修复情况。 结果12例患者术后6个月、12个月的IKDC评分分别为(83.7±5.6)、(91.7±3.7),Lysholm评分分别为(87.5±5.2)、(93.6±2.1),均较术前IKDC评分(53.9±6.7)(F＝158.877)、Lysholm评分(59.1±7.2)(F＝104.258)明显改善(均为P<0.05);每2个时间点之间的IKDC评分、Lysholm评分,差异均具有统计学意义(P<0.05)。术后12个月MRI检查显示,所有患者的移植软骨恢复良好,均未出现移植物脱落或局部水肿。术后随访期内,所有患者均未出现膝关节感染。 结论自体软骨细胞联合Ⅰ型胶原蛋白三维支架能有效治疗膝关节剥脱性骨软骨炎。     

补体因子Ⅰ缺乏患儿1例分子与临床特征研究

目的探讨1例补体因子Ⅰ(complement factorⅠ,CFⅠ)缺乏患儿CFⅠ基因突变、蛋白表达水平、免疫表型及临床特征。方法对1例临床表现为反复头痛伴发热,脑电图及脑脊液检查异常的疑似无菌性脑膜脑炎患儿行免疫学筛查,免疫相关基因新一代测序及ELISA检测CFⅠ蛋白表达。结果该患儿补体C3水平明显降低,抗体水平及外周血精细免疫分型正常,经基因分析发现CFⅠ基因第5号内含子拼接位点发生纯合772+1G>T突变,患儿父母均为该突变的携带者。ELISA检测示患儿CFⅠ蛋白表达量与正常对照相比明显降低。结论通过临床、免疫学筛查、基因分析及蛋白检测,确诊1例发生CFⅠ基因突变的补体缺乏患儿,为此前未见报道的新发突变。对反复发热伴头痛,脑膜脑炎诊断不明确及C3降低的患儿应考虑补体缺乏并进行补体相关基因分析以最终确诊。     

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients.     

Antiphospholipid antibodies in epilepsy: A systematic review and meta-analysis

Background

Autoimmunity is believed to play an important causative role in the pathogenesis of epilepsy. There are evidences for the presence of autoantibodies in patients with epilepsy. To date, many studies have assessed the presence of antiphospholipid antibodies (aPLs) in epilepsy patients, though the relationship has been inconclusive.

Fine‐scale geographic clustering pattern of human T‐cell leukemia virus type 1 infection among blood donors in Kyushu‐Okinawa,Japan

Human T‐cell leukemia virus type I (HTLV‐1) infection is endemic in Japan, particularly clustered in the southwestern district, Kyushu‐Okinawa, which consists of eight prefectures that further consist of 274 municipalities. However, no information is available about the fine‐scale distribution of HTLV‐1 infection within Kyushu‐Okinawa. To assess the municipal‐level distribution of people with HTLV‐1 infection in Kyushu‐Okinawa, we performed a cross‐sectional study using a fine‐scale geographic information system map based on HTLV‐1 screening test results from the Japanese Red Cross database from September 2012 to February 2014. Of the 881 871 (646 914 male, 234 957 female) screened blood donors, 981 were seropositive for HTLV‐1 by confirmatory test. The seroprevalence was 0.11% (95% confidence interval [CI] 0.10%‐0.12%) for all, 0.094% (95% CI, 0.09%‐0.10%) for male, and 0.16% (95% CI, 0.14%‐0.18%) for female individuals. The sex‐ and age‐specific HTLV‐1 seroprevalence varied significantly across municipalities; particularly, the seroprevalence among women aged 50 years was significantly higher than that of men in both the mainland of Kyushu‐Okinawa and the satellite island, in all of which the seroprevalence of HTLV‐1 was more than 1.2%. These results show that, even in the Kyushu‐Okinawa district, there are endemic clusters of HTLV‐1 in small areas. This suggests that public health education programs are needed to eliminate new HTLV‐1 infection in these areas.