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.

Methamphetamine (METH) abuse is associated with significant neurotoxicity, high addiction potential, and behavioral abnormalities. Recent studies have identified a connection between the gut microbiota and METH-induced neurotoxicity and behavioral disorders. However, the underlying causal mechanisms linking the gut microbiota to METH pathophysiology remain largely unexplored. In this study, we employed fecal microbiota transplantation (FMT) and antibiotic (Abx) intervention to manipulate the gut microbiota in mice administered METH. Furthermore, we supplemented METH-treated mice with short-chain fatty acids (SCFAs) and pioglitazone (Pio) to determine the protective effects on gut microbiota metabolism. Finally, we assessed the underlying mechanisms of the gut-brain neural circuit in vagotomized mice. Our data provide compelling evidence that modulation of the gut microbiome through FMT or microbiome knockdown by Abx plays a crucial role in METH-induced neurotoxicity, behavioral disorders, gut microbiota disturbances, and intestinal barrier impairment. Furthermore, our findings highlight a novel prevention strategy for mitigating the risks to both the nervous and intestinal systems caused by METH, which involves supplementation with SCFAs or Pio.

Methamphetamine (Meth) abuse can cause serious mental disorders, including anxiety and depression. The gut microbiota is a crucial contributor to maintaining host mental health. Here, we aim to investigate if microbiota participate in Meth-induced mental disorders, and the potential mechanisms involved. Here, 15 mg/kg Meth resulted in anxiety- and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor (SIGMAR1)/BDNF/TRKB pathway in the hippocampus. Meanwhile, Meth impaired gut homeostasis by arousing the Toll-like receptor 4 (TLR4)-related colonic inflammation, disturbing the gut microbiome and reducing the microbiota-derived short-chain fatty acids (SCFAs). Moreover, fecal microbiota from Meth-administrated mice mediated the colonic inflammation and reproduced anxiety- and depression-like behaviors in recipients. Further, SCFAs supplementation optimized Meth-induced microbial dysbiosis, ameliorated colonic inflammation, and repressed anxiety- and depression-like behaviors. Finally, Sigmar1 knockout (Sigmar1^-/-) repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure, and eliminated the anti-anxiety and -depression effects of SCFAs. The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety- and depression-like behaviors. Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis, and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner. This study confirms the crucial role of microbiota in Meth-related mental disorders and provides a potential preemptive therapy.

Objective To study the application of clinical nursing pathway in reducing the leakage of contrast agent on CT scan and improving satisfaction.Methods A total of 200 patients were randomly divided into experimental group with clinical nursing pathway and the control group with conventional nursing care, with 100 cases in each group.The leakage of contrast agent on CT scan, nursing errors, scanning failure by the injection errors, scanning time, satisfaction of scanning technicians and patients were analyzed and compared between the two groups.Results The leakage of contrast agent and nursing errors had no significant difference between the two groups (P>0.05).But the scanning failure by injection error, scanning time, patients''satisfaction and scanning technicians''satisfaction in the experimental group were better than that in the observation group (P<0.05).Conclusion Clinical nursing pathway can barely reduce the leakage of contrast agent but can significantly increase the satisfaction.

Objective To study the application of clinical nursing pathway in reducing the leakage of contrast agent on CT scan and improving satisfaction.Methods A total of 200 patients were randomly divided into experimental group with clinical nursing pathway and the control group with conventional nursing care, with 100 cases in each group.The leakage of contrast agent on CT scan, nursing errors, scanning failure by the injection errors, scanning time, satisfaction of scanning technicians and patients were analyzed and compared between the two groups.Results The leakage of contrast agent and nursing errors had no significant difference between the two groups (P>0.05).But the scanning failure by injection error, scanning time, patients''satisfaction and scanning technicians''satisfaction in the experimental group were better than that in the observation group (P<0.05).Conclusion Clinical nursing pathway can barely reduce the leakage of contrast agent but can significantly increase the satisfaction.

Objective To investigate the correlation between two single nucleotide polymorphisms of the leukotriene A4 hydrolase (LTA4H) gene (rs2660845 and rs2540493) and risk of ischemic stroke in population of southern Zhejiang Province.Methods A total of 300 ischemic stroke patients and 300 healthy controls,recruited from the Department of Neurology,Third Affiliated Hospital of Wenzhou Medical University between September 2010 and June 2013,were enrolled in this study.Two single nucleotide polymorphisms of the LTA4H gene (rs2660845 and rs2540493) were analyzed by polymerase chain reaction and matrix-assisted laser desorption/ionization time of flight,respectively.Sixty-seven patients and thirty controls were randomly selected (complete randomization) and detected the serum leukotriene B4 (LTB4)concentration by ELISA method.Results There was no evidence of association between the two variants of LTA4H gene and the risk of ischemic stroke or its TOAST (Trial of Org 10 172 in acute stroke treatment)subtypes (P ＞ 0.05).Analysis of LTB4 levels revealed that there was no statistically significant difference in serum LTB4 concentration between patients (n =67) and controls (n =30; 0.991 ± 0.305 vs 1.035 ± 0.498 ; P =0.692),and no statistically significant difference in LTB4 concentration was found among the three genotypes of rs2660845 as well (AG genotype vs AA genotype vs GG genotype:0.938 ± 0.269 vs 1.038 ± 0.268 vs 1.043 ± 0.383 ; P =0.401).Conclusion The present study suggests that there is no association between the two polymorphisms in the LTA4H gene and risk of ischemic stroke in population of southern Zhejiang Province.