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 investigate the value of methylation levels of Discs large-associated protein5(DLGAP5)and Ras association domain family 1A(RASSF1A)in peripheral blood in the differential diagnosis of benign and malignant lung nodules.Methods 110 patients with pulmonary nodules admitted to the Seventh People's Hospital of Hebei Province from December 2022 to June 2024 were selected as study subjects.Based on the diagnosis confirmed by pathological examination,52 patients with malignant lung nodules were included in the malignant group and 58 patients with benign lung nodules were included in the benign group.The methylation levels of DLGAP5 and RASSF1A genes in peripheral blood were determined by quantitative real-time polymerase chain reaction(qRT-PCR).The diagnostic value of methylation of DLGAP5 and RASSF1A genes in peripheral blood on the benign and malignant nature of lung nodules and their relationship with clinicopathological characteristics of patients with malignant lung nodules were analyzed.Spearman's method was used to analyze the correlation between DLGAP5 and RASSF1A gene methylation levels and clinicopathological features.Results Compared with the benign group,the methylation levels of DLGAP5 and RASSF1A genes were higher in the peripheral blood of patients in the malignant group,and the differences were statistically significant(χ2=27.010,24.350,all P<0.001).The sensitivities of DLGAP5 methylation and RASSF1A methylation alone in the detection of malignant lung nodules were 61.54%,67.31%,and the specificity were 86.21%,79.31%,and the accuracies were 74.55%,73.63%,respectively.The sensitivity(84.62%)and accuracy(83.64%)of the combined two-gene methylation test for malignant lung nodules were better than that of single gene methylation(Z=2.816,2.497,all P<0.05).The concordance Kappa values of DLGAP5 methylation and RASSF1A methylation alone and in combination with the pathological results were 0.583,0.569 and 0.712,respectively.The nodules size,histological differentiation degree,lymph nodes and spiculation sign of patients with malignant pulmonary nodules were correlated with DLGAP5 and RASSF1A methylation levels,and the differences were statistically significant(χ2DLGAP5=4.644～14.981,χ2RASSF1A=4.293～12.629,all P<0.05).Correlation analysis showed that the methylation levels of DLGAP5 and RASSF1A genes were positively correlated with nodule size,histologic differentiation,lymph node metastasis and spiculation sign(rDLGAP5=0.512～0.683,rRASSF1A=0.527～0.691,all P<0.05).Conclusion The methylation levels of DLGAP5 and RASSF1A gene in peripheral blood were closely related to histological differentiation,lymph node metastasis and clinical staging.The combined detection of the two has high diagnostic value fro the benign and malignant nature of pulmonary nodules.

Objective To evaluate the efficacy and safety of dupilumab combined with 2％cleboride ointment in the treatment of moderate to severe atopic dermatitis,as well as its impact on serological indica-tors.Methods A retrospective analysis was conducted on the clinical data of 67 patients with moderate to se-vere atopic dermatitis(AD)admitted to the Department of Dermatology of Shaoxing University Affiliated Hospital from March 2021 to December 2024.The study subjects were divided into an experimental group(n=35)and a control group(n=32)according to the treatment method.The experimental group was treated with Dupilumab injection and 2％Cleboride ointment,while the control group was treated with ebastine tab-lets and 2％cleboride ointment.Clinical and related serological indicators of patients after 16 weeks of treat-ment were collected,and the itch digital scale score,eczema area and severity(EASI)score,IL-4,IL-13 levels,and incidence of local skin adverse reactions were analyzed before and after treatment in both groups.Results The total effective rate of the experimental group after treatment was 94.29％(33/35),which was higher than the control group[53.13％(17/32)],and the difference was statistically significant(x2=12.862,P＜0.001).There was no statistically significant difference in symptom scores,IL-4,and IL-13 levels between the two groups before treatment(P＞0.05).After treatment,the symptom scores of the experimental group were lower than those of the control group,and the difference was statistically significant(P＜0.05).The lev-els of IL-4 and IL-13 in the experimental group were lower than those in the control group,and the difference was statistically significant(P＜0.05).The incidence of adverse reactions in the experimental group was 2.86％(1/35),significantly lower than the 34.38％(11/32)in the control group,and the difference was sta-tistically significant(x2=9.252,P=0.002).Conclusion The combination of dupilumab injection and 2％cleboride ointment is effective in relieving skin symptoms,regulating cellular immune function,reducing in-flammatory reactions,and minimizing local skin adverse reactions in patients with moderate to severe AD.It is worthy of clinical promotion and use.

