Objective To study the efficacy and mechanism of probiotic assisted glucocorticoid on the treatment of the patients with eczema. Methods 92 cases with eczema from February 2015 to March 2017 were divided into two groups according to the treatment methods, the conventional group and the combined group, 46 cases in each group. The conventional group were given glucocorticoid, and the combined treatment group were received probiotics combined with glucocorticoid. The levels of serum inflammatory factors, the treatment effects of eczema and the incidence of adverse reactions were compared between the two groups before and after treatment. Results The treatment effect of eczema in combined group was higher than that in routine group (P<0.05). No severe adverse reactions occurred in the two groups. There was no significant difference in serum inflammatory factors between the two groups before treatment. The level of serum inflammatory factors in combined group was significantly better than that in tconventional group (P<0.05). Conclusion Probiotic assisted glucocorticoid is effective in the treatment of eczema. It can lower the level of inflammation and improve the condition of the body. It has no obvious adverse reaction which has the characteristics of safety and effectiveness.

Anemia ; metabolism ; physiopathology ; Animals ; Cell Hypoxia ; Genetic Therapy ; Humans ; Hypoxia-Inducible Factor 1 ; genetics ; metabolism ; physiology ; Neovascularization, Pathologic ; metabolism ; pathology ; Neovascularization, Physiologic ; Osteogenesis ; RNA, Messenger ; metabolism

Objective To assess the differences in the specificity and the sensitivity in detecting specific IgM by indirect ELISA and capturing-ELISA methods,and to analyze the possible causes of those differences.Methods The HBc-IgM and EHF-IgM level in serum samples from activity Hepatitis B patients and hemorrhagic fever patients with renal syndrome were determined by both indirect-ELISA and capturing-ELISA methods,and the differences in the positive rate,positive threshold value and the specificity between those two methods were compared. Results Specific murine IgM diluted in PBS were detected by indirect-ELISA and capturing-ELISA,and the specificity and sensitivity of those two methods were similar.Results showed that sensitivity of indirect-ELISA was lower than capturing-ELISA in detecting specific IgM in serum from patients with activity Hepatitis B and hemorrhagic fever patients with renal syndrome.The IgM level in hepatitis B and hemorrhagic group treated with thioglycol became negative detected by those two methods,suggesting that both of them have the anti-IgM epitope-specificity.Cross reaction results demonstrated that the reagent detecting IgM from the two methods had the specificity to the specific antigen. Conclusion It is recommended to detect IgM level by capturing-ELISA method for the early diagnosis of acute infectious disease,pathological changes,immune reaction and prognoses of chronic continuous infectious disease.Applying the indirect-ELISA method to detect IgM level to diagnose acute infectious disease is to discuss in the future.

Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Neovascularization, Physiologic ; Osteogenesis

OBJECTIVETo explore the mechanism of protective effect of Sphingosine-1-phosphate(S1P) in cultured neonatal rat cardiomyocytes dining simulated hypoxia/reoxygenation.

METHODSOn the basis of culturing neonatal rat cardiomyocytes, the model of hypoxia-reoxygennation was built by using method of Liquid Paraffin covering, the impact of S1P on apoptosis and p-Akt and mitochondrial membrane potential were studied by using method of Propidine Iodide staining and Western blot and Bhodanmine123 staining.

RESULTSSiP could reduce apoptosis rate (P < 0.01) and stabilize the mitochondrial membrane potential (P < 0.05) and improved the level of p-Akt1 (P < 0.01) in hypoxia/reoxygenation cardiomyocytes significantly. But wonnannin could block these effects of S1P partially.

CONCLUSIONSiP can obviously restrain apoptosis in curtured rat neonatal cardiomyocytes during simulated hypoxia/reoxygenation. Stabilization of mitochondrial membrane potential by P13K-AM signaling pathway is likely to play a role in protective action of S1P.

Animals ; Animals, Newborn ; Apoptosis ; drug effects ; Cell Hypoxia ; Cells, Cultured ; Female ; Lysophospholipids ; pharmacology ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Myocardial Reperfusion Injury ; prevention & control ; Myocytes, Cardiac ; cytology ; Oncogene Protein v-akt ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Primary Cell Culture ; Protective Agents ; pharmacology ; Rats ; Signal Transduction ; Sphingosine ; analogs & derivatives ; pharmacology

