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@#Carboxymethylcysteine (CMC) is a common drug for the clinical treatment of chronic obstructive pulmonary disease, yet its long-term use can cause severe irritation to the gastrointestinal tract.As the substrate of nitric oxide (NO) synthase (NOS), L-arginine can be converted in the body into NO beneficial to the cardiovascular system, the gastrointestinal tract and so on.As a basic amino acid, L-arginine can be salified with some compounds containing acidic groups to improve the water solubility of the parent drug and may enhance the activity and alleviate side effects due to NO release.In this study, we designed and synthesized carboxymethylcysteine L-arginate (CMCA), and tested its physico-chemical properties, and the abilities to scavenge reactive oxygen species (ROS), inhibit apoptosis and release NO in cigarette smoke-induced injury model of human bronchial epithelial cells.The results revealed that CMCA is superior to CMC or L-arginine in that it could capture ROS, release NO and suppress apoptosis, suggesting that CMCA is worthy of further research and development.
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@#Hydrogen sulfide(H2S)is an endogenous gas messenger molecule with extremely broad biological activities including vasodilation, anti-oxidation, anti-inflammation, cardioprotection and anti-tumor. Similar to other gas messenger molecules, the biological activity of H2S is dependent on its location, concentration and duration of exposure. Therefore, the key scientific issue is how to improve the selectivity of H2S donor molecules to release appropriate concentrations of H2S at the target site(commonly pathological place), exerting therapeutic efficacy with limited side-effects. This article reviews the structures and H2S release mechanisms of two classes of H2S donors focusing on the advances in the recently developed H2S donors with controllable release potential of H2S, thus providing new ideas for future H2S-based drug research.
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OBJECTIVE： To analyze the occurrence of the adverse reactions （ADRs） caused by the compatibility of Ceftriaxone sodium for injection and dexamethasone in the same bottle， and to explore the regularity and characteristics of ADRs， so as to provide reference for clinical rational use of drugs. METHODS： The ADRs caused by the compatibility of ceftriaxone sodium and dexamethasone in the same bottle， reported to the National Adverse Drug Reaction Monitoring System from January 1， 2007 to December 31， 2016 were analyzed statistically， including the type of report， route of administration， type of reporting unit， gender and age of patients， occurrence time and month of occurrence of ADR， involved systems/organs and outcome， etc. the potential reasons were analyzed. RESULTS： A total of 2 111 cases were searched， and 1 289 cases （2 177 case times） were collected， of which 166 cases （12.88％） were severe ADR； route of administration was mainly intravenous drip （1 275 cases， 98.91％）； ADR reports mainly came from primary medical institutions （838 cases， 65.01％）； the male （679 cases， 52.68％） were slightly more than the female （610 cases， 47.32％）； the age of patients ranged 18 days-111 years old. The children under 4 years of age had more ADR （“number/age span” value was 141/5＝28.20 and higher than other age groups）； ADR occurred within 1 min to 14 d after medication， most of which occurred within 30 min （853 cases， 66.18％）； in summer （6-8 months）， ADR occurred more frequently （424 cases， 32.89％）； systems/organs involved in ADR were mainly skin and its appendants （1 059 case times， 48.64％ of total case times）， followed by gastrointestinal system （343 case times， 15.76％ of total case times）， systemic injury （291 case times， 13.37％ of total case times）. Among 1 289 ADR patients， 1 255 cases （97.36％） were cured or recovered， 28 cases （2.17％） were died， 4 cases （0.31％） did not improve， and 2 cases （0.16％） had sequelae. The compatibility of ceftriaxone sodium and dexamethasone in bottles had the risk of physical and chemical changes， which can reduce the efficacy and cause more ADR. Dexamethasone in the same bottle was not enough to completely prevent the allergic reaction of ceftriaxone sodium. CONCLUSIONS： In clinic， ceftriaxone sodium and dexamethasone should be avoided to be administered in the same bottle； clinical pharmacists and physicians can improve the ability of clinical pharmaceutical care in primary medical institutions， strengthen monitoring and publicity for patients， and prevent the occurrence of adverse drug reactions.
