Histone deacetylase 6 (HDAC6) is an unique subtype of histone deacetylases with two tandem deacetylase domains and substrate specificity for non-histone proteins. It is involved in many important physiological and pathological processes and has become a promising therapeutic target in recent decades. Different kinds of potent HDAC6-selective inhibitors have been reported around the world. This paper reviews the progress in the study of structure and functions of HDAC6 as well as the development of HDAC6-selective inhibitors.
Histone Deacetylase Inhibitors ; pharmacology ; Histone Deacetylases ; chemistry ; Humans ; Substrate Specificity

Budd-Chiari Syndrome ; diagnosis ; diagnostic imaging ; Humans ; Magnetic Resonance Angiography ; Magnetic Resonance Imaging ; Tomography, X-Ray Computed ; Ultrasonography

Objective:To analyze the satisfaction degree and related factors of community health services among residents in Zhejiang province.Methods:A service satisfaction survey was conducted during July to October 2019; using purpose sampling method three community health service centers were selected as survey sites in Hangzhou, Jiaxing, and Lishui cities, representing high, medium, and low economic development levels in Zhejiang province. The short-form Patient Satisfaction Questionnaire (PSQ-18) was used in the survey. SPSS 19.0 was adapted for data analysis, and multivariate logistic regression was applied use of analyze the affecting factors of satisfaction.Results:A total of 464 questionnaires were distributed, and 429 valid ones were returned with a response rate of 92.46%. Among them, 112 were from Hangzhou, 159 from Jiaxing, and 158 from Lishui. The overall satisfaction score of community health services was (4.22±0.59), and the satisfaction rate was 85.8%(368/429).Among the three cities, the overall satisfaction score in Lishui was the highest (4.28±0.51) with a satisfaction rate of 88.7% (140/158). The satisfaction scores of service quality, doctors' interpersonal communication ability, doctor-patient communication level, economic efficiency of service, timeliness of service, and accessability of service were (3.99±0.57), (4.10±0.77), (4.27±0.56), (3.54±0.84), (4.13±0.68) and (3.88±0.55); the satisfaction rates of those items were 59.6%(256/429), 79.4%(340/429), 86.3%(370/429), 43.6%(187/429), 78.9%(338/429)and 50.3%(216/429), respectively. Multivariate logistic regression analysis indicated that the quality of service, doctors' interpersonal communication ability, doctor-patient communication level and accessability of service were the affecting factors of the residents' satisfaction to community health services ( OR=3.734, 2.928, 7.732, 4.275; P<0.05). Conclusion:The residents of Zhejiang province have a high overall satisfaction with community health services. The quality of service, doctors' interpersonal communication ability, doctor-patient communication level and accessability of service are the affecting factors of the overall satisfaction degree.

Objective To explore the mechanism of Didang Qigui Recipe on preventing diabetes. Methods Ten female rats were set randomly as normal group, and others 70 were injected with STZ (60 mg/kg) to establish the diabetic model. After the model was established, 50 model rats were randomly divided into five groups:the model group, Didang Qigui Recipe group, the gliclazide group, Didang Qigui Recipe high-dose group, Didang Qigui Recipe and gliclazide group, with 10 rats in each group. All groups were given a gavage with related medicine. With treatment being given respectively, eight weeks later, contents of IL-1βand IL–2 in serum were detected by ELISA and structure of pancreatic β cells was observed by immunohistochemistry and microscope. Results Compared with the model group, the contents of IL-1βand IL-2 in serum of rats decreased in treatment groups, especially in Didang Qigui Recipe group and Didang Qigui and gliclazide group (P<0.05). The degree of apoptosis in pancreaticβcells, especially in the above two groups, has been less affected than other groups (P<0.05). Conclusion Didang Qigui Recipe has preventive and therapeutic effects on diabetes by inhibition of inflammatory response and protection structure of pancreaticβcells.

ObjectiveTo investigate the effect of arsenic trioxide (As2O3) on the metastasis capability of Ewing's sarcoma ceils. MethodsMTT assays were performed to choose appropriate concentrations of As2O3 (＜ 2 μmol/L) for the experiments.Migration and invasion assays were performed to assess the effect of As2O3 on the metastasis of Ewing's sarcoma cells. Changes in matrix metalloproteinase(MMP)-9 expressions were detected by gel zymography assay and the phosphoinositide 3-kinase/AKT(PI3K-AKT)pathway was investigated using Western blot. ResultsThe amount of Ewing's sarcoma cells across basal membrane of Transwell in migration and invasion assay decreased gradually with the increase in As2O3 concentration. The average quantities of A-673 across the membrane after treatment by gradual concentrations accounted for 54.3 ％,49.0 ％ and 17.0 ％ of that of untreated group respectively in migration assay (F=112.78,P ＜ 0.01), while 52.7 ％, 32.3 ％ and 10.3 ％ in invasion assay(F =183.76, P ＜ 0.01). Similarly, the percentage of RD-ES was 46.0 ％,39.0 ％ and 8.0 ％ in migration assay (F =408.25,P ＜ 0.01) and 58.7 ％,22.3 ％ and 9.0 ％ in invasion assay (F =373.25, P ＜ 0.01)respectively. The difference had statistics significance.The expression of MMP-9 was suppressed by As2O3 treatment according to gel zymography assay.Western blot assay showed that PI3K-AKT pathway was inhibited and nuclear factor kappa B(NF-κB)was inactivated.ConclusionLow-concentration As2O3 may inhibit metastasis capability of Ewing's sarcoma cells.

