OBJECTIVE:To virtually screen lignanoid compounds with inhibitory effect of histone deacetylase(HDAC)by vir-tual screening method. METHODS:Using“lignanoid”as keyword,requiring CNKI,VIP,PubMed and other database,lignanoid compounds were collected as ligand to establish ligand base, histone deacetylase receptor HDAC2 (PDB code:4LXZ) and HDAC8 (PDB code:1T69) were selected from PDB database,and then ligands and 3D active site of receptors were docked by SYBYL-X 2.0 software. The affinity of receptors to ligand was reflected by total score. RESULTS:345 lignanoid compounds, 4LXZ and 1T69 primary ligand were used to establish ligand base which included 347 ligands. Ligands No.275,271,110,200, 056,258,181,129,037,270,187 were demonstrated good affinity with receptors HDAC2 and HDAC8. Ligands and receptors residue were docked via hydrogen bond. CONCLUSIONS:Lignanoid compounds have inhibitory effect on HDAC;virtual screen-ing method is effective in natural product activity prediction,which can provide quick access to and theoretical guidance for new pharmacological studies of lignanoid compounds.

Objective To evaluate the effect of exogenous hydrogen sulfide (H2S) on mitochondrion-dependent apoptosis in lung tissues of rats with endotoxemia.Methods Forty healthy male SpragueDawley rats,aged 2-3 months,weighing 250-310 g,were divided into 5 groups (n=8 each) using a random number table:control group (group C),lipopolysaccharide (LPS) group,low dose sodium hydrosulphide (NaHS) group (group L-NaHS),moderate dose NaHS group (group M-NaHS) and high dose NaHS group (group H-NaHS).Endotoxemia was induced by Ⅳ LPS 5 mg/kg in chloral hydrate-anesthetized rats.The equal volume of 0.9％ sodium chloride solution was intravenously injected in group C.NaHS (an exogenous donor of H2S) 0.78,1.56 and 3.12 mg/kg were intraperitoneally injected at 3 h after LPS injection in L-NaHS,M-NaHS and H-NaHS groups,respectively.The rats were sacrificed at 6 h after injection of LPS or 0.9％ sodium chloride solution,and lungs were removed for examination of the mitochondrial ultrastructure of lung tissues and for determination of apoptosis in lung cells (by flow cytometry) and expression of caspase-3,caspase-9,Bcl-2 and Bax protein and mRNA in lung tissues (by Western blot or real-timne polymerase chain reaction).The apoptosis rate and ratio of Bcl-2 expression to Bax expression (Bcl-2/Bax ratio) were calculated.The expression of cytochrome c (Cyt c) in cytoplasm and mitochondria of lung tissues was detected by Western blot.Results The apoptosis rate was significantly increased,the expression of caspase-3,caspase-9,Bcl-2 and Bax protein and mRNA was up-regulated,Bcl-2/Bax ratio was decreased,the expression of Cyt c in cytoplasm was up-regulated,and the expression of Cyt c in mitochondria was down-regulated in group LPS (P ＜0.05 or 0.01).Compared with group LPS,the apoptosis rate was significantly decreased,the expression of caspase-3 and Bax protein and mRNA was down-regulated,the expression of Bcl-2 protein and mRNA was up-regulated,Bcl-2/Bax ratio was increased,the expression of Cyt c in cytoplasm was down-regulated,and the expression of Cyt c in mitochondria was up-regulated in L-NaHS,M-NaHS and H-NaHS groups,the expression of caspase-9 protein and mRNA was significantly down-regulated in M-NaHS and H-NaHS groups,and the expression of caspase-9 was significantly down-regulated (P ＜0.05 or 0.01),and no significant change was found in caspase-9 mRNA expression in group L-NaHS (P＞0.05),and the damage to mitochondrial ultrastructure was significantly mitigated in MNaHS and H-NaHS groups.Conclusion The mechanism by which exogenous H2S inhibits cell apoptosis in lung tissues may be related to inhibition of mitochondrion-dependent apoptosis in rats with endotoxemia.