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Objective To study the factors influencing prognosis in the patients with recurrent glioblastoma muhiforme (GBM) and to investigate the effect of retreatemt.Methods The retrospective analysis method was adopted to collect the clinical and follow up data in 36 cases of recurrent GBM retreatment in the neurosurgery department of this hospital from March 2008 to March 2013.The prognosis influencing factors were analyzed.Results The univariate analysis results showed that the gender,resection degree,treatment mode and initial scheme had the influence on the progression free survival(P＜0.05).The resection degree had an impact on the overall survival(P＜0.05).The multivariate analysis results showed that KPS score,resection degree and treatment mode had effect on the progression free survival(P＜0.05).The resection degree had an influence on the overall survival (P＜0.05).Conclusion If the patients with recurrent GBM still hasthe chance of operation whole excision,the re-treatment can reach the effect for relieving the symptoms,improving the quality of life and prolonging the survival period.
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To search for potent drugs against non-small-cell lung cancer(NSCLC),a series of hybrids(9a-9e, 10a-10e and 11a-11e﹚ from anilinopyrimidines and diazeniumdiolates were designed and synthesized.The MTT assay was employed to evaluate their antiproliferative activity against H1975 cells harboring epithelial growth factor receptor(EGFR)L858R/T790M mutation.The results showed that compounds 9a-9e displayed remarkable inhibitory activity on H1975 cells.Among these compounds, the most potent was compound 9b(IC50=0.65 μmol/L),which was superior to the positive control gefitinib.Additionally,molecular docking study indicated that 9b could bind with EGFR T790M by forming hydrogen bond, electrostatic interactions, et al, suggesting that compound 9b may be a potential anti-NSCLC agent for further investigation.
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Objective To investigate the clinical effect of using uninterrupted vacuum sealing drainage combined with routine debridement and pedicled periosteal flap sealing frontal sinusitis in treating frontal sinusitis after craniotomy.Methods The clinical data in 31 cases of frontal sinusitis after craniotomy in our hospital from January 2006 to December 2014 were retrospectively analyzed.Seventeen cases adopted simple debridement and drainage treatment and 14 cases were treated with continuous vacuum sealing drainage combined with routine debridement treatment.Postoperative follow up lasted over 1 year.Results In simple debridement and drainage,12 cases were cured,the other 5 cases recurred after operation,and the cure rate was 70.6 ％.But in the continuous vacuum sealing drainage combined with routine debridement treatment,14 cases were cured,no case recurred after operation,and the cure rate was 100％.Therefore,the cure rate of continuous vacuum sealing drainage treatment combined with routine debridement was higher than that of simple debridement and drainage treatment(P＜0.05).Conclusion Adopting vacuum sealing drainage combined with routine debridement and pedicled periosteal flap sealing frontal sinusitis can promote the infection focus clearance and wound healing,and increases the cure rate.
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In order to search for new antiplatelet agents with higher potency, a series of tetramethylpyrazine ( TMP) /chalcone hybrids ( 2-26) were synthesized and evaluated based on the principle of bioisostere and hybrid-ization. They exerted inhibitory activity against adenosine diphosphate ( ADP )-induced and arachidonic acid ( AA)-induced platelet aggregation to varied extent. Among them, compound 8 was the most potent with IC50 of 0. 14 mmol/L on ADP-induced platelet aggregation ( 9. 1 folds of TMP and 10. 5 folds of chalcone ) and 0. 09 mmol/L on AA-induced platelet aggregation ( 8. 8 folds of TMP and 10. 0 folds of chalcone) , which was superior to clinically used anti-platelet drug aspirin ( ASP, IC50 =0. 15 mmol/L) .
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Based on the known IRAK4 inhibitors MK-32 and AU-5,we designed and synthesized 12 pyridine-based target compounds by adopting open-ring and hybrid strategies,and combining molecular docking technology.The bioassays determined by radioisotope labeling demonstrated that the target compounds displayed good inhibitory activity against IRAK4.Among them,the IC50 value of 5 compounds was less than 1 μmol/L,suggesting that these compounds may be candidates for further investigation.
