ObjectiveTo systematically characterize the in vitro chemical constituents of Entada phaseoloides and its absorbed prototype compounds and metabolites in a neuropathic pain （NP） model， thereby elucidating the potential pharmacological material basis underlying its analgesic activity. MethodsUltra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to analyze the constituents of the 80% methanol extract of E. phaseoloides. Thirty-six mice were divided into a blank group， low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， an aspirin group （400 mg·kg^-1）， and a morphine group （10 mg·kg^-1）， with six mice in each group. The tail-flick threshold was measured. Twenty-four mice were randomly divided into a blank group and low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， with six mice in each group， and motor coordination was evaluated. A spinal nerve ligation （SNL） model was established in mice. Twenty-four mice were randomly divided into a sham-operated （Sham） group， an SNL group， an SNL + E. phaseoloides extract group （750 mg·kg^-1）， and an SNL + pregabalin group （20 mg·kg^-1）， with 6 mice in each group. Mechanical allodynia and thermal hyperalgesia were evaluated. Behavioral assessments were combined to determine the optimal onset time of the analgesic effect， and plasma samples were collected at this time point. Absorbed components and metabolites were systematically identified based on accurate mass， MS/MS fragmentation patterns， retention time， and comparisons with literature data and reference standards. Meanwhile， network pharmacology， target similarity analysis， and molecular docking validation were integrated to evaluate the potential effects of absorbed components on disease intervention. ResultsCompared with the blank group， the high-dose E. phaseoloides extract group and morphine group showed significantly increased pain response thresholds （P<0.01）， without affecting motor coordination in normal mice. Compared with the Sham group， the SNL group exhibited significantly decreased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. Compared with the SNL group， the SNL + E. phaseoloides extract group and SNL + pregabalin group showed significantly increased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. The analgesic effect of E. phaseoloides was most significant at 2 h after administration. A total of 70 constituents were identified in vitro， and 22 prototype compounds and 29 metabolites were detected in plasma. The targets of the absorbed components were mainly enriched in biological processes associated with pain signal perception and transmission and showed a high degree of overlap with disease genes related to neuropathic pain. In addition， multiple components exhibited strong binding energies with core pain-related targets. Based on integrated analysis of in vitro content， plasma exposure levels， and target associations， ketanthamide A-β-D-pyranoside and ketengzide were identified as the most representative pharmacologically active substances responsible for the analgesic effect. ConclusionThis study systematically elucidates the material basis of E. phaseoloides intervention in neuropathic pain from three aspects， including chemical constituent characteristics， in vivo behavioral characteristics， and potential targets， providing important theoretical foundations and experimental support for further studies on its pharmacological mechanism and analgesic drug development.

Objective:To investigate the drug resistance factors in postoperative gemci-tabine chemotherapy after radical resection of pancreatic cancer.Methods:The retrospective case-control study was constructed. The clinicopathological data of 255 patients with pancreatic cancer who were firstly admitted to the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi ′an Jiaotong University from January 2018 to June 2021 were collected. There were 140 males and 115 females, aged (59±10)years. All patients underwent radical resection of pancreatic cancer and received postoperative gemcitabine-based adjuvant chemotherapy. Observation indicators: (1) follow-up; (2) postoperative chemotherapy; (3) drug resistance and changing of regimen; (4) factors influencing postoperative chemotherapy resistance. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the Pearson chi-square test. Univariate analysis was conducted using the corresponding statistical methods based on data type. Multivariate analysis was conducted using the Logistic regression model with forward method. Kaplan-Meier method was used to draw survival curve, and Log-Rank test was used for survival analysis. Results:(1) Follow-up. All 255 patients were followed up for 18.6(16.7,21.4)months. The median survival time of 255 patients was 18.2[95% confidence interval ( CI) as 15.8-20.6]months. (2) Postoperative chemotherapy. Of the 255 patients, there were 5 cases receiving postoperative chemotherapy as gemcitabine monotherapy, 167 cases receiving postoperative chemotherapy as the AG combination (gemcitabine plus albumin-bound paclitaxel), 74 cases receiving postoperative chemotherapy as the GS combination (gemcitabine plus S-1) and 9 cases receiving postoperative chemotherapy as the GP combination (gemcitabine plus platinum). (3) Drug resistance and changing of regimen. Of the 255 patients, 81 cases completed the course of postoperative chemotherapy and evaluation. Of the 81 patients, there were 18 cases with no recurrence or metastasis of tumor, 10 cases with tumor local recurrence, 40 cases with tumor lymph node metastasis or distant metas-tasis, 3 cases with tumor local recurrence combined with distant metastasis, 10 cases with elevation of CA19-9. Of the 81 patients, 18 cases responded to chemotherapy, 63 cases underwent resistant to chemotherapy, including 11 cases with primary resistance and 52 cases with acquired resistance. The 63 patients with chemotherapy resistance underwent changing of regimen. (4) Factors influencing postoperative chemotherapy resistance. Results of multivariate analysis showed that chemotherapy cycle<6 is an independent risk factor for postoperative chemotherapy resistance in patients ( hazard ratio=17.18, 95% CI as 2.07-142.28, P<0.05). Conclusion:Adjuvant chemotherapy cycle <6 is an independent risk factor for postoperative chemotherapy resistance for gemcitabine based chemo-therapy in pancreatic cancer patients receiving radical resection.