The Offsite Medical Accounting Information Supervising System was developed for patients of Sichuan new rural cooperative medical scheme (NRCMS) using the C#programming language under .NET development environ-ment based on Microsoft Visual Studio 2010 in order to solve the problems in offsite medical accounting information statistics and supervision for patients of NRCMS.The system is a B/S-based MVP 3-tier structure with VPN hard-ware firewall and VPN client software plus certificate built-in, and can thus be used to supervise the offsite medical accounting for patients of NRCMS, analyze their medical advice seeking indexes at other places, and provide data for the NRCMS fund management .

Objective To assess the feasibility of chondrocyte and osteoblast composites in vitro cultured in bioreactor in repairing cartilage defects.Methods Marrow mesenchymal stem cells were isolated and cultured in vitro,and then were induced to chondrocytes and osteoblasts by growth factor.Chondrocytes and osteoblasts were cocultured in bioreactor for 21 days to form the composites.The adhesion,extension and proliferation of chondrocytes and osteoblasts were observed under scanning electron microscope.The cartilage defects on canine model were repaired with the chondrocyte and osteoblast composites.Results The induced chondrocytes and osteoblasts had fine adhesion,extension and proliferation in the β-TCP scaffold.The repaired tissues in experimental group maintained their thickness to the full depth of the original tissues.A statistical difference was observed between negative control group and experimental group(q=12.337 0,P ＜ 0.01)and between blank control group and experimental group (q=31.539 3,P ＜0.01).Conclusion Perfusion bioreactor makes chondrocyte and osteoblast survive and proliferate in a three-dimensional scaffold and increases the composition rate of the chondrocyte and osteoblast.

Locoweeds are presently defined as those species of the genera Oxytropis and Astragalus (family Leguminosae) that specifically contain the key toxic constituent,swainsonine.After ingesting locoweeds,livestock can develop poisoning disease characterized by chronic dysfunction of the nervous system,which causes severe economic losses to the pastoral areas.In addition,swainsonine has attracted a great attention from toxicology and medicine fields,due to its dual role of toxicity and pharmacological activity.This review not only summarizes the latest research progress of toxicity and its poisoning mechanism,pharmacological activity,source,and biosynthesis pathway of swainsonine,but also speculates the possible regulatory enzymes involved in the synthesis pathway.Moreover,the future research on swainsonine is also looked ahead,which provide references for the prevention and treatment of locoism.

Objective:To explore the application of speckle tracking imaging (STI) stratification strain technique in the assessment of circumferential myocardial function and the myocardial protection of ATP-postconditioning (ATP-PostC) in a rabbit model of acute myocardial infarction.Methods:A total of 40 rabbits were randomly divided into 2 groups: pure ischemia reperfusion group (IR group)and ATP-PostC group. STI images were recorded before and 45 min after occlusion of coronary artery, post low-dose dobutamine stress echocardiography, 60 and 120 min after reperfusion, respectively. The following parameters were obtained: left ventricular ejection fraction(LVEF), heart rate (HR), endocardial circumferential systolic strain (CSsys-endo), mid-myocardial circumferential systolic strain (CSsys-mid) and epicardial circumferential systolic strain (CSsys-epi) at left ventricular short-axis level. At different time points after occlusion and reperfusion, 5 experimental rabbits were killed in each group for pathological examination.Results:①Forty-five min after coronary artery occlusion in both groups, the values of LVEF and HR were decreased( P<0.05), and the absolute values of CSsys-endo, CSsys-mid and CSsys-epi were significantly reduced( P<0.01). After LDDSE, the absolute values of CSsys-endo, CSsys-mid and CSsys-epi were increased, which were different from those after blockade( P<0.05). ②After reperfusion, the circumferential strains were not significantly different from those after blockade in IR group ( P>0.05). After blockade, the absolute values of circumferential strains were increased significantly in the ATP-PostC group compared with IR group( P<0.05). In the ATP-PostC group, the absolute values of CSsys-endo at different time points after reperfusion increased significantly compared with that after blockade ( P<0.05). The absolute values of CSsys-endo and CSsys-mid 120 min after reperfusion continued to increase significantly compared with those 60 min after reperfusion( P<0.05). ③Pathological examination: After 60 min of blockade, there was no significant difference in myocardial infarction area between the IR group and the ATP-PostC group( P>0.05). The percentage of infarct areas at each time point of reperfusion in the ATP-PostC group was decreased compared with that after blockade( P<0.05). Compared with the IR group, the percentage of infarct area in the ATP-PostC group was smaller after 120 minutes of reperfusion and the difference was statistically significant ( P<0.05). Conclusions:The applications of STI stratification strain technique and LDDSE can assess left ventricular circumferential strains at each of myocardial layers before and after reperfusion in rabbit myocardial ischemia ATP-PostC model, identify and evaluate the function of viable myocardium, and exhibit the significant protective effects of ATP-PostC on myocardial reperfusion injury.