The study reports the detection of neuroprotective effect of 10 kinds of coumarin derivatives and explores their possible mechanism. MTT method was used to screen the neuroprotective effect of 10 coumarin derivatives on neurotoxic agents (Aβ25-35 and rotenone) or OGD (oxygen-glucose deprivation). A compound with better protective effect was obtained. Then the effect of this compound on neurotoxic agents on PC12 was detected by the morphological observation. Furthermore, the effect of compound 3 on microglia with lipopolysaccharide (LPS) induced inflammation was detected. And the inflammatory factor was tested. Finally, direct free radical scavenging ability was detected. Compound 3 was found to be the best compound through three neurons toxic models. Not only compound 3 ameliorated cell viability reduced by three neurons toxic models, but also significantly inhibited the production of inflammatory factor (TNF-α and IL-1β). And its free radical scavenging ability is very good, especially the effect on superoxide anion, which is comparable with vitamin C. The significant scavenging effect of compound 3 on superoxide anion might be the mechanism of the neuroprotection. Compound 3 as a potential neural cell protective agent merits further investigation.

ObjectiveTo explore the effect of radiation dose on survival for stage Ⅳ non-small cell lung cancer (NSCLC) treated with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT).Methods From Jan.2003 to Jul.2010,201 Stage Ⅳ NSCLC patients were enrolled.Nineteen patients who received only one cycle chemotherapy were not included in survival analysis.Of the 182 patients eligible for survival analysis,all patients received platinum-based chemotherapy of two drugs.The median number of cycles was 4.The median dose to planning target volume of primary tumor ( DTPTV )was 63 Gy. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression models were used to examine the effect of DTPTV on overall survival.ResultsThe follow-up rate of 201 patients was 97.5％.with 201,170 and 134 patients finished ＜ 1,1 -2 and ≥3 years' follow-up.The 1-,2-,3-year overall survival rate and median survival time was 20％,14％,0％ and 7.1 months;27％,10％,3％ and 9.6 months;and 59％,22％,16％ and 14.9 months,respectively for patients treated with DTPTV ＜ 45.0 Gy,45.0 - 62.1 Gy and ≥63.0 Gy,respectively ( χ2 =27.88,P =0.000 ) ;43％,19％,0％and 1 1 months and 2 0 ％,1 1％,5 ％ and 8 months,respectively for those received 2 - 3 cycles of chemotherapy and radiation dose ≥63 Gy and ＜ 63 Gy,respectively (χ2 =2.99,P =0.084) ;66％,23％,19％ and 16 months and 29％,12％,0％ and 8.8 months,respectively for those received 4 - 5 cycles chemotherapy and radiation dose ≥ 63 Gy and ＜ 63 Gy,respectively (χ2=15.87,P=0.000).No significant difference was found for patients received 2 - 3 cycles chemotherapy concurrently with DTP,Tv ≥63 Gy and 4 -5 cycles chemotherapy concurrently with DTPTV ＜63 Gy,respectively (χ2 =1.93,P =0.165).Multivariate analysis showed that 4 -5 cycles chemotherapy concurrently with DTPTv ≥63 Gy ( β =0.243,P =0.019),and improved KPS after treatment ( β =1.268,P =0.000) were independent favorable factors for survival.ConclusionChemotherapy concurrent with CCTTRT can prolong survival time of patients with stage Ⅳ NSCLC,especially for those treated with DTPTV ≥63 Gy.

The expression or dysfunction of long non-coding RNAs (lncRNAs) is closely related to various hereditary diseases, autoimmune diseases, metabolic diseases and tumors. LncRNAs were also recently recognized as functional regulators of fibrosis, which is a secondary process in many of these diseases and a primary pathology in fibrosis diseases. We review the latest findings on lncRNAs in fibrosis diseases of the liver, myocardium, kidney, lung and peritoneum. We also discuss the potential of disease-related lncRNAs as therapeutic targets for the clinical treatment of human fibrosis diseases.
Autoimmune Diseases ; Fibrosis ; Genetic Diseases, Inborn ; Humans ; Kidney ; Liver ; Lung ; Metabolic Diseases ; Myocardium ; Pathology ; Peritoneum ; RNA, Long Noncoding

