1.The effects of premature atrial contractions on hemodynamics with coronary heart disease and hypertension without basic cardiovascular disease
Yuanfang GUO ; Bo YANG ; Shaoyong CHENG ; Meihui LI ; Zhuoqing WANG ; Congchun HUANG ; Junhua WANG ; Jianchang WANG
Chongqing Medicine 2015;(28):3930-3932
Objective To explore the effects of premature atrial contractions on hemodynamics combined with coronary heart disease and hypertension .Methods According to the advance rate ,62 patients with premature atrial contractions were invided into 3 groups :< 20% group(n= 18) ,20% - 40% group(n= 20) and > 40% group(n= 24) .All of the patients were performed imped‐ance cardiography .The hemodynamics indexes at different times were compared ,and the variation rates in hemodynamics of the three groups combined with basic diseases were analyzed .Results Stroke volume(SV) ,stroke index(SI) ,aortic compliance(AC) , stroke work(SW) ,stroke work index(SWI) ,and heather index(HI) were smallest when premature atrial contractions ,which were middle when the first sinus beats before premature atrial contractions ,and largest when the first sinus beats after premature atrial contractions(P< 0 .05) .The variation rates in hemodynamics were smallest in < 20% group ,which were middle in 20% - 40%group ,and largest in > 40% group(P< 0 .05) .The percentage of patients with basic heart diseases was lowest in < 20% group , which was middle in 20% - 40% group ,and highest in > 40% group(P< 0 .05) .Conclusion The advance rate is relatively large in patients with basic cardiovascular disease .Premature atrial contractions has certain effects on hemodynamics ,and the effects are positively correlated with advance rate .
2.The impact of flat deformity of the cerebral cortex on motor functioning and cognition
Yunyi LIU ; Jingpu ZHAO ; Yingying NI ; Jiafa LIU ; Mengliang MA ; Shaoyong DENG ; Guojun LI ; Lina CHENG ; Xiao LYU ; Tiebin YAN
Chinese Journal of Physical Medicine and Rehabilitation 2017;39(10):753-755
Objective To investigate the impact flat deformity of the cerebral cortex induced by congenital hydrocephalus on motor functioning and cognition.Methods Tomography was used to confirm the presence of flat cortex deformity in three congenital hydrocephalus patients ranging in age from 20 to 33.Their motor control,balance,cognition and ability in the activities of daily living (ADL) were evaluated using the Fugl-Meyer assessment (FMA),the Berg balance scale (BBS),the mini-mental state examination (MMSE) and the modified Barthel index (MBI).Speech dysfunction was judged on the basis of clinical communication.The patients were scanned using a 64-slice spiral CT and size-of-ventricle indices were calculated.Results All 3 patients underwent ventrideperitoneal shunt.Their FMA scores were 75.5,83 and 100,with BBS scores of 4,24 and 56,MMSE scores of 14,23 and 26,and the MBIs of 40,90 and 100.CT images showed obvious ventricle enlargement and a thinner cortex layer in all three,with the thinnest part 0.18 cm,0.22 cm and 0.57 cm.Their ventricle indexes were 303%,288% and 192%,respectively.Conclusion Although there is no systematic rehabilitation therapy for such patients,their motor,cognition and speech functioning were good,indicating the great potential for plasticity of the human brain.
3.Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells.
Qiufen ZHANG ; Yingyi CHEN ; Duan NI ; Zhimin HUANG ; Jiacheng WEI ; Li FENG ; Jun-Cheng SU ; Yingqing WEI ; Shaobo NING ; Xiuyan YANG ; Mingzhu ZHAO ; Yuran QIU ; Kun SONG ; Zhengtian YU ; Jianrong XU ; Xinyi LI ; Houwen LIN ; Shaoyong LU ; Jian ZHANG
Acta Pharmaceutica Sinica B 2022;12(2):876-889
SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.