微球给药系统的工艺优化研究

目的 :阐述微球制备工艺中的优化技术。方法 :检索近年来国内外文献并进行整理和归纳。结果 :单因素设计、正交设计、均匀设计、因子设计是目前微球工艺中常用的优化方法。结论 :通过上述方法优化微球的制备工艺 ,可在一定条件下达到经济、高效的目的 ,更理想的优化技术尚有待研究     

三维CT评估发育性髋关节脱位的骨性形态学特征

目的:通过使用CT三维测量髋臼发育情况及髋臼对股骨头覆盖率对比性观察,整体反映髋臼发育情况。方法:①观察对象:选择2003-06/2005-04对41例发育性髋关节脱位患者55个髋关节。其中男12例,女29例;年龄18个月～6岁。患髋右侧23例,左侧32例,其中双侧12例。健康侧27髋。患儿家属均知情同意。②实验方法:所有患儿使用PQ6000型多层螺旋CT扫描,扫描数据进行骨组织三维重建。将测量数据制成图表,显示三维的髋臼发育情况,并量化表示髋臼的缺损情况。③实验评估:计算不同截面正常侧髋臼指数、中心边缘角(假设符合正态分布)的均数、标准差、分布范围及95%可信区间。观察发育性髋关节脱位术前术后骨骼形态学变化。分别在术前、术后测量患者患侧髋臼指数、中心边缘角和前倾角,测量值均分别与正常值进行对比。结果:患侧55个髋,健康侧27髋,均进入结果分析。①发育性髋关节脱位术前术后骨骼形态学变化:术前55侧发育性髋关节脱位髋关节脱位程度为,参照T"nnis分类方法,Ⅰ度5髋(9.1%),Ⅱ度11髋(20%),Ⅲ度32髋(58.2%),Ⅳ度7髋(12.7%)。术后患者均表现髋臼α角均>90°,头臼呈同心圆对位,Shenton线连续,股骨头较术前明显发育,原先未出现头骺的患者,出现头骺,但较正常仍偏小;髋臼口呈类圆形,髋臼边缘欠光滑,髋臼整体呈一定程度前倾。②术前术后髋臼指数、中心边缘角和前倾角变化对比:术后患者的髋臼指数和前倾角与正常对照组之间差异无显著性(P>0.05),术后患者的中心边缘角大于正常对照组[(33.4±2.6)°(29.1±2.0)°,P<0.01],术后患者的髋臼指数和前倾角测量值均小于术前(P<0.01)。结论:介绍了一种对髋臼形态测量的新方法,它能够全面反映髋臼的发育情况,不但增加了对中心边缘髋臼病理改变的认识程度,还为手术提供了精确的可信度较高的矫形设计方案。     

The epidemiology of hyperuricaemia and gout in Taiwan aborigines

To determine the prevalence of hyperuricaemia, gout and gout-related factors in Central Taiwan Atayal aborigines, 342 subjects over 18 yr old were interviewed and examined. A questionnaire was designed to screen for signs and symptoms of gout and gout-related risk factors. Serum uric acid, triglyceride and creatinine were measured in all subjects. The prevalence of hyperuricaemia was 41.4% and that of gout 11.7% in aborigines. The uric acid level was 7.9+/-1.7 mg/dl in males and 5.7+/-1.5 in females, and differed significantly under age 70 yr (P < 0.001). Significantly increased triglyceride, creatinine and alcoholism was found in gouty patients compared with non-gouty patients. In 40 cases with gout, 54% had tophi and 35% of their first- degree relatives had gout. The high prevalence of hyperuricaemia and gout in Taiwan Atayal aborigines, a significant family predisposition, increased creatinine level and alcoholism suggest multiple factors affecting the hyperuricaemia.      

Intestinal pseudo-obstruction as an initial presentation of systemic sclerosis in two children

Two children are reported in whom intestinal pseudo-obstruction was the initial manifestation of systemic sclerosis. Gastrointestinal symptoms and skin changes resolved or improved in both children following treatment with prednisone and penicillamine (case 1) or methotrexate (case 2), although radiological changes of the gastrointestinal tract persisted at 3 and 2 yr of follow-up, respectively.      

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Ultra‐deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V

Gln506-factor V (FV) was purified from plasma of an individual homozygous for an Arg506Gln mutation in FV that is associated with activated protein C (APC) resistance. Purified Gln506-FV, as well as Gln506-FVa generated by either thrombin or FXa, conveyed APC resistance to FV-deficient plasma in coagulation assays. Clotting assay studies also suggested that APC resistance does not involve any abnormality in FV-APC-cofactor activity. In purified reaction mixtures, Gln506-FVa in comparison to normal FVa showed reduced susceptibility to APC, because it was inactivated approximately 10-fold slower than normal Arg506-FVa. It was previously reported that inactivation of normal FVa by APC involves an initial cleavage at Arg506 followed by phospholipid- dependent cleavage at Arg306. Immunoblot and amino acid sequence analyses showed that the 102-kD heavy chain of Gln506-FVa was cleaved at Arg306 during inactivation by APC in a phospholipid-dependent reaction. This reduced but measurable susceptibility of Gln506-FVa to APC inactivation may help explain why APC resistance is a mild risk factor for thrombosis because APC can inactivate both normal FVa and variant Gln506-FVa. In summary, this study shows that purified Gln506- FV can account for APC resistance of plasma because Gln506-FVa, whether generated by thrombin or FXa, is relatively resistant to APC.