Objective To investigate the value of methylation levels of Discs large-associated protein5(DLGAP5)and Ras association domain family 1A(RASSF1A)in peripheral blood in the differential diagnosis of benign and malignant lung nodules.Methods 110 patients with pulmonary nodules admitted to the Seventh People's Hospital of Hebei Province from December 2022 to June 2024 were selected as study subjects.Based on the diagnosis confirmed by pathological examination,52 patients with malignant lung nodules were included in the malignant group and 58 patients with benign lung nodules were included in the benign group.The methylation levels of DLGAP5 and RASSF1A genes in peripheral blood were determined by quantitative real-time polymerase chain reaction(qRT-PCR).The diagnostic value of methylation of DLGAP5 and RASSF1A genes in peripheral blood on the benign and malignant nature of lung nodules and their relationship with clinicopathological characteristics of patients with malignant lung nodules were analyzed.Spearman's method was used to analyze the correlation between DLGAP5 and RASSF1A gene methylation levels and clinicopathological features.Results Compared with the benign group,the methylation levels of DLGAP5 and RASSF1A genes were higher in the peripheral blood of patients in the malignant group,and the differences were statistically significant(χ2=27.010,24.350,all P<0.001).The sensitivities of DLGAP5 methylation and RASSF1A methylation alone in the detection of malignant lung nodules were 61.54%,67.31%,and the specificity were 86.21%,79.31%,and the accuracies were 74.55%,73.63%,respectively.The sensitivity(84.62%)and accuracy(83.64%)of the combined two-gene methylation test for malignant lung nodules were better than that of single gene methylation(Z=2.816,2.497,all P<0.05).The concordance Kappa values of DLGAP5 methylation and RASSF1A methylation alone and in combination with the pathological results were 0.583,0.569 and 0.712,respectively.The nodules size,histological differentiation degree,lymph nodes and spiculation sign of patients with malignant pulmonary nodules were correlated with DLGAP5 and RASSF1A methylation levels,and the differences were statistically significant(χ2DLGAP5=4.644～14.981,χ2RASSF1A=4.293～12.629,all P<0.05).Correlation analysis showed that the methylation levels of DLGAP5 and RASSF1A genes were positively correlated with nodule size,histologic differentiation,lymph node metastasis and spiculation sign(rDLGAP5=0.512～0.683,rRASSF1A=0.527～0.691,all P<0.05).Conclusion The methylation levels of DLGAP5 and RASSF1A gene in peripheral blood were closely related to histological differentiation,lymph node metastasis and clinical staging.The combined detection of the two has high diagnostic value fro the benign and malignant nature of pulmonary nodules.

ObjectiveTo investigate the effect of Ziziphi Spinosae Semen-Albiziae Flos on the nucleotide-binding oligomerization domain，NOD-like receptor thermal protein domain associated protein 1 （NLRP1）/chemokine ligand 1 （CXCL1）/chemokine receptor 2 （CXCR2） pathway in the hippocampus of the rat model of chronic unpredictable mild stress （CUMS）-induced depression. MethodA total of 120 male SD rats were randomized into blank，CUMS，CUMS + low-，medium-，and high-dose （4，8，16 g·kg^-1） Ziziphi Spinosae Semen-Albiziae Flos，and CUMS + venlafaxine hydrochloride （0.008 g·kg^-1） groups，with 20 rats in each group.The rat model of depression was established by solitary feeding combined with CUMS.The behaviors and spatial learning and memory abilities of rats were examined by sugar water consumption test，tail suspension test，forced swimming test，and Morris water maze test.Quantitative real-time PCR （Real-time PCR） and Western blot were employed to determine the expression of factors associated with the NLRP1/CXCL1/CXCR2 pathway in the hippocampus.Enzyme-linked immunosorbent assay was employed to determine the levels of tumor necrosis factor-α （TNF-α），interleukin （IL）-18，IL-1β，and IL-6 in the hippocampus.The immunofluorescence assay was used to measure the levels of reactive oxygen species （ROS） in the hippocampus. ResultCompared with the blank group，the CUMS group showed decreased preference to sugar water and times of crossing the platform （P<0.01），and increased immobility time of tail suspension，forced swimming floating time，and escape latency （P<0.01）.Compared with the CUMS group，the administration of Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride alleviated the effects of CUMS on the above-mentioned behaviors and spatial learning and memory abilities of the rats （P<0.05，P<0.01）.Compared with the blank group，the CUMS group showed up-regulated protein levels of NLRP1，CXCL1，and CXCR2 （P<0.01） and elevated levels of IL-18，IL-1β，TNF-α，and IL-6 （P<0.01） in the hippocampus.The treatment with Ziziphi Spinosae Semen-Albiziae Flos and venlafaxine hydrochloride attenuated the activation of NLRP1/CXCL1/CXCR2 signaling pathway and lowered the levels of inflammatory cytokines in the hippocampus of CUMS rats （P<0.05，P<0.01）.In addition，Ziziphi Spinosae Semen-Albiziae Flos lowered the level of ROS in the hippocampus （P<0.05，P<0.01）. ConclusionZiziphi Spinosae Semen-Albiziae Flos can mitigate the depressive behaviors of the rat model of CUMS-induced depression by inhibiting the activation of NLRP1/CXCL1/CXCR2 signaling pathway.