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Objective To investigate the expression of miRNA-203 in skin lesions of patients with psoriasis vulgaris,and to explore its effect on the proliferation of a human keratinocyte cell line HaCaT.Methods Lesional skin and adjacent non-lesional skin tissues were obtained from 23 patients with psoriasis vulgaris from 2014 to 2016.Fluorescence-based quantitative PCR was performed to determine the expression of miRNA-203 in these skin tissues.Targeted miRNA in skin tissues was in situ hybridized by using 5'and 3'digoxigenin-labelled probes,so as to localize the expression of miRNA-203 in skin tissues.Cultured HaCaT cells were divided into 3 groups:miRNA-203 mimic group and negative control group transfected with miRNA-203 mimics and negative control miRNA-203 respectively,and blank control group receiving no treatment.Methyl thiazolyl tetrazolium (MTT) assay,flow cytometry and Western blot analysis were performed to investigate changes in cellular proliferative activity,cell cycle and its related proteins Cyclin D1 and Cyclin B1 in HaCaT cells respectively.Results MiRNA-203 was specifically expressed in epidermal keratinocytes.Besides the cell nuclei,it could be expressed in the cytoplasm.In the patients with psoriasis vulgaris,the expression of miRNA-203 was significantly higher in lesional skin tissues than in non-lesional skin tissues (1.35 ± 0.28 vs.0.52 ± 0.09,t =6.76,P =0.012).The transfection with miRNA-203 mimics could significantly inhibit the proliferation of HaCaT cells (F =9.36,P =0.007).Additionally,the blank control group,negative control group and miRNA-203 mimic group all showed a gradual increase in proliferative activity of HaCaT cells over time (F =18.68,P ＜ 0.001).HaCaT cells were arrested in G2/M phase in the miRNA-203 mimic group with the percentage of cells in G2/M phase being 31.33％ ± 4.56％,compared to 17.02％ ± 3.53％ in the negative control group (P ＜ 0.05) and 16.67％ ± 3.32％ in the blank control group (P ＜ 0.05).Moreover,the miRNA-203 mimic group showed significantly higher protein expression of Cyclin D1 (1.15 ± 0.13),but significantly lower protein expression of Cyclin B1 (0.43 ± 0.08),compared with the negative control group (0.52 ± 0.05,0.93 ± 0.16,respectively,both P ＜ 0.05) and blank control group (0.56 ± 0.07,0.91 ± 0.0.15,respectively,both P ＜ 0.05).Conclusion MiRNA-203 may participate in the occurrence and development of psoriasis vulgaris.
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Objective To investigate the expression of miRNA-203 in skin lesions of patients with psoriasis vulgaris,and to explore its effect on the proliferation of a human keratinocyte cell line HaCaT.Methods Lesional skin and adjacent non-lesional skin tissues were obtained from 23 patients with psoriasis vulgaris from 2014 to 2016.Fluorescence-based quantitative PCR was performed to determine the expression of miRNA-203 in these skin tissues.Targeted miRNA in skin tissues was in situ hybridized by using 5'and 3'digoxigenin-labelled probes,so as to localize the expression of miRNA-203 in skin tissues.Cultured HaCaT cells were divided into 3 groups:miRNA-203 mimic group and negative control group transfected with miRNA-203 mimics and negative control miRNA-203 respectively,and blank control group receiving no treatment.Methyl thiazolyl tetrazolium (MTT) assay,flow cytometry and Western blot analysis were performed to investigate changes in cellular proliferative activity,cell cycle and its related proteins Cyclin D1 and Cyclin B1 in HaCaT cells respectively.Results MiRNA-203 was specifically expressed in epidermal keratinocytes.Besides the cell nuclei,it could be expressed in the cytoplasm.In the patients with psoriasis vulgaris,the expression of miRNA-203 was significantly higher in lesional skin tissues than in non-lesional skin tissues (1.35 ± 0.28 vs.0.52 ± 0.09,t =6.76,P =0.012).The transfection with miRNA-203 mimics could significantly inhibit the proliferation of HaCaT cells (F =9.36,P =0.007).Additionally,the blank control group,negative control group and miRNA-203 mimic group all showed a gradual increase in proliferative activity of HaCaT cells over time (F =18.68,P ＜ 0.001).HaCaT cells were arrested in G2/M phase in the miRNA-203 mimic group with the percentage of cells in G2/M phase being 31.33％ ± 4.56％,compared to 17.02％ ± 3.53％ in the negative control group (P ＜ 0.05) and 16.67％ ± 3.32％ in the blank control group (P ＜ 0.05).Moreover,the miRNA-203 mimic group showed significantly higher protein expression of Cyclin D1 (1.15 ± 0.13),but significantly lower protein expression of Cyclin B1 (0.43 ± 0.08),compared with the negative control group (0.52 ± 0.05,0.93 ± 0.16,respectively,both P ＜ 0.05) and blank control group (0.56 ± 0.07,0.91 ± 0.0.15,respectively,both P ＜ 0.05).Conclusion MiRNA-203 may participate in the occurrence and development of psoriasis vulgaris.
