Sphingosine-1-phosphate receptor 1(S1PR1) is a new member of G protein-coupled receptor family. A great body of data suggest S1PR1 is capable of regulating lots of downstream signaling molecules and cellular processes. It is found that S1P/S1PR1 plays an important role in the development and mainte-nance of pain. However, it is controversial whether activation of S1PR1 would enhance or attenuate pain. Here, recent studies ＜br> and current perspectives are discussed in order to better under-stand the biological and pathological roles of S1PR1 in pain mod-ulation.

Objective To investigate the expression of CD40-CD154 co-stimulatory pathway in peripheral circulation and intestinal mucosa in patients with inflammatory bowel disease (IBD),the difference between the expression of CD40-CD154 in patients with IBD and that in healthy controls,and the correlation between CD40-CD154 levels and disease activity. Methods A total of 62 patients with Crohn's disease (CD),64 patients with ulcerative colitis (UC) and 56 healthy controls were enrolled. Enzyme-Linked Immuno Sorbent Assay (ELISA),SYBR-green real time PCR and immunohistochemical assay were respectively applied to evaluate expression of CD40-CD154 in plasma,mononuclear cells of peripheral blood and intestinal mucosa. Results Levels of CD40 (P=0. 000) and CD154 (P=0. 001) in plasma,mononuclear cells of peripheral blood and intestinal mucosa were significantly higher in patients with CD and UC than in healthy controls. However,no correlation between disease activity and CD40-CD154 expression in peripheral circulation or intestinal mucosa was detected (P ＞ 0. 05 ). Conclusion CD40-CD154 pathway activation is found in plasma,peripheral blood mononuclear cells and intestinal mucosa in patients with IBD,but is not correlated with disease activity.

Orphan nuclear receptor NR4A1 from the NR4A subfamily is one of the transcriptional factors that have not identified specific ligands .Previous studies have found that NR4A1 could regulate cell proliferation ,apoptosis ,differentiation and stress responses by changing gene expression ,post-translational modification and interactions between coregulatory pro-teins .Recently ,it has shown that NR4A1 has an abnormal expression in human atherosclerotic lesions and has been identified as a key regulator gene in vascular cells dysfunction .Regulating NR4A1 expression can have an important impact on the prolif-eration of smooth muscle cell and endothelial cell activation ,meanwhile it could reduce inflammation ,foam cell formation and lipid deposition ,inhibit vascular remodeling ,and prevent the development of atherosclerosis .These studies suggest that NR4A1 might be a novel target for drug development in prevention and treatment of atherosclerosis .

Objective To investigate the expression of CD27-CD70 co-stimulatory pathway in peripheral circulation and intestinal mucosa of patients with inflammatory bowel disease, and to find the difference between the expression of CD27-CD70 in patients with inflammatory bowel disease and in healthy controls. Methods A total of 62 patients with Crohn's disease, 64 patients with ulcerative colitis and 56 healthy controls were enrolled. Enzyme-linked immunosorbent assay was applied to evaluate plasma CD27-CD70 protein expression in patients with inflammatory bowel disease and healthy controls. SYBR-green real time PCR was applied to access CD27-CD70 mRNA expression in peripheral blood mononuclear cells in patients with inflammatory bowel disease and healthy controls.And CD27-CD70 protein expression in intestinal mucosa was determined by immunohitochemistry.Results Plasma levels of CD27 (P=0. 025) and CD70 (P=0. 000) were significantly higher in patients with Crohn's disease than in healthy controls. However, CD27 (r= 0. 055, P= 0. 673) and CD70 (r= 0. 024, P = 0. 852) were not significantly associated with endoscopic disease activity in patients with Crohn's disease. Similarly, CD27 (P=0. 001) and CD70 (P=0. 000) were significantly higher in patients with ulcerative colitis than in healthy controls. And CD27 (r=0. 077, P=0. 547)and CDT0 (r=0.021, P=0. 869) were not significantly associated with endoscopic disease activity in patients with ulcerative colitis. Moreover, CD27 and CD70 mRNA expression in peripheral blood mononuclear cells were significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P=0. 000), and immunostaining indicated that CD27 and CD70 expression in intestinal mucosa were significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy controls (all P=0. 000). Conclusions CD27-CD70 pathway activated in plasma, peripheral blood mononuclear cells and intestinal mucosa of patients with inflammatory bowel disease. However,plasma levels of CD27 and CD70 can not reflect endoscopic disease activity.

