Synthesis and protective effect of carboxymethylcysteine L-arginate in bronchial epithelial cells / 中国药科大学学报

@#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.

Research advances in hydrogen sulfide donors / 中国药科大学学报

@#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.

Analysis of 1 289 Cases of Adverse Drug Reactions Induced by Cefatriaxone Sodium for Injection Compatible with Dexamethasone in the Same Bottle / 中国药房

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.

Analysis on clinical data in 36 cases of recurrent glioblastoma retreatment / 重庆医学

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.

Design,synthesis and anti-NSCLC activity of hybrids of anilinopyrimidines and diazeniumdiolates / 中国药科大学学报

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.

Design, synthesis and antiplatelet evaluation of tetramethylpyrazine/chalcone hybrids / 中国药科大学学报

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) .

Design, synthesis and biological evaluation of pyridine-based IRAK4 inhibitors / 中国药科大学学报

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.

Expression of miRNA-203 in psoriasis vulgaris skin lesions and its effect on the proliferation of HaCaT cells / 中华皮肤科杂志

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.

Expression of miRNA-203 in psoriasis vulgaris skin lesions and its effect on the proliferation of HaCaT cells / 中华皮肤科杂志

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.

Analysis on effect of vacuum sealing drainage combined with routine debridement in treatment of frontal sinusitis after craniotomy / 重庆医学

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.

Determination of Content and Content Uniformity of Bisacodyl Enteric-coated Tablet by HPLC / 中国药房

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.

Simultaneous Determination of 18α-Glycyrrhizic Acid and 18β-Glycyrrhizic Acid in Diammonium Glycyr-rhizinate by HPLC / 中国药师

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 .

Regulatory effects of miRNA-146a on peripheral blood CD4+ T lymphocytes from patients with psoriasis vulgaris / 中华皮肤科杂志

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.

Changes of Rho kinase activity in peripheral blood T lymphocytes from patients with atopic dermatitis and their significance / 中华皮肤科杂志

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.

Design, synthesis and anti-inflammatory evaluation of CDDO-Me ester prodrugs / 中国药科大学学报

@#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.

Design, synthesis and evaluation of hydrogen sulfide-releasing derivatives of ring opening 3-n-butylphthalide as novel platelet aggregation inhibitors / 中国药科大学学报

@#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.

The effect of signal transduction pathway of triggering receptor-1 expressed on myeloid cells in acute lung injury induced by paraquat in rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the transduction pathway of triggering receptor-1 expressed on myeloid cells (TREM-1) in acute lung injure induced by paraquat in rats through the activating or blocking TREM-1, to observe the effect of signal transduction pathway in the acute lung injure induced-paraquat.</p><p><b>METHODS</b>80 SD rats were randomly divided into normal saline control group (n=20) , PQ poisoning group (n=20) , antibody group (n=20) , and LP17 group (n=20). poisoning group, antibody group and LP17 group were given saline diluting PQ 80 mg/kg of disposable lavage after 2 h, a single set of intraperitoneal injection of anti-TREM-1 mAb (250 g/kg) , tail intravenous LP17 group synthetic peptide (3.5 mg/kg) , poisoning group was given equal normal saline intraperitoneal injection, control group given normal saline 1 mg/kg after 2 h after lavage, given the amount of intraperitoneal injection of saline solution. The expression of NF-κB in lung tissue was determined by immunohistochemistry.The levels of TNF-a, IL-10, TREM-1, and soluble TREM-1 (sTREM-1) in lung tissue and serum were measured by ELISA. Pathology changes of lung were observed under light microscope, and lung score of pathology was compared.</p><p><b>RESULTS</b>Administration of anti-TREM-1 mAb after PQ poisoning modeling significantly increased the NF-κB expression in lung tissue at 48 h, resulting in a large number of pro-inflammatory cytokines releasing in the lung tissue and serum and lung pathology injury score increasing.Administration of LP17 after modeling significantly down-·regulated the expressions of NF-κB and proinflammatory cytokines, while led to a slight increase of anti-inflammatory cytokines and a decline of lung pathology injury score.</p><p><b>CONCLUSION</b>TREM-1 may involve in inflammatory response by promoting the generation of inflammatory factors via NF-κB pathway, thus lead to lung pathological changes.</p>