Objective:To evaluate the effect of tropisetron on pyroptosis in cardiomyocytes subjected to hypoxia-reoxygenation (H/R) and the relationship with α7 nicotinic acetylcholine receptor (α7nAChR).Methods:Routinely cultured H9C2 cardiomyocytes were divided into 4 groups ( n=6 each) using a random number table method: control group (C group), H/R group, tropisetron plus H/R group (Tro+ H/R group), and α7nAchR antagonist MLA plus tropisetron plus H/R group (MLA+ Tro+ H/R group). H/R was produced by 12 h exposure of cells to hypoxia followed by 6 h reoxygenation in the other three groups except group C. Tropisetron at the final concentration of 10 nmol/L was added at 1 h before hypoxia in group Tro+ H/R.In group MLA+ Tro+ H/R, MLA was added at 2 h before hypoxia, and then 1 h later tropisetron at the final concentration of 10 nmol/L was given.At 6 h of reoxygenation, the pyroptosis rate of cardiomyocytes was determined by fluorescence immunostaining of caspase-1-AlexaFluor 488/DAPI, the concentrations of interleukin-1beta (IL-1β) and IL-18 in the supernatant were determined by enzyme-linked immunosorbent assay, the activity of LDH in the supernatant was measured by 2, 4 dinitrophenylhydra-zine colorimetric method, and the expression of α7nAchR, NLRP3 and caspase-1 in cardiomyocytes was detected by Western blot. Results:Compared with group C, the pyroptosis rate, activity of LDH and concentrations of IL-1β and IL-18 in the supernatant were significantly increased, the expression of NLRP3 and caspase-1 was up-regulated, and the expression of α7nAchR was down-regulated in group H/R ( P<0.05). Compared with group H/R, the pyroptosis rate, activity of LDH and concentrations of IL-1β and IL-18 in the supernatant were significantly decreased, the expression of NLRP3 and caspase-1 was down-regulated, and the expression of α7nAchR was up-regulated in group Tro+ H/R ( P<0.05). Compared with group Tro+ H/R, the pyroptosis rate, activity of LDH and concentrations of IL-1β and IL-18 in the supernatant were significantly increased, the expression of NLRP3 and caspase-1 was up-regulated, and the expression of α7nAchR was down-regulated in group MLA+ Tro+ H/R ( P<0.05). Conclusion:α7nAchR is involved in the process of tropisetron inhibiting pyroptosis in cardiomyocytes subjected to H/R.

Objective To compare different kinds of urinary volume measurement methods among patients with continuous bladder irrigation.Methods The urinary samples of 30 patients with continuous bladder irrigation were repeated measured by using measuring cup, electronic scale and syringe.Results The accuraey of urinary volume calculated by electronic scale was superior to syringe and measuring cup. In addition, electronic scale was time-saving compared with using syringe.Conclusions Using electronic scale for measuring urinary volume is an accurate and convenient method.It can provide reliable data and improve quality of nursing.

Animals ; Cardiomegaly ; Constriction ; Heart ; Mice

Objective Toanalyzethepersonnelallocationandbasicqualitystructureofmiddle-levelcadresinCDCsof ZhejiangProvince.Methods DatawerecollectedfromthenationalbasicinformationsystemofCDCs.Anddescriptive statistics,chi-square test and Kruskal -Wallis H test were used to analyze the differences of middle -level cadres'personnelallocationandbasicqualityamongthreelevelsofCDCs.Results Theallocationratioofmiddle-levelcadresin management departments was 25.58%,27.32% and 23.58% for provincial level,city level and county level of CDCs respectively,which was 74.42%,72.68% and 76.42% in management departments respectively.There were significant differences in ages,working years,education levels,majors and titles across different levels of CDCs (P<0.05 ).And there were significant differences in education levels across counties with different economic levels (P<0.05 ). Conclusion Thepersonnelallocationofmiddle-levelcadreswithexcellentbasicqualityindifferentlevelsofCDCsin Zhejiang Province was reasonable.

Objective To analyze the present post setting situation of CDCs in Zhejiang Province, and to provide evidence for further improvement and standardization of post setting. Methods The data of post setting were collected by questionnaires from all levels of CDCs in Zhejiang Province. The compliance and rationality of post setting structure were evaluated by national and provincial normative policy documents. Results Ninety seven CDCs had implemented the post setting. Professional technical posts had the highest proportion (above 80%) among three kinds of posts. As the approved proportions of posts classification and professional titles were approved by the local government, there were differences between different levels of CDCs. The approved proportion of ground skilled posts and management posts between municipal and county CDCs had a relatively higher degree of dispersion, and the CVs of ground skilled posts and management posts of municipal CDCs were 72.3% and 65.6%, and the CVs of county CDCs were 101.6% and 82.1%. In terms of the approved professional titles structural proportion, the degree of dispersion appeared to be higher in senior titles and primary titles approved proportion of municipal CDCs (CV=29.1%, 28.5%), while the degree of dispersion was higher in senior titles and vice-senior titles of county CDCs (CV=58.9%, 21.8%) . Meanwhile, the approved proportions of senior titles in municipal and county CDCs were lower with the averages of 32.2% and 17.0%. The posts of infectious disease prevention and control and laboratory detection were accounting for the majority posts in municipal and county CDCs with average percentages of 47.8% and 45.1% . Conclusion The present situation of post structural proportion meets the relevant requirements generally. However, there are some phenomena of non-standard approved proportion of ground skilled posts and management posts and low senior titles approved proportion. Meanwhile, the percentage of infectious disease prevention and control and laboratory detection posts appears to be lower in county CDCs.