Objective:To retrieve, evaluate, and summarize the best evidence for peripherally inserted central catheter (PICC) related thrombosis in children.Methods:Guideline websites, relevant society websites, and databases at China and abroad were searched for guidelines, evidence summaries, expert consensuses, and systematic reviews related to thrombosis before and after PICC catheterization in children published up to June 30, 2021 based on evidence-based nursing. The quality of the literature was independently evaluated by 2 researchers with reference to Appraisal of Guidelines for Research and Evaluation InstrumentⅡ and the criteria of the Joanna Briggs Institute (JBI) in Australia (2016) . Data were extracted from the literatures that met the standards through expert demonstration, and the evidence was graded and recommended according to the JBI evidence pre-grading system (2014 edition) .Results:A total of 11 articles were included, including 4 guidelines, 1 systematic review, 1 expert consensus, and 5 evidence summaries. 27 pieces of evidence were summarized from 7 aspects: organizational management, catheter selection, blood vessel selection and puncture, location of catheter tip, physical prevention, drug prevention, and evaluation.Conclusions:This paper summarizes and analyzes the best evidence for PICC-related thrombosis in children and provides an evidence-based reference for the clinical application and practice of PICC-related thrombosis in children.

Objective:To explore the pain perception and cognition of children with malignant tumor and their parents during the disease treatment.Methods:Using the convenient sampling method, a total of 179 children with malignant tumors and their 179 parents who were admitted to the day ward of Hematology and Oncology Center of Beijing Children's Hospital, Capital Medical University from June 2017 to February 2019 were selected as the research objects. The children and their parents were surveyed by using the self-developed Pain Questionnaire for Children with Malignant Tumor and the Pain Questionnaire for Parents of Children with Malignant Tumor. A total of 179 questionnaires were distributed, 179 valid questionnaires were recovered, and the effective recovery rate was 100.0%.Results:The incidence of pain during treatment in 179 parents and 179 children was 100.0% (179/179) and 98.3% (176/179) , respectively. The average scores of 179 parents and 179 children who considered the most severe pain during disease treatment were respectively (5.82±2.30) and (5.41±2.09) , and the average pain scores were (4.04±1.90) and (3.95±1.66) , respectively. There were statistically significant differences in pain perception between children and their parents during lumbar puncture/thecal injection, bone puncture, PICC catheter placement, indwelling needle puncture and venous blood collection ( P<0.05) . A total of 77.1% (138/179) of parents and 65.4% (117/179) of children had concerns about the use of analgesics, respectively. Conclusions:There is a high consistency between the severity of pain experienced by parents and the children's feelings during treatment. However, the parents feel that the unbearable treatment-related pain during the treatment of the disease is higher than that of children, and they are more passive than children in the attitude of receiving analgesics. Medical staff can listen to their parents' opinions during pain assessment, pay attention to education of parents before treatment-related operations, take measures to reduce or even avoid the occurrence of treatment-related pain and strengthen the training of pain relief measures.

