Network Meta-Analysis of Randomized Controlled Trials: Efficacy and Safety of UDCA-Based Therapies in Primary Biliary Cirrhosis

Major ursodeoxycholic acid (UDCA)-based therapies for primary biliary cirrhosis (PBC) include UDCA only, or combined with either methotrexate (MTX), corticosteroids (COT), colchicine (COC), or bezafibrate (BEF). As the optimum treatment regimen is unclear and warrants exploration, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse events (AE).PubMed, the Cochrane Library, and Scopus were searched for randomized controlled trials up to August 31, 2014. We estimated the hazard ratios (HRs) for MOLT and odds ratios (ORs) for AE. A sensitivity analysis based on the dose of UDCA was also executed.Thirty-one eligible articles were included. Compared with COT plus UDCA, UDCA (HR 0.38, 95% confidence interval [CI] 0.09–1.39), BEF plus UDCA (HR 0.29, 95% CI 0.02–4.83), COC plus UDCA (HR 0.39, 95% CI 0.07–2.25), MTX plus UDCA (HR 0.28, 95% CI 0.05–1.63), or OBS (HR 0.49, 95% CI 0.11–2.01) all provided an increased risk of MOLT. With respect to drug AE profile, although not differing appreciably, BEF plus UDCA was associated with more AEs compared with UDCA (OR 3.16, 95% CI 0.59–20.67), COT plus UDCA (OR 2.27, 95% CI 0.15–33.36), COC plus UDCA (OR 1.00, 95% CI 0.09–12.16), MTX plus UDCA (OR 2.03, 95% CI 0.23–17.82), or OBS (OR 3.00, 95% CI 0.53–20.75). The results of sensitivity analyses were highly consistent with previous analyses.COT plus UDCA was the optimal UDCA-based regimen for both MOLT and AEs. BEF plus UDCA was most likely to cause AEs, whereas monotherapy with UDCA and coadministriation of COT plus UDCA appeared to be associated with the fewest AEs for PBC treatment.     

TLR9在不同胎龄新生儿脐血中的表达变化

目的 通过观察早产儿不同胎龄Toll样受体9（TLR9）的表达，探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份，按胎龄分为4组，28~31周组，31~34周组，34~37周组，≥37周组，采用流式细胞术和实时荧光定量PCR方法，分别检测其TLR9的蛋白和mRNA表达情况，了解其与胎龄之间的关系，并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组，31~34周组，34~37周组，≥37周组分别为（15.93±6.23）%，（11.63±6.70）%，（13.66±6.88）%，（20.51±12.06）%；其在胎龄28~31周较高，至31~34周逐渐下降至最低，两组差异有统计学意义（P<0.05）；34~37周后TLR9阳性细胞率表达逐渐升高，至≥37周达最高，两胎龄组比较，差异具有统计学意义（P<0.05）。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关（r=0.273，P=0.006）。TLR9 mRNA表达在28~31周组，31~34周组，34~37周组，≥37周组分别为（4.95±3.44）%，（8.89±8.49）%，（13.91±10.92）%，（7.19±7.11）%；其在28~36周逐渐升高，与胎龄呈正相关（r=0.355，P< 0.001）。≥37周TLR9 mRNA表达量下降，该值虽高于28~31周，但差异无统计学意义（P>0.05）。相关性分析表明，同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关（r=-0.227，P=0.011）。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异，TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加，TLR9 mRNA在28~36周间随着胎龄的增加而增加。     

Mimengosides J and K: two new neuroprotective triterpenoids from the fruits of Buddleja lindleyana

Two new 11-methoxyl substituted triterpenoids, named as mimengosides J (1) and K (2), along with seven known compounds, were isolated from the fruits of Buddleja lindleyana. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the new ones were evaluated for protective effects against damage of SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium ion (MPP⁺) and the results indicated that those may be one of the candidate compositions of Buddleja lindleyana for the treatment of neurodegenerative disease.

