Effect of Xifeng Capsule on blood stasis in patients with rheumatoid arthritis by regulating miR-126-VEGF/PI3K/AKT signaling pathway

Objective:From the perspective of miR-126-vascular endothelial cytokine(VEGF)/phosphatidylinositol 3-kinase(PI3K)/ser-threonine protein kinase(AKT)signaling pathway,Xinfeng Capsule(XFC)can improve rheumatoid arthritis(RA))The mechanism of the patient's blood stasis state.Methods:Sixty RA patients meeting the diagnostic criteria were selected and divided into XFC treatment group 30 cases and Leflunomide(LEF)control group 30 cases according to the random number table method.The treatment group took Xinfeng Capsules(3 capsules each time,3 times/d),and the control group took Leflunomide(1 capsule each time,1 times/d).Observe the blood stasis symptom scores of RA patients,and detect the laboratory indicators erythrocyte sedimentation rate(ESR),c-reactive protein(CRP),rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody(CCP),thrombin time(TT),part prothrombin time(APTT),prothrombin time(PT),D dimer(DD),fibrinogen(FBG),platelets(PLT),mean platelet volume(MPV),platelet distribution width(PDW)levels.Real-time fluorescent quantitative PCR method was used to detect the level of miR-126,and the ELISA method was used to detect the levels of tumor necrosis factor(TNF-α),interleukin-6(IL-6),IL-35,VEGF,PI3K,and AKT.Spearman method was used to analyze the correlation between the total score of blood stasis symptoms,blood stasis-related indicators and disease activity indicators,cytokines,miR-126,VEGF,PI3K,and AKT in RA patients.Results:Comparing the two groups after treatment,the XFC group improved blood stasis symptoms,disease activity indicators,decreased miR-126,VEGF,PI3K,AKT,TNF-α,IL-6,D-D,FBG,PLT,and increased IL-35 The level was significantly better than the LEF group,with statistical significance(P<0.05,P<0.01).Correlation analysis showed that there was a certain correlation between the total score of blood stasis symptoms,blood stasis related indicators and disease activity indicators,cytokines,miR-126,VEGF,PI3K,and AKT in RA patients.Conclusion:There is blood stasis in RA patients.XFC may improve the cytokine network disorder of patients through miR-126-VEGF/PI3K/AKT signaling pathway,thereby improving the blood stasis status of RA patients.

Study on the correlation between TCM syndrome differentiation and immune inflammation index of Sjogren's syndrome

Objective:To observe the relationship between the distribution of TCM Syndromes of primary Sjogren's syndrome(pSS)and the changes of erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM.Methods:157 diagnosed PSS patients were divided into dampness heat obstructing collaterals syndrome,dryness evil invading lung syndrome,Qi blood stasis syndrome,liver kidney yin deficiency syndrome and Qi Yin deficiency syndrome according to TCM syndrome differentiation standard.The age,course of disease,general health score in international universal quality of life scale,self rating Anxiety scale(SAS),self rating Depression Scale(SDS)and erythrocyte sedimentation rate were observed and detected(ESR,C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),immunoglobulin IgA,IgG and IgM and other immune inflammatory indexes were detected.The relationship between different TCM Syndromes of PSS and molecular level changes of immune inflammatory indexes was analyzed and compared,as well as the impact on quality of life and mental emotion.Results:The overall health score of patients with Qi Yin deficiency syndrome was significantly lower than that of patients with dampness heat obstructing collaterals and dampness evil invading lung syndrome(P<0.01),while the SAS and SDS scores of patients with Qi Yin deficiency syndrome were significantly higher than those of patients with dampness heat invading lung syndrome and dampness heat obstructing collaterals syndrome(P<0.05,P<0.01);ESR,CRP,RF,TNF-α,IL-6,IgA,IgG and IgM related laboratory indexes of patients with dampness heat obstructing collaterals syndrome were significantly higher than those of patients with dry evil invading lung syndrome,liver kidney yin deficiency syndrome and liver kidney yin deficiency syndrome Qi Yin deficiency syndrome and Qi blood stasis syndrome(P<0.05,P<0.01).Correlation test found that the above five syndrome types were positively correlated with hs-CRP,IL-6,TNF-ɑindicators(P<0.05).Conclusion:The overall health,SAS,SDS and related hs-CRP,IL-6,TNF-ɑand some others indexes of SS patients are associated with TCM syndromes.

Nuclear AhR and membranous PD-L1 in predicting response of non-small cell lung cancer to PD-1 blockade

Dear Editor,Programmed cell death 1 ligand 1(PD-L1)has been used as a biomarker for immune checkpoint inhibitors(ICIs)which exert durable efficacy in non-small cell lung cancer(NSCLC).^(1,2)However,many PD-L1-high patients only marginally respond to,and PD-L1-low patients still benefit from,ICIs.^(3,4)

Safety and efficacy of thalidomide in patients with transfusiondependentβ-thalassemia:a randomized clinical trial

Thalidomide inducesγ-globin expression in erythroid progenitor cells,but its efficacy on patients with transfusion-dependentβ-thalassemia(TDT)remains unclear.In this phase 2,multi-center,randomized,double-blind clinical trial,we aimed to determine the safety and efficacy of thalidomide in TDT patients.A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks,followed by an extension phase of at least 36 weeks.The primary endpoint was the change of hemoglobin(Hb)level in the patients.The secondary endpoints included the red blood cell(RBC)units transfused and adverse effects.In the placebo-controlled period,Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0(range,2.5 to 37.5)g/L,whereas Hb in patients treated with placebo did not significantly change.Within the 12 weeks,the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4±5.0 U and 10.3±6.4 U,respectively(P<0.001).Adverse events of drowsiness,dizziness,fatigue,pyrexia,sore throat,and rash were more common with thalidomide than placebo.In the extension phase,treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9±19.0 g/L,without blood transfusion.Significant increase in Hb concentration and reduction in RBC transfusions were associated with nonβ0/β0 and HBS1L-MYB(rs9399137 C/T,C/C;rs4895441 A/G,G/G)genotypes.These results demonstrated that thalidomide is effective in patients with TDT.

Tobacco carcinogen induces tryptophan metabolism and immune suppression via induction of indoleamine 2,3-dioxygenase 1

Indoleamine 2,3-dioxygenase 1(IDO1),the enzyme that catabolizes tryptophan(Trp)metabolism to promote regulatory T cells(Tregs)and suppress CD8+T cells,is regulated by several intrinsic signaling pathways.Here,we found that tobacco smoke,a major public health concern that kills 8 million people each year worldwide,induced IDO1 in normal and malignant lung epithelial cells in vitro and in vivo.The carcinogen nicotine-derived nitrosaminoketone(NNK)was the tobacco compound that upregulated IDO1 via activation of the transcription factor c-Jun,which has a binding site for the IDO1 promoter.The NNK receptorα7 nicotinic acetylcholine receptor(α7nAChR)was required for NNK-induced c-Jun activation and IDO1 upregulation.In A/J mice,NNK reduced CD8+T cells and increased Tregs.Clinically,smoker patients with non-small-cell lung cancer(NSCLC)exhibited high IDO1 levels and low Trp/kynurenine(Kyn)ratios.In NSCLC patients,smokers with lower IDO1 responded better to anti-PD1 antibody treatment than those with higher IDO1.These data indicate that tobacco smoke induces IDO1 to catabolize Trp metabolism and immune suppression to promote carcinogenesis,and lower IDO1 might be a potential biomarker for anti-PD1 antibodies in smoker patients,whereas IDO1-high smoker patients might benefit from IDO1 inhibitors in combination with anti-PD1 antibodies.