Vitamin D-dependent rickets type I and type II

Two distinct hereditary defects, vitamin D-dependent rickets type I (VDDR I) and type II (VDDR II), have been recognized in vitamin D metabolism. VDDR I is suggested to be a deficiency of the renal 25-hydroxyvitamin D (25(OH)D)-1α-hydroxylase. Muscle weakness and rickets are the prominent clinical findings. A normal physiologic dose of 1α-hydroxyvitamin D₃ and 1,25-dihydroxyvitamin D₃ is sufficient to maintain remission of rickets in this disorder. VDDR II consists of a spectrum of intracellular vitamin D receptor (VDR) defects and is characterized by the early onset of severe rickets and associated alopecia. This can be attributed to mutations in the VDR gene. Massive doses of vitamin D analogs and calcium supplementation is usually required for the treatment; however, the response to therapy is sometimes variable.     

Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men

Experimental and human epidemiologic data suggest a protective rolefor vitamin D in large bowel cancer. To investigate this association, weconducted a nested case-control study within a Finnish clinical trial cohort.Cases (n = 146) were participants diagnosed with primary adenocarcinoma ofthe large bowel. Controls were matched (2:1) to cases on age, date ofbaseline blood draw, and study clinic. Prediagnostic serum levels of thevitamin D metabolites, 25-hydroxyvitamin D (25-OH D), and1,25-dihydroxyvitamin D (1,25-DIOHD) were used as primary exposure measures.The baseline geometric-mean serum level of 25-OH D was 11.6 percent lower incases than in controls (12.2 cf 13.8 ug/l, P = 0.01) while serum levels of1,25-DIOH D did not differ by case-control status. No association was seenbetween serum levels of 1,25-DIOH D and large bowel cancer risk. However, theestimated relative risk (RR) of large bowel cancer decreased with increasinglevel of serum 25-OH D and the associa tion was more pronounced for rectalcancer (55 cases; RR by quartile = 1.00, 0.93, 0.77, 0.37; trend P = 0.06).Neither exclusion of early cases nor multivariate adjustment for potentialconfounders materially altered these estimates. There was no evidence ofeffect modification by level of 1,25-dihydroxyvitamin D or with other knownrisk-factors for large bowel cancer.     

Low vitamin D status is associated with low cord blood levels of the immunosuppressive cytokine interleukin-10

The cytokine interleukin-10 (IL-10) plays a pivotal regulatory role in tolerizing exogenous antigens. Experimental data indicate that low cellular availability of the vitamin D hormone 1,25-dihydroxyvitamin D [1,25(OH)2D] results in a down-regulation of IL-10 concentrations. The tissue production of an adequate amount of 1,25(OH)2D depends on a high circulating 25-hydroxyvitamin D (25-OHD) level. The present study was thus aimed at evaluating the associations between season of birth, vitamin D status, and the allergy risk markers IL-10 and total immunoglobulin (IgE) in newborns. Cord blood was obtained from 49 infants born during the summer half year (mid-April to mid-October, geographic latitude 51 degrees N) and from 47 infants born during the winter half year (mid-October to mid-April, geographic latitude of 51 degrees N). Serum levels of 25-OHD were 99% higher, and IL-10 levels were 43% higher in the summer half year compared with the winter half year (p < 0.001 and p = 0.018). Moreover, the ratio of IL-10 to total IgE was 124% higher in the summer half year compared with the winter half year (p = 0.039). Serum levels of 25-OHD were correlated with IL-10 levels (r = +0.22; p < 0.05). Mothers' age, gestational ages, birth weights and serum 1,25(OH)2D levels did not differ between study groups. We conclude that the low vitamin D status of infants born in winter may at least in part adversely affect biomarkers of allergy risk.     

CD4^＋CD25^high Regulatory Cells in Peripheral Blood of NSCLC Patients

The proportion and changes of CD4 CD25high regulatory T cells (Trs) in peripheral blood of non-small cell lung cancer (NSCLC) patients were analyzed and their clinical significance explored. The peripheral blood was collected from 61 patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the blood samples were evaluated with the flow cytometry for lymphocyte subsets (CD3 , CD4 and CD8 ) and CD4 CD25high Tr cells. The results showed that the proportion of CD4 CD25high Tr cells in NSCLC group was significantly higher than in control group [(4.36±2.07) % vs (2.04±1.03) %, P<0.01]. The proportion of CD4 CD25 high Tr cells in late stage was higher than that in early stage [stages I II (2.26 0.6) %; stage III (3.28 1.38) %; stage IV (6.06±4.08) %] (P<0.05). Kaplan-Meier survival analysis revealed that the prognosis of the patients who had higher proportion of CD4 CD25high Tr cells in peripheral blood was worse (P=0.0026). In conclusion, the relative increase in CD4 CD25high Tr cells in peripheral blood may be related to im-munosuppression and tumor progression in patients with NSCLC. This finding suggests that CD4 CD25 high Tr cells in peripheral blood of NSCLC may be positive for prognosis analysis. The use of depletion of the CD4 CD25high Tr cell therapy to treat NSCLC patients may be an effective strategy.     