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Objective:To establish an HPLC method for the simultaneous determination of 18α-glycyrrhizic acid and 18β-glycyr-rhizic acid in diammonium glycyrrhizinate .Methods:A Diamonsil C18 column (200 mm ×4.6 mm, 5 μm) was used with the mobile phase of water (water-60%perchloric acid solution:48∶0.5, adjusting pH to 8.0 with ammonium hydroxide)-methanol (48∶52). The detection wavelength was set at 248 nm and the flow rate was 1.0 ml· min-1 .The column temperature was 30℃and the injection volume was 20 μl.Results:18α-Glycyrrhizic acid and 18β-glycyrrhizic acid were well separated .They had a good linear relationship within the range of 0.005 0-1.000 0 mg· ml-1(r=0.999 7 and 0.999 3).The average recovery was 99.7%and 99.1%, and RSD was 0.9%and 0.4%, respectively (n=9).Conclusion:The method is accurate, simple and reproducible, which can be used for the simultaneous determination of the two constituents in diammonium glycyrrhizinate .
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OBJECTIVE:To establish a method for the determination of content and content uniformity in Bisacodyl enter-ic-coated tablet. METHODS:HPLC method was performed on the column of Agilent ZORBAX C18 with mobile phase of acetoni-trile-20 mmol/L ammonium acetate(adjusted pH to 5.0 with acetic acid)(55∶45,V/V),the detection wavelength was 265 nm,col-umn temperature was 30℃,flow rate was 1.0 ml/min,and the volume injection was 20 μl. RESULTS:The linear range of bisaco-dyl was 50-1 000 μg/ml(r=0.999 9);RSDs of precision,stability and reproducibility tests were lower than 1%;recovery was 99.50%-101.17%(RSD=0.5%,n=9). CONCLUSIONS:The method is reproducible with high accuracy,and suitable for the quali-ty control of Bisacodyl enteric-coated tablet.
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Objective To evaluate regulatory effects of miRNA-146a on peripheral blood CD4 + T lymphocytes from patients with psoriasis vulgaris, and to investigate the role of miRNA-146a in the pathogenesis of psoriasis vulgaris. Methods Totally, 30 patients with psoriasis vulgaris and 30 healthy human controls were enrolled into this study. Venous blood samples were obtained from these subjects, and CD4 + T lymphocytes were isolated from these samples by using magnetic activated cell sorting (MACS). Real-time quantitative PCR (RT-PCR)was performed to measure the expression of miRNA-146a in peripheral blood CD4+ T lymphocytes, and enzyme-linked immunosorbent assay(ELISA)to determine plasma levels of interferon-γ(IFN-γ)and interleukin 4(IL-4). Some CD4+ T lymphocytes were divided into 3 groups to be transfected with 50 nmol/L negative control miRNA (control group), miRNA-146a mimics(miRNA-146a group)or miRNA-146a inhibitor (miRNA-146a inhibitor group). After 24-hour additional culture, flow cytometry was conducted to determine the number of Th1 and Th2 cells, Western-blot analysis and RT-PCR were performed to measure the protein and mRNA expressions of IFN-γ receptor α (IFN-γRα), T-box expressed in T cells (T-bet)and GATA-binding protein-3 (GATA-3)respectively, and ELISA was carried out to determine the levels of IFN-γ and IL-4 in supernatants of CD4 + T lymphocytes. Results Compared with the healthy control group, the patient group showed significantly increased miRNA-146a expression in peripheral blood CD4 + T lymphocytes (243.81% ± 94.32% vs. 105.74% ± 22.93%, t = 6.653, P 0.05). Conclusion miRNA-146a may play an important role in the pathogenesis of psoriasis vulgaris by participating in the regulation of peripheral blood CD4+ T lymphocytes via affecting Th1 cell differentiation and function.