Objective:To retrieve and summarize the best evidence of peripherally inserted central catheters (PICC) related bloodstream infection prevention and to evaluate the evidence, so as to provide reference for clinical implementation of preventive measures for catheter-related bloodstream infection.Methods:National Institute for Health and Care Excellence (NICE) , National Guideline Clearinghouse (NGC) , Guidelines International Network (GIN) , Scottish Intercollegiate Guidelines Network (SIGN) , Australian Joanna Briggs Institute (JBI) Evidence-based Health Centre Database, UpToDate, BMJ Best Practice, Cochrane Library, China National Knowledge Infrastructure (CNKI) , Wanfang and related professional websites such as Infusion Nursing Society (INS) , Medlive and official website of the National Health Commission were searched for all clinical decisions, guidelines, expert consensus, evidence summary and systematic reviews related to the prevention of PICC catheter-related bloodstream infections. The retrieval time limit was from the establishment of the databases to May 2021. Four researchers evaluated the quality of the literature, and two researchers extracted and summarized the evidence.Results:A total of 9 articles were included, including 1 clinical decision, 1 standard of practice, 4 guidelines and 3 evidence summaries. Finally, 29 pieces of evidence were included from 5 dimensions, including organization management, infusion tool selection, catheterization maintenance and use, health education and extubation.Conclusions:The summary of the best evidence for the prevention of PICC related bloodstream infection covers a wide range of areas. Managers and clinical medical staff should apply the evidence according to the specific medical situation to reduce the occurrence of clinical PICC catheter-related bloodstream infection.

Objective:To analyze the public demands for information about congenital birth defects in “Baidu zhidao” based on word frequency retrieval.Methods:Based on discussion between obstetrics and gynecology experts and epidemiological experts, the key words related to congenital birth defects were determined and the search strategy was formulated. Python 2.7 was used for web crawler search. Questions related to congenital birth defects were obtained on the “Baidu zhidao” platform, and then the R 4.0.2 software was used to process the data, complete the semantic analysis of keywords and statistical analysis of word frequency, and draw word cloud graph and polar chart to describe the key results.Results:A total of 16668 non-repetitive questions were retrieved from “Baidu zhidao” platform, and the frequency of semantic words was 15 371. Among them, 35.02% were the names and symptoms of congenital birth defects. In addition, the frequency of congenital heart disease was the highest (26.09%). The results of subject analysis of key words of birth defects showed that the average word frequency of diagnosis and treatment semantic words (49.55) was significantly higher than that of etiology and prevention semantic words (12.47). In addition, the key words of examination, cause, treatment, development and heredity were more frequently used in the semantic words related to the seven types of systemic malformations.Conclusion:The public in China has a high demand for information on congenital birth defect related diseases, and their causes, prevention and treatment, especially congenital heart disease.

Objective:To investigate the complication and compliance of different supine time and the degree of obedience in children with leukemia after intrathecal chemotherapy.Methods:A total of 553 children with leukemia after intrathecal chemotherapy from April 1, 2017 to March 28, 2019 in Beijing Children′s Hospital Affiliated to Capital Medical University were selected. Children who received intrathecal injection from April 1, 2017 to December 31, 2017 were selected as control group(274 cases), from January 1, 2018 to March 28, 2019 were selected as research group(279 cases). The children in research group were supine 2 hours but control group were supine 4 hours after intrathecal. The complications that occurred after injection and within one week after injection and compliance were observed.Results:Finally, 457 children included in this study, there were 235 cases in research group and 222 cases in control group. The number of cases of limb numbness and local pressure reddening in the research group and the control group were 18, 20 and 31, 34, respectively, with statistically significant differences between the two groups( χ2 values were 4.74, 5.07, P<0.05). After intrathecal injection, the patients' compliance with the time of supine removal was completely acceptable to the research group, relatively acceptable, acceptable, and required efforts to adhere to the number of cases were 65, 83, 42, 45, respectively, while the control group were 34, 50, 76, 62, respectively, the differences were significant ( χ2 value was 30.04, P<0.05). Conclusions:Supine for 2 hours after intrathecal injection can reduce the incidence of complications and improve compliance, which is safe and feasible. So, supine for 2 hours after intrathecal injection is recommended.