OBJECTIVE To investigate the expression levels of nucleotide-binding oligomerization domain-like recep-tor pyrin domain-associated protein 3(NLRP3)inflammasome pathway and toll-like receptors(TLRs)pathway in serofast patients with syphilis infection,and their correlation with helper T lymphocytes(Th)1/Th2.METHODS A total of 549 patients with syphilis admitted to Tianjin Chest Hospital and Tianjin Medical University General Hospital from Jan.2021 to Dec.2022 were selected.Among them,62 patients who had not received anti-syphilis treatment were assigned to the syphilis group,238 patients whose serum remained positive after anti-syphilis treatment were selected as the fixed group,249 patients whose serum turned negative after anti-syphilis treatment were selected as the negative conversion group,and another 565 healthy people who underwent medical examina-tion in the hospital during the same period were selected as the control group.TLR2,TLR4,nuclear factor(NF)-κB,NLRP3,apoptosis-associated speck-like protein(ASC),cysteinyl aspartate proteolytic enzyme 1(Caspase-1),in-terleukin(IL)-1β mRNA and interferon-γ(IFN-γ),IL-12,IL-13 and IL-10 levels were compared between each group.Pearson's analysis was used to analyze the correlation between the mRNA expression of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1,and IL-1β and the levels of IFN-γ,IL-12,IL-13,and IL-10 in serologically fixed patients with syphilis.RESULTS Compared with the control group,the mRNA expression of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β was elevated in the negative conversion and the syphilis groups,and the expres-sion of the above indicators was decreased in the fixed group(P＜0.05).Compared with negative conversion group,mR-NA expressions of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β were increased in syphilis group,while the expression of the above indicators was decreased in fixed group(P＜0.05).Compared with fixed group,mRNA ex-pressions of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β in syphilis group were increased in the syphilis group(P＜0.05).Compared with the control group,IFN-γ and IL-12 levels were decreased in the negative conversion group,syphilis group and fixed group,and IL-13 and IL-10 levels were increased(P＜0.05).Compared with the nega-tive conversion group,IFN-γ and IL-12 levels in the syphilis group and fixed group were decreased,while IL-13 and IL-10 levels were increased(P＜0.05).Compared with the fixed group,the levels of IFN-γ and IL-12 in syphilis group were increased,while the levels of IL-13 and IL-10 were decreased(P＜0.05).The mRNA levels of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β were positively correlated with the levels of IFN-γ and IL-12 in serum fixed patients with syphilis infection(r=0.698,0.602,0.636,0.702,0.645,0.617,0.583 and 0.669,and 0.693,0.641,0.702,0.623,0.618 and 0.647,respectively,all P＜0.05),and negatively correlated with the levels of IL-13 and IL-10(r=-0.639,-0.705,-0.614,-0.590,-0.598,-0.651 and-0.628,and-0.704,-0.649,-0.606,-0.655,-0.650,-0.641 and-0.539,respectively,all P＜0.05).CONCLUSION The NLRP3 inflammasome pathway and TLRs pathway are abnormally expressed in sero-fast patients with syphilis infection,positively correlated with the expression of Th1 cytokines IFN-γ and IL-12,and negatively correlated with the expression of Th2 cytokines IL-13 and IL-10.