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Objective To evaluate changes of Rho kinase (ROK)activity in peripheral blood T lymphocytes from patients with atopic dermatitis (AD), and to analyze their clinical significance. Methods Eight milliliters of heparin-anticoagulated blood samples were collected from 60 patients with AD and 60 healthy human controls followed by separation of T lymphocytes and sera from these blood samples as well as culture of isolated T lymphocytes with 10% fetal bovine serum for 24 hours. Both patient- and control-derived T lymphocytes were classified into two groups to be cultured with patient- or control-derived sera. In addition, some patient-derived T lymphocytes were classified into 4 groups:Y27632 group treated with the Rho kinase-specific inhibitor Y2763, CD3/CD28 group treated with anti-CD3/anti-CD28 monoclonal antibodies, Y27632 + CD3/CD28 group treated with Y27632 and anti-CD3/anti-CD28 monoclonal antibodies, and control group treated with patient-derived sera. Subsequently, Western-blot analysis was performed to evaluate ROK activity in cells, methyl thiazolyl tetrazolium(MTT)assay to evaluate proliferative activity of T lymphocytes, and ELISA to measure interleukin 6 (IL-6)and IL-10 levels in supernatants of T lymphocytes. Results ROK activity was significantly lower in fresh T lymphocytes from patients than in those from healthy controls (2.47% ± 0.89% vs. 0.65% ± 0.35%, t =2.729, P 0.05). Compared with T lymphocytes cultured with control-derived sera, those cultured with patient-derived sera showed significantly increased ROK activity (F = 8.22, P < 0.001). Concretely speaking, ROK activity was significantly higher in patient-derived T lymphocytes cultured with patient-derived sera than in those cultured with control-derived sera (2.41% ± 0.87% vs. 0.76% ± 0.41%, P < 0.05), and higher in control-derived T lymphocytes cultured with patient-derived sera than in those cultured with control-derived sera(2.17% ± 0.85% vs. 0.64% ± 0.33%, P< 0.05)at 24 hours. Y27632 could significantly inhibit the proliferation of as well as secretion of IL-6 (F = 18.68, 22.95, respectively, both P < 0.001)by patient-derived T lymphocytes, but had insignificant effects on secretion of IL-10. The cellular proliferative activity and IL-6 supernatant level were significantly lower in the Y27632 group than in the control group, and lower in the Y27632 + CD3/CD28 group than in the CD3/CD28 group (all P < 0.05). Conclusion Aberrant activation of ROK exists in T lymphocytes from patients with AD, which may play a certain role in the pathogenesis of AD.
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@#In order to search for new anti-inflammatory agents with strong activity and less toxicity relative to CDDO-Me, the ester prodrugs 2-8 of CDDO-Me were synthesized by treatment of oleanolic acid(OA)with DMF/K2CO3 to generate 1, followed by esterification of 1 with various aliphatic and aromatic carboxylic acids, respectively. All the target compounds showed strong inhibitory effects on LPS-induced NO production in RAW 264. 7 cells. Among them, compounds 2 and 7 possessed the most potent inhibitory effects with IC50=(2. 34±0. 67)and(3. 83±0. 97)nmol/L, respectively. Moreover, MTT assay indicated that all the target compounds(2-8)displayed much weaker anti-proliferative activity against RAW 264. 7 cell lines than CDDO-Me, suggesting that they may be less toxic than CDDO-Me.
