Development and validation of a score predicting mortality for older patients with mitral regurgitation.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS: The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Modified Huangqi Chifeng decoction inhibits excessive autophagy to protect against Doxorubicin-induced nephrotic syndrome in rats via the PI3K/mTOR signaling pathway.

The aim of the present study was to investigate whether modified Huangqi Chifeng decoction (MHCD) could be an effective treatment against Doxorubicin-induced nephrosis in rats and whether it regulates autophagy via the phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathway. A total of 40 male Sprague-Dawley rats were randomly divided into blank, model, telmisartan and MHCD groups. The rat model of nephrosis was induced by intragastric administration of Doxorubicin for 8 weeks. Rats were housed in metabolic cages and urine was collected once every 2 weeks to measure 24-h protein levels. Blood samples were obtained from the abdominal aorta and levels of albumin (ALB), total cholesterol (TCH), triacylglyceride (TG) and serum creatinine (Scr) were assessed. Renal pathological changes were examined using hematoxylin-eosin, Masson's trichome and periodic acid-Schiff staining. Podocytes and autophagosomes were observed using an electron microscope. The expression and distribution of microtubule-associated proteins 1A/1B light chain 3B (LC3), LC3-I, LC3-II, beclin-1, PI3K and mTOR were determined using immunohistochemistry and western blotting. At weeks 6 and 8, 24-h proteinuria significantly decreased in the MHCD group compared with the model group (P<0.05). Compared with the model group, the MHCD group exhibited significantly reduced levels of TG, TCH and Scr, as well as significantly increased ALB levels (P<0.05). MHCD was demonstrated to prevent glomerular and podocyte injury. The number of autophagosomes was significantly decreased and the expression of beclin-1, LC3, LC3-I and LC3-II was inhibited following MHCD treatment compared with the model group (P<0.05). MHCD treatment significantly increased the expression of PI3K and mTOR in Doxorubicin nephrotic rats compared with the model group (P<0.05). In conclusion, MHCD was demonstrated to ameliorate proteinuria and protect against glomerular and podocyte injury by inhibiting excessive autophagy via the PI3K/mTOR signaling pathway.

Efficacy and safety of Danggui Buxue Decoction in combination with western medicine treatment of anemia for renal anemia: a systematic review and meta-analysis.

BACKGROUND: To evaluate the efficacy and safety of Danggui Buxue Decoction for renal anemia when combined with western medicine treatment of anemia. METHODS: Electronic searching Medline, Embase, Web of Science, Cochrane Library, Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), WanFang data, Chinese Sci-tech periodical full-text database (VIP). Randomized controlled trials reported results of efficacy and safety of Danggui Buxue Decoction in combination with western medicine treatment of anemia for renal anemia. The "risk of bias assessment tool (Version 5.1.0)" of Cochrane Handbook was applied to assess the quality of included trials and RevMan 5.3 software was used for data analysis. RESULTS: A total of 111 studies was retrieved, seven studies including 460 cases were included, the methodological quality of included trials was poor. The result of meta-analysis demonstrated that there was no difference in hemoglobin (Hb) [weighted mean differences (WMD) =-8.75, 95% confidence interval (CI): (-18.64, 1.13), P=0.08], whereas the subgroup analysis showed the difference was significant when the ratio of Radix Astragali to Radix Angelicae Sinensis was 5:1 [WMD =-16.27, 95% CI: (-28.73, -3.80), P=0.01], increase of Hb was more effective in experimental group than control group and the difference was not significant when the ratio of Radix Astragali to Radix Angelicae Sinensis was 5≠1 [WMD =-0.57, 95% CI: (-4.52, 3.39), P=0.78]. There were significant differences in red blood cell (RBC) [WMD =-0.49, 95% CI: (-0.69, -0.28), P<0.00001], hematocrit (HCT) [WMD =-1.92, 95% CI: (-3.15, -0.69), P=0.002] and clinical efficacy [odd ratio (OR) =0.30, 95% CI: (0.13, 0.69), P=0.004] between Danggui Buxue Decoction combination group and control group, the experimental group was better than control group. There was no adverse event reported in the experimental group. CONCLUSIONS: Danggui Buxue Decoction in combination with conventional western medicine (CWM) for renal anemia might be superior to CWM alone and there was no adverse event in the experimental group, it might be more effective when the ratio of Radix Astragali to Radix Angelicae Sinensis was 5:1. However, the quality of included studies was not high, and less attention was paid to the safety, high quality randomized controlled trials are needed to further confirm the findings.