Objective To explore the diagnosis and treatment of atypical severe combined immunodeficiency disease (SCID). Methods The clinical data of atypical SCID in 7 children with IL2RG,JAK3,and RAG1 mutations were reviewed and analyzed from September 2012 to June 2017. Results In 7 cases (6 males and 1 female), there were 5 infants, 1 toddler and 1 school-age child. Cases 2, 4, and 6 were classic SCID clinical phenotypes. Cases 1, 3, 5, 7 were atypical SCID clinical phenotypes. Case 6 were diagnosed with Omenn syndrome. Cases 2, 5 were classic SCID immune phenotypes, cases 1, 3, 4, 6, 7 were atypical SCID immune phenotypes, and case 1 had maternal chimera. The next generation sequencing indicated that case 1 had a compound heterozygous JAK3 mutation with c.3097-1G>A/c.946-950GCGGA>ACinsGGT.Cases 2,3,and 4 had IL2RG mutations,with c.865C>T/p.R289X,c.664C>T/R222C,52delG,respectively.Case 5 had JAK3 mutations with c.2150A>G/p.E717G and c.1915-2A>G.Sanger sequencing indicated that case 6 had a RAG1 mutation of complex heterozygosity with c.994C>T/p.R332X and c.1439G>A/p.S480N. Case 7 had homozygous RAG1 mutation with c.2095C>T/p.R699W.Conclusion Under certain conditions,gene mutation can lead to atypical clinical and/or immune phenotypic SCID.

Objective To determine the effects of Tongsaimai tablet on cardiac function,myocardial injury,inflammation and fibrosis in rats with acute myocardial infarction(AMI)and investigate possible mechanism.Methods A total of 73 rats were subjected to establish rat model of AMI by ligation of the left anterior descending coronary artery.The 60 successfully modeled AMI rats were randomly divided into model group,p38 mitogen-activated protein kinase(MAPK)inhibitor group(10 mg/kg),low-and high-dose Tongsaimai tablet groups(0.28 and 0.56 g/kg),and high-dose Tongsaimai tablet+p38 MAPK inhibitor group(as above doses),with 12 rats in each group.Another 12 normal rats served as the sham operation group.After corresponding intervention for 14 d,echocardiography was applied to evaluate the heart function,including left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left ventricular ejec-tion fraction(LVEF),and left ventricular short axis shortening rate(LVFS).The levels of myo-cardial injury indexes[cardiac troponin Ⅰ(cTnⅠ),lactate dehydrogenase(LDH)]and inflammatory factors(TNF-α,IL-6,IL-10)were detected by ELISA.HE and Masson staining were used to ob-serve pathological changes and fibrosis in myocardial tissues.The expression of Collagen Ⅰ and Collagen Ⅲ in myocardial tissue was detected by immunohistochemical staining.The protein expression of p38 MAPK/matrix metalloproteinase(MMP)-9 pathway related proteins in myo-cardial tissues was detected by Western blotting.Results Compared with model group,the condi-tions were alleviated in the p38 MAPK inhibitor group,and low-and high-dose Tongsaimai tablet groups,with milder pathological damage in myocardial tissue,obviously decreased LVEDV,LVESV,cTnⅠ,LDH,TNF-α and IL-6 levels,CVF,expression of Collagen Ⅰ,Collagen Ⅲ,p-p38 MAPK/p38 MAPK and MMP-9,and increased LVEF,LVFS and IL-10 level(P＜0.05).Com-pared with p38 MAPK inhibitor group and high-dose Tongsaimai tablet group,high-dose Tong-saimai tablet+p38 MAPK inhibitor group had LVEDV,LVESV,cTnⅠ,LDH,TNF-α,IL-6,CVF and Collagen Ⅰ,Collagen Ⅲ,p-p38 MAPK/p38 MAPK and MMP-9 decreased significantly,and LVEF[(64.31±7.78)％vs(52.89±7.05)％,(57.40±7.42)％]and LVFS[(34.51±5.29)％vs(27.02±5.01)％,(25.04±4.13)％]increased obviously(P＜0.05).Conclusion Tongsaimai tab-let can improve cardiac function,myocardial injury,inflammation and fibrosis in AMI rats,which may be due to its inhibition of p38 MAPK/MMP-9 signaling pathway.