Objective: To explore therapeutic effects of calcium channel blocker combined statins on aged patients with hypertension, and their influence on inflammatory factor levels.Methods: A total of 124 aged patients with hypertension, who were treated in our hospital from Oct 2014 to Oct 2015 , were randomly and equally divided into amlodipine group (received amlodipine therapy based on routine treatment) and combined treatment group (received atorvastatin calcium based on amlodipine group) according to random number table.Levels of blood pressure, C reactive protein (CRP), interleukin (IL)-6, endothelin (ET) and blood lipids before and after treatment, and therapeutic effect and incidence of adverse reactions were compared between two groups.Results: Compared with amlodipine group after treatment, there were significant reductions in levels of systolic blood pressure [(143.57±3.14) mmHg vs.(131.73±3.42) mmHg], diastolic blood pressure [(82.17±3.26) mmHg vs.(76.51±3.27) mmHg], CRP [(7.32±0.71) mg/L vs.(5.57±0.76) mg/L], IL-6 [(133.42±27.31) ng/L vs.(123.73±22.81) ng/L], ET [(50.74±4.96) pg/L vs.(45.71±5.78) pg/L], total cholesterol [(5.32±0.66) mmol/L vs.(4.12±0.52) mmol/L], triglyceride [(1.56±0.42)mmol/L vs.(1.21±0.37) mmol/L] and low density lipoprotein cholesterol [(3.12±0.48) mmol/L vs.(2.43±0.43) mmol/L], and significant rise in high density lipoprotein cholesterol level [(1.41±0.12) mmol/L vs.(1.55±0.17) mmol/L] in combined treatment group, P<0.05 or <0.01.Compared with amlodipine group, there was significant rise in total effective rate (77.4% vs.91.9%) in combined treatment group, P=0.025.There was no significant difference in incidence rate of adverse reactions between two groups (P>0.05).Conclusion: Calcium channel blocker combined statins possesses definite therapeutic effects on aged patients with hypertension.It can reduce levels of blood pressure and blood lipids and inflammations and improve vascular endothelial cell function, which is worth extending.

Objective To investigate the relationship between human leptin receptor(LEPR)gene G3057A polymorphism and type 2 diabetes complicated with non-alcoholic fatty liver disease(NAFLD).Methods 216 cases of newly diagnosed type 2 diabetes(104 cases complicated with NAFLD)and 108 cases of normal glucose tolerances(NGT)were recruited.Hemi-nested PCR-RFLP and PCR direct sequence analysis were conducted to detect the polymorphisms of LEPR G3057A polymorphism.The plasma leptin and insulin levels were measured by ELISA kit.Plasma lipid and glucose metabolic parameters were measured routinely.Liver ultrasound scanning Was carried out among all subjects.Results Type 2 diabetic patients complicated with NAFLD had higher plasma alanine aminotransferase(ALT),triglycerides(TG),low density lipaprotein cholesterol(LDL-C),leptin levels and lower plasma insulin levels than those cages without NAFLD and NGT.The variant frequency at nucleotide 3057 G to A transversion Was 76.0% in type 2 diabetic patients complicated with NAFLD,which Was also significant higher than those cases without NAFLD(62.1%)or NGT cases(53.2%)(x2=14.63,P＜0.01).Conclusions The polymorphism of LEPR gene 3057 probably contributes to the onset of NAFLD in type 2 diabetes by regulating lipid metabolism and affecting insulin sensitivity.

OBJECTIVETo evaluate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine levels in patients with type 2 diabetes mellitus and diabetic retinopathy (DR).

METHODSTotal of 208 patients with type 2 diabetes mellitus and 57 controls were recruited into the study. MTHFR genetic C677T polymorphisms were determined by PCR-RFLP. Plasma total homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection.

RESULTSThe frequencies of MTHFR TT homogeneous type, CT heterogeneous type and allele T (28.18%, 41.82%, 49.09%) were significantly higher in the type 2 diabetes mellitus with diabetic retinopathy group than those without retinopathy (18.37%, 29.59%, 33.16%) and those of controls (17.54%, 28.07%, 31.58%). The presence of the T allele appeared to have a strong association with the development of diabetic retinopathy. The odds ratio was 1.94 with a 95% confidence interval of 1.31 - 2.88. Moreover, plasma homocysteine levels were remarkably higher in patients with TT or CT genotype than in patients with the CC genotype.

CONCLUSIONMTHFR gene C677T mutation associated with a predisposition to increased plasma homocysteine levels may be considered as a genetic risk factor for diabetic microangiopathy (such as DR) in Chinese patients with type 2 diabetes mellitus.

Aged ; Diabetes Mellitus, Type 2 ; complications ; Diabetic Retinopathy ; etiology ; Female ; Genotype ; Homocysteine ; blood ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Mutation ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Polymorphism, Genetic

OBJECTIVETo evaluate the role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine levels in Chinese patients with type 2 diabetes mellitus and diabetic retinopathy (DR).

METHODSMTHFR genetic C677T polymorphisms were determined by PCR-restriction fragment length polymorphism. Total plasma homocysteine levels were measured using high-performance liquid chromatography (HPLC) with fluorescence detection.

RESULTSThe frequencies of MTHFR T homogenetic type and CT heterogenetic type and allele T (28.18%, 41.82%, 49.09%) in type 2 diabetic patients with diabetic retinopathy were significantly higher than those in diabetic patients without retinopathy (18.37%,29.59%,33.16%) or the normal controls (17.54%, 28.07%, 31.58%). Howerver, there were no significant differences in the frequency of MTHFR genotype and allele between the type 2 diabetic patients without retinopathy and the normal controls. The presence of T allele appeared to have a strong association with the development of diabetic retinopathy. The odds ratio was 1.94 and the 95% confidence interval was 1.31-2.88. Moreover, the plasma homocysteine levels in patients with TT or CT genotype were markedly higher than those in patients with CC genotype.

CONCLUSIONMTHFR gene C677T mutation associated with a predisposition to increase of plasma homocysteine may represent a genetic risk factor for diabetic retinopathy in Chinese type 2 diabetes mellitus.

Adult ; Alleles ; DNA ; genetics ; metabolism ; Deoxyribonucleases, Type II Site-Specific ; metabolism ; Diabetes Mellitus, Type 2 ; blood ; complications ; genetics ; Diabetic Retinopathy ; blood ; etiology ; genetics ; Female ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; Middle Aged ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Point Mutation ; Polymorphism, Genetic

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*