The key challenge to generate engineered cells by synthetic biology for producing 7-dehydrocholesterol (7-DHC) in a high titer is the match between functional module and chassis. Our study focused on solving this problem by combining different promoters and yeast chassis to increase 7-DHC production. To optimize the chassis in order to accumulate zymosterol, the substrate for 7-DHC synthesis, we overexpressed truncated HMG-CoA reductase (tHmglp) and squalene epoxidase (Erglp), both are key genes of yeast endogenous zymosterol biosynthetic pathway. In addition, we knocked out C-24 methyl transferase (Erg6p) and C-22 dehydrogenase (Erg5p) to inhibit the conversion of zymosterol to ergosterol. By introducing heterologous C-24 reductase under three promoters with different strengths, namely TDH3p, PGK1p and TDH1p, we constructed functional modules of diverse activities. Nine engineeredcells were generated based on the combination of these three modules and three chassis. The result shows that the engineered cell composed of functional module regulated by TDH3p and chassis SyBE_000956 had the highest 7-DHC production, indicating a better match than others. This study provides evidences for importance of match and empirical support for rational design of subsequent researches.
Cholesterol ; metabolism ; Cytochrome P-450 Enzyme System ; genetics ; Dehydrocholesterols ; metabolism ; Gene Knockout Techniques ; Hydroxymethylglutaryl CoA Reductases ; metabolism ; Industrial Microbiology ; Methyltransferases ; genetics ; Promoter Regions, Genetic ; Saccharomyces cerevisiae ; genetics ; metabolism ; Saccharomyces cerevisiae Proteins ; genetics ; Synthetic Biology

Objective To evaluate the change of left ventricular diastolic function and investigate the relation between left ventricular diastolic function and disease activity in rheumatoid arthritis (RA) without clinical manifestations of heart diseases. Methods Seventy consecutive active RA in-patients without clinical manifestations of heart disease were enrolled, while the control group was recruited from outpatient health physical check-up center and consisted of 60 age- and sex-matched healthy subjects. Cardiac related parame-ters were determined by echocardiography and the correlation between left ventricular diastolic function and the disease activity indexes were evaluated. Chi-square test, t test, Pearson or Spearman′s correlation test and Stepwise backward linear regression analysis were used for statistical analysis. Results RA patients had lower mitral inflow E/A ratio (1.2±0.4, 1.5±0.4, P<0.01), higher E/Em ratio (9.6±3.7, 7.8±2.0, P<0.01), longer isovolumetric relaxation time(IVRT)[(64±16) ms,(58±16) ms, P<0.05] than control group. Whilst, RA patients had higher pulmonary venous inflow A wave velocity-time integral (ArVTI) and A wave duration (DAr)[3.2±0.7,(2.8±0.6) cm; 117±11,(102±9) ms, P<0.05]. Moreover, the E/Em was positively corre-lated with C-reactive protein(CRP)(r=0.581, P<0.01), DAS28(r=0.456, P<0.01). Anti-CCP level was also associated with Em and early diastolic pulmonary venous inflow peak velocity(PVD)(r=-0.359, P<0.05;r=-0.305, P<0.05). In addition, multivariate analysis also revealed that there was linear regression relation-ship between E/Em and CRP, DAS28(t=3.266, P=0.002; t=2.949, P=0.005). Conclusion The study has revealed that left ventricular diastolic function is impaired in RA patients and the left ventricular diastolic function parameters is associated with the disease activity indexes. These results suggest that the decline of left ventricular diastolic function is associated with the inflammation activity in RA patients without clinical manifestations of heart disease.

Objective Aimed to clarify the molecular mechanism after subarachnoid hemorrhage （SAH） by investigating the expression of tight junction protein Claudin-5 and ZO-1 and the effects of SP600125 on them. Methods Seventy-five male Sprague Dawley rats （300 to 350 g） were randomly divided into sham,SAH,SAH ＋ DMSO （dimethyl sufoxide） solution,SAH ＋SP600125 （C-Jun N-terminal kinase inhibitor）10 mg/kg,and SAH ＋SP600125 30 mg/kg groups. The standard endovaseular perforation was performed to produce experimental SAH. The JNK inhibitor SP600125 was intraperitoneally administered at 1 hour before and 6 hours after SAH. Results At 24 hours after SAH,signs of microvessels injury were observed in brain cortex. Compared with the sham group,expression of Claudin-5 and ZO-1 was sig- nificantly decreased （P 〈 0.05 ）. JNK inhibitior SP600125 suppressed the decrease of Claudin-5 and ZO-1 expression, attenuated blood-brain barrier disruption in rats after SAH. Conclusions The blood-brain barrier disruption is an important mechanism of early brain injury after SAH. JNK inhibitor SP600125 improves neurological outcomes and provides neuropmtecfion against acute events after SAH such as bloodbrain barrier disruption and cell apoptosis.

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by ¹H NMR, ¹³C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC₅₀ = 0.26 μmol·L^-1) was 6.7 times than the lead compound A (IC₅₀ = 1.73 μmol·L^-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

To strengthen the quality control of palbociclib, three related substances were separated from the bulk drug. These substances were identified as 8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido ［2, 3-d］ pyrimidin-7(8H)-one(A), 8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridine-2-yl)amino)-6-vinylpyrido ［2, 3-d］ pyrimidin-7(8H)-one(B), tert-butyl4-(6-((6-acetyl-8-cyclopentyl-5-methyl-7-oxo-7, 8-dihydropyrido ［2, 3-d］ pyrimidin-2-yl)amino)pyridin-3-yl)piperazi-ne-1-carboxylate(C). Based on the structures of the impurities, the possible routes to them were discussed, and their structures were elucidated by 1H NMR and MS.