1.The Past, Present and Future of External Counterpulsation
Journal of Sun Yat-sen University(Medical Sciences) 2006;27(6):601-605
Enhanced external counterpulsation(EECP) was developed in our laboratory and applied in clinical setting since 1976. Before the year of 1990, the mechanism of this treatment was supposed to promoting collateral circulation by increasing diastolic pressure during counterpulsation. According to a series of investigations, we discovered and confirmed that the flow shear stress were increased obviously during EECP, regulating a series of reaction of shear stress responsive elements, inducing vascular endothelial cell (VEC) repair mechanism, improving VEC function, all of which contribute to the inhibition of development of atherosclerosis. A new generation of EECP device was designed based on the advances above and aimed at promoting the aterial flow shear stress more effectively in turn to protect vascular endothelium.
2.Recent Proceedings in Research of Tumor-associated Disorders of Glucose Metabolism
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):222-228
Metabolic rearrangement is a typical hallmark of cancer cells ,especially the disorders in glucose metabolism. Normal cells rely on the steps of oxidative phosphorylation within the mitochondria to metabolize glucose and yield energy upon enough oxygen ,yet turning to glycolysis in the absence of oxygen . Nevertheless ,tumor cells exhibit high levels of glycolytic flux in different environments ,due to the requirement of malignant proliferation. This phenomenon was named as the Warburg effect ,the initiation of which is driven by multiple mechanisms ,including the influence of tumor microenvironment ,the activa?tion of tumor-promoting signaling pathways ,and the aberrant levels of metabolic enzymes. Moreover ,our recent findings sug?gest that inhibition of gluconeogenesis ,the general reversal of glycolysis ,would further promote the Warburg effect and tumor progression.
3.Role of NLRP3 Inflammasome in Cardiovascular Diseases
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):215-221
Inflammasomes are molecular platforms built around several proteins ,composed of intracellular pattern-recognition receptors,the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)and caspase-1. The inflammasome was believed as the cellular machinery triggering the maturation of proinflammatory cytokines such as interleukin-1β(IL-1β)to engage innate immune defenses. Several types of inflammasomes have been identified ,and among them NLRP3 inflam?masome is currently the most fully characterized inflammasome. Recent studies showed that a variety of cardiovascular risk factors , including dyslipidemia,hypertension and kidney disease,hyperhomocysteinemia,obesity,diabetes and metabolic syndrome,can activate NLRP3 inflammasomes,process the maturation of proinflammatory cytokines IL-1βand IL-18,and promote atherosclerosis. The activation of NLRP3 inflammasomes was also associated with decreased stability of atherosclerotic plaque. These studies suggested an important role of NLRP3 inflammasomes in the pathogenesis of cardiovascular disease. Targeting NLRP3 inflammasome at the stage of its assembling or activation may be a novel strategy for prevention and treatment of cardiovascular disease.
4.Inhibition of Tumor Angiogenesis by Targeted Induction of Endothelial Cell Apoptosis
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):204-214
Angiogenesis is one of the important pathological characteristics in the development of tumor growth. Hence ,an?ti-angiogenes is has become a hot topic in the field of cancer research. The current strategy for anti-angiogenesis therapy is to restore the angiogenic balance which is broken in the tumor via either block of proangiogenic factorsor application of angiogenic inhibitors. Endogenous angiogenic inhibitors show more promising prospects compared with proangiogenic factor antagonists. However ,the un?derlying mechanisms for the angiogenic inhibitors remain to be thoroughly elucidated. There are two kinds of endogenous angiogenic inhibitors,one is the hydrolyzed fragments of precursor protein,such as plasminogen Kringle 5(K5),angiostatin/kringle 1~4,end?ostatin,etc;the other is cell secreted proteins,such as pigment epithelium-derived factor(PEDF),kallikrein-binding protein (KBP/kallistatin),antithrombin,etc. Here we summarized the research progresses on the biological functions,underlying mecha?nisms of tumor angiogenesis and application prospects of K5,PEDF,and KBP,so as to provide insights into the antiangiogenic ther?apies of tumor in the future.
