芽胞杆菌治疗幽门螺杆菌感染疗效的Meta分析

目的评价芽胞杆菌(Bacillus)联合根除标准疗法治疗幽门螺杆菌(H.pylori)感染的有效性。方法收集关于芽胞杆菌联合治疗H.pylori感染的随机对照试验(RCT),检索时限为建库至2020年5月;对符合纳入标准的研究进行偏倚风险评价及Meta分析。结果最终纳入14个RCT。Meta分析结果显示芽胞杆菌联合治疗能提高H.pylori根除率(ITT分析:RR=1.13,95%CI:1.08~1.18,P0.001;PP分析:RR=1.13,95%CI:1.09~1.17,P0.001),降低不良反应发生率(RR=0.42,95%CI:0.35~0.50,P0.001)。根据亚组分析结果,芽胞杆菌联合H.pylori两种常规治疗方案[三联疗法(RR=1.22,95%CI:1.10~1.36,P=0.003),铋剂四联疗法(RR=1.11,95%CI:1.07~1.15,P0.001)]以及芽胞杆菌联合H.pylori常规治疗的两种疗程[10 d(RR=1.14,95%CI:1.04~1.24,P=0.006),14 d(RR=1.14,95%CI:1.07~1.21,P0.001)]均提高H.pylori根除率;而亚组分析芽胞杆菌种类中,地衣芽胞杆菌差异有统计学意义(RR=1.14,95%CI:1.10~1.19,P0.001),凝结芽胞杆菌与蜡样芽胞杆菌需扩大样本量进一步统计分析。结论芽胞杆菌联合疗法能有利于提高H.pylori根除率,并降低总不良反应的发生,相对于标准疗法有一定的意义。     

母乳喂养与婴儿HCV感染关系的研究

目的：探讨母乳喂养与婴儿HCV感染的关系。方法：采用Meta分析方法对中国生物医学数据库、雏普数据库、方正数据库、PUBMED数据库和MEDLINE报道的文献进行分析。纳入标准依据Abdolmaleky HM方法。用RevMan4．2软件对纳入文献计算特异OR值。x^2test检验OR值异质性。联系的强度采用0R值进行评价。结果：共有120篇文献,37篇为综述,只有6篇文献符合纳入标准。Meta分析OR值为0．60（95％CI=0．22-1．60）,证实母乳喂养与婴儿HCV感染无关。结论：母乳喂养不是婴儿感染HCV的危险因素。     

预防造影剂肾病水化时机选择的Meta分析

目的 评价预防造影剂肾病(CIN)不同口服水化时机选择的效果,为降低CIN发生率提供依据.方法 运用计算机检索PubMed、EMbase、The Cochrane Library、中国知网、万方数据库、维普数据库以及中国生物医学文献数据库关于口服水化预防造影剂肾病的随机对照试验(RCT),检索时间从建库至2020年9月...     

Meta‐Analysis of Diagnostic Test Accuracy Studies with Multiple Thresholds using Survival Methods

Diagnostic tests play an important role in clinical practice. The objective of a diagnostic test accuracy study is to compare an experimental diagnostic test with a reference standard. The majority of these studies dichotomize test results into two categories: negative and positive. But often the underlying test results may be categorized into more than two, ordered, categories. This article concerns the situation where multiple studies have evaluated the same diagnostic test with the same multiple thresholds in a population of non‐diseased and diseased individuals. Recently, bivariate meta‐analysis has been proposed for the pooling of sensitivity and specificity, which are likely to be negatively correlated within studies. These ideas have been extended to the situation of diagnostic tests with multiple thresholds, leading to a multinomial model with multivariate normal between‐study variation. This approach is efficient, but computer‐intensive and its convergence is highly dependent on starting values. Moreover, monotonicity of the sensitivities/specificities for increasing thresholds is not guaranteed. Here, we propose a Poisson‐correlated gamma frailty model, previously applied to a seemingly quite different situation, meta‐analysis of paired survival curves. Since the approach is based on hazards, it guarantees monotonicity of the sensitivities/specificities for increasing thresholds. The approach is less efficient than the multinomial/normal approach. On the other hand, the Poisson‐correlated gamma frailty model makes no assumptions on the relationship between sensitivity and specificity, gives consistent results, appears to be quite robust against different between‐study variation models, and is computationally very fast and reliable with regard to the overall sensitivities/specificities.     

Light Activation of Rhodopsin: Insights from Molecular Dynamics Simulations Guided by Solid-State NMR Distance Restraints

Structural restraints provided by solid-state NMR measurements of the metarhodopsin II intermediate are combined with molecular dynamics simulations to help visualize structural changes in the light activation of rhodopsin. Since the timescale for the formation of the metarhodopsin II intermediate (> 1 ms) is beyond that readily accessible by molecular dynamics, we use NMR distance restraints derived from ¹³C dipolar recoupling measurements to guide the simulations. The simulations yield a working model for how photoisomerization of the 11-cis retinylidene chromophore bound within the interior of rhodopsin is coupled to transmembrane helix motion and receptor activation. The mechanism of activation that emerges is that multiple switches on the extracellular (or intradiscal) side of rhodopsin trigger structural changes that converge to disrupt the ionic lock between helices H3 and H6 on the intracellular side of the receptor.     

