Objective:To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality.Methods:This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone.Results:A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa), P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg, P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg, P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions:RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Objective To establish a lipid differentiation model of primary rat bone marrow mesenchymal stem cells(rBMSCs)in vitro using homocysteine(Hcy),and analyze the specific effects of Hcy on lipid and bone differentiation of BMSCs;to comprehensively explore the effects of mangiferin on lipid and bone differentiation of BMSCs,and further reveal the potential mechanism of mangiferin in the treatment of osteoporosis through the inter-vention of Hcy-induced BMSCs by different concentrations of mangiferin.Methods First,rBMSCs were extracted and isolated.The rBMSCs that were well-cultured to a certain generation were placed in culture medium containing different concentrations of Hcy(0.125,0.250,0.5,1,2,4 mmol/L)to establish lipid differentiation model of rBMSCs.Then,different concentrations of mangiferin(37.5,75,150 μmol/L)were applied to the experimental cells for intervention.After culture for a certain period of time,the cells were collected for the following tests:The accumulation of lipids in the cells was detected by semi-quantitative method of oil red 0 dye solution to evaluate the degree of lipid differentiation;The activity of alkaline phosphatase(ALP)was measured by pNPP method;The expression of bone morphogenetic protein-2(BMP-2)and type Ⅰ collagen(Col Ⅰ)were detected by western blot assay to evaluate the degree of bone differentiation.Results Mangiferin could significantly up-regulate the expression of BMP-2 and Col Ⅰ in vitro,increase the level of ALP,and promote bone differentiation of rBMSCs.Hcy promoted lipid differentiation of rBMSCs by increasing lipid accumulation,and down-regulated the expression of BMP-2 and Col Ⅰ,reduced the intracellular ALP level,thereby inhibiting bone differentiation of rBMSCs.How-ever,the above Hcy-related effects could be successfully reversed by mangiferin.Conclusion Mangiferin can sig-nificantly promote bone differentiation of rBMSCs in vitro,while Hcy can inhibit bone differentiation of rBMSCs and promote its lipid differentiation.Mangiferin has the ability to reverse this effect,indicating that mangiferin has certain potential in the treatment of osteoporosis-related diseases.

Objective To establish a lipid differentiation model of primary rat bone marrow mesenchymal stem cells(rBMSCs)in vitro using homocysteine(Hcy),and analyze the specific effects of Hcy on lipid and bone differentiation of BMSCs;to comprehensively explore the effects of mangiferin on lipid and bone differentiation of BMSCs,and further reveal the potential mechanism of mangiferin in the treatment of osteoporosis through the inter-vention of Hcy-induced BMSCs by different concentrations of mangiferin.Methods First,rBMSCs were extracted and isolated.The rBMSCs that were well-cultured to a certain generation were placed in culture medium containing different concentrations of Hcy(0.125,0.250,0.5,1,2,4 mmol/L)to establish lipid differentiation model of rBMSCs.Then,different concentrations of mangiferin(37.5,75,150 μmol/L)were applied to the experimental cells for intervention.After culture for a certain period of time,the cells were collected for the following tests:The accumulation of lipids in the cells was detected by semi-quantitative method of oil red 0 dye solution to evaluate the degree of lipid differentiation;The activity of alkaline phosphatase(ALP)was measured by pNPP method;The expression of bone morphogenetic protein-2(BMP-2)and type Ⅰ collagen(Col Ⅰ)were detected by western blot assay to evaluate the degree of bone differentiation.Results Mangiferin could significantly up-regulate the expression of BMP-2 and Col Ⅰ in vitro,increase the level of ALP,and promote bone differentiation of rBMSCs.Hcy promoted lipid differentiation of rBMSCs by increasing lipid accumulation,and down-regulated the expression of BMP-2 and Col Ⅰ,reduced the intracellular ALP level,thereby inhibiting bone differentiation of rBMSCs.How-ever,the above Hcy-related effects could be successfully reversed by mangiferin.Conclusion Mangiferin can sig-nificantly promote bone differentiation of rBMSCs in vitro,while Hcy can inhibit bone differentiation of rBMSCs and promote its lipid differentiation.Mangiferin has the ability to reverse this effect,indicating that mangiferin has certain potential in the treatment of osteoporosis-related diseases.

Objective To investigate the relationship between putative rs5744168 of Toll-like receptors 5 (TLR5)and ANCA associated small vasculitis (AAV) in Guangxi Han nationality. Methods Polymorphism was analyzed by polymerase chain restricted fragments length polymorphism in 120 cases with AAV and 212 controls. Results (1)There were two genotypes of CC and CT in AAV group and control group. The frequencies distribution of CC and CT in 120 AAV patients were 82.50% and 17.50% respectively and the frequencies of allele C and T 91.25% and 8.75%,respectively. In controls,the genotypefrequencies of CC and CT were 88.68% and 11.3%, and frequencies of allele C and T 94.34% and 5.66%, respectively. No significant difference was found in either genotype distribution or allele frequencies between the patients and the controls ( P > 0 . 05 ) . ( 2 ) Significant reductions in the incidence of BUN, uric acid, quantitative test of 24 h urinary protein and erythrocyte sedimentation rate(ESR) were found in CC genotype (P < 0.05). (3) Binary regression model with a logit link function found total cholesterol was related with AAV. Conclusion The susceptibility of AAV in Guangxi Han population has nothing to do with the polymorphism of rs5744168.In AAV patients, polymorphism of rs5744168 may be associated with ESR, BUN, uric acid and quantitative test of 24 h urinary protein levels.

Objective To investigate the correlation between Toll-like receptor2 (TLR2) gene promoter region -597T/C polymorphism and primary ANCA associated small vasculitis (AAV) in Guangxi Han people. Methods A case contrastive control study was adopted in the study. Patients with AAV (patients group, n=110) and healthy people (control group, n = 200) were recruited. Associated serum indexes were detected and polymorphisms of TLR2 gene promoter 597T/C were analyzed by polymerase chain restricted fragment length polymorphisms (PCR-RFLP). Results (1)Three TLR2-597T/C genotypes were discovered in 110 AAV patients, namely, TT, TC and CC, with the frequency of 54.55%,40.00% and 5.45% respectively. And the frequencies of allele T and C were 74.55% and 25.45%. In control group, the genotype frequencies of TT, TC and CC were 56.00%,40.50% and 3.50%, with 76.25% of allele T and 23.75% of allele C. No significant differences were found in neither genotype distribution nor allele frequencies between the patients group and control group ( P > 0 . 05 ) . ( 2 ) Significant differences were found in the incidence of proteinuria rate and the hemoglobin (P< 0.05)in AAV patients. (3)There was no significant difference between AI and CI in TT, TC and CC genotype in AAV patients. Conclusions Polymorphism of TLR2-597T/C may be correlated with the incidence of proteinuria and the level of hemoglobin, while no obvious correlation with the genetic susceptibility of ANCA in vasculitis patients of Guangxi Han people.