Bayer AG.

The development of cardiac hypertrophy in response to increased hemodynamic load and neurohormonal stress is initially a compensatory response that may eventually lead to ventricular dilation and heart failure. Regulator of G protein signaling 5 (Rgs5) is a negative regulator of G protein-mediated signaling by inactivating Gα(q) and Gα(i), which mediate actions of most known vasoconstrictors. Previous studies have demonstrated that Rgs5 expresses among various cell types within mature heart and showed high levels of Rgs5 mRNA in monkey and human heart tissue by Northern blot analysis. However, the critical role of Rgs5 on cardiac remodeling remains unclear. To specifically determine the role of Rgs5 in pathological cardiac remodeling, we used transgenic mice with cardiac-specific overexpression of human Rgs5 gene and Rgs5 −/− mice. Our results demonstrated that the transgenic mice were resistant to cardiac hypertrophy and fibrosis through inhibition of MEK-ERK1/2 signaling, whereas the Rgs5 −/− mice displayed the opposite phenotype in response to pressure overload. These studies indicate that Rgs5 protein is a crucial component of the signaling pathway involved in cardiac remodeling and heart failure.

Background/Aims: Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure, but the mechanisms undelying cardiac fibrosis remained unknown. microRNAs (miRNAs) are novel mechanisms leading to fibrotic diseases, including cardiac fibrosis. Previous studies revealed that miR-22 might be a potential target. However, the roles and mechanisms of miR-22 in cardiac fibrosis remained ill defined. The present study thus addressed the impact of miR-22 in cardiac fibrosis. Methods: After seven days following coronary artery occlusion in mice, tissues used for histology were collected and processed for Masson's Trichrome staining. In addition, cardiac fibroblasts were transfected with mimics and inhibitors of miR-22 using Lipofectamin 2000, and luciferase activity was measured in cell lysates using a luciferase assay kit. Western blotting was used to detect the expression of collagen1, α-SMA and TGFβRI proteins levels, and real time-PCR was employed to measure the Col1α1, Col3α1, miR-22 and TGFβRI mRNA levels. Results: In this study, we found that miR-22 was dynamically downregulated following MI induced by permanent ligation of the left anterior descending coronary artery for 7 days, an effect paralleled by significant collagen deposition. Inhibition of miR-22 with AMO-22 resulted in increased expression of Col1α1, Col3α1 and fibrogenesis in cultured cardiac fibroblasts. Conversely, overexpression of miR-22 in cultured cardiac fibroblasts significantly abrogated angiotensin II-induced collagen formation and fibrogenesis. Furthermore, we found that TGFβRI is a direct target for miR-22, and downregulation of TGFβR may have mediated the antifibrotic effect of miR-22. Conclusion: Our data clearly demonstrate that miR-22 acts as a novel negative regulator of angiotensin II-induced cardiac fibrosis by suppressing the expression of TGFβRI in the heart and may represent a new potential therapeutic target for treating cardiac fibrosis.

Backgrounds:Observational studies had suggested an inverse association between whole grain consumption and concentration of inflammatory markers, but evidence from interventional studies was inconsistent. Therefore, we conducted a meta-analysis of randomized trials to have a better understanding of this issue.Methods:This study has been registered in PROSPERO (ID: CRD42018096533). We searched PubMed, Web of Science, Embase, Medline, and Cochrane Library for articles focusing on the topic from inception to 1 January, 2018. Summary standardized mean difference (SMD) and 95% confidence interval (CI) were calculated by using either random effect model or fixed effect model according to the heterogeneity of included studies. Subgroup analysis was also performed.Results:Totally 9 randomized trials included 838 participants were identified. In a pooled analysis of all studies, consumption of whole grains had an inverse association with inflammatory markers (SMD 0.16, 95% CI, 0.02–0.30), including C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β). Specific analyses for CRP and IL-6 yielded that whole grain diet was related with a significant decrease in the concentration of CRP (SMD 0.29, 95% CI, 0.08–0.50) and IL-6 (SMD 0.19, 95% CI, 0.03–0.36).Conclusions:The evidence suggested that citizens could benefit from increased whole grain intake for reducing systemic inflammation. Further well-designed studies are required to investigate the mechanism under the appearance.

