Association between the NEP rs701109 polymorphism and the clinical efficacy and safety of sacubitril/valsartan in Chinese patients with heart failure.

OBJECTIVE: Sacubitril/valsartan is a commonly used medicine for treating heart failure (HF) patients, but the treatment effects significantly vary. Neprilysin (NEP) and carboxylesterase 1 (CES1) play an important role in the efficacy of sacubitril/valsartan. The purpose of this study was to explore the relationship between NEP and CES1 gene polymorphisms and the efficacy and safety of sacubitril/valsartan treatment in HF patients. METHODS: Genotyping of 10 single nucleotide polymorphisms (SNPs) of the NEP and CES1 genes in 116 HF patients was performed by the Sequenom MassARRAY method, and logistic regression and haplotype analysis were used to evaluate the associations between SNPs and the clinical efficacy and safety of sacubitril/valsartan in HF patients. RESULTS: A total of 116 Chinese patients with HF completed the whole trial, and T variations in rs701109 in NEP gene were an independent risk factor (P = 0.013, OR = 3.292, 95% CI:1.287-8.422) for the clinical efficacy of sacubitril/valsartan. Furthermore, haplotype analysis of 6 NEP SNPs (including rs701109) was performed and showed that the CGTACC and TGTACC haplotypes were significantly associated with clinical efficacy (OR = 0.095, 95%CI: 0.012-0.723, P = 0.003; OR = 5.586, 95% CI: 1.621-19.248, P = 0.005). Moreover, no association was found between SNPs of other selected genes in terms of efficacy in HF patients, and no association was observed between SNPs and symptomatic hypotension. CONCLUSION: Our results suggest an association between rs701109 and sacubitril/valsartan response in HF patients. Symptomatic hypotension is not associated with the presence of NEP polymorphisms.

[Expression of cancerous inhibitor of protein phosphatase 2A in tissue microarray of colorectal cancer and its clinical significance].

OBJECTIVE: To investigate the expression of cancerous inhibitor of protein phosphatase 2A(CIP2A) in human colorectal cancer, and to examine the association of CIP2A expression with clinicopathology and prognosis. METHODS: CIP2A expression in colorectal cancer tissue microarray of 92 cases was detected by immunohistochemistry method. RESULTS: Up-regulated CIP2A expression was closely related with TNM staging, histological type, peritoneal seeding and liver metastasis (all P<0.05), but not related with gender, age, tumor location, CEA, family history and grade of differentiation. Overall survival rates of 1-, 3-, 5-, and 10-year in high CIP2A expression group were 97.1%, 71.4%, 59.2%, and 44.4% respectively, significantly lower than 98.2%, 85.7%, 80.3%, and 74.9% in low CIP2A expression group(P=0.021). Multivariate analysis showed that CIP2A was not an independent factor associated with prognosis(P=0.099, HR=1.982, 95%CI:0.879 to 4.469). CONCLUSIONS: Up-regulated CIP2A expression is closely related to clinicopathology of colorectal cancer. CIP2A may be used as a potential predictive marker of metastasis, prognosis and therapeutic target in colorectal cancer.

[Effect of the liposome albendazole and Huai-Er fungus extract on hepatic infection of Echinococcus granulosus in mice].

OBJECTIVE: To explore the effect of Huai-Er fungus extract (HEF) and liposome albendazole (L-ABZ) on the hepatic infection of Echinococcus granulosus (Eg) in mice, and understand the influence of improved host immunity on postoperative recurrence. METHODS: Female Kunming mice were immune by intraperitoneal injection Eg cyst fluid from sheep, IgG positive mice were divided into drug treatment groups (A, B and C) and control group (D). Mice in group A were administered by gavage with single L-ABZ (75 mg/kg), group B with single HEF (15,000 mg/kg), and group C with combination therapy (L-ABZ 75 mg/kg plus HEF 15,000 mg/kg), once every two days for one week. The protoscoleces were treated with balanced solution for 20 minute and inoculated in the liver by open abdomen of the anesthetized mice. Imitating to an "open sub-adventitial total exocystectomy", protoscoleces outside the cyst led to a reinfection. 72 hours later, groups A, B and C were re-treated for a month. Mice in group D were given with distilled water (0.3 ml per mouse). Group E was set as blank control (n=8). Another 120 IgG positive mice were divided as groups F, G, H and I, and treated in parallel with the groups A, B, C and D respectively; these mice were inoculated with protoscoleces which were treated in advance with 75% alcohol, 20% hypertonic saline, L-ABZ and PBS for 20 min respectively. In 3 months after infection, all the mice were sacrificed to evaluate the efficacy, which covered infection rate, pathological change, spleen index, level of IgG and IgE, CD4+ and CD8+ cells. RESULTS: The recurrence rate in group C (5.7%) was lower than that of groups A (17.1%) and B (24.2%), with hydatid cysts in white colour and nodular, showing degeneration of the germinal and laminated layers. Groups A, B and C showed lower spleen index (A: 3.84+/-0.86, B: 3.95+/-1.01, and C: 3.27+/-0.52), and lower IgE level (A: 0.06+/-0.08, B: 0.07+/-0.08 and C: 0.03+/-0.03) than group D (5.46+/-0.52 and 0.20+/-0.02, respectively) (P<0.05), especially in group C; and also lowerCD8+ in groups A (16.61+/-3.89), B (18.18+/-3.90) and C (15.38+/-2.63) than group D (32.90+/-4.71) (P<0.05), but higher CD4+/CD8+ in groups A (3.21+/-0.70), B (3.05+/-0.66) and C (3.53+/-0.57) than group D (1.57+/-0.26) (P<0.05), especially in group C. The infection rate of mice in group F, Gand H was 0, 0 and 23.1% respectively, and that of group I, 31.2% (P<0.01). CONCLUSION: The combination of HEF and L-ABZ considerably improves the immunity of the hosts and HEF may have a synergetic action to L-ABZ in reducing the recurrence of "sub-adventitial total exocystectomy". 75% alcohol and 20% hypertonic saline show better effect of inactivating protoscoleces than L-ABZ in surgical operation.