5.Research Progress on Biological Characteristics and Function of Volume Regulated Cl-Channel in Vascular Smooth Muscle Cells
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):177-183
Volume regulated chloride channel (VRCC) enhances cell proliferation through PI3K/Akt signal pathway ,and inhibits cell apoptosis through mitochondrial pathway in vascular smooth muscle cells ,and accelerates the process of atherosclerosis through JNK/p38 MAPK signal pathway,resulting in increasing SR-A expression and ox-LDL uptake. Cerebrovascular remodeling is mediated by VRCC. This effect of VRCC on remodeling is related to accelerating cell proliferation ,migration and accumulation of. extracellular matrix. As to the molecular identification of VRCC ,it is very complex. VRCC is diversity in various cells or tissues , rather than a single ubiquitous channel,VRCC may be contain variedcell type-or tissue-specific subunitcompositions. ClC-3 volume regulated Cl-channel is regulated by both integrin-Src and Rho/RhA-Rock signal pathways.
6.Research Progress and Therapeutic Prospect of Angiogenesis Inhibitors in the Microvascular Complication of Diabetic Mellitus
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):169-176
Microvascular complications of diabetic mellitus injure entire organs of the body. Diabetic retinopathy,foot ulcer, erectile dysfunction and diabetic nephropathy are the major pathogenesis of blindness,non-traumatic amputation,kidney failure and even death,respectively. Thus,early intervention of microvascular complications is the optimized strategy for improving the quality and prolonging the lifespan. Angiogenesis is the one of most significant pathologic features in microvascular complications of diabetic mellitus.Angiogenesis inhibitors are closely involved in the balance regulation of angiogenesis. Therefore ,this review aims to present the research progress and the therapeutic prospect of angiogenesis inhibitors in the microvascular complication of diabetic mellitus.
7.Related Risk Factors between Diabetic Retinopathy and Diabetic Peripheral Neuropathy in Newly Diagnosed Type 2 Diabetes Mellitus
Min FANG ; Yun YU ; Zhenglong OUYANG ; Dan LIU ; Mei WANG
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):315-320
[Objective]To analyze the clinical features and related risk factors in diabetic retinopathy(DR)and diabetic periph?eral neuropathy(DPN),the two micro-peripheral vascular diseases in newly diagnosed type 2 diabetes mellitus.[Methods]A retro?spective study of 211 cases of newly diagnosed type 2 diabetes mellitus inpatient from 2009 to 2012 ,and compare the two micro-peripheral vascular complications.[Results]The morbidity of DPN was(33.6%),which was higher than that of DR,some cases of DR co-existed with DPN,DR was related with DPN(r=0.158,P=0.020). Age and systolic blood pressure were the common risk factors in DR and DPN by single factor analysis.[Conclusion]It should be paid attention to the screening of both DR and DPN in each age group in newly diagnosed type 2 diabetes mellitus. Except for the control of blood glucose ,the control of the systolic blood pressure is important in the prevention and treatment in the two micro-peripheral vascular diseases.
