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

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 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 investigate the physicochemica l properties and immunobiological activity of a polysaccharide (RAP-B-1) from stems of Rubus amabilis. Methods The crude polysaccharide (RAP) was obtained successively by boiling, ethanol precipitating and dialyzing. RAP was isolated with DEAE-cellulose and Sephadex G-100 to obtain a polysaccharide RAP-B-1. The physicochemical properties of RAP-B-1 were studied by hydrolysis, periodate oxidation, Smith degradation and methylation, CE, IR, NMR and GC-MS. The immunobiological activities were estimated by the proliferative activity of spleen lymphocytes and phagocytic activity of peritoneal macrophages in mice. Results The molecular weight of RAP-B-1 was 4.80×104 with specific optical rotation value [α] 20D+68.3 (c=1,H2O), and was composed of eight monosaccharides. The molar ratios were as Xyl: Ara: Glc: Rha:Gal: Man: GlcA: GalA = 1.0:6.9:0.8:1.1:6.9:0.3:0.5:3.3. RAP-B-1 was an arabinogalactan. The linkages of arabinose were →1) Ara (2,3→,→1) Ara(5→and→1) Ara, and the linkages of galactose were→1) Gal(4→,→1) Gal(6→and→1) Gal. RAP-B-1 could improve the proliferative activity of spleen T cells(P<0.05) and booste phagocytic activity of peritoneal macrophages at 50μg/ml concentration(P<0.01). Conclusion RAP-B-1 is an arabinogalactan and has immunobiological activity.

In order to alleviate the "difficulty and annoyance in dispensing medicine" of patients with chronic diseases and promote hierarchical healthcare system, the policy of long-term prescription for chronic diseases has been implemented in the country. This article summarizes the current status and effectiveness of implementation of the long-term prescription, and explores the existing problems. The improvement of prescription formulation, review, deployment, distribution of drugs, health education and other issues to ensure the safety of treatment are discussed. Meanwhile, we suggest that the relevant supporting policies of medical insurance should be improved to further promote the long-term prescription.

Objective To analyze the clinical, imaging characteristics and NOTCH3 mutations of cerebral autosomal dominant arteriopathy with the subcortical infarcts and leukoencephalopathy (CADASIL) in Henan, China.Methods CADASIL patients diagnosed by gene or biopsy in People′s Hospital of Zhengzhou University between 2012-2016 were recruited.Clinical and imaging features of these patients were analyzed retrospectively.The distribution of NOTCH3 gene mutations hotspots was described in Henan region at the same time.Results There were 37 patients from 19 families who were diagnosed as CADASIL by genetic testing or biopsy, 27 of whom had symptoms of CADASIL.Two families were confirmed by pathological examination and 17 by genetic testing.Of these 17 families, 13 mutations were found.Mutations in exon 11 were found in eight families, in exon 4 were detected in four families, and in exon 13 were found in two families.Mutation in exons 3, 8 and 20 was detected in one family respectively.Most patients presented with stroke and several presented with cognitive decline.Twelve patients had been attacked by risk factors.Magnetic resonance imaging (MRI) was performed on 22 patients.White-matter lesions were distributed in brain stem, basal ganglia, subcortical, temporal pole, external capsule.There were 19 patients with white-matter lesions in temporal pole and seven in capsula externa, showed as a high signal in T2WI.Conclusions CADASIL patients can be associated with risk factors.T2WI hyperintensities in the anterior temporal lobe were more common than that in the capsular external.Exon 11 and exon 4 were the hotspots for the NOTCH3 mutation in Henan patients.

Mild encephalitis/encephalopathy with reversible splenial lesion has special clinical-imaging features. According to the extent of lesion involvement, it can be divided into type Ⅰ and type Ⅱ. Clinically, type Ⅰ is more common, and type Ⅱ is rare. A rare case of recurrent type Ⅱ mild encephalitis/encephalopathy with reversible splenial lesion is reported. The patient presented with typical type Ⅱ mild encephalitis/encephalopathy with reversible splenial lesion for the first time, involving the corpus callosum and the deep white matter, and the lesions disappeared after a short-term reexamination. Two years later, the lesions recurred, and the scope of the lesions was similar to that of the first time, and the lesions disappeared after a short-term reexamination. The clinical and imaging findings are analyzed in combination with relevant literatures review in order to deepen the understanding of the disease and improve the level of diagnosis and treatment.