Changes of CD(4)(+) Foxp3+ regulatory T cells and CD(4)(+)IL-17+T cells in acrolein exposure rats / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the changes of CD(4)(+) IL-17+T (Th17) and CD(4)(+)Foxp3+regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF) , and therefore to explore the role of Th17 and Treg in acrolein exposure airway inflammation in rats.</p><p><b>METHODS</b>Forty male Wistar rats were randomly divided into 4 groups: a 2 wk acrolein exposure group, a 4 wk acrolein exposure group, a 2 wk control group and a 4 wk control group (n=10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts.IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17+T and CD(4)(+) Foxp3+Treg in peripheral blood and BALF were determined by flow cytometry.The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups.</p><p><b>RESULTS</b>Levels of IL-17 were remarkable increased in the 2 wk acrolein exposure group and the 4 wk acrolein exposure group in serum [(52.64 ± 1.89) ng/L, (76.73 ± 5.57) ng/L], and BALF [(79.07 ± 5.67) ng/L, (96.61 ± 6.44) ng/L] compared with the 2 wk control group [(40.05 ± 3.12) ng/L, (56.75 ± 4.37) ng/L] and the 4 wk control group [(38.75 ± 3.23) ng/L, (53.27 ± 4.48) ng/L], all P<0.01. IL-6 was increased in the 2 wk and the 4 wk acrolein exposure group [ (33.28 ± 2.27) ng/L, (46.24 ± 3.16) ng/L] compared with the 2 wk and the 4 wk control group [ (16.37 ± 1.49) ng/L, (17.02 ± 1.43) ng/L] in BALF.Ratio of Th17 was higher in the 2 wk and the 4 wk acrolein exposure groups in peripheral blood (1.82 ± 0.18) %, (3.75 ± 0.48) % and BALF [(7.23 ± 0.27) %, (8.12 ± 0.38) %] compared with the 2 wk [(0.96 ± 0.07) %, (5.64 ± 0.63) %] and the 4 wk control group [(1.01 ± 0.08) %, (5.86 ± 0.57) %]. Ratio of Treg in BALF was higher in the acrolein exposure groups [ (8.83 ± 0.52) %, (12.05 ± 0.74) %] compared with the control groups [(4.37 ± 0.27) %, (5.01 ± 0.37) %]. The level of IL-17 mRNA was increased in the 2 wk and the 4 wk acrolein exposure group in peripheral blood [(25.78 ± 2.31), (34.69 ± 2.01) ] and in BALF [(23.04 ± 1.78), (34.56 ± 3.12)] compared with the 2 wk [(11.04 ± 2.53), (11.08 ± 2.05)] and the 4 wk [(12.03 ± 2.34), (12.69 ± 2.69)] control groups. Foxp3 mRNA was increased in the acrolein exposure groups [ (26.37 ± 3.24), (33.19 ± 2.98)] (24.4 ± 2.7), (30.3 ± 2.7) compared with the control groups [(12.37 ± 2.56), (13.12 ± 3.08)]. Th17 in acrolein exposure groups was positively correlated with counts of total cells and macrophages (r=0.5126, 0.5437, all P<0.01).</p><p><b>CONCLUSIONS</b>A changed expression of Th17 and Treg cells and an vary of inflammatory cytokines were evident in airway inflammation of acrolein exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in acrolein induced airway inflammation in rats.</p>

Expression of myeloid-derived suppressor cells in patients with post-traumatic multiple organ dysfunction syndrome / 国际检验医学杂志

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 .

Synthesis and antiplatelet aggregation/antioxidant activity of 3-alkyl-benzo c selenophen-1 3 H -ones / 中国药科大学学报

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.