8.Distribution of Genetic Polymorphisms about CYP2C19 Gene in the Elderly Chinese Han Populations of Guangzhou and the Comparison in Different Populations
Xuanhao XIAO ; Tao ZENG ; Xiuxia LEI ; Ze LI ; Jin ZHOU ; Zhiyuan WANG ; Xiaoping PAN
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):307-314
[Objective]To investigate the genetic polymorphisms of the CYP2C19 gene in the elderly Chinese Han populations of Guangzhou,and compare the frequencies of CYP2C19 gene polymorphisms in different populations,in order to provide accurate data for the appropriate prescription.[Methods]To detect the genetic polymorphisms of the CYP2C19 gene by the DNA microarray,and compare the frequencies of CYP2C19 gene polymorphisms in Chinese Han populations from different areas and the different races.[Results]There were 2312 case samples in our study. The allele frequencies of CYP2C19*1,CYP2C19*2 and CYP2C19*3 were 64.27%,30.75%,and 4.98%,respectively. As the genotype,EM(*1/*1)was 41.44%(n=958),IM(*1/*2,*1/*3)was 45.67%(n=1056),and PM(*2/*2,*2/*3 and*3/*3)was 12.89%(n=298). The ratios of EM and IM in Chinese Han populations from different areas and all the subtypes of the CYP2C19 genotype in different minority were statistically significant. As the races,there were difference in all the subtypes of the CYP2C19 genotype when Asian populations were compared with white races(P<1304.64)and black races(P<0.01),which was also statistically significant.[Conclusions]The distributions of the CYP2C19 gene polymorphisms were significantly different in Chinese han populations and in different races,and the main subtypes of the CYP2C19 genotype in the elderly of Chinese han populations were IM and EM,which is beneficial for prescribing appropriate in the elderly populations.
9.Analysis of Prognostic Factors and Development of Prognostic Model for Resectable Acral Melanoma Patients
Yao WANG ; Xizhi WEN ; Ya DING ; Dandan LI ; Ruiqing PENG ; Jingjing LI ; Xiaoshi ZHANG
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):301-306
[Objective]To analyze the prognostic factors of resectable acral melanoma patients ,then develop a novel prognostic model and examined its prognostic value.[Methods]The study retrospectively analyzed clinicopathological characteristics and inflam?matory markers of 232 acral melanoma patients who underwent radical surgical resection between 2000 and 2011 at the Sun Yat-sen University Cancer Center. Kaplan-Meier curves were plotted to estimate overall survival. Significantly predictive factors were identified by multivariate Cox regression analyses and a prognostic model based on these variables was constructed to predict survival.[Results]Cox regression analysis revealed that age,lactic dehydrogenase(LDH),stage,globulin(GLB)and C-reactive protein (CRP)were independently related to survival. After computing these scores ,patients were classified into three risk groups. The new prognostic model identified three categories of patients with different prognoses(P<0.001)and significantly stratify patient prognosis in different tumor stages. The 5-year survival rate was 42.9%,25.7%,and 3.7%in groups 1,2,and 3,respectively. The AUC of new prognostic model is 0.664(95%CI:0.599-0.724).[Conclusion]Age,LDH,stage,GLB and CRP were independently related to survival in our study population,and the prognostic model is useful to stratify patients into different risk groups and it is a useful complement to AJCC staging for Asian patients with acral melanoma.
10.Alterations of Whole Brain Networks Degree Centrality in Patients with Primary Insomnia after Acupuncture Therapy:A Voxel-based Resting-state fMRI Research
Xiaoyue XU ; Shui WANG ; Ru LU ; Xiaofen MA ; Guihua JIANG ; Shishun FU ; Wenfeng ZHAN ; Jin FANG
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(2):296-300
[Objective]To investigate the value of degree centrality(DC),a novel resting-state fMRI parameter,in voxel-wise whole-brain functional networks analysis in primary insomnia(PI)after acupuncture therapy.[Methods]The resting state fMRI were performed in 29 PI patients and 22 age,education,and sex-matched normal healthy subjects. Analysis of DC map changes between the two patient groups and the control group were performed by two sample t test.(threshold at P<0.05).[Results]Compared with the control group,patients with PI showed significantly reduced DC value in middle temporal gyrus(MTG. R);hippocampus(HIP. B);parahippocampal gyrus(PHG. R);putamen(PUT. R);cuneus(CUN. L).[Conclusions]Changes of DC value occurred in some region of brain in the PI patient groups when compared with the control group. It was indicated that DC ,as a novel resting-state fMRI parameter in the voxel-wise whole-brain functional networks ,might be an appealing alternative approach for further study on pathologic and neuropsychological states of PI.