Objective:To develop a monitoring tool for evaluating health literacy level of general practitioners.Methods:The health literacy monitoring questionnaire for general practitioners was preliminarily developed by referring to the National Residents′ Health Literacy Monitoring Questionnaire. The Delphi method was used to conduct two rounds of consultation among 15 experts to improve the questionnaire.Results:The effective response rates of the two rounds of expert consultation were 100.0%, the expert authority coefficients of the two rounds of consultation were 0.87 and 0.86, the mean scores of the two rounds of expert questions were 3.93 -5.00 and 4.47-5.00. The variance coefficients of the two rounds of expert scores were 0-0.32 and 0-0.20, and the Kendall harmony coefficients of the two rounds of expert scores were 0.167 and 0.102, respectively (all P<0.05). Finally, the basic theory literacy dimension (including 8 chronic disease prevention items, 5 maternal and child health items and 5 infectious disease prevention items), and the basic skill literacy dimension (including 6 safety and first aid items, 8 health information items), and the healthy lifestyle and behavior dimension (7 items, including regular physical examination, exercise, diet and so on) were established. A total of 39 items and 3 dimensions were used to monitor the health literacy level of general practitioners. Conclusion:The monitoring tool of health literacy level for general practitioners based on Delphi method has been preliminarily constructed, which can be used to evaluate the health literacy level of general practitioners.

Objective:To build a system for evaluation on post competency of general practitioners.Methods:From April to October 2020, the Delphi method was used to consult on the importance of 4 first-level indicators and 48 second-level indicators for evaluation on post competency of general practitioners. Excel 2016 and SPSS 22.0 was used for data entry and statistical analysis.Results:There were 16 consulting experts, and the positive coefficients of the two rounds were 100% and 75%, respectively. The overall authority coefficient Cr of experts was 0.85. For the first-level indicators, the mean values of the importance of the two rounds were 8.07-9.00 and 8.67-9.00, and the coefficient of variation were 0-0.16 and 0-0.09, respectively. For the second-level indicators, the mean values of the importance of the two rounds were 6.79-9.00 and 8.17-9.00, and the coefficient of variation were 0-0.38 and 0-0.16, respectively. All the coordination coefficient tests were statistically significant ( P<0.001). Finally, the evaluation system was established including 4 first-level indicators and 32 second-level indicators. Conclusion:The constructed post competency evaluation system for general practitioners has a relatively high coordination and credibility, which can provide a reference for the post competency evaluation of general practitioners.

Objective To evaluate the range of motion of gastroesophageal junction (GEJ) adenocarcinoma during preoperative radiotherapy.Methods Fourteen consecutive patients who received preoperative chemoradiotherapy for GEJ adenocarcinoma were included in this study.Fiducial markers were placed on the upper and lower edges of and around the primary tumor under a gastroscope.Eight patients underwent four-dimensional computed tomography to obtain 98 intrafractional images containing 8 fiducial markers at the GEJ.Twelve patients underwent cone-beam computed tomography at the 1 st to 5th,7th,12th,17th,and 22nd courses of radiotherapy to obtain 90 interfractional images.The paired t test was used for difference analysis.Results The intrafractional tumor displacements in left-right (LR),ventro-dorsal (VD),and cranio-caudal (CC) directions were 0.92±0.95 mm,2.27±2.73 mm,and 9.95±5.48 mm,respectively;the motion in CC direction was larger than that in LR or VD direction (P=0.000 or P=0.000);the motion in VD direction was larger than that in LR direction (P=0.000).The interfractional tumor displacements in LR,VD,and CC were 6.56±4.19 mm,5.69±3.29 mm,and 6.49±4.37 mm,respectively;the motion in LR or CC direction was larger than that in VD direction (P=0.031 or P=0.044);there was no significant difference between the motions in LR and CC directions (P=0.956).In order to ensure 95% of prescribed dose to at least 90% of the tumor volume,the margins from GEJ lesion in LR,VD,and CC directions were 19.4 mm,14.6 mm,and 27.2 mm,respectively,which could cover both intrafractional and interfractional tumor displacements during preoperative radiotherapy.Conclusions GEJ tumor has a wide range of movement in preoperative intra-and inter-fractional radiotherapy.This should be considered for precise radiotherapy,and a new method should be selected to limit tumor movement.