1α,25-二羟维生素D_3对患者PBMC分泌的IFN-α和IL-10水平的影响

目 的 探 讨 １α，２５－二羟 维生 素 Ｄ_３（１α，２５－（ＯＨ ）２Ｄ ）对 系 统性 红斑 狼 疮（ＳＬＥ）患 者 外周 血 单个 核 ３细 胞（ＰＢＭ Ｃ）分 泌的 白细 胞 介素 （ＩＬ）－１０ 和 干扰 素 （ＩＦＮ ）－α水平 的 影响 。方法 ２０ 例 ＳＬＥ 患 者和 １０ 名健 康 志愿者 ＰＢＭ Ｃ 的提 取 采 用 Ｆｉｃｏｌ密 度 梯 度 离 心 法 ，ＳＬＥ 组 和 对 照 组 在 不 加 或 加 入 １α，２５－（Ｏ Ｈ ）２Ｄ３ 的 情 况 下 孵 育 ７２ ｈ收 集培 养 上清 ，上 清液 ＩＬ－１０ 和 ＩＦＮ－α水平 检 测采 用酶 联 免疫 吸附 试 验（ＥＬＩＳＡ ）。结 果 与 正常 对 照组 相比 ，ＳＬＥ组 ＰＢＭ Ｃ 中 ＩＬ－１０ 和 ＩＦＮ－α水 平 明 显 增高 （Ｐ＜０．０１）。０．０１ ｍ ｏｌ／Ｌ １α，２５－（Ｏ Ｈ ）２Ｄ３ 的 加 入 明 显 抑 制 了 ＳＬＥ 组ＰＢＭ Ｃ 中 ＩＦＮ －α的 产 生 （Ｐ＜０．０１），增 加 了 ＳＬＥ 组 ＰＢＭ Ｃ 中 ＩＬ－１０ 的 产 生 （Ｐ＜０．０１），但 对 正 常 对 照 组 ＩＦＮ －α和ＩＬ－１０ 水平 无明 显 影响 。结 论 １α，２５－（ＯＨ ）２Ｄ 可 能 抑制 体外 培 养的 ＳＬＥ 患 者 ＰＢＭ Ｃ ＩＦＮ －α的产 生     

25G内定位联合微创巩膜外加压治疗孔源性视网膜脱离

目的：观察Resight非接触广角镜辅助下25G光纤内照明联合微创巩膜外加压治疗孔源性视网膜脱离的临床效果。

方法：回顾性分析2011-05/2015-03入院的视网膜脱离患者43例43眼,术前散瞳后前置镜、三面镜检查裂孔定位不明确,术中25G套管穿刺光纤内照明,Resight非接触广角镜下顶压查找裂孔,进行微创巩膜外加压。对所有患者在手术后第1wk,1、3、6mo各随访1次,采用手术前相同的设备和方法记录视力、眼压,观察视网膜复位和裂孔封闭情况。

结果：所有患者中,41例41眼一次性复位,复位率为95.3%。1例1眼患者视网膜未完全复位,视网膜下积液残留,加压嵴位置欠佳,再次巩膜外加压手术复位; 1例1眼发生增殖性玻璃体视网膜病变(PVR)形成裂孔,采取玻璃体视网膜手术后完全复位。

结论：对于术前检查裂孔不明确的视网膜脱离患者,采用25G内定位联合微创巩膜外加压术可以做到微创、定位准确,并可提高手术成功率。     

Bluetongue Virus Infection of Goats: Re-Emerged European Serotype 8 vs. Two Atypical Serotypes

In recent years, numerous atypical Bluetongue virus (BTV) strains have been discovered all around the world. Atypical BTV strains are phylogenetically distinct from the classical BTV serotypes 1–24 and differ in terms of several biological features. For the first time, the atypical strains BTV-25-GER2018 and BTV-33-MNG3/2016 as well as the re-emerged classical strain BTV-8-GER2018 were evaluated comparatively in a pathogenesis study in goats—the natural host of atypical BTV. A substantial number of in-contact animals were included in this study to detect potential contact transmissions of the virus. After infection, EDTA blood, ocular, nasal and oral swab samples as well as serum were collected regularly and were used for virological and serological analyses, respectively. Our study showed differences in the immunological reaction between the two atypical BTV strains (no group-specific antibody detection) and the classical BTV strain BTV-8-GER2018 (group-specific antibody detection). Furthermore, we observed an increase in the total WBC count (neutrophils and lymphocytes) in goats infected with the atypical BTV strains. No horizontal transmission was seen for all three strains. Our study suggests that the atypical BTVs used in the trial differ from classical BTVs in their immunopathogenesis. However, no evidence of direct contact transmission was found.     

