Synthesis,AM<Subscript>1</Subscript> calculation,and biological studies of thiopyran-4-one and their azine derivatives

Some novel N(1)-arylidene-N(2)-cis-2,6-diphenyltetrahydrothiopyran-4-one azine derivatives were synthesised and their antibacterial activity against Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and antifungal activity against Candida-6, Candida-51, Aspergillus niger, and Aspergillus flavus were evaluated.     

散发性结直肠癌中SMAD4基因的突变

目的观察SMAD4基因在散发性结直肠癌中的突变，并探讨其对散发性结直肠癌发生发展的意义。方法对本院83例散发性结直肠癌患者，应用聚合酶链反应-单链构象多态性（PCR—SSCP）分析癌组织中SMAD4基因各外显子的突变情况，基因突变率与临床病理参数间采用，检验；应用多态性微卫星标记研究SMAD4基因所在18q21区的杂合性缺失。结果SMAD4基因在83例散发性结肠癌的患者中共有9例发生突变，平均突变率为10．8％。经Χ^2检验SMAD4基因突变率在肿瘤的Dukes分期及有无远处转移间差异有统计学意义（P〈0．05），而与肿瘤的分化程度、发生部位及患者的性别差异无统计学意义（P〉0．05）。18q21区的杂合性缺失率为62．71％，其中发生突变的9例均存在18q21区的杂合性缺失。结论SMAD4基因的突变可能介导了散发性结直肠癌后期的发生发展。     

CTLA4-Ig在异体移植方面的相关研究进展

CTLA4-Ig是一种融合免疫球蛋白,可以选择性地阻断CD28与B7的信号传导通路,导致T细胞免疫失能,诱导对特异性抗原的免疫耐受. 本文介绍了其生物学特性、免疫诱导耐受机制及在异体移植方面的研究进展和局限性,其在异体移植方面展示了良好的应用前景.     

Oct4在干细胞和肿瘤细胞中的表达

干细胞按分化能力分为全能性、多能性和专能性干细胞。Oct4是全能性或多能性干细胞标记物，在胚胎干细胞、胚胎生殖细胞和胚胎／生殖细胞肿瘤中阳性表达，但在分化的组织中均表达降低或消失，提示其在胚胎干细胞、生殖细胞和胚胎／生殖肿瘤中的表达与这些细胞的多能性分化特性密切相关。在成体组织和体细胞肿瘤中亦发现Oct4阳性表达。迄今为止，Oct4在成体组织中的表达主要局限于具有干细胞特性的细胞，如皮肤基底细胞层中的个别细胞、乳腺干细胞和胃干细胞等。本文简要综述Oct4在胚胎干／生殖细胞、成体和肿瘤组织中表达的研究现状，并对其在成体肿瘤中的表达及与肿瘤干细胞的关系进行讨论。     

重组人骨形态发生蛋白4基因腺相关病毒载体对兔骨髓基质干细胞生物学行为的影响

目的应用重组人骨形态发生蛋白4基因腺相关病毒载体(AAV-hBMP4)转染兔骨髓基质干细胞(BMSCs),观察其对BMSCs生物学行为的影响,从而为骨组织工程寻找理想的病毒载体及种子细胞。方法全骨髓法培养兔BMSCs,按感染复数(MOI)值不同设定为四组,分别转染兔BMSCs,观察病毒量对细胞形态的影响。选取影响最小的MOI值,进行后续实验。转染兔BMSCs,MTT法描记细胞生长曲线,观察AAV对细胞增殖活性的影响。以重组增强型绿色荧光蛋白基因的腺相关病毒载体(AAV-EGFP)为参照,行流式细胞仪检测,计算转染效率。AAV-hBMP4与对照病毒AAV-EGFP分别转染细胞,观察细胞形态,行碱性磷酸酶(ALP)染色、Von Kossa染色及ALP含量测定,观察成骨活性。兔肌袋实验观察异位成骨情况。结果MOI值为5×10~4 vg/cell时,AAV对细胞形态影响最小,以此值进行后续实验。AAV转染后,细胞增殖活性良好,转染效率为55％～65％。AAV-hBMP4转染后,细胞形态呈现典型的成骨改变,ALP染色及Von Kossa染色均出现成骨的特征性改变,而AAV-EGFP组无上述改变。细胞上清ALP含量测定显示,实验组ALP含量显著增高,与对照组比较差异有统计学意义(t=218．65,P＜0．01)。兔肌袋实验术后4周组织学检测可见大量钙盐沉积,矿化结节形成。结论AAV-hBMP4转染效率高,对BMSCs的增殖活性影响小,AAV-hBMP4转染的BMSCs可望成为组织工程化骨的理想种子细胞。     

