Objective: To explore the effect of suberoylanilide hydroxamic acid (SAHA) improving cardiac hypertrophy via inhibiting histone deacetylases (HDAC) in experimental mice and to provide a new idea for prevention and treatment of cardiac hypertrophy. Methods: Cardiac hypertrophy mice model was established by thoracic aorta ligation. A total of 60 Kunming mice were randomly divided into 4 groups: Normal control group, Sham operation group, Cardiac hypertrophy (CH) group and CH+SAHA group. There were 6 mice used in each group. Myocardial cell morphology was observed by HE staining, cardiac function was assessed by echocardiography, mRNA and protein expressions of HDAC5 (the isoform of HDAC) and β-MHC were examined by RT-PCR and Western blot analysis. Results: The mice in CH group had myocardial cell hypertrophy, disordered arrangement and hyperchromatic nucleus. Compared with Sham operation group, CH group showed decreased left ventricular end diastolic diameter (LVEDD), left ventricular end diastolic volume (LVEDV) and increased thickness of inter-ventricular septum (IVS), allP<0.05; CH group presented elevated mRNA and protein expressions of HDAC5 and β-MHC,P<0.05. SAHA obviously decreased HDAC5 expression, down regulated cardiac hypertrophy related β-MHC gene expression, improved cardiac function and hypertrophy, all P<0.05. Conclusion: HDAC were involved in myocardial hypertrophy; SAHA could inhibit HDAC expression and therefore,improved myocardial hypertrophy in experimental mice.

Objective To explore the effect of exogenous hydrogen sulfide (H2S) donor NaHS on depression rat models induced by chronic stress,and provide a new idea for preventing and treating depression.Methods Thirty Sprague Dawley rats were randomly divided into normal control group,model group,model+NarHS group,model+normal saline group and normal control+NaHS group (n=6).Depression models were induced by sustained stimulations for three weeks;rats in the model+NaHS group and model+normal saline group were performed intraperitoneal injection of NaHS (10 mg/kg) or equivalent normal saline once a week,respectively.The weight,food intake,water intake,sugar water preference,adrenal gland weight index and behavioral indexes were observed in these rats;the hippocampus of the rats were collected,and the mRNA and protein expressions of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) in the hippocampus of rats were assayed by real-time PCR and Western blotting,respectively;the concentrations ofinterleukin (IL)-6 and tumor necrosis factor (TNF)-cα in the serum were assayed by ELISA,and hippocampal neurons were observed by Nissl staining.Results The weight,food intake,water intake,sugar water preference,number of horizontal movement and vertical erect of rats in the model+NaHS group were significantly decreased as compared with those in model group (P＜0.05),while opposite trend was noted in the adrenal index,with significant difference (P＜0.05).The contents of malonaldehyde,corticosterone,adrenocorticotropic hormone,IL-6 and TNF-α in the model group were significantly increased as compared with those in the normal control group (P＜0.05),but the indexes mentioned above,except for TNF-α,in the model+NaHS group were attenuated significantly as compared with those in the model group (P＜0.05).The results of real-time PCR and Westem blotting showed that the mRNA and protein expressions of GR and MR in hippocampal tissues of rats in the model group were statistically decreased as compared with those in the normal control group (P＜0.05),but the mRNA and protein expressions of GR and MR in hippocampal tissues of rats in model+NaHS group were significantly higher than those in the model group (P＜0.05).Nissl staining showed decreased level of nissl bodies and disordered arrangement of pyramidal cells in the hippocampus of the model group;however,model+NaHS group had alleviated loss ofnissl bodies and disordered arrangement of pyramidal cells in CA3 area of hippocampus as compared with the model group.Conclusion Chronic stress could lead to depression of rats,and exogenous H2S donor NarHS could attenuate chronic stress induced-depression of rats by up-regulating the expressions of GR and MR and down-regulating the content of stress hormone in rats.

Objective:To evaluate the diagnostic and therapeutic effect of percutaneous intranodal lymphography in patient with chylous leakage.Methods:The clinical data of percutaneous intranodal lymphography in patients with chylous leakage from January 2019 to November 2019 in Cancer Hospital Chinese Academy of Medical Sciences were retrospectively analyzed. A total of 8 patients (5 males and 3 females, median age 64 years old) were enrolled. Four patients were iatrogenic chylothorax, 3 patients iatrogenic chyloperitoneum, and 1 patient chyloperitoneum with unknown cause. All 8 patients were received inguinal lymph nodes puncture under ultrasound guidance, and contrast agent iodinated oil was injected for lymphography. The procedure complications were recorded and the follow-up data were collected for efficacy assessment.Results:The percutaneous intranodal lymphography was successfully performed in all patients (8/8). The median amount of iodinated oil used was 17.5 ml; the median operation time was 88 min, without complications found during the procedure. The results of percutaneous intranodal lymphography was positive in 5/8 cases, of which chylothorax and chyloperitoneum was 4/4 and 1/4, respectively. Four cases with chylothorax showed contrast extravasation at different level of thoracic duct, and 1 case after pancreatic cancer resection showed contrast extravasation at L3-4 level. The chylous leakage was treated in 5 patients (5/8) during and resolved after percutaneous intranodal lymphography, with 3 chylothorax and 2 chyloperitoneum cases, respectively.Conclusion:Percutaneous intranodal lymphography is a safe and effective lymphography method for the diagnosis of chylous leakage, and also has application values in the treatment of chylous leakage.

Objective:To evaluate the feasibility and safety of a novel transjugular intrahepatic portosystemic shunt (TIPS) puncture set for transjugular intrahepatic portal puncture in swine.Methods:Thirteen domestic swine were randomly divided into experimental group ( n=7) and control group ( n=6) and received transjugular intrahepatic portal puncture with the novel puncture set and the R?sch-Uchida Transjugular Liver Access Set (RUPS-100), respectively. Three swines in each group were randomly selected and sacrificed immediately after the procedure and the rest were sacrificed 1 week later. The intraoperative technical success rate, puncture attempts, procedure time, fluoroscopy time, vital signs and occurrence of complications related to the procedure as well as the changes of liver and kidney function before, immediately after and 1 week after the procedure were compared between two groups. Independent sample t test, paired t test, Mann-Whitney U test, chi-square test or Fisher′s exact test were performed to compare the differences between groups. Results:The technical success rate was 100% for both groups. No significant difference in portal puncture attempts [2.0 (1.0, 5.0) vs. 2.0(1.0, 5.5), P>0.999], procedure time [(47.7±20.6) vs. (52.5±28.0)min, P=0.729] and fluoroscopy time [(725.1±489.2) vs. (763.7±562.4)s, P=0.897] was observed between two groups. In addition, no significant difference of the major liver and kidney function between two groups before, immediately after and 1 week after procedure ( P>0.05 at all time points). No significant difference of the major liver and kidney function change in two groups during perioperative period was identified (all P>0.05). Furthermore, no significant difference of non-target puncture occurrence was observed between two groups ( P>0.999). In the meantime, no significant difference of occurrence of small hematomas around hepatic hilar was discovered among swine sacrificed immediately after procedure between two groups ( P>0.999). No other major complications were identified in either group. Conclusion:The novel TIPS puncture set is feasible and safe to perform transjugular intrahepatic portal puncture in swine.

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.