加味五子衍宗方总黄酮对大鼠海马锥体细胞VGCC通道的影响

目的:探讨加味五子衍宗方总黄酮成分对Aβ_(25-35)作用后的大鼠海马CA1区锥体神经元电压门控钙通道电流的作用.方法:应用全细胞膜片钳技术记录海马神经元I_(Ca)电流,采用内向电流的幅度作为观察指标,观察模型药物及干预药物对其的作用.采用出生7 d的乳鼠取海马后制成脑片,选取立体感强、状态好的锥体细胞形成全细胞膜片钳记录,从-50 mV到+50 mV范围(步进为5 mV)一系列去极化电压脉冲刺激(脉冲宽度500 ms),以激发出电压依赖性的内向钙离子电流.记录电流后加入Aβ_(25-35)后,再加入总黄酮进行干预.结果:Aβ_(25-35)淀粉蛋白可以通过增强I_(Ca)可引起胞内钙超载,正常幅度平均为-(157.1±19.9)pA,Aβ_(25-35)作用后增大为-(323.2±23.4)pA,125,250,500 mg·L~(-1)的总黄酮作用之后,分别下降为-(257.9±31.6),-(196.4±29.8),-(169.3±34.0)pA.结论:引起胞内钙离子超载可能是Aβ_(25-35)产生神经毒性作用的机制之一,加味五子衍宗方总黄酮成分可通过抑制钙离子内流对神经元起一定保护作用.     

喘可治注射液对大鼠抗炎和免疫调节机制的研究

目的:探讨喘可治注射液治疗支气管哮喘(简称哮喘)的作用机制.方法:60只雄性Wistar大鼠随机分为正常组、模型组、地塞米松组(0.5 ml·kg-1 ·d-1,肌内注射),高、中、低剂量(10、5、2.5 ml·kg-1·d-1,腹腔注射)喘可治注射液组.以2％卵蛋白为激发液,雾化吸入致敏,建立哮喘模型.治疗后,大鼠肺叶经HE染色后行病理切片,采用酶联免疫吸附(ELISA)法分别测定大鼠外周血中白介素-4(IL-4)和γ-干扰素(IFN-γ)浓度,采用流式细胞仪测定大鼠外周血中CD4+ CD25+T调节细胞和CD3- CD161a+自然杀伤(NK)细胞占淋巴细胞的百分比.结果:各剂量喘可治注射液组大鼠肺叶局部炎症反应均较模型组轻,IL-4浓度均明显下降,与模型组相比差异有显著性(P＜0.01),但各治疗组间、治疗组和正常组间IL-4浓度无显著差异.各治疗组IFN-γ的浓度均较模型组有所上升,其中高剂量组上升最为明显,与模型组比较有显著差异(P＜0.01).高、中、低剂量喘可治注射液组CD4+ CD25+T调节细胞百分比均明显上升,与模型组相比有显著差异(P＜0.05).CD3- CD161.+ NK细胞的百分比各组间比较无显著性差异.结论:喘可治注射液可增加血中IL-4、IFN-γ浓度,及CD4+ CD25+T调节细胞含量,纠正免疫失衡,这可能是其治疗哮喘的机制之一.     

抗肿瘤有效成分20(R)-25-OCH3-原人参二醇的结晶法分离

目的 从25-OCH₃-原人参二醇（25-OCH₃-PPD）非消旋体混合物中分离得到抗肿瘤有效成分20(R)-25-OCH₃-PPD （AD-1）。方法 采用结晶法拆分25-OCH₃-PPD非消旋体混合物中的AD-1,并对所用溶剂的种类、用量及结晶温度等分离条件进行了优化,探讨溶剂的介电常数和25-OCH₃-PPD非消旋体混合物的S/R比例间的关系。结果 25-OCH₃-PPD非消旋体混合物（R：59.34%;S：38.35%）,在最优条件下,丙酮26 mL、4 ℃时,可以获得AD-1的产率与纯度分别为38.76%、97.83%。结论 溶剂的电解质范围在20.7左右,低饱和度的溶剂以及低温有利于AD-1的分离。