Immunoadsorption in Severe C4d-Positive Acute Kidney Allograft Rejection: A Randomized Controlled Trial

Antibody-mediated rejection (AMR) frequently causes refractory graft dysfunction. This randomized controlled trial was designed to evaluate whether immunoadsorption (IA) is effective in the treatment of severe C4d-positive AMR. Ten out of 756 kidney allograft recipients were included. Patients were randomly assigned to IA with protein A (N = 5) or no such treatment (N = 5) with the option of IA rescue after 3 weeks. Enrolled recipients were subjected to tacrolimus conversion and, if indicated, 'anti-cellular' treatment. All IA-treated patients responded to treatment. One death unrelated to IA occurred after successful reversal of rejection. Four control subjects remained dialysis-dependent. With the exception of one patient who developed graft necrosis, non-responders were subjected to rescue IA, however, without success. Because of a high graft loss rate in the control group the study was terminated after a first interim analysis. Even though limited by small patient numbers, this trial suggests efficiency of IA in reversing severe AMR.     

P16INK4、PCNA在肺癌中表达的研究

目的 通过检测肺癌组织中p16、PCNA的表达，探讨其在肺癌发生发展中的作用及相互关系。方法 采用S—P免疫组化方法，检测83例肺癌标本及15例正常肺组织标本中P16^INK4和PCNA的表达。结果 P16^INK4和PCNA在正常肺组织和肺癌组织中表达的阳性率存在显著性差异。P16^INK4表达的阳性率在小细胞癌与非小细胞癌之间有显著性差异。PNTM分期高的肺癌标本P16^INK4及PCNA表达阳性率显著高于分期低的肺癌标本。不同分化程度的肺癌组织P16^INK4及PCNA表达阳性率有显著性差异。结论 肺癌的发生与P16^INK4的低表达和PCNA的高表达有关。而P16^INK4的表达与肺癌的组织学类型、分化程度、临床分期有关；PCNA的表达与肺癌的分化程度、临床分期有关。     

Histopathological characterisation of effects of the mouse Pax6 missense mutation on eye development

Mutations in PAX6/Pax6 lead to a variety of ocular anomalies in humans and mice. The aim of the study was to characterise the ocular abnormalities caused by the missense Pax6^Leca4 mutation and compare them to published observations on Pax6 alleles that are functionally equivalent to Pax6⁻ null alleles (such as Pax6^Sey and Pax6^Sey-Neu) and human inherited eye diseases. Ocular features of homozygous Pax6^Leca4/Leca4 and heterozygous Pax6^Leca4/+ embryos at E12.5-E18.5, heterozygous Pax6^Leca4/+ young mice at P18 and heterozygous Pax6^Leca4/+ adults at 12 weeks were analysed histologically with their wild-type Pax6^+/+ littermates. Homozygous Pax6^Leca4/Leca4 fetuses died perinatally with no eyes although an optic cup rudiment with pigmented cells developed. Pax6^Leca4/+ mice were microphthalmic and a range of other severe ocular phenotypes affected both the anterior and the posterior segments. In contrast to Pax6^+/−, the Pax6^Leca4/+ eyes had no goblet cells in the corneal epithelium, the iris was not hypoplastic and there was no lens-corneal epithelial plug. However, microphthalmia was more severe, corneal vascularisation occurred earlier (during fetal stages), pigmented cells were present in the vitreous and corneal stroma and the ciliary body was malformed or abnormal. These results show that, although Pax6^Leca4/+ lacked some eye abnormalities commonly seen in Pax6^Sey/+ and Pax6^Sey-Neu/+ eyes, in most respects their eyes were more severely affected. These differences probably reflect both differences between the Pax6^Leca4 and the Pax6^Sey-Neu mutations and differences in modifier gene expression in different genetic backgrounds. The presence of pigmented cells in the cornea is a novel observation. Some Pax6^Leca4/+ ocular abnormalities were similar to those present in human Peters' anomaly and persistent hyperplastic primary vitreous (PHPV) so Pax6^Leca4/+ mice provide a useful model for some inherited eye diseases.     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.