Meta-analysis and trial sequential analysis of ezetimibe for coronary atherosclerotic plaque compositions

Background: Lipid aggregation, inflammatory cell infiltration, fibrous cap formation, and disruption are the major causes of atherosclerotic cardiovascular disease (ASCVD) and the pathologic features of atherosclerotic plaques. Although ezetimibe’s role in decreasing blood lipids is widely known, there are insufficient data to determine which part of the drug has an effect on atherosclerotic plaque compositions.Objective: The study aimed to systematically evaluate the efficacy of ezetimibe for coronary atherosclerotic plaque compositions.Methods: Two researchers independently searched the PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) on the efficacy of ezetimibe for coronary atherosclerotic plaques from inception until 22 January 2023. The meta-analysis and trial sequential analysis (TSA) were performed using Stata 14.0 and TSA 0.9.5.10 Beta software, respectively.Results: Four RCTs were finally included this study, which comprised 349 coronary artery disease patients. Meta-analysis findings showed that, compared with the control group, intervention measures could effectively reduce the fibro-fatty plaque (FFP) volume [WMD = −2.90, 95% CI (−4.79 and −1.00), and p = 0.003 < 0.05]; there were no significant difference in the reduction of fibrous plaque (FP) volume [WMD = −4.92, 95% CI (−11.57 and 1.74), and p = 0.15 > 0.05], necrotic core (NC) volume [WMD = −2.26, 95% CI (−6.99 and 2.46), and p = 0.35 > 0.05], and change dense calcification (change DC) volume [WMD = −0.07, 95% CI (−0.34 and 0.20), and p = 0.62 > 0.05] between the treatment group and the control group. TSA findings showed more studies are still required to confirm the efficacy of ezetimibe for FP and NC in the future.Conclusion: Compared to the control group, ezetimibe significantly decreased FFP, but it had no statistically significant difference on FP, NC, or change DC. According to TSA, further research will be required to confirm the efficacy of ezetimibe for FP and NC in the future

Genome-Wide Identification, Evolutionary Expansion, and Expression Profile of Homeodomain-Leucine Zipper Gene Family in Poplar (Populus trichocarpa)

BACKGROUND: Homeodomain-leucine zipper (HD-ZIP) proteins are plant-specific transcriptional factors known to play crucial roles in plant development. Although sequence phylogeny analysis of Populus HD-ZIPs was carried out in a previous study, no systematic analysis incorporating genome organization, gene structure, and expression compendium has been conducted in model tree species Populus thus far. PRINCIPAL FINDINGS: In this study, a comprehensive analysis of Populus HD-ZIP gene family was performed. Sixty-three full-length HD-ZIP genes were found in Populus genome. These Populus HD-ZIP genes were phylogenetically clustered into four distinct subfamilies (HD-ZIP I-IV) and predominately distributed across 17 linkage groups (LG). Fifty genes from 25 Populus paralogous pairs were located in the duplicated blocks of Populus genome and then preferentially retained during the sequential evolutionary courses. Genomic organization analyses indicated that purifying selection has played a pivotal role in the retention and maintenance of Populus HD-ZIP gene family. Microarray analysis has shown that 21 Populus paralogous pairs have been differentially expressed across different tissues and under various stresses, with five paralogous pairs showing nearly identical expression patterns, 13 paralogous pairs being partially redundant and three paralogous pairs diversifying significantly. Quantitative real-time RT-PCR (qRT-PCR) analysis performed on 16 selected Populus HD-ZIP genes in different tissues and under both drought and salinity stresses confirms their tissue-specific and stress-inducible expression patterns. CONCLUSIONS: Genomic organizations indicated that segmental duplications contributed significantly to the expansion of Populus HD-ZIP gene family. Exon/intron organization and conserved motif composition of Populus HD-ZIPs are highly conservative in the same subfamily, suggesting the members in the same subfamilies may also have conservative functionalities. Microarray and qRT-PCR analyses showed that 89% (56 out of 63) of Populus HD-ZIPs were duplicate genes that might have been retained by substantial subfunctionalization. Taken together, these observations may lay the foundation for future functional analysis of Populus HD-ZIP genes to unravel their biological roles

Up-regulated serum lactate dehydrogenase could become a poor prognostic marker in patients with bladder cancer by an evidence-based analysis of 2,182 patients

BackgroundA growing number of studies have considered serum lactate dehydrogenase (LDH) as an indicator of bladder cancer (BC) prognosis. However, a meta-analysis of the serum LDH’s influence on BC prognosis is still missing.MethodsPubMed, EMBASE, Web of Science and Cochrane Library were exhaustively searched for studies comparing oncological outcomes between high-LDH and low-LDH patients. Standard cumulative analyses using hazard ratios (HR) with 95% confidence intervals (CI) were performed using Review Manager (version 5.3) for overall survival (OS) in patients with BC.ResultsSix studies involving 2,182 patients were selected according to predefined eligibility criteria. The results showed that serum LDH level was significantly associated with OS (HR = 1.86, 95%CI = 1.54-2.25, p<0.0001) in BC. Sensitivity analysis showed the stability of the results. Subgroup analysis revealed that the levels of serum LDH had a significant impact on the OS of BC patients among different groups including publication time, research country, sample size, tumor stage, LDH cut-off value, therapy and follow-up time (all HR>1 and p<0.05), revealing that the ability of serum LDH is not affected by other factors.ConclusionOur findings indicated that a high level of serum LDH was associated with inferior OS in patients with BC. However, caution must be taken before recommendations are given because this interpretation is based upon very few clinical studies and a small sample

Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: A Chronic Graft-versus-Host Disease Consortium study

Background The National Institutes of Health Consensus Conference proposed the term “overlap” graft-versus-host disease to describe the situation when both acute and chronic graft-versus-host disease are present. Design and Methods We examined whether the overlap subtype of graft-versus-host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to “classic” chronic graft-versus-host disease without any acute features. Results Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft-versus-host disease based on reported organ involvement. Overlap cases had a significantly shorter median time from transplantation to cohort enrollment (P=0.01), were more likely to be incident cases (P\u3c0.001), and had a lower platelet count at onset of the graft-versus-host disease (P\u3c0.001). Patients with overlap graft-versus-host disease had significantly greater functional impairment measured by a 2-minute walk test, higher symptom burden and lower Human Activity Profile scores. Quality of life was similar, except patients with overlap graft-versus-host disease had worse social functioning, assessed by the Short Form-36. Multivariable analysis utilizing time-varying covariates demonstrated that the overlap subtype of graft-versus-host disease was associated with worse overall survival (HR 2.1, 95% CI 1.1–4.7; P=0.03) and higher non-relapse mortality (HR 2.8, 95% CI 1.2–8.3; P=0.02) than classic chronic graft-versus-host disease. Conclusions These findings suggest that the presence of acute features in patients with chronic graft-versus-host disease is a marker of adverse prognosis, greater functional impairment, and higher symptom burden

Glycyrrhetinic acid regulates impaired macrophage autophagic flux in the treatment of non-alcoholic fatty liver disease

Macrophages are involved in hepatocyte steatosis and necroinflammation and play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Impaired autophagy function (decreased autophagy or blocked autophagic flow) leads to cell damage and death and promotes NAFLD progression. The experimental and clinical research of glycyrrhetinic acid (GA) in the treatment of NAFLD has gradually attracted attention with clear pharmacological activities such as immune regulation, antiviral, antitumor, antioxidant, liver protection, and anti-inflammatory. However, the effects of GA on the STAT3-HIF-1α pathway and autophagy in macrophages are still unclear, and its mechanism of action in the treatment of NAFLD remains to be further elucidated. We constructed a NAFLD mouse model through a high-fat and high-sugar diet to investigate the therapeutic effects of GA. The results showed that GA reduced weight, improved the pathological changes and hepatic lipid deposition of liver, and abnormally elevated the levels of serum biochemical (AST, ALT, TG, T-CHO, LDL-C, and HDL-C) and inflammatory indexes (IL-1β, IL-4, IL-6, MCP-1, and TNF-α) in NAFLD mice. Further examination revealed that GA ameliorates excessive hepatic macrophage infiltration and hepatocyte apoptosis. The results of the cell experiments further elaborated that GA modulated the PA-induced macrophage STAT3-HIF-1α pathway and ameliorated impaired autophagic flux (blockade of autophagosome–lysosome fusion) and overactivation of inflammation. Excessive hepatocyte apoptosis caused by the uncontrolled release of inflammatory cytokines was also suppressed by GA.ConclusionThis study demonstrated that GA could regulate the STAT3-HIF-1α pathway of macrophages, ameliorate the impaired autophagy flux, and reduce the excessive production of inflammatory cytokines to improve the excessive apoptosis of liver cells, thus playing a therapeutic role on NAFLD

A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation

Cutaneous sclerosis (CS) occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life

TREAT: a bioinformatics tool for variant annotations and visualizations in targeted and exome sequencing data

Summary: TREAT (Targeted RE-sequencing Annotation Tool) is a tool for facile navigation and mining of the variants from both targeted resequencing and whole exome sequencing. It provides a rich integration of publicly available as well as in-house developed annotations and visualizations for variants, variant-hosting genes and host-gene pathways

Observation of ηc→ωω\eta_c\to\omega\omega in J/ψ→γωωJ/\psi\to\gamma\omega\omega

Using a sample of $(1310.6\pm7.0)\times10^6$ $J/\psi$ events recorded with the BESIII detector at the symmetric electron positron collider BEPCII, we report the observation of the decay of the $(1^1 S_0)$ charmonium state $\eta_c$ into a pair of $\omega$ mesons in the process $J/\psi\to\gamma\omega\omega$. The branching fraction is measured for the first time to be $\mathcal{B}(\eta_c\to\omega\omega)= (2.88\pm0.10\pm0.46\pm0.68)\times10^{-3}$, where the first uncertainty is statistical, the second systematic and the third is from the uncertainty of $\mathcal{B}(J/\psi\to\gamma\eta_c)$. The mass and width of the $\eta_c$ are determined as $M=(2985.9\pm0.7\pm2.1)\,$MeV/$c^2$ and $\Gamma=(33.8\pm1.6\pm4.1)\,$MeV.Comment: 13 pages, 6 figure