Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Objective To use the cognitive reinforcement comprehensive intervention program constructed by our team to intervene in patients with spinal cord injury and evaluate its clinical application effect.Methods A non-randomized trial design was adopted to select 97 patients with spinal cord injury from November 2021 to September 2022.Forty-four patients from March to September 2022 in a Grade A hospital in Hefei City were included in the experimental group,and 53 patients from November 2021 to February 2022 were included in the control group.The cognitive reinforcement comprehensive intervention program was used to intervene in the experimental group,and the conventional rehabilitation nursing was used to intervene in the control group.The intervention lasted for 12 weeks in both groups.The Changsha Montreal Scale,Social Support Rating Scale,Rehabilitation Exercise Self-efficacy Scale,Spinal Cord Injury Independence Rating Scale and Hamilton Anxiety Scale were used to measure the two groups before intervention,1 month after intervention and 3 months after intervention.Results 40 cases in the experimental group and 48 cases in the control group completed the study.Repeated measurement ANOVA showed that the temporal,interactive and intergroup effects of cognitive function scores and anxiety scores were statistically significant(P＜0.05).The time effect and interaction effect of the subjective support dimension score,coping self-efficacy dimension score of the two groups were statistically significant(P＜0.05).One month after the intervention,the cognitive function scores of test group were higher than before intervention and control group,and the anxiety scores were lower than before intervention and control group(P＜0.05).Three months after the intervention,the scores of cognitive function,subjective support dimension and coping self-efficacy dimension of experimental group were higher than those before intervention and control group,and the scores of anxiety level were lower than those before intervention and control group(P＜0.05).Conclusion Comprehensive intervention of cognitive reinforcement can improve the cognitive function of patients with spinal cord injury,delay the process of cognitive impairment,enhance self-confidence,relieve anxiety,and promote physical and mental rehabilitation of patients.

Objective:To explore the mediating effect of self-efficacy and fatigue between depression and cognitive function in patients with spinal cord injury.Methods:General information questionnaire, Hamilton Depression Scale, Montreal Cognitive Scale, Rehabilitation Exercise Self-Efficacy Scale, Fatigue Revised Scale were used to investigate 256 cases of spinal cord injury patients from December 2018 to August 2020. The deviation-corrected percentile Bootstrap method was used to test the chain mediating effect of rehabilitation exercise self-efficacy and fatigue on depression and cognitive function.Results:Correlation analysis showed that depression was negatively correlated with cognitive function ( r=-0.146, P<0.01), self-efficacy of rehabilitation exercise ( r=-0.115, P<0.01), and positively correlated with fatigue ( r=0.317, P<0.01), self-efficacy of rehabilitation exercise was positively correlated with cognitive function ( r=0.903, P<0.01), and negatively correlated with fatigue ( r=-0.889, P<0.01), and fatigue was negatively correlated with cognitive function ( r=-0.217, P<0.01). The mediation model test showed that depression had a significant direct effect on cognitive function, with an effect value of -0.141 and an effect size of 50.20%. Self-efficacy of rehabilitation exercise and fatigue had a significant mediating effect between depression and cognitive function. The effect value was -0.096, -0.026, the effect size was 34.1%, 9.3%, and the chain mediation effect of rehabilitation exercise self-efficacy-fatigue was also significant, the effect value was -0.018, and the effect size was 6.4%. Conclusions:Depression in patients with spinal cord injury not only directly affects cognitive function, but also indirectly affects cognitive function through the mediating effects of self-efficacy of rehabilitation exercise and fatigue, and the chain-type mediating effect of rehabilitation exercise self-efficacy and fatigue.