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 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.

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 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.

Objective To explore the difference of gene expression profiling between normal basilar arteries and basilar arteries of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in rabbits. Methods cDNA chip of normal basilar arteries and basilar arteries of CVS after SAH in rabbits were downloaded from GEO database. The chip was analyzed and screened by Bioconductor software, and function enrichment and pathway analysis of the differentially expressed genes were analyzed by Cytoscape software. Then 6 adult male Japanese rabbits were used, and randomly divided into normal control group (n=3) and SAH model group (n=3). Rabbit SAH models were established by cisterna secondary-blood-injection method. RNA data of normal basilar artery specimens on the 0 day and basilar artery specimens after SAH on the 5-day were used to validate the parts of differentially expressed genes by qRT-PCR. Results A total of 4356 differentially expressed genes were found in normal basilar arteries and basilar arteries of CVS after SAH in rabbits. Among them, 920 genes were considered to be significant with P-value<0.05, such as GRIK1, MYH13, ZNF45, SAA3, RLN1, MSR1 and others. Function enrichment analysis indicated that the differentially expressed genes were involved in regulation of Ca2+transmembrane transporter activity, negative regulation of ion transmembrane transport, regulation of potassium ion transport, positive regulation of JAK-STAT signaling cascades and other biological processes. Pathway analysis showed that calcium signaling pathway, cGMP-PKG signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway and other signaling pathways maybe related with the differentially expressed genes. qRT-PCR verification showed that the expression of MSR1 in SAH model group was consistent with that of the chip result. Conclusion The gene expressions of basilar arteries of CVS after SAH in rabbits are significantly different, and MSR1 gene can be used as a potential target for studying the pathological mechanism of CVS.

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.

Objective To investigate and compare the clinical effects of radiochemotherapy alone or in combination with adoptive immunotherapy with cytokine-induced killer ( CIK) cells in patients with locally advanced non-small cell lung cancer (NSCLC).Methods The clinical data of 125 patients with locally advanced NSCLC who were admitted from 2011 to 2012 and did not undergo surgery were analyzed retrospectively, and among these patients, 102 received radiochemotherapy alone ( control group) , and 23 received radiochemotherapy combined with adoptive immunotherapy with CIK cells ( multimodality therapy group) .The two groups were matched at a ratio of 1:2 using propensity score matching, and the factors considered included tumor stage, radiochemotherapy regimen, and outcome after radiochemotherapy.Then 59 patients ( 22 from the multimodality therapy group and 37 from the control group) were enrolled, and survival and tumor control were compared between the two groups.The Kaplan-Meier method was used to calculate survival rates and the log-rank test was used for survival difference analysis and univariate prognostic analysis.Results The 1-, 2-, and 3-year overall survival ( OS) rates were 73%, 32%, and 16%, respectively, in the control group, and 91%, 59%, and 41%, respectively, in the multimodality therapy group ( P=0.030) .The 1-, 2-, and 3-year progression-free survival rates were 61%, 21%, and 17%, respectively, in the control group, and 45%, 10%, and 10%, respectively, in the multimodality therapy group ( P=0.538) .As for the patients with stage ⅢB NSCLC, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group (47%vs.11%, P=0.026). In the patients receiving sequential chemoradiotherapy, those in the multimodality therapy group had a significantly higher 3-year OS rate than those in the control group ( 46%vs.11%, P=0.003) .As for the
patients with squamous cell carcinoma, those in the multimodality therapy group had a significantly higher 3-year distant metastasis-free survival rate than those in the control group ( 73%vs.22%, P=0.029) .The two groups showed similar incidence rates of adverse events, and compared with the control group, the multimodality therapy group had a lower incidence rate of radiation pneumonitis (9%vs.15%, P=0.889) and a higher incidence rate of radiation esophagitis (12%vs.7%, P=0.097).Conclusions Some patients with locally advanced NSCLC can benefit from radiochemotherapy combined with adoptive immunotherapy with CIK cells, but the intended population, timing, and dose safety still need further investigation.

Objective To evaluate transoral Orvil EEA stapler (OrVil) procedure in laparoscopic total gastrectomy for cardiac carcinoma compared with conventional anvil head method (purse-string suture).Methods From May 2014 to December 2014 20 cases were included into OrVil group,and 25 cases into purse-string suture group.Results The two groups had similar mean numbers of dissected lymph nodes [(25 ± 3) vs.(24 ± 4),t =1.067,P =0.292],the mean time of operation,intraoperative blood loss,and postoperative complications (5 vs.6,P =0.938).The length of incision was significantly shorter [(5 ±1) cm vs.(11 ± 2) cm,t =-10.724,P ＜ 0.0l] and the esophagojejunostomy time was significantly less [(28 ± 4) min vs.(39 ± 5) min,t =-7.996,P ＜ 0.01] with the use of OrVil.The time to first flatus and postoperative hospital stay were (3.7 ± 0.9) d vs.(4.4 ± 1.0) d,t =-2.485,P =0.017 and (13 ± 5) d vs.(16 ±4) d,t =-2.184,P =0.035.Conclusions OrVil is a technically safe and feasible surgical procedure for esophagojejunostomy in laparoscopy assisted total gastrectomy in the treatment of cardiac carcinoma.