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  • Brown Hu posted an update 1 day, 11 hours ago

    To explore the causal relationship between blood metabolites and the risk of coronary artery disease (CAD) using a two-sample Mendelian randomization (MR) approach.

    Based on the data from a large-scale metabolome-based genome-wide association study (mGWAS) and the GWAS of CAD, we investigated the causality between blood metabolites and CAD using an inverse variance weighted (IVW) method and another 4 two-sample MR models. Heterogeneity, horizontal pleiotropy, and sensitivity tests were performed to evaluate the stability and reliability of the results.

    Among the 486 blood metabolites, 32 metabolites showed nominally causative association with CAD with the IVW method (

    < 0.05), including 11 known metabolites and 21 unknown metabolites. Three known metabolites [N-acetylornithine, bradykinin-des-arg(9), and succinylcarnitine] were statistically significant in at least 3 MR models, but their causal effects on CAD were no longer significant after sensitivity analysis using leave-one-out method and elimination of the confounding instrumental variables.

    There is no strong evidence to support a robust causal relationship between the 486 blood metabolites and the risk of CAD.

    There is no strong evidence to support a robust causal relationship between the 486 blood metabolites and the risk of CAD.

    To assess the effect of salt intake on residual renal function in rats and explore the possible mechanism.

    SD rats were 5/6-nephrectomized to induce chronic renal failure followed by peritoneal dialysis for 4 weeks (

    =18) or without dialysis treatment (control group;

    =18). In both groups, the rats were divided into 3 subgroups and were given lowsalt diet (0.02% NaCl), normal salt diet (0.4% NaCl), and high-salt diet (4% NaCl). After 8 and 12weeks, blood pressure and creatinine and sodium levels in the blood, urine, and peritoneal dialysate of the rats were examined. Glomerular sclerosis, tubulointerstitial fibrosis, and protein expression levels of RAS components (ACE-1, AGT, and AT-1) in renal cortical tissue of the rats were evaluated.

    The residual renal function of the rats all decreased especially in rats with high salt intake for 8and 12 weeks. In peritoneal dialysis group, the rats with high-salt diet showed signficiantly increased renal interstitial fibrosis score (

    =0.036), glomerular scleroion of the renal RAS system, increases blood pressure, and agrevates renal fibrosis to accelerate the decline of residual renal function, and peritoneal dialysis partially reduces the damage of residual renal function induced by high-salt diets by removing excessive sodium.

    To explore the effect of

    decoction (HQD) on group 3 innate lymphoid cells (ILC3s) and helper T cells (Th) for treatment of ulcerative colitis (UC).

    Male Balb/c mice were randomly divided into control group, DSS group, mesalazine group (ME, 400 mg/kg), and 2.275 g/kg, 4.55 g/kg and 9.1 g/kg HQD groups. All the mice were given free access to normal chow. Except for those in the normal control group, all the mice were given 3% DSS solution for 7 days to establish models of UC. The mice in ME group and 3 HQD groups were given mesalazine or HQD via oral gavage at the specified doses once a day. Flow cytometry was performed to analyze the ILC3s, MHC Ⅱ, Th1 and Treg in the lamina propria lymphocytes in the colon. Milliplex was performed to determine cytokine levels of in the colon tissues.

    Compared with those in DSS group, the mice in the 3 HQD groups all showed obviously lessened symptoms of UC with significantl decreased DAI score (

    < 0.001) and macroscopic score (

    < 0.001). The results of flow cytometry showed that HQD treatment significantly increased the percentage of ILC3s (

    < 0.05) and expression of MHCⅡ (

    < 0.05), obviously reduced the proportion of Th1 (

    < 0.05) but increased Treg cells (

    < 0.05) in the colon tissues. Milliplex showed that HQD treatment significantly reduced the expressions of Th-related pro-inflammatory cytokines including IL-2 (

    < 0.05), IL-17A (

    < 0.05), IL-23 (

    < 0.05), TNF-α (

    < 0.05), and IFN-γ (

    < 0.05).

    HQD alleviates DSS- induced UC in mice by increasing ILC3s and MHC Ⅱ expression to suppress the function of Th17 and Th1 cells and promote Treg and Th2 cells.

    HQD alleviates DSS- induced UC in mice by increasing ILC3s and MHC Ⅱ expression to suppress the function of Th17 and Th1 cells and promote Treg and Th2 cells.

    To investigate the efficacy of anlotinib plus S-1 for treatment of patients with recurrent or metastatic esophageal squamous cell carcinoma with failed first-line chemotherapy.

    Twenty-six patients with recurrent or metastatic esophageal squamous cell carcinoma patients who experienced progression after first-line paclitaxel plus platinum chemotherapy in our hospital between July, 2018 and February, 2020 were enrolled in this study. The patients received oral anlotinib along with S-1 treatment (anlotinib at 12 mg once daily and S-1 at 50 mg twice daily for two weeks; 3 weeks per cycle). The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and adverse effects were evaluated for all the patients.

    No complete remission (CR) was observed in the 26 patients. Partial remission (PR) was achieved in 6 cases, stable disease (SD) in 12 cases, and progressive disease (PD) occurred in 8 cases, with an ORR of 23.1% and a DCR of 69.2% in these patients. The median PFS was 4.5 months (95%

    2.7-6.4 months). Univariate analysis showed that the patients with moderate or high tumor differentiation had significantly longer PFS than those with low tumor differentiation (6.1 months

    1.9 months,

    < 0.05). Multivariate analysis suggested that pathological differentiation grade (HR=6.778, 95%

    1.997-23.012) was an independent factor for a prolonged PFS. Tacrolimus The adverse effects in the patients included mainly fatigue, hypertension and hand-foot syndrome, mostly of grade 1 to 2.

    Patients with recurrent or metastatic esophageal squamous cell carcinoma can benefit from a second-line anlotinib plus S-1 treatment, which has relatively mild adverse effects with a good safety profile.

    Patients with recurrent or metastatic esophageal squamous cell carcinoma can benefit from a second-line anlotinib plus S-1 treatment, which has relatively mild adverse effects with a good safety profile.