肝癌组织IFITM3蛋白表达水平及其与肝细胞癌患者手术切除术后肝内肿瘤复发的相关性分析*

目的 探讨肝细胞癌（HCC）组织干扰素诱导跨膜蛋白 3（IFITM3）表达水平及其临床意义。方法 在我院接受根治性手术切除治疗的43例HCC患者,术中取癌组织和癌旁肝组织,分别采用Western blot法和免疫组化法检测组织IFITM3蛋白表达情况,比较肝内肿瘤复发与未复发患者癌组织IFITM3表达的差异。结果 经Western blot法检测肝癌组织IFITM3表达水平为（1.2386±0.1901）,显著高于癌旁组织的（0.9496±0.0995,t=8.832,P=0.000）;免疫组化法检测显示肝癌组织IFITM3蛋白阳性率为72.1%（31/43）,明显高于癌旁组织的14.0%（6/43,x²=29.647,P=0.000）;中分化肝癌组织IFITM3蛋白阳性率为90.9%（10/11）,低分化肝癌组织为95.2%（20/21）,均明显高于高分化组的9.1%（1/11）（x²=14.727, P=0.000;x²=23.748,P=0.000）;术后复发组癌组织IFITM3蛋白阳性率为81.0%（17/21）,未复发组为22.7%（5/22）,两者比较差异具有统计学意义（x²=14.578,P=0.000）。结论 HCC组织IFITM3蛋白呈高表达,且肝癌分化越差,IFITM3表达也越强,并可能与术后肿瘤复发有关。     

热处理对磁性附着体固位力的影响

目的:研究热处理对磁性附着体固位力的影响。方法:磁性附着体Magfit EX 400W型、Magfit EX 600 W型和Magfit EX 800W型各10个试件,通过模具固定在万能力学试验机的测试台上,测试其固位力,然后将磁性附着体经过水浴热处理,再次进行固位力测试。采用SPSS11.0软件包对数据进行统计学分析。结果:磁性附着体Magfit EX400W型、Magfit EX 600W型和Magfit EX 800W型的初始固位力测量值分别为(1.64±0.11)N、(2.67±0.19)N和(3.02±0.25)N;经热处理后,其固位力测量值分别为(1.58±0.12)N、(2.65±0.14)N和(3.02±0.24)N。热处理前、后,其固位力无显著差异(P>0.05)。结论:磁性附着体的磁体部分可进行水浴热处理以减少单体,而其固位力无显著改变。     

致敏受体排斥异基因供体骨髓细胞的实验研究

目的 建立致敏动物模型,研究致敏对异基因骨髓细胞植入的影响及机制.方法 将C57 BL/6小鼠脾细胞经尾静脉注射到BALB/c小鼠体内建立致敏动物模型,应用二抗结合实验及补体依赖细胞毒性反应检测血清抗体.以非致敏或致敏BALB/c小鼠为受鼠,经照射预处理后予以1 ×10 7C57BL/6供鼠骨髓细胞.移植后于不同时间点(2、12和48 h)分离受鼠外周血、脾脏及骨髓等细胞,检测供鼠细胞在致敏受鼠体内各组织的分布.移植后记录各组受鼠的生存情况,监测造血重建与骨髓恢复情况.体外分离非致敏或致敏受鼠的血清及脾细胞,与异基因骨髓细胞相孵育,通过免疫实验计算细胞毒性指数.结果 二抗结合实验和补体依赖细胞毒性反应均证实致敏受鼠血清中含有高滴度的供鼠反应性抗体.骨髓移植归巢实验结果表明,与非致敏组相比,异基因骨髓细胞在致敏受鼠的外周血、脾脏及股骨的分布均明显减少.生存分析结果发现非致敏组小鼠于照射后能长期存活,而致敏组小鼠于照射后12～15 d全部死亡.移植后第14天,非致敏组受鼠外周血白细胞和股骨骨髓细胞计数分别为(3240±300)×106/L和(396±27)×106/股骨,而致敏组受鼠外周血白细胞和股骨骨髓细胞计数分别为(320±80)×106/L和(6±2)×106/股骨,两组差异有统计学意义(P＜0.01).移植后第7天,供鼠细胞在非致敏组和致敏组骨髓所占的百分比分别为(48.07±4.70)％和(0.77±0.11)％,两者差异有统计学意义(P＜0.01).体外通过补体依赖细胞毒性反应实验、细胞毒性淋巴细胞的杀伤作用和抗体依赖细胞介导细胞毒性作用实验表明,致敏组受鼠的细胞毒性指数均明显高于非致敏组.结论成功建立脾细胞输注致敏的小鼠动物模型,致敏受体完全排斥异基因供体骨髓细胞,作用机制与免疫损伤途径有关.     