Constitutive activity of a UV cone opsin

Vertebrate visual pigment proteins contain a conserved carboxylic acid residue in the third transmembrane helix. In rhodopsin, Glu113 serves as a counterion to the positively charged protonated Schiff base formed by 11-cis retinal attached to Lys296. Activation involves breaking of this ion pair. In UV cone pigments, the retinyl Schiff base is unprotonated, and hence such a salt bridge is not present; yet the pigment is inactive in the dark. Mutation of Glu108, which corresponds to rhodopsin's Glu113, to Gln yields a pigment that remains inactive in the dark. The apoproteins of both the wild-type and mutant, however, are constitutively active with the mutant being of significantly higher activity. Thus, one important role for preserving the negatively charged glutamate in the third helix of UV pigments is to maintain a less active opsin in a manner similar to rhodopsin. Ligand binding itself in the absence of a salt bridge is sufficient for deactivation.     

Agonist-induced conformational changes in bovine rhodopsin: insight into activation of G-protein-coupled receptors

Activation of G-protein-coupled receptors (GPCRs) is initiated by conformational changes in the transmembrane (TM) helices and the intra- and extracellular loops induced by ligand binding. Understanding the conformational changes in GPCRs leading to activation is imperative in deciphering the role of these receptors in the pathology of diseases. Since the crystal structures of activated GPCRs are not yet available, computational methods and biophysical techniques have been used to predict the structures of GPCR active states. We have recently applied the computational method LITiCon to understand the ligand-induced conformational changes in β₂-adrenergic receptor by ligands of varied efficacies. Here we report a study of the conformational changes associated with the activation of bovine rhodopsin for which the crystal structure of the inactive state is known. Starting from the inactive (dark) state, we have predicted the TM conformational changes that are induced by the isomerization of 11-cis retinal to all-trans retinal leading to the fully activated state, metarhodopsin II. The predicted active state of rhodopsin satisfies all of the 30 known experimental distance constraints. The predicted model also correlates well with the experimentally observed conformational switches in rhodopsin and other class A GPCRs, namely, the breaking of the ionic lock between R135^3.50 at the intracellular end of TM3 (part of the DRY motif) and E247^6.30 on TM6, and the rotamer toggle switch on W265^6.48 on TM6. We observe that the toggling of the W265^6.48 rotamer modulates the bend angle of TM6 around the conserved proline. The rotamer toggling is facilitated by the formation of a water wire connecting S298^7.45, W265^6.48 and H211^5.46. As a result, the intracellular ends of TMs 5 and 6 move outward from the protein core, causing large conformational changes at the cytoplasmic interface. The predicted outward movements of TM5 and TM6 are in agreement with the recently published crystal structure of opsin, which is proposed to be close to the active-state structure. In the predicted active state, several residues in the intracellular loops, such as R69, V139^3.54, T229, Q237, Q239, S240, T243 and V250^6.33, become more water exposed compared to the inactive state. These residues may be involved in mediating the conformational signal from the receptor to the G protein. From mutagenesis studies, some of these residues, such as V139^3.54, T229 and V250^6.33, are already implicated in G-protein activation. The predicted active state also leads to the formation of new stabilizing interhelical hydrogen-bond contacts, such as those between W265^6.48 and H211^5.46 and E122^3.37 and C167^4.56. These hydrogen-bond contacts serve as potential conformational switches offering new opportunities for future experimental investigations. The calculated retinal binding energy surface shows that binding of an agonist makes the receptor dynamic and flexible and accessible to many conformations, while binding of an inverse agonist traps the receptor in the inactive state and makes the other conformations inaccessible.     

Déjà vu in proteomics. A hit parade of repeatedly identified differentially expressed proteins

After reading many 2-DE-based articles featuring lists of the differentially expressed proteins, one starts experiencing a disturbing déjà vu. The same proteins seem to predominate regardless of the experiment, tissue or species. To quantify the occurrence of individual differentially expressed proteins in 2-DE experiment reports, we compiled the identities of differentially expressed proteins identified in human, mouse, and rat tissues published in three recent volumes of Proteomics and calculated the appearance of the most predominant proteins in the dataset. The most frequently identified protein is a highly abundant glycolytic enzyme enolase 1, differentially expressed in nearly every third experiment on both human and rodent tissues. Heat-shock protein 27 (HSP27) and heat-shock protein 60 (HSP60) were differentially expressed in about 30 percent of human and rodent samples, respectively. Considering protein families as units, keratins and peroxiredoxins are the most frequently identified molecules, with at least one member of the group being differentially expressed in about 40 percent of all experiments. We suggest that the frequent identification of these proteins must be considered in the interpretation of any 2-DE studies. We consider if these commonly observed changes represent common cellular stress responses or are a reflection of the technical limitations of 2-DE.