     

前房注射卡波姆建立大鼠高眼压模型的观察

目的　前房注射卡波姆建立大鼠高眼压模型，观察卡波姆升眼压效果及对大鼠眼前节和视网膜的影响。方法　随机选取30只SD大鼠，注射前3 d早晚测量基线眼压。右眼定为实验眼，左眼定为对照眼，右眼放出房水后将30 μL的5 g·L^-1卡波姆混悬液注入前房，每日早10时、晚22时在大鼠清醒状态下测量眼压。每周进行双眼眼前节照相并对比。4周末处死26只大鼠（另4只持续观察眼压变化至注射后9周）并取双眼眼球行HE染色，观察实验眼与对照眼视网膜形态，对比视网膜厚度及房角形态。结果　注射前，实验眼白天和夜间眼压分别为（11.10±0.90）mmHg（1 kPa=7.5 mmHg）和（11.92±1.07）mmHg，对照眼分别为（11.22±1.07）mmHg和（11.76±1.08）mmHg；实验眼与对照眼相比，白天、夜间眼压差异均无统计学意义（均为 P＞0.05）；白天与夜间眼压相比，实验眼、对照眼差异均有统计学意义（均为P<0.05）。卡波姆在前房中呈现出弥散型和沉积型两种存在方式，弥散型和沉积型大鼠1周内眼压分别为（17.83±3.54）mmHg和（13.00±1.55）mmHg，两者相比差异具有统计学意义（P＜0.05）。注射后第1天至第19天，实验眼与对照眼白天眼压相比差异均具有统计学意义（均为P＜0.05）；注射后第1天至第27天，实验眼与对照眼夜间眼压相比差异均具有统计学意义（均为P＜0.05）。实验眼视网膜形态发生改变，注射后4周视网膜厚度为（254.70±21.80）μm，与对照眼的（346.73±24.63）μm相比，差异有统计学意义（P=0.00）。实验眼前房充满卡波姆及虹膜的混合成分，紧贴角膜内皮并延伸至房角，堵塞小梁网结构，正常虹膜形态消失；对照眼房角形态正常。结论　前房注射卡波姆建立大鼠高眼压模型，可维持高眼压4周以上，昼夜眼压差异较为明显，夜间眼压较白天更高，4周后视网膜出现高眼压损伤后的表现。     

细菌性阴道炎患者致病菌分布与耐药性分析

目的分析细菌性阴道炎患者主要致病菌分布及耐药状况,为临床治疗提供依据。方法回顾性分析2013年1月至2015年10月送检本院检验科的450例细菌性阴道炎患者的临床资料,将阴道分泌物标本分别进行细菌培养和PCR检测,比较两种方法检出的细菌性阴道炎患者主要致病菌分布,药敏试验观察主要致病菌的耐药状况。结果细菌培养法和PCR法检出的主要致病菌依次为金黄色葡萄球菌,凝固酶阴性葡萄球菌,大肠埃希菌,肺炎克雷伯菌等,比较差异具有统计学意义(P<0.05);药敏试验结果显示,G~+球菌对青霉素、红霉素耐药率较高,而对头孢唑啉、万古霉素的耐药率较低;G-杆菌对复方新诺明、庆大霉素的耐药率较高,而对青霉素、亚胺培南的耐药率较低。结论革兰氏阳性(G~+)球菌是细菌性阴道炎的主要致病菌;临床上应根据致病菌的耐药状况,慎重及合理使用抗生素,以降低细菌性阴道炎的发病率。     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

Association of genetic variants at MYP10 and MYP15 with high myopia in a Han Chinese population

Background: Previous genome-wide association study (GWAS) has revealed the association between MYP10 at 8p23 and MYP15 at 10q21.1 and high myopia (HM) in a French population. This study is managed to discover the connection between some single nucleotide polymorphism (located at MYP10 and MYP15) and Han Chinese HM.

Methods and Results: This case-control association study contained 1673 samples, including 869 ophthalmic patients and 804 controls. Twelve tag SNPs have been selected from the MYP10 and MYP15 loci and genotyped by SNaPshot method. Among 12 SNPs, rs4840437 and rs6989782 in TNKS gene were found significant association with HM. Carriers of rs4840437G allele and rs4840437GG genotype created a low risk of high myopia (P = .036, OR = 0.81, 95%CI = 0.71–0.93; P = .016, OR = 0.73, 95%CI = 0.56–0.96; respectively). Carriers of rs6989782T allele and rs6989782TT+CT genotype also had a decreased risk of high myopia (P = .048, OR = 0.82, 95%CI = 0.71–0.94; P = .006, OR = 0.74, 95%CI = 0.59–0.92; respectively). Other 10 SNPs displaced nonsignificant association with HM. Additionally, the risk haplotype AC and the protective haplotype GT, generated by two SNPs in TNKS, were considerably more likely to be association with HM (for AC, P = .002 and OR = 1.26; for GT, P = .027 and OR = 0.84).

Conclusions: Our results demonstrated that some heritable variants in the TNKS gene are associated with HM in the Han population. The possible functions of TNKS in the development and pathogenesis of hereditary high myopia still require further researches to identify.