Application of sustained delivery microsphere of cyclosporine A for preventing posterior capsular opacification in rabbits

AIM: To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes after cataract extraction.METHODS: Twenty New Zealand white rabbits accepted cataract extraction plus intraocular lens implantation and their left eyes were intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid (PLGA) as a carrier and their right eyes were injected with empty MS. The changes in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA concentration in aqueous humor were examined postoperatively and all the eyes were enucleated 3 months after surgery for histopathological and morphological examination with light microscopy and electron microscopy.RESULTS:Conjunctival hyperemia, corneal edema, intraocular pressure and anterior chamber response of experimental and control eyes were similar, while PCO in CsA-MS injected eyes was greatly improved compared with that in control eyes. Posterior capsules in CsA-MS injected eyes were smooth and lens epithelial cells (LEC) did not proliferate significantly (P>0.05), while LEC in posterior capsule of control eyes had different degrees of proliferation and cortical regeneration. LEC in CsA-MS injected eyes were not functionally active and underwent apoptosis, whereas LEC in control eyes were functionally active (F-test, P=0.025). In addition, the corneal ultrastructure showed no differences between CsA-MS and MS injected eyes.CONCLUSION: CsA-MS has high bioavailability in rabbit eyes and could inhibit postoperative PCO occurrence and development during the study period, suggesting that CsA-MS may be a promising, effective and safe administration route to prevent PCO in clinic.     

Beyond peroxisome proliferator-activated receptor gamma signaling: the multi-facets of the antitumor effect of thiazolidinediones

Certain members of the thiazolidinedione (TZD) family of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, such as troglitazone and ciglitazone, exhibit antitumor activities; however, the underlying mechanism remains inconclusive. Substantial evidence suggests that the antiproliferative effect of these TZD members in cancer cells is independent of PPARgamma activation. To discern the role of PPARgamma in the antitumor effects of TZDs, we have synthesized PPARgamma-inactive TZD analogs which, although devoid of PPARgamma activity, retain the ability to induce apoptosis with a potency equal to that of their parental TZDs in cancer cell lines with varying PPARgamma expression status. Mechanistic studies from this and other laboratories have further suggested that troglitazone and ciglitazone mediate antiproliferative effects through a complexity of PPARgamma-independent mechanisms. Evidence indicates that troglitazone and ciglitazone block BH3 domain-mediated interactions between the anti apoptotic Bcl-2 (B-cell leukemia/lymphoma 2) members Bcl-2/Bcl-xL and proapoptotic Bcl-2 members. Moreover, these TZDs facilitate the degradation of cyclin D1 and caspase-8-related FADD-like IL-l-converting enzyme (FLICE)-inhibitory protein through proteasome-mediated proteolysis, and down-regulate the gene expression of prostate-specific antigen gene expression by inhibiting androgen activation of the androgen response elements in the promoter region. More importantly, dissociation of the effects of TZDs on apoptosis from their original pharmacological activity (i.e. PPARgamma activation) provides a molecular basis for the exploitation of these compounds to develop different types of molecularly targeted anticancer agents. These TZD-derived novel therapeutic agents, alone or in combination with other anticancer drugs, have translational relevance in fostering effective strategies for cancer treatment.     

佝偻病维生素D受体基因多态性与25-羟维生素D3相关性

目的：研究1~3岁佝偻病患儿中维生素D受体基因多态性FokⅠ位点与佝偻病相关性,初步探讨维生素D受体基因多态性FokⅠ位点在佝偻病发病中的作用。方法：病例组（佝偻病患儿）62例与对照组（正常健康儿童）60例,用ELISA方法检测血清25-羟维生素D3水平,比较两组之间血清25-羟维生素D3水平。用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测病例组和对照组维生素D受体基因多态性FokⅠ位点,比较两组之间基因型和等位基因分布频率。结果病例组血清25-羟维生素D3水平较对照组明显降低,差异有统计学意义（9.1±4.1 ng/mL vs 16.1±6.9 ng/mL;P＜0.05）。维生素D受体基因多态性FokⅠ位点病例组FF基因型明显高于对照组（53% vs 25%）,基因型分布频率差异有统计学意义（χ2=10.221,P＜0.05）,病例组F等位基因频率明显高于对照组（73% vs 57%）,等位基因分布频率差异有统计学意义（χ2=7.511,P＜0.05）。结论维生素D受体基因多态性FokⅠ位点与佝偻病有相关性,提示其在佝偻病遗传易感性方面起重要作用。［中国当代儿科杂志,2010,12（7）：544-546］     

Two new lignans from Mentha spicata L

Two new lignans named spicatolignan A (1) and spicatolignan B (2) have been isolated from the whole herbs of Mentha spicata L.     

eIF4A controls germline stem cell self-renewal by directly inhibiting BAM function in the Drosophila ovary

Stem cell self-renewal is controlled by concerted actions of extrinsic niche signals and intrinsic factors in a variety of systems. Drosophila ovarian germline stem cells (GSCs) have been one of the most productive systems for identifying the factors controlling self-renewal. The differentiation factor BAM is necessary and sufficient for GSC differentiation, but it still remains expressed in GSCs at low levels. However, it is unclear how its function is repressed in GSCs to maintain self-renewal. Here, we report the identification of the translation initiation factor eIF4A for its essential role in self-renewal by directly inactivating BAM function. eIF4A can physically interact with BAM in Drosophila S2 cells and yeast cells. eIF4A exhibits dosage-specific interactions with bam in the regulation of GSC differentiation. It is required intrinsically for controlling GSC self-renewal and proliferation but not survival. In addition, it is required for maintaining E-cadherin expression but not BMP signaling activity. Furthermore, BAM and BGCN together repress translation of E-cadherin through its 3′ UTR in S2 cells. Therefore, we propose that BAM functions as a translation repressor by interfering with translation initiation and eIF4A maintains self-renewal by inhibiting BAM function and promoting E-cadherin expression.