Objective: To observe the changes of PD-1 expression, mRNA level and cytotoxic activity of CD19 CAR-T cells during the culture process of CAR-T cells. Methods: The peripheral blood T cells of 6 lymphoma patients with high expression of PD-1 and 6 healthy volunteers were the source of CAR-T cells. The expression of PD-1 was analyzed by flow cytometry. The mRNA level of PD-1 was analyzed by PCR. The cell proliferation was analyzed by CCK-8 assay. The cytotoxicity was analyzed by LDH assay. Results: ①The transfection efficiency of high PD-1 expression T cells and healthy volunteer T cells were as the same (P>0.05) . ②The cell proliferation capacity of CD19 CAR-T cells from high PD-1 expression T cells or healthy volunteer T cells, with or without PD-1 inhibitor were as the same (P>0.05) . ③The cytotoxicity to lymphoma cells of high PD-1 expression T cells and CAR-T cells were lower than that of these two T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer T cells (P<0.001) . There was no difference of the cytotoxicity between the CAR-T cells from high PD-1 expression T cells combined with PD-1 inhibitor and the CAR-T cells from healthy volunteer (P>0.05) . ④There was no difference of the expression of PD-1 in all CAR-T cell groups during the culture process (P>0.05) . There was no difference of mRNA level of PD-1 in all groups during the culture process (P>0.05) . ⑤The PD-1 expression of CAR-T cells increased by the time of culture after contacting with lymphoma cells (P<0.001) . The PD-1 inhibitors could antagonize this effect. There was no difference of mRNA level of PD-1 in all groups after contacting with lymphoma cells (P>0.05) . Conclusion: The PD-1 expression of CAR-T cells from high PD-1 expression T cells increased by the time of culture after contacting with lymphoma cells. However, the mRNA level of PD-1 of all groups did not change, even if PD-1 inhibitor was applied.
Antigens, CD19 ; Humans ; Programmed Cell Death 1 Receptor/genetics* ; RNA, Messenger ; Receptors, Antigen, T-Cell ; T-Lymphocytes

In recent years,molecular biology has rapidly devel-oped,and molecular targeted therapy of non-small cell lung cancer has become a hot spot for the research. Although the tar-geted therapy has a big advantage compared with traditional chemotherapy,it is inevitable to encounter drug resistance in targeted therapy. Therefore,drug resistance has become the sig-nificant obstacle of targeted drugs for the treatment of non-small-cell lung cancer(NSCLC). Curcumin is the main extract of tu-meric rhizome,which harbours a wide range of antitumor activi-ties,and several studies have identified that curcumin exhibits reversion drug resistance against a variety of cancer cells. How-ever,there are few studies on curcumin reversion molecular tar-geted drug resistance. This review summarizes the recent pro-gress in resistance mechanism of targeted drug and the reversion resistance of curcumin.

OBJECTIVETo investigate the blood flow characteristics of hepatitis B cirrhosis based on Couinaud's hepatic segments and to analyze the correlation between perfusion parameters of liver cirrhosis in the hepatic segments and between the different Child-Pugh classifications by using the pattern of whole liver perfusion detected by multi-slice spiral computed tomography (MSCT).

METHODSWhole-liver perfusion enhanced CT imaging scan was performed for 51 patients with hepatitis B cirrhosis (including 24 classified as Child-Pugh A, 19 as Child-Pugh B, and 8 as Child-Pugh C) and 20 patients without any liver abnormalities (who served as the control group).The perfusion parameters of Couinaud's segments were measured in order to compare the blood perfusion differences among the Couinaud's hepatic segments in liver cirrhosis. The blood flow characteristics were analyzed for each lobe and compared between groups, and the time to peak and peak of enhancement values of the aorta and portal veins and spleen were recorded and compared between groups.The F-test was used for statistical analysis.

RESULTSThe liver cirrhosis group showed higher time to peak for aorta and portal veins and spleen but lower peak of enhancement values than the control group. The hepatic arterial perfusion (HAP) was significantly higher in segment 3 than in segment 7 were (11.40+/- 5.72 vs.9.46+/-5.18 mL/min/100 mL; P less than 0.05). In addition, the differences of the portal venous perfusion (PVP) and total hepatic perfusion (THP) were significant between the liver lobes in various groups (P less than 0.05). The HAP and hepatic perfusion index (HPI) were not significantly different between the groups, but the HAP and HPI in every lobe were higher in the Child C subgroup than in either the Child A or Child B subgroups.

CONCLUSIONThe cirrhotic liver has different blood flow in the various Couinaud's segments. Whole-liver perfusion MSCT can reflect the hemodynamic changes of liver cirrhosis and Child-Pugh classification, and as such may be helpful for distinguishing the normal liver from the cirrhotic liver.

Hemodynamics ; Hepatic Artery ; Hepatitis B ; complications ; Humans ; Liver Cirrhosis ; diagnostic imaging ; etiology ; Liver Neoplasms ; Perfusion ; Perfusion Imaging ; Portal Vein ; Spleen ; Tomography, Spiral Computed