Ahmed青光眼引流阀植入术治疗玻璃体切除术后难治性青光眼

目的：评价Ahmed 青光眼阀植入术治疗玻璃体手术后继发性青光眼的临床疗效。

方法：回顾分析在我院眼科应用Ahmed青光眼阀植入术治疗玻璃体手术后继发性青光眼患者23例23眼。

结果：患者术后平均随访29±3.7mo,术前平均眼压48.79±7.12mmHg,手术后24mo时平均眼压23.28±10.53mmHg,与术前眼压相比明显降低,具有显著性统计学差异(P<0.05); 术后1mo时,手术成功率82.6%,随访12、24mo时手术成功率分别为65.2%、52.2%。

结论：采用Ahmed青光眼阀植入术治疗玻璃体手术后的继发性青光眼是比较有效和相对安全的治疗方法。     

低机械指数实时超声造影对肾良恶性肿瘤诊断的临床价值

目的：评估低机械指数实时超声造影在肾局灶性病变诊断中的临床价值。方法32例肾占位性病变患者进行超声造影检查,观察造影增强的时间、增强水平,将病灶分为富血供、乏血供和无血供。手术切除肾实质肿瘤经病理诊断证实其良恶性,与增强CT检查结果进行对比分析。结果肾透明细胞癌富血供为91%,乏血供为9%;乳头状肾细胞癌富血供为50%,乏血供为50%;嫌色细胞癌乏血供为100%,浸润性尿路上皮癌富血供为100%,血管平滑肌脂肪瘤富血供为100%。32例患者中,3例增强CT未能显示增强,而超声造影显示所有病灶均可见造影剂进入,对>5 cm病灶的血流量检测差异有统计学意义（P<0.05）。结论超声造影能很好地反应肿瘤的血供情况,与增强CT相比,对乏血供肾肿瘤的检测更具敏感性。     

Relative Bioavailability of Rifampicin in Four Chinese Fixed-dose Combinations Compared with Rifampicin in Free Combinations

Background:

Decreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure. Therefore, we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B, C, and D) used in China, compared with RFP in free combinations of these drugs (reference), in healthy volunteers.

Methods:

Eighteen and twenty healthy Chinese male volunteers participated in two open-label, randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study, respectively. The washout period between treatments was 7 days. Bioequivalence was assessed based on 90% confidence intervals, according to two one-sided t-tests. All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China, Shanghai, China).

Results:

Mean pharmacokinetic parameter values of RFP obtained for formulations A, B, C, and D products were 11.42 ± 3.41 μg/ml, 7.86 ± 5.78 μg/ml, 13.05 ± 6.80 μg/ml, and 16.18 ± 3.87 μg/ml, respectively, for peak plasma concentration (C_max), 91.43 ± 30.82 μg·h⁻¹ ·ml⁻¹, 55.49 ± 37.58 μg·h⁻¹ ·ml⁻¹, 96.50 ± 47.24 μg·h⁻¹ ·ml⁻¹, 101.47 ± 33.07 μg·h⁻¹ ·ml⁻¹, respectively, for area under the concentration-time curve (AUC_{0−24 h}).

Conclusions:

Although the concentrations of RFP for formulations A, C, and D were within the reported acceptable therapeutic range, only formulation A was bioequivalent to the reference product. The three two-drug FDCs (formulations B, C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451).     

粪菌移植在儿科应用的研究进展北大核心CSCD

粪菌移植(FMT)可将健康人粪便中的各种肠道微生物、代谢产物和天然抗菌物质等移植到受者肠道内,可重建肠道菌群平衡、修复肠黏膜屏障、控制炎症反应、调节机体免疫,是治疗肠道菌群失调所致疾病的新方法。FMT治疗儿童复发性艰难梭菌感染已写入复发性艰难梭菌感染的诊疗指南。FMT治疗儿童炎症性肠病、孤独症谱系障碍的有效性及安全性较好。     

中电导钙激活钾通道渊IKCa通道冤在HeLa细胞中的表达及其对细胞增殖的影响

目的：本研究旨在探讨中电导钙激活钾通道(IKCa通道)在宫颈癌HeLa细胞中的表达及其对细胞增殖的作用。方法：以宫颈癌HeLa细胞株为研究对象,构建包含IKCa通道特异性shRNA片段的pGenesil-IK质粒;运用荧光定量PCR和Western Blotting比较pGenesil-IK质粒转染干预前后宫颈癌HeLa细胞中IKCa通道基因和蛋白表达水平的变化;运用WST-1检测技术和流式细胞术观察转染干扰质粒后对HeLa细胞增殖的影响。结果：[1]转染pGenesil-IK干扰质粒后HeLa细胞IKCa通道mRNA及蛋白表达水平较对照组显著降低(P<0.05)。[2]转染pGenesil-IK1干扰质粒显著抑制HeLa细胞增殖和细胞周期(P<0.05)。结论：宫颈癌HeLa细胞上有较高的IKCa通道表达,抑制宫颈癌HeLa细胞株IKCa通道表达能有效抑制癌细胞增殖,提示IKCa通道可能是宫颈癌的治疗靶点之一。     

GPC5基因在肺腺癌细胞系中的功能研究

目的 研究GPC5基因在肺腺癌细胞系中的表达情况及其对肺腺癌细胞系生物学行为的影响.方法 采用逆转录PCR (RT-PCR)、实时定量PCR (qRT-PCR)以及Western blot分析肺腺癌细胞系中GPC5基因mRNA及蛋白表达情况;构建GPC5过表达载体及干扰载体,通过转染构建GPC5过表达细胞系及GPC5沉默细胞系;利用CCK-8法分析肺腺癌细胞系生长情况;通过流式细胞术检测肺腺癌细胞系的周期及凋亡变化.结果 检测了GPC5基因在4株肺腺癌细胞系(A549、H1299、H358和H1975)和1株肺正常上皮细胞系(HBE)中的mRNA表达情况,发现与HBE细胞系相比,GPC5基因在A549细胞系中呈低表达,在H1299细胞系中高表达,同时蛋白检测结果与mRNA水平一致;A549细胞中过表达GPC5基因可抑制细胞生长,引起细胞周期阻滞;在H1299细胞中干扰GPC5基因表达促进细胞生长,促进细胞周期;在过表达和干扰细胞模型中均未发现GPC5基因对细胞凋亡的显著影响.结论 GPC5基因可以对肺腺癌细胞系的生物学行为产生影响,可能是肺腺癌的抑癌基因.     