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@#A series of hydrogen sulfide-releasing derivatives of open ring 3-n-butylphthalide(5a-5f)were designed, synthesized, and their structures were confirmed by MS and 1H NMR. The inhibitory activity of the target compounds against adenosine diphosphate(ADP)and arachidonic acid(AA)-induced platelet aggregation was evaluated in vitro by Born′s turbidimetric assay. In comparison with 3-n-butylphthalide(NBP), compound 5e possessed better antiplatelet aggregation activity. Therefore, it may be utilized as a lead compound for further investigation.
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Objective To estimate the activity of the phosphatidylinositol3-kinase (PI3K) signaling pathway in peripheral blood T cells from patients with atopic dermatitis (AD),and to investigate its clinical significance.Methods T cells were isolated by using the Rosettsep T cell purification kit from the peripheral blood of 38 patients with AD and 38 healthy human controls,and classified into several groups to be treated with anti-CD3 monoclonal antibody,anti-CD28 monoclonal antibody,and LY294002 (an inhibitor of PI3K) respectively.The activity of PI3K signaling pathway in T cells was estimated by immunoprecipitation and enzyme-linked immunosorbent assay (ELISA).Western blot was performed to measure the expressions of total Akt and phosphorylated Akt in T cells,methyl thiazolyl tetrazolium (MTT) assay to examine the proliferation of T cells,and ELISA to determine the levels of interleukin 6 (IL-6) and IL-10.Results The activity of PI3K and Akt was significantly higher in freshly isolated patient-derived T cells than in control-derived T cells (both P ＜ 0.05).However,the difference in the activity of PI3K and Akt between patient-derived and control-derived T cells disappeared (both P ＞ 0.05) after 24-hour in vitro culture.The activity of PI3K and Akt in control-derived T cells was significantly increased after 24-hour incubation with sera from the patients with AD (both P ＜ 0.05).In addition,compared with patient-derived T cells treated with patients' sera or anti-CD3/CD28 monoclonal antibody alone,those treated with the combination of LY294002 and patients' sera or anti-CD3/CD28 monoclonal antibody showed a significant decrease in the proliferative activity (63％ ± 11％ vs.123％ ± 25％,125％ ± 22％ vs.195％ ± 28％,both P＜ 0.05),supematant levels of IL-6 ((168 ± 33) vs.(265 ± 46) ng/L,(431 ± 64) vs.(823 ± 128) ng/L,both P＜ 0.05) and IL-10 ((56 ± 14) vs.(98 ± 25) ng/L,(120 ± 21) vs.(213 ± 35) ng/L,both P＜ 0.05).Eczema area and severity index (EASI) was unassociated with the activity of PI3K or Akt in fresh T cells from patients with AD (both P ＞ 0.05).Conclusions The PI3K signaling pathway is abnormally activated in peripheral blood T cells from patients with AD,which is associated with the proliferation of,as well as secretion of cytokines by,T cells,suggesting that there exist serum factors activating this pathway in peripheral blood of patients with AD.
