Objective To investigate the effects of Tubastatin A Hcl,a selective HDAC6 inhibitor,on the development of chronic asthmatic mice with airway inflammation,airway remodeling and airway hyperresponsiveness. Methods BALB/C mice were randomly divided into control group, asthma group,dexamethasone group and Tubastatin A Hcl group. The airway resistance,total cells and different cells in BALF,IL?4,IL?5,TGF?β1 were detected by ELISA. HE、AB?PAS and Masson trichrome staining were carried out to assess the airway inflammation and remodeling. Immuno?histochemical staining and western blotting were adopted to determine the expression ofα?SMA and TGF?β1. Results After drugs treatment,air?way resistance decreased,and levels of IL?4,IL?5,TGF?β1,total inflammatory cells and eosinophils in BALF were relieved. Meanwhile,inflamma?tory cells infiltration,goblet cells metaplasia and collagen deposition in lung tissue were also reduced,but all of above the effects of dexamethasone were better than Tubastatin A Hcl. The expression ofα?SMA and TGF?β1 in the lung tissue decreased significantly after treatment ,in which Tu?bastatin A Hcl were slightly better than dexamethasone treatment. Conclusion Tubastatin A Hcl can effectively relieve airway inflammation ,air?way remodeling and airway hyperresponsiveness in chronic asthmatic mice ,but its effect of anti?inflammatory is worse than dexamethasone treat?ment,while it is better than dexamethasone in the effect of relief airway remodeling.

[ ABSTRACT] AIM:To investigate the depressant effect of FK228 combined with rapamycin on the human breast cancer cell line MCF-7 and MDA-MB-435.METHODS:FK228, a new histone deacetylase inhibitor, and rapamycin, the specific inhibitor of the mammalian target of rapamycin ( mTOR) protein, were used in the study.MCF-7 cells and MDA-MB-435 cells were exposed to different concentrations of FK228 and rapamycin.The inhibitory rate of cell growth was de-termined by SRB assay.Combination index ( CI) was used to evaluate the interaction between FK228 and rapamycin.The expression of the apoptotic proteins, cycle proteins and nucleic acid proteins were detected by Western blotting.The cell cycle was analyzed by flow cytometry.RESULTS: Both FK228 and rapamycin showed growth inhibitory effects on the breast cancer cell lines in a time-and dose-dependent manner.CI of the 2 drugs was less than 1 when the inhibitory rate of the cell growth was 50%effective dose (ED50)~ED70, indicating a synergistic effect.The combination therapy of FK228 with rapamycin increased the apoptotic proteins, and induced the down-regulation of phosphorylated Akt and over-expres-sion of caspase-3 compared with a single use of the drugs.The combination therapy of FK228 with rapamycin reduced the cycle proteins, and the cell cycle was arrested in G2/M.The levels of phosphorylated H2AX and acetylated H3 were ob-viously increased after combination therapy.CONCLUSION:The combination therapy of FK228 with rapamycin inhibits the cell proliferation and increases apoptosis with a synergistic effect, which may become a new trend for treating endometri-al cancer.

OBJECTIVETo assess the association of single nucleotide polymorphisms (SNPs) of leptin receptor (LEPR) gene with essential hypertension (EH) and body mass index (BMI) among ethnic Mongolian and Han Chinese from Inner Mongolia region.

METHODSIn total 411 Han Chinese patients with EH and 480 healthy controls, together with 658 Mongolian patients with EH and 403 healthy controls, were collected. The SNPs of the LEPR gene were determined with ligase detection reaction (LDR). Logistic regression was used to analyze the association of the polymorphisms of each locus with EH and BMI. MDR software was used to analyze the interaction between above loci and environmental factors.

RESULTSGenotypic frequencies of LEPR gene rs7555955, rs1137100 and rs1137101 loci had differed significantly among ethnic Hans with EH and the control group (All P<0.05). While those of rs7555955, rs1805094, rs1137100, rs11579567, rs1805134 and rs6669354 loci had differed significantly among ethnic Mongolians with EH and the control group (All P<0.05). After adjustment for confounders, logistic regression analysis indicated that age (OR=2.97, 95%CI:1.94-3.99), BMI (OR=3.93, 95%CI:2.91-5.96), and rs1137101 (AA) (OR=3.96, 95%CI:1.32-11.90) were independent risk factors for EH among ethnic Hans, while age (OR=2.99, 95%CI:2.98-4.57), BMI (OR=3.03, 95%CI:1.05-1.27), rs7555955 (AG, AA) (OR=12.12, 95%CI:2.80-52.43; OR=6.35, 95%CI:1.44-27.94), and rs7555955 (GG) were independent risk factors for EH among ethnic Mongolians (P<0.05).

CONCLUSIONAge and BMI are independent risk factors for EH in both ethnic Han and Mongolian Chinese. rs1137101 locus is associated with EH among ethnic Hans, while rs7555955 locus is associated with EH among ethnic Mongolians.

Ahmed glaucoma drainage valve (AGV) implantation is one of the main methods for the treatment of refractory glaucoma with a higher success rate than conventional filtration surgery.However, as a foreign body, the AGV often causes hyperplasia of scar tissue in the filtration area, wrapping around the drainage plate, thereby inhibiting aqueous fluid outflow and causing the intraocular pressure to rise again, leading to surgical failure.Although multiple injections of anti-metabolic drugs during and after AGV implantation can inhibit postoperative scarring, multiple postoperative subconjunctival injections will not only cause discomfort to patients, but also lead to complications.Therefore, it is necessary to improve the AGV to avoid repeated injection of the drug, achieve slow local release of the drug, and reduce the foreign body reaction of AGV at the same time.Recently, the development of new materials, such as Ologen collagen, poly (2-hydroxyethyl methacrylate), poly lactic-co-glycolic acid and opal shale and new techniques provides new methods to inhibit the scarring of filtration area after AGV implantation.This article reviews the methods and progress of inhibition of scar formation in filtration area from the aspects of development of AGV drainage plate materials, construction of drug delivery system of AGV combined with new materials, and improvement of AGV drainage plate structure.

Esophageal cancer is a common malignant tumor of the digestive system in China. Currently, surgical resection is the main treatment for localized and resectable esophageal cancer. Minimally invasive treatment of esophageal cancer has the advantages of small trauma, neat incision, less pain, quick postoperative recovery, low postoperative complication incidence and mortality, and the treatment effect is comparable to traditional open surgery. Therefore, minimally invasive surgery for esophageal cancer has gradually become the mainstream choice for esophageal surgery. Various minimally invasive treatment approaches for esophageal cancer have correspon-dingly different indications, advantages and disadvantages. With the continuous development of minimally invasive technology, the shortcomings of various minimally invasive surgical approaches have been continuously overcome, which has brought about the diversification of minimally invasive treatment options. The authors comb the latest research progress at home and abroad, discuss and summarize the current application of minimally invasive techniques in esophageal surgery, hoping to provide references for the clinical minimally invasive treatment of esophageal cancer.

Mice ; Animals ; Acetylation ; NF-kappa B/metabolism* ; Histone Deacetylases/metabolism* ; Inflammation ; Histone Deacetylase Inhibitors