1.Office blood pressure combined with ambulatory blood pressure monitoring in hypertension diagnosis
DING Fang ; YU Wei ; HU Shiyun ; XUAN Cheng ; YU Liuyan ; CHEN Qifeng ; FAN Minhua ; LIU Qingmin ; XU Xiaoling ; YAN Jing
Journal of Preventive Medicine 2020;32(5):460-465
Objective:
To evaluate the effects of office blood pressure(OBP)combined with ambulatory blood pressure monitoring(ABPM)on the diagnosis of hypertension.
Methods:
The residents aged 35-79 years without hypertension history,whose casual OBP were 120~159 mm Hg/80~99 mm Hg,were enrolled from 4 communities of Hangzhou and Zhuji from 2015 to 2018. They were performed OBP measurements on other two days in 4 weeks and ABPM in a week. There were 2 criteria of OBP as elevated OBP on the first day or in 3 different days,and 4 criteria of ABPM as elevated mean BP in 24 hours, daytime, nighttime and either of the above time. Receiver operating characteristic(ROC)curve was employed to evaluate the effects of different OBP criteria combined with ABPM criteria on the diagnosis of masked hypertension(MH)and white-coat hypertension(WCH).
Results:
Taking 3-day-OBP as a golden standard,the 1-day-OBP with 4 ABPM criteria had the areas under the ROC curve(AUC)of 0.79-0.81,sensitivity of 57.58%-62.77% and specificity of 100.00% in MH;had the AUC of 0.95-0.98,sensitivity of 100.00% and specificity of 88.96%-96.80% in WCH. The Kappa values were all less than 0.6,known as low consistency. Taking either time of ABPM as a golden standard,24 hours,daytime and nighttime ABPM criteria with OBP had the AUC of 0.90-0.92,sensitivity of 79.17%-83.90% and specificity of 100.00% in MH(all Kappa>0.6),when with 1-day-OBP,the Kappa values were all more than 0.8,known as high consistency;had the AUC of 0.95-1.00,sensitivity of 100.00% and specificity of 89.54%-99.37% in WCH,the Kappa values of daytime ABPM were all more than 0.6,known as high consistency.
Conclusions
If limited by options, 1-day-OBP could be used instead of 3-day-OBP for detection of WCH or exclusion of MH yet with less accuracy; 24 hours or daytime ABPM instead of either time of ABPM was reliable.
2.Chaperone-mediated Autophagy Regulates Cell Growth by Targeting SMAD3 in Glioma.
Hanqun LIU ; Yuxuan YONG ; Xingjian LI ; Panghai YE ; Kai TAO ; Guoyou PENG ; Mingshu MO ; Wenyuan GUO ; Xiang CHEN ; Yangfu LUO ; Yuwan LIN ; Jiewen QIU ; Zhiling ZHANG ; Liuyan DING ; Miaomiao ZHOU ; Xinling YANG ; Lin LU ; Qian YANG ; Pingyi XU
Neuroscience Bulletin 2022;38(6):637-651
Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.