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Objective To investigate the effects of miRNA-146a on the differentiations and functions of CD4+ T lymphocytes in patients with psoriasis vulgaris.Metbods Thirty patients with psoriasis vulgaris and twenty heathy subjects were enrolled in this study.Quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of miRNA-146a in CD4+ T lymphocytes isolated from the peripheral blood samples.The levels of IFN-γ and IL-4 in serum samples were determined by using enzyme-linked immunosorbent assay (ELISA).Mononuclear cells were isolated from human peripheral blood samples by using Ficoll-Hypaque density-gradients centrifugation,from which the CD4+ T lymphocytes were separated by magnetic-activated cell sorting.The CD4+ T cells (2× 106/ml) were seeded in culture plates with 6 wells.The CD4+ T lymphocytes were divided into 3 groups including the control group,miRNA-146a group and miRNA-146a inhibitor group.The numbers of Th1 and Th2 cells were measured by flow cytometry analysis (FACS).The expression of IFN-γRα,T-bet and GATA-3 at mRNA and protein levels were measured by using RT-PCR and Western blot assay,respectively.The levels of IFN-γ and IL-4 in culture supernatants of CD4+ T lymphocytes were detected by using ELISA.Results In comparison with the normal control group,there were significant increases in the expression of miRNA-146a in CD4+ T lymphocytes and the level of IFN-γin serum samples from patients with psoriasis vulgaris [(2.43±0.94) vs (1.05±0.23),(27.69±7.64) ng/L vs (9.75±2.81) ng/L,all P＜0.01].A positive correlation between the expression of miRNA-146a and the level of IFN-γ in serum was observed (r=0.837,P＜0.01).Results of the in vitro culture of CD4+ T lymphocytes showed that the number of Th1 cells,the expression of T-bet at mRNA and protein levels and the level of IFN-γin culture supernatant were significantly increased,while the expression of IFN-γRα protein was decreased in the miRNA-146a group in comparison with those of the control group (all P＜0.01).No significant differences in the number of Th2 cells,the expression of GATA-3 protein,the expression of GATA-3 and IFN-γRα at mRNA level and the level of IL-4 in culture supernatants were found between the control and miRNA-146a groups (all P＞0.05).The miRNA-146a inhibitor could effectively attenuate the effects of miRNA-146a on Th1 cells.Conclusion The miRNA-146a could promote the differentiation and enhance the function of Th1 cells.It might play an important role in the pathogenesis of psoriasis vulgaris.
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Objective To study the quantity change and significance of myeloid‐derived suppressor cells(MDSCs) in patients withpost‐traumaticmultipleorgandysfunctionsyndrome(MODS).Methods 66patientswithMODS,34patientswithnon‐system‐ic inflammatory response syndrome(SIRS)and 37 healthy volunteers were enrolled in this study .Peripheral blood was collected and CD14-CD11b+ CD33+ were used as markers of MDSCs .The percentage of MDSCs was determined by flow cytometry and serum interleukin‐10(IL‐10) and tumor necrosis factor‐α(TNF‐α) levels were determined by ELISA .The MODS scoring system was used to assess patients′disease severity .The relationship was analyzed between MDSCs and TNF‐αand MODS score .Results The per‐centage of MDSCs in peripheral blood of healthy volunteers was(1 .18 ± 0 .22)% .after MODS ,the percentage of MDSCs in periph‐eral blood was(11 .84 ± 2 .18)% and(6 .52 ± 0 .37)% in patients with non‐MODS ,the percentages of MDSCs in three groups showed significant differences(P<0 .05) .Serum IL‐10 and TNF‐αin patients with MODS group and non‐MODS group were signif‐icant differences(P<0 .05) .The correlation was found between MDSCs percentage in peripheral blood and MODS score and TNF‐α(r=0 .342 6 ,0 .387 9 respectively ,P<0 .05) .Conclusion The increase proportion of MDSCs in peripheral blood correlates with the onset of infection in patients with MODS ,indicating that the expansion of MDSCs in peripheral blood may play important roles in immune dysfunction after MODS .
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Phthaloyl dichloride (1)was reacted with LiAlSeH2 to give benzo[c]selenophene-1;3-dione (2);which was treated with the Grignard reagents to generate hydroxyl compounds 3a-3h.These compounds were finally converted to target products 4a-4h by treatment with hydriodic acid.The structures of 4a-4h were confirmed by MS and 1 H NMR.Their inhibitory activity against adenosine diphosphate (ADP)-induced platelet aggregation was evaluated by Born′s turbidimetric assay;free radical scavenging activity was assayed by xanthine oxidasemethod and 1;10-phenanthroline spectrophotometric method.It was found that compound 4 f displayed more potent inhibi-tory effect on platelet aggregation than 3-n-butylphthalide and comparable hydroxyl free radical scavenging activity in vitro to that of edaravone.Therefore;compound 4 f might be the candidate for further investigation.