Objective To study the mechanisms of the drug resistance of DNA mismatch repair (MMR) deficient color-ectal cancer (CRC) HCT-116 to 5-fluorouracil (5-Fu) .Methods MLH1 deficiency HCT-116 cells were transfected with pcD-NA3 .1-MLH1 Vector .The expression of MLH1 was detected by Western blot .The change of resistance against 5-Fu was ex-amined by detecting the cell viability with CCK-8 kits .The expression of CD133 (cancer stem cell marker ) and CK8 & CK20 (cell differentiation marker) were detected by flow cytometry .Results Comparing to HCT-116 control group ,the viability of HCT-116 cells was markedly decreased (P<0 .01) after stable expressing MLH1 ,accompanied by the down-regulated expres-sion of CD133 on the cell surface .Moreover ,the up-regulation of cell differentiation marker CK8 and CK20 was observed in HCT-116 cells with stable expressing MLH1 .Conclusion Our data indicated that the expression of MLH1 was associated with down-regulated CD133+ stem-like cells in colorectal cancer HCT-116 with MLH1 deficiency .Therefore ,CD133+ stem-like cells may related to the drug resistance of MMR deficiency tumor .This study provides a possible theory to explain the 5-FU resist-ance in the colorectal cancer patients with MMR deficiency .

Objective To investigate the effect of trichostatin A(TSA),a histone deacetylase inhibitor, on s-100-induced autoimmune hepatitis in mice.Methods A total of 26 six-week-old male C57BL/6 mice were randomly divided into control group,model group and TSA group(six in each group),and the rest 8 mice were used to extract the s-100 protein from liver tissue.Mice of model group and TSA group were injected intraperitoneally with s-100 with complete Freund's adjuvant to induce autoimmune hepatitis model.At day 21, TSA group mice were injected intraperitoneally with TSA 2 mg/(kg·d)for 7 days,and 0.9% sodium chloride solution containing 1% dimethyl sulfoxide was injected into the control and model group mice.Alanine transaminase(ALT)and aspartate aminotransferase(AST)in serum were measured and liver histopathology was observed.The protein levels of nuclear factor(NF)-κB and acetylated histone H3 in liver tissue were detected by Western Blot.The hepatic mRNA levels of NF-κB,HDAC3,toll-like receptor 4(TLR4)and TNF-α were measured by real-time PCR.ELISA was used to determine the TNF-α in serum.The results were analyzed with t test.Results The serum levels of ALT in control group,model group and TSA group were(122.00 ± 45.29),(459.33 ± 167.58)and(217.33 ± 49.25)U/L,respectively.The differences between model group and control group or TSA group were significant(t=4.76 and 3.41,respectively,both P<0.05).The serum levels of AST in control group,model group and TSA group were(127.83 ± 18.55),(389.67 ± 87.14)and (249.50 ± 71.72)U/L,respectively.The differences between model group and control group or TSA group were also significant(t= 7.20 and 3.04,respectively,both P< 0.05).The inflammation of the liver histopathology induced by s100 was alleviated by TSA.The relative expressions of NF-κB protein,NF-κB mRNA,TNF-α mRNA,HDAC3 mRNA and TLR4 mRNA in the liver tissue of model group mice were 2.43 ± 0.42,9.51 ± 0.36,10.53 ± 0.74,2.90 ± 0.22,and 4.50 ± 0.73,respectively,which were significantly higher than those of the control group(1.28 ± 0.49,1.28 ± 0.49,1.06 ± 0.14,1.72 ± 0.73,and 1.01 ± 0.31, respectively)(t=4.68,37.14,30.69,4.33 and 10.85,respectively,all P <0.05).In TSA group,the relative expressions of NF-κB protein,NF-κB mRNA,TNF-α mRNA,HDAC3 mRNA and TLR4 mRNA were decreased(1.30 ± 0.36,1.30 ± 0.36,2.38 ± 0.36,2.13 ± 0.32 and 2.40 ± 0.51,respectively),which were statistically lower than those in model group(t=4.58,30.62,24.12,2.81 and 5.81,respectively,all P<0.05).The serum TNF-α levels in control group,model group and TSA group were(122.37 ± 68.12), (1361.44 207.13)and(691.64 ± 162.12)ng/L,respectively.Compared with model group,the differences were statistically significant(t=13.92 and 6.24,respectively,both P<0.05).The relative expression of ac-H3 protein in the model group was 1.10 ± 0.08,which was higher than that in the control group 0.96 ± 0.17(t=2.27,P<0.05).That in TSA group was 1.30 ± 0.04,which was higher than the model group(t=-0.30, P <0.05).Conclusion Histone deacetylase inhibitor TSA alleviates autoimmune hepatitis by enhancing histone acetylation and inhibiting NF-κB and inflammatory factors.

