Objective:To explore the effect of irbesartan in the treatment of the patients with hypertension complicated with diabetes mellitus and its influence on urine trace albumin. Methods:Totally 62 cases of patients with hypertension complicated with diabetes mel-litus were divided into the observation group and the control group randomly with 31 patients in each. The patients in the control group were given the conventional blood sugar and blood pressure control, and the patients in the observation group were treated with irbesartan additionally. The treatment course was 3 months. The changes of blood pressure and urine trace albumin of the patients in the two groups before and after the treatment were compared, and the effect of blood pressure control and the adverse effects were evaluated as well. Re-sults:The total effective rate of the observation group was 96. 8%, which was much higher than that of the control group (83. 9%, P<0. 05) , and the difference had statistical significance (P<0. 05). After the treatment, the systolic blood pressure and diastolic blood pressure of the patients in the two groups were reduced significantly (P<0. 05), and the urinary albumin excretion rate (UAER) and the level of urine trace albumin (mAlb) of the patients in the two groups were obviously lowered (P<0. 05), and the decrease in the obser-vation group was more notable than that in the control group (P<0. 05). No significant difference in the incidence of adverse reactions was shown between the two groups(P>0. 05). Conclusion:The clinical effect of irbesartan in the treatment of patients with hypertension complicated with diabetes mellitus is promising with low incidence of adverse effects,which can effectively protect renal function as well.

Objective To investigate the effects of Tangshen Formula on liver oxidative stress in diabetic rats, and their mechanisms thereof.Methods Rat model of type 2 diabetes mellitus and nonalcoholic fatty liver disease was estab?lished by intraperitoneally injecting small dose of chain urea with cephalosporins (STZ) and feeding high fat fodder . The model rats were randomly divided into control group, model group, Tangshen Formula group and metformin group.The se?rum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), cholesterol (CHO), low density lipoprotein-cholesterol(LDL-C), and superoxide dismutase (SOD), catalase(CAT), vitamin E(VE), nitric oxide (NO) and nitric oxide synthase (NOS) in liver were compared between four groups. Changes of pathological morphology were ob?served under light microscopy. Results There were significantly decrease in serum levels of ALT, AST, TG, CHO, LDL-C in Tangshen Formula group and metformin group compared with those of model group. There were significantly higher levels of SOD, CAT and VE, and lower levels of NO and NOS of liver homogenate in Tangshen Formula group than those of model group. There were higher levels of SOD and CAT, and lower levels of NO and NOS in liver homogenate in metformin group than those of model group. HE staining showed that liver fatty degeneration was significantly reduced in metformin group and Tangshen Formula group compared with that of model group. Conclusion The fatty liver in type 2 diabetic rats is signifi?cantly improved by Tangshen Formula treatment, which is probably associated with the regulation of the response level to oxi?dative stress in liver.

Humans ; Aged ; Processing Speed ; Cross-Sectional Studies ; Cognition ; Hearing Loss/psychology* ; Cohort Studies ; Cognitive Dysfunction

OBJECTIVE：To establish a meth od for the simultaneous determination of 7 active components in Mori Australis Cortex and Mori Cortex from different sources in Chongqing area ，so as to provide reference for improving the quality control standards of Mori Australis Cortex and Mori Cortex and comparing the equivalence of their quality. METHODS ：HPLC method was used to determine the contents of neochlorogenic acid ，mulberroside A ，chlorogenic acid ，astragalin，kaempferol，morusin and isoquercetin in 58 batches of Mori Australis Cortex and Mori Cortex. The chromatographic column was Diamonsil C 18 with mobile phase consisted of 0.1％ formic acid solution-acetonitrile （gradient elution ） at the flow rate of 1.0 mL/min. The detection wavelength was 280 nm，column temperature was 30 ℃，and the injection volume was 10 μL. Using SPSS 22.0 software， independent sample t-test，principal component analysis and cluster analysis were used to analyze the content difference of the above-mentioned 7 active components in Mori Australis Cortex and Mori Cortex. RESULTS ：There was a good linear relationship between the peak area and the concentration of the above 7 active components （r≥0.999 0）. The RSDs of precision ，stability（24 h），repeatability，durability and recovery were less than 3％. The average contents of neochlorogenic acid ，mulberroside A ， chlorogenic acid ， astragalin， kaempferol， morusin and 023-58576130。E-mail：1025473978@qq.com isoquercetin in Mori Australis Cortex were 0.304，22.462， 1.730，1.308，1.593，2.842 and 0.657 mg/g，respectively. Those of Mori Cortex were 0.305，22.995，2.486，2.438， 2.916，4.158 and 1.264 mg/g，respectively. The results of independent sample t-test showed that only the content of kaempferol in the above 7 active components of Mori Australis Cortex and Mori Cortex had significant difference （P＜0.05）. The results of principal component analysis and cluster analysis showed that there was no significant difference in the contents of above 7 active components between Mori Australis Cortex and Mori Cortex. CONCLUSIONS：The established HPLC method is simple ，sensitive and accurate ，which can provide a reference for improving the quality control standard of Mori Australis Cortex and Mori Cortex. Mori Australis Cortex and Mori Cortex have certain quality equivalence in main active components ，and the Mori Australis Cortex from M. australis and M. cathayana can be used as a substitute for the Mori Cortex.

BRAF is a serine/threonine kinase that harbors activating mutations in ∼7% of human malignancies and ∼60% of melanomas. Despite initial clinical responses to BRAF inhibitors, patients frequently develop drug resistance. To identify candidate therapeutic targets for BRAF inhibitor resistant melanoma, we conduct CRISPR screens in melanoma cells harboring an activating BRAF mutation that had also acquired resistance to BRAF inhibitors. To investigate the mechanisms and pathways enabling resistance to BRAF inhibitors in melanomas, we integrate expression, ATAC-seq, and CRISPR screen data. We identify the JUN family transcription factors and the ETS family transcription factor ETV5 as key regulators of CDK6, which together enable resistance to BRAF inhibitors in melanoma cells. Our findings reveal genes contributing to resistance to a selective BRAF inhibitor PLX4720, providing new insights into gene regulation in BRAF inhibitor resistant melanoma cells.