OBJECTIVE To investigate the expression levels of nucleotide-binding oligomerization domain-like recep-tor pyrin domain-associated protein 3(NLRP3)inflammasome pathway and toll-like receptors(TLRs)pathway in serofast patients with syphilis infection,and their correlation with helper T lymphocytes(Th)1/Th2.METHODS A total of 549 patients with syphilis admitted to Tianjin Chest Hospital and Tianjin Medical University General Hospital from Jan.2021 to Dec.2022 were selected.Among them,62 patients who had not received anti-syphilis treatment were assigned to the syphilis group,238 patients whose serum remained positive after anti-syphilis treatment were selected as the fixed group,249 patients whose serum turned negative after anti-syphilis treatment were selected as the negative conversion group,and another 565 healthy people who underwent medical examina-tion in the hospital during the same period were selected as the control group.TLR2,TLR4,nuclear factor(NF)-κB,NLRP3,apoptosis-associated speck-like protein(ASC),cysteinyl aspartate proteolytic enzyme 1(Caspase-1),in-terleukin(IL)-1β mRNA and interferon-γ(IFN-γ),IL-12,IL-13 and IL-10 levels were compared between each group.Pearson's analysis was used to analyze the correlation between the mRNA expression of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1,and IL-1β and the levels of IFN-γ,IL-12,IL-13,and IL-10 in serologically fixed patients with syphilis.RESULTS Compared with the control group,the mRNA expression of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β was elevated in the negative conversion and the syphilis groups,and the expres-sion of the above indicators was decreased in the fixed group(P＜0.05).Compared with negative conversion group,mR-NA expressions of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β were increased in syphilis group,while the expression of the above indicators was decreased in fixed group(P＜0.05).Compared with fixed group,mRNA ex-pressions of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β in syphilis group were increased in the syphilis group(P＜0.05).Compared with the control group,IFN-γ and IL-12 levels were decreased in the negative conversion group,syphilis group and fixed group,and IL-13 and IL-10 levels were increased(P＜0.05).Compared with the nega-tive conversion group,IFN-γ and IL-12 levels in the syphilis group and fixed group were decreased,while IL-13 and IL-10 levels were increased(P＜0.05).Compared with the fixed group,the levels of IFN-γ and IL-12 in syphilis group were increased,while the levels of IL-13 and IL-10 were decreased(P＜0.05).The mRNA levels of TLR2,TLR4,NF-κB,NLRP3,ASC,Caspase-1 and IL-1β were positively correlated with the levels of IFN-γ and IL-12 in serum fixed patients with syphilis infection(r=0.698,0.602,0.636,0.702,0.645,0.617,0.583 and 0.669,and 0.693,0.641,0.702,0.623,0.618 and 0.647,respectively,all P＜0.05),and negatively correlated with the levels of IL-13 and IL-10(r=-0.639,-0.705,-0.614,-0.590,-0.598,-0.651 and-0.628,and-0.704,-0.649,-0.606,-0.655,-0.650,-0.641 and-0.539,respectively,all P＜0.05).CONCLUSION The NLRP3 inflammasome pathway and TLRs pathway are abnormally expressed in sero-fast patients with syphilis infection,positively correlated with the expression of Th1 cytokines IFN-γ and IL-12,and negatively correlated with the expression of Th2 cytokines IL-13 and IL-10.

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective:To analyze the prognostic value of the coagulation index in stereotactic radio surgery(SRS)for patients with non-small cell lung cancer(NSCLC)and brain metastases(BMS).Methods:We retrospectively analyzed clinical data from 512 patients diagnosed with NSCLC and BMS,who were treated with SRS at Tianjin Huanhu Hospital from October 2015 to September 2018.The overall survival(OS)and progression-free survival(PFS)rates were analyzed.The Cox model was employed to examine prognostic factors.Subsequently,the receiver operating characteristic(ROC)curve was constructed based on multi-factor analysis usin the Cox model.The area under the ROC curve(AUC)was used to assess the prognostic value of coagulation indexes in patients with NSCLC and BMS who underwent SRS.Results:In 1,2,3,and 4 years,PFS rates were 79.9%,69.9%,56.6%,and 43.2%,respectively,and OS rates were 93.4%,83.2%,69.9%,and 57.6%,respectively.Smoking and average fibrinogen(Fib)levels,prothrombin time(PT),and D-dimer(D-D)levels were correlated with a longer PFS(P<0.05).Av-erage activated partial thromboplastin time(APTT),Fib,and D-D levels were correlated with a longer OS(P<0.05).Smoking and mean Fib and D-D levels were significantly correlated with a longer PFS(P<0.05),while The average levels of Fib and D-D are each significantly associated with longer OS rates(P<0.05).The combined detection of Fib and D-D in predicting the prognosis of NSCLC patients with brain metastases undergoing SRS treatment shows a significantly higher AUC compared to the detection of Fib and D-D individually(P<0.05).Conclusions:Co-agulation indexes have a certain correlation with the prognosis of patients with NSCLC and BMS treated with SRS.Furthermore Fib and D-D are independent risk factors for the prognosis of these patients and can be used to assess their outcomes.The combined evaluation of the indexes provides a more ideal prognostic assessment.