BackgroundNowadays， idolatry is an important part of the spiritual life of secondary school students， making a significant impact on their physical and mental development. Previous research has examined the two-by-two relationship between idolatry， peer attachment， life satisfaction and perceived social support， but the potential mediating mechanisms between these variables remain to be explored. ObjectiveTo explore the mediating role of peer attachment and life satisfaction between idolatry and perceived social support， so as to provide references for mental health education for secondary school students. MethodsIn June 2022， 1 059 students currently enrolled in secondary school in Qiannan State， Guizhou Province were selected according to stratified random sampling method. In this study， assessment was performed using Celebrity Attitude Scale （CAS）， Peer Attachment Subscale from Revised Inventory of Parent and Peer Attachment （IPPA-R）， Satisfaction with Life Scale （SWLS） and Perceived Social Support Scale （PSSS）. Pearson correlation analysis was used for correlation test. Model 6 in the SPSS Macro Process 3.3 was used to examine the mediating effect of peer attachment and life satisfaction between idolatry and perceived social support in secondary school students. Results①CAS score indicated positive correlation with scores of IPPA-R Peer Attachment Subscale， SWLS and PSSS （r=0.117， 0.097， 0.115， P<0.01）. IPPA-R score indicated positive correlation with scores of SWLS and PSSS （r=0.279， 0.421， P<0.01）. SWLS score was positively correlated with PSSS score （r=0.552， P<0.01）. ②The direct effect of idolatry on perceived social support was significant （β=0.059， P<0.05）. Both separate and chain mediating effects of peer attachment and life satisfaction between idolatry and perceived social support were significant （95% CI： 0.007~0.130， 0.004~0.054， 0.001~0.016， P<0.01）. The three effects above respectively accounted for 33.56%， 13.54% and 3.93% of the total effect. ConclusionIdolatry can affect secondary school students' perceived social support both directly and indirectly through peer attachment and life satisfaction.