[Effect of Modified Hangqi Chifeng Decoction Containing Serum on the Expression of Col IV, MMP-2, and TIMP-2 in Glomerular Mesangial Cells Induced by LPS].

OBJECTIVE: To explore the effect of Modified Hangqi Chifeng Decoction (MHCD) on levels of collagen type IV (Col IV), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2) in extracellular matrix (ECM) of glomerular mesangial cells (GMCs) in LPS induced mice. METHODS: Normal serum and telmisartan, high, medium, low dose MHCD containing serums were prepared by using serum pharmacology method. GMCs were cultured in vitro. The proliferation of mesangial cells were induced using LPS as stimulating factor. GMCs were divided into six groups, i.e., the normal group, the model group, the telmisartan group, high, medium and low dose MHCD groups. Col IV content in the supernatant of mesangial cells was detected using ELISA. Protein expressions of MMP-2 and TIMP-2 were detected using Western blot. RESULTS: Compared with the normal group, Col IV content obviously increased in the model group after 72-h LPS stimulation; protein expressions of MMP-2 and TIMP-2 were obviously up-regulated, and MMP-2/TIMP-2 ratio was down-regulated in the model group (P < 0.01). Compared with the model group, Col IV content obviously decreased in high and medium dose MHCD groups and the telmisartan group (P < 0.01); protein expressions of MMP-2 were obviously down-regulated in medium and low dose MHCD groups (P < 0.01, P < 0.05); the protein expression of TIMP-2 was obviously down-regulated in high, medium, low dose MHCD groups and the telmisartan group (P < 0.01). The pro- tein expression of TIMP-2 was obviously lower in the high dose MHCD group than in the low dose MHCD group (P < 0.01). MMP-2/TIMP-2 ratio was obviously up-regulated in the telmisartan group, high and medium dose MHCD groups (P < 0.01). CONCLUSION: MHCD could regulate disordered MMP-2/TIMP-2 ratio in LPS induced ECM, inhibit excessive production of Col IV in ECM, promote the degradation of ECM, reduce the accumulation of ECM, thereby, delaying the process of glomerular sclerosis.

[Anti-renal Fibrosis Mechanism of Modified Huangqi Chifeng Decoction Based on TGF-p1/Smad Signal Pathway].

Objective To observe the effect of Modified Huangqi Chifeng Decoction (MHCD) on TGF-ß1/Smad signal pathway, and to explore its anti-renal fibrosis mechanism. Methods Adopting ser- um pharmacology method, rats were intragastrically administered with MHCD and telmisartan to prepare drug containing serum. Mouse mesangial cells were cultured in vitro, using lipopolysaccharides (LPS) as stimulating factor. The cells were divided into six groups, i.e., the normal group, the model group, the telmisartan group, high, medium and low dose MHCD groups. The cell supernatant was collected in each group after mouse mesangial cells were intervened by drug containing serum for 72 h. Contents of laminin (LN) and fibronectin (FN) were measured using ELISA. Protein expression levels of TGF-P, , p-Smad2/3, Smad7, and connective tissue growth factor (CTGF) were detected using Western blot. Results (1) Compared with the normal group, contents of LN and FN in supernatant significantly increased in the model group (P <0. 01). Compared with the model group, contents of LN and FN were significantly reduced in the telmisartan group and the medium dose MHCD group (P <0. 05, P <0. 01). FN content in su- pernatant significantly decreased in the low dose MHCD group (P <0. 01). (2) Compared with the normal group, protein expressions of TGF-ß1 , p-Smad2/3, and CTGF were significantly increased, Smad7 protein expression significantly decreased in the model group, with statistical difference (P <0. 01). Compared with the model group, protein expressions of TGF-ß1 and CTGF significantly decreased in the telmisartan group and 3 MHCD groups (P <0. 01 , P <0. 05) ; protein expression of p-Smad23 significantly decreased in the telmisartan group, high and medium dose MHCD groups (P <0.01); Smad7 protein expression were significantly increased in high and medium dose MHCD groups (P <0. 05). Conclusion MHCD could inhibit increased inflammatory factors induced secretion of extracellular matrix in glomerular mesangial cells, and restrain excessive activation of TGF-ß1/Smad signal pathways, which might be one of its anti-renal fibrosis mechanisms.