Suppressor of cytokine signaling 3 A+930-->G (rs4969168) polymorphism is associated with apolipoprotein A1 and low-density lipoprotein cholesterol

This study aimed to detect the association of the suppressor of cytokine signaling 3 gene (SOCS3) A+930-->G (rs4969168) single nucleotide polymorphism (SNP) and environmental factors with serum lipid levels in the Han and Mulao populations. Genotyping of the SOCS3 A+930-->G (rs4969168) SNP was performed in 752 of Han and 690 of Mulao participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype and allele frequencies were significantly different between the Han and Mulao populations (GG, 57.71% vs. 51.16%, GA, 36.97% vs. 41.16%, AA, 5.32% vs. 7.68%, P = 0.023; G, 76.20% vs. 71.74%, A, 23.80% vs. 28.26%; P = 0.006; respectively). Serum apolipoprotein (Apo) A1 levels in Han were different among the genotypes (P < 0.05). Subgroup analyses showed that the levels of ApoA1 in Han females, and ApoA1 and low-density lipoprotein cholesterol (LDL-C) in Mulao males were different among the genotypes (P < 0.05). Serum lipid parameters were also associated with several environmental factors in both ethnic groups (P < 0.05-0.001). These findings suggest that there may be a racial/ethnic- and/or sex-specific association between the SOCS3 A+930-->G (rs4969168) SNP and serum lipid parameters in some populations.     

Inhibiting effect of antisense oligonucleotides phosphorthioate on gene expression of TIMP-1 in rat liver fibrosis

AIM To observe the inhibition of antisenseoligonucleotides(asON)phosphorthioate to thetissue inhibitors metalloproteinase-1(TIMP-1)gene and protein expression in the liver tissue ofimmunologically induced hepatic fibrosis rats.The possibility of reversing hepatic fibrosisthrough gene therapy was observed.METHODS Human serum albumin(HSA)wasused to attack rats,as hepatic fibrosis model,inwhich asONs were used to block the gene andprotein expressing TIMP-1.According to theanalysis of modulator,structure protein,codingseries of TIMP-1 genome,we designed fourdifferent asONs.These asONs were injected intothe hepatic fibrosis models through coccygealvein.The results was observed by RT-PCR formeasuring TIMP-1 mRNA expression,immunohistochemistry and in situ hybridizationfor collagen Ⅰ,Ⅲ,special staining of collagenfiber,and electron microscopic examination.RESULTS Hepatic fibrosis could last within 363days in our modified model.The expressinglevel of TiMP-1 was high during hepatic fibrosisprocess.It has been proved by theimmunohistochemical and the electronmicroscopic examination that the asON phosphorthioate of TIMP-1 could exactly expressin vivo,The effect of colchicine wasdemonstrated to inhibit the expressing level ofmRNA and the content of collagen Ⅰ,Ⅲ in theliver of experimental hepatic fibrosis rats,However,the electron microscopy research andthe pathologic grading of hepatic fibrosisshowed that there was no significant differencebetween the treatment group and the modelgroup(P>0.05).CONCLUSION The experimental rat model ofhepatic fibrosis is one of the preferable modelsto estimate the curative effect of anti-hepaticfibrosis drugs.The asON phosphorthioate ofTIMP-1 could block the gene and proteinexpression of TIMP-1 in the liver of experimentalhepatic fibrosis rats at the mRNA level.It ispossible to reverse hepatic fibrosis,and it isexpected to study a new drug of anti-hepaticfibrosis on the genetic level.Colchicine has verylimited therapeutic effect on hepatic fibrosis,furthermore,its toxicity and side effects areobvious.     

In Vitro Functional Assessment of 22 Newly Identified CYP2D6 Allelic Variants in the Chinese Population

Cytochrome P450 2D6 (CYP2D6) is one of the most widely investigated CYPs related to genetic polymorphisms and is responsible for one‐quarter of the currently used clinical drugs. We previously detected 22 novel, non‐synonymous, mutated sites in the Chinese population, but nothing is known about the functional effects of these mutations in terms of specific CYP2D6 substrates. In this study, wild‐type CYP2D6, two common allelic variants and 22 newly reported CYP2D6 isoforms were transiently expressed in 293FT cells, and the enzymatic activities of these variants were systematically assessed using dextromethorphan and bufuralol as the probing substrates. Consequently, 19 and 21 allelic variants were found to exhibit significantly decreased enzymatic activities for dextromethorphan and bufuralol, respectively. Of 22 novel CYP2D6 variants, six allelic isoforms (CYP2D6.89, CYP2D6.92, CYP2D6.93, CYP2D6.96, E215K and R440C) exhibited absent or extremely reduced metabolic activities compared with those observed for the wild‐type enzyme. Our in vitro functional data can be useful for CYP2D6 phenotype prediction and provide valuable information for the study of clinical impact of these newly found CYP2D6 variants in China.