BackgroundThe objective of this study was to conduct the first systematic evaluation of the long‐term economic impact of arsenic trioxide (ATO) plus all‐trans retinoic acid (ATRA) for the treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) from the perspective of the Chinese health care system.MethodsOn the basis of clinical data from a randomized phase 3 trial, a time‐dependent Markov model with 4 health states (complete remission, relapse or treatment failure, post‐treatment failure, and death) was used to evaluate the incremental costs per quality‐adjusted life‐year (QALY) gained from the ATO plus ATRA regimen compared with the ATRA plus chemotherapy (CT) regimen over a 30‐year period. All costs were adjusted to 2018 levels based on the Chinese Consumer Price Index. Both costs and health outcomes were discounted by 3% annually. One‐way sensitivity analysis and probability sensitivity analysis were performed.ResultsCompared with the ATRA plus CT strategy, the ATO plus ATRA strategy was associated with 1.38 additional QALYs gained and $392.05 (estimated in 2018 US dollars) in incremental costs per patient over 30 years. Consequently, the incremental cost‐effectiveness ratio was $284.02 per QALY gained, which was far below the Chinese willingness‐to‐pay threshold of $29,306 per QALY gained. Sensitivity analyses demonstrated the robustness of these results.ConclusionsFrom the perspective of the Chinese health care system, the ATO plus ATRA strategy is cost‐effective for patients with newly diagnosed APL compared with the ATRA plus CT strategy. Therefore, the authors strongly suggest that China's health authorities choose the former strategy for these patients, whether for the elderly or for young people.

No abstract

The FTS program can decrease inflammation, maintain immune homeostasis, and improve rehabilitation effects in colorectal surgery patients.

Background Enhanced recovery after surgery (ERAS) is a multidisciplinary, stress-minimizing approach that is associated with improved postoperative outcomes. However, whether the level of compliance with ERAS protocols impacts the postoperative outcome of patients with primary liver cancer undergoing liver resection is unknown. The study aimed to analyze the association between compliance with ERAS protocols and liver resection outcomes. Methods This prospective cohort study consecutively recruited patients with primary liver cancer who were scheduled for elective liver surgery between January 2019 and December 2020 at the Department of Biliary Surgery, West China Hospital of Sichuan University. Twenty individual ERAS items were assessed in all patients. The patients were divided into two groups according to their degree of compliance with the ERAS interventions: an ERAS-compliant (ERAS-C) group of individuals who complied with over 75% of the ERAS components and an ERAS-noncompliant (ERAS-N) group. The primary outcomes were ERAS compliance, occurrence of major complications within 30 days postoperatively, and length of postoperative hospital stay. The secondary outcomes were 30-day readmissions, reoperations and other rehabilitation indicators. The study was registered at www.chictr.org.cn (identity number ChiCTR2000040021). Results Overall, 436 patients were enrolled; their mean age was 54 years (interquartile range [IQR], 47–66). Of these patients, 206 were allocated to the ERAS-C group, and the other 230 patients comprised the ERAS-N group. The overall compliance rate was 70% (IQR, 65%-80%). The ERAS-C group had higher compliance rates [80.00% (IQR, 75.00–85.00%)] than the ERAS-N group [65.00% (IQR, 65.00–70.00%)], P < 0.001). The ERAS-C group had significantly fewer major complications (7.77% vs. 15.65%, OR, 0.449, 95% CI, 0.241–0.836, P = 0.012) and shorter postoperative hospital stays (5 days [IQR, 4–6] vs. 6 days [IQR, 5–7], P < 0.001) than the ERAS-N group. Subgroup analysis indicated that compliance rates greater than 80%, between 65 and 80%, and lower than 65% were associated with decreased major complication rates (6.25%, 8.48% and 22.83%, respectively) and shorter postoperative hospital stays. However, the rates of ICU stay, readmission, reoperation and mortality within 30 days after surgery were not different between groups (P > 0.05). Conclusion The results of this study suggest that higher compliance with ERAS components is associated with a lower incidence of major postoperative complications and a shorter postoperative hospital stay.