Objective To investigate the effect of high-fat diet(HFD)on liver damage caused by autoimmune hepatitis(AIH)in mice.Methods Fifty C57BL/6 male mice were divided randomly into four groups:standard chow(SC)group,HFD group,AIH + SC group and AIH+ HFD group.AIH model was built after feeding for one week and all mice were sacrificed after four weeks.Liver and spleen tissues and serum were collected. Liver histopathology was detected by HE staining. Serum alanine aminotransperase(ALT)and aspartate aminotransferase(AST)levels were measured.Western blot analysis and real-time polymerase chain reaction(PCR)analysis were used to test the expressions of NLR pyrin domain containing 3(NLRP3)and cysteinyl aspartate specific proteinase 1(Caspase-1).The concentrations of interleukin(IL)-6,IL-1β and tumor necrosis factor(TNF)-α were analyzed using enzyme linked immunosorbent assay technology.The amount of Th17 cells in spleen was analyzed by FACS.Means among groups were analyzed with one-way ANOVA.SNK-q analysis was used for groups with homogeneity of variance, while nonparametric test was used for groups with variance nonhomogeneity.Results Histologically,the H&E staining of liver tissue from HFD group showed adipose degeneration,and there was inflammation around vessel in AIH+SC group.Moreover,in AIH+HFD group,the inflammation was more serious with mildly adipose degeneration.Compared with SC group,serum levels of ALT and AST increased in HFD group and AIH +SC group,and greatest increase was observed in AIH+ HFD group.The differences were statistically significant(F=57.12 and 37.58, both P<0.05).The proportions of Th17 cells in SC group,HFD group,AIH+ SC group and AIH+HFD group were(2.98 ± 0.90)%,(6.89 ± 0.99)%,(6.47 ± 1.08)% and(9.96 ± 0.83)%, respectively.The differences among all groups were statistically significant(F=54.05,P<0.05).The concentrations of IL-1β,IL-6 and TNF-α in each group were as follows:SC:IL-1β[(7.62 ± 2.81)ng/L],IL-6 [(106.54 ± 53.08)ng/L],T NF-α[(107.26 ± 36.20)ng/L];HFD:IL-1β[(25.06 ± 7.09)ng/L],IL-6 [(220.11 ± 47.41)ng/L],TNF-α[(273.77 ± 33.62)ng/L];AIH+SC:IL-1β[(17.49 ± 5.68)ng/L],IL-6 [(260.73 ± 50.29)ng/L],TNF-α[(250.49 ± 81.63)ng/L];AIH+ HFD:IL-1β[(52.04 ± 10.22)ng/L], IL-6[(785.93 ± 70.91)ng/L],TNF-α[(913.97 ± 64.57)ng/L].The differences were statistically significant(F=44.66,242.15 and 233.49,respectively,all P<0.05).The expressions of NLRP3 and Caspase-1 were significantly increased in AIH+ HFD group than the other three groups(all P<0.05). Conclusions High-fat diet potentiates liver damage induced by autoimmune hepatitis,which might relate to the secretion of pro-inflammatory cytokines,the activation of Th17 cells and the NLRP3 inflammasome as well as pyroptosis.

Objective To study the immunoregulatory effect of sodium butyrate(NaB)on T helper cell 17(Th17)and the effect on toll-like receptor 4(TLR4)signal pathway in autoimmune hepatitis (AIH).Methods Fifty male C57BL/6 mice(6 weeks of age)according to the random number table method divided into control group(n=10),AIH group(n=10),NaB group(n=10)and high roughage diet(HRD)group(n=10),and the other ten mice were used to extract hepatic sytosolic S-100.After the establishment of AIH model,mice in NaB group were given sodium butyrate 500 mg/(kg·d)by gavage and those in HRD group were fed with high-fiber stuff.After 3 weeks of treatment,all the mice were sacrificed.The pathological change was observed.The serum levels of alanine aminotransferase(ALT), aspartate transaminase(AST),IL-17A and TNF-α,the proportion of Th17 in spleen,the expression levels of TLR4 and myeloid differentiation factor 88(MyD88)in liver were observed in each group.The tests of normality and homogeneity of variance were used to compare the means of each group.One-way analysis of variance and multiple comparative analyses were used in the statistical analysis.Results HE staining showed that inflammatory cell infiltration and hepatocyte necrosis were significantly reduced in mice treated with NaB and HRD compared to AIH group.Serum ALT levels in control group,AIH group,NaB group and HRD group were(24.833 ± 2.229),(88.333 ± 9.543),(27.167 ± 3.189)and (29.833 ± 6.113)U/L,respectively,while AST levels in each group were(97.00 ± 14.953),(285.000 ± 35.434),(139.500 ± 38.976)and(127.167 ± 28.687)U/L,respectively.The differences among groups were all statistically significant(F=156.49 and 44.118,respectively,both P<0.01).The proportion of Th17 in spleen and the expressions of the transcription factors retinoid-related orphan receptor gamma t in the spleen of the NaB group and HRD group were significantly lower than those of AIH group.The differences were statistically significantly(F=21.780 and 68.283,respectively,both P<0.05).The expressions of TLR4 and MyD88 in liver of AIH group were significantly higher than control group,but those were inhibited in NaB group and HRD group.The differences were statistically significantly(F= 26.235 and 28.293,respectively,both P<0.01).The expressions of IL-17 and TNF-α in liver and serum decreased in NaB group and HRD group.Conclusion NaB exerts an immunoregulatory effect in AIH and improves inflammatory reaction in liver.