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 study the growth inhibition of Thunberg Fritillary extract on non-small cell lung cancer.Methods:The Thunberg Fritillary extract was prepared and characterized by UPLC-QE/MS.Replicated Lewis lung carcinoma ectopic tumor-bear-ing mouse model,yeast injection induced acute inflammation,compared the effect of Thunberg Fritillary extract combination with acute inflammation on the growth,tumor volume and tumor suppression rate of Lewis lung carcinoma mice,and determine the content of inflammatory factors by the flow CBA method(IL-6,IL-1β,IL-1α,IL-10,IL-27,IL-17A,IL-12p70,IL-23,TNF-α,IFN-γ,IFN-β,GM-CSF,MCP-1).Results:The inhibition of Lewis lung carcinoma mice was similar to that of cisplatin alone,and the tumor suppression rate was 35%;the tumor suppression rate of Thunberg Fritillary extract combined with acute inflammatory stimulation of yeast was 62%,1.8 times that of cisplatin alone.The decrease in the expressions of cytokines IL-23,MCP-1 after acute inflammatory stimulation in yeast was associated with tumor suppression;while the increased expressions of IL-6,IL-1β,IL-1α,IL-10,IL-27,IL-17A,IL-12p70,TNF-α,IFN-γ,IFN-β and GM-CSF cytokines were associated with tumor suppression.Conclusion:The Thun-berg Fritillary extract combination with acute inflammation can play a positive role against non-small cell lung cancer,which will pro-vide new research ideas and methods for the prevention and treatment of non-small cell lung cancer.

A 70-year-old female patient presented with fatigue and edema for 3 months and was found to have elevated serum creatinine for 3 weeks. During the course of the disease, she had fever and cough. Examinations revealed multiple ground-glass opacities in both lungs and positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibodies (ANCA), leading to a diagnosis of ANCA-associated vasculitis. The patient′s condition initially improved after pulse glucocorticoid therapy combined with cyclophosphamide. During treatment, however, the patient developed hematochezia, and colonoscopy revealed multiple colonic ulcers. Immunohistochemistry of colonic mucosal biopsy confirmed cytomegalovirus (CMV) positivity, establishing a diagnosis of CMV colitis. The patient was found to have concurrent Clostridioidesdifficile and pulmonary infections. During the disease course, the patient also developed deep vein thrombosis and roxadustat-associated central hypothyroidism. Given the presence of multiple comorbidities, rituximab was subsequently used for vasculitis treatment, resulting in sustained remission. This case highlights the importance of highly individualized treatment strategies for older patients with vasculitis, requiring adjustment of immunosuppressive therapy intensity based on disease progression.

Objective:To study the growth inhibition of Thunberg Fritillary extract on non-small cell lung cancer.Methods:The Thunberg Fritillary extract was prepared and characterized by UPLC-QE/MS.Replicated Lewis lung carcinoma ectopic tumor-bear-ing mouse model,yeast injection induced acute inflammation,compared the effect of Thunberg Fritillary extract combination with acute inflammation on the growth,tumor volume and tumor suppression rate of Lewis lung carcinoma mice,and determine the content of inflammatory factors by the flow CBA method(IL-6,IL-1β,IL-1α,IL-10,IL-27,IL-17A,IL-12p70,IL-23,TNF-α,IFN-γ,IFN-β,GM-CSF,MCP-1).Results:The inhibition of Lewis lung carcinoma mice was similar to that of cisplatin alone,and the tumor suppression rate was 35%;the tumor suppression rate of Thunberg Fritillary extract combined with acute inflammatory stimulation of yeast was 62%,1.8 times that of cisplatin alone.The decrease in the expressions of cytokines IL-23,MCP-1 after acute inflammatory stimulation in yeast was associated with tumor suppression;while the increased expressions of IL-6,IL-1β,IL-1α,IL-10,IL-27,IL-17A,IL-12p70,TNF-α,IFN-γ,IFN-β and GM-CSF cytokines were associated with tumor suppression.Conclusion:The Thun-berg Fritillary extract combination with acute inflammation can play a positive role against non-small cell lung cancer,which will pro-vide new research ideas and methods for the prevention and treatment of non-small cell lung cancer.

In recent years,the incidence rate of type 1 diabetes is on the rise.The causes of the disease are extremely complex,and the pathogenesis has not yet been fully clarified.Different types of studies have confirmed that the occurrence and evolution of type 1 diabetes is a typical process of polygene,multifactor,multi-stage and multi-channel,which is considered to be caused by the combined effect of genetic and environ-mental factors.At present,it is believed that environmental factors are related to the interaction of infection factors,diet factors,early exposure events,intestinal flora,immune factors,other factors and genetic factors.This article reviews the research on environmental factors of type 1 diabetes in recent years.

A 70-year-old female patient presented with fatigue and edema for 3 months and was found to have elevated serum creatinine for 3 weeks. During the course of the disease, she had fever and cough. Examinations revealed multiple ground-glass opacities in both lungs and positivity for myeloperoxidase-anti-neutrophil cytoplasmic antibodies (ANCA), leading to a diagnosis of ANCA-associated vasculitis. The patient′s condition initially improved after pulse glucocorticoid therapy combined with cyclophosphamide. During treatment, however, the patient developed hematochezia, and colonoscopy revealed multiple colonic ulcers. Immunohistochemistry of colonic mucosal biopsy confirmed cytomegalovirus (CMV) positivity, establishing a diagnosis of CMV colitis. The patient was found to have concurrent Clostridioidesdifficile and pulmonary infections. During the disease course, the patient also developed deep vein thrombosis and roxadustat-associated central hypothyroidism. Given the presence of multiple comorbidities, rituximab was subsequently used for vasculitis treatment, resulting in sustained remission. This case highlights the importance of highly individualized treatment strategies for older patients with vasculitis, requiring adjustment of immunosuppressive therapy intensity based on disease progression.

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.

Objective:To explore the value of iterative decomposition of water and fat with asymmetry and least squares estimation-quantitative fat imaging (IDEAL-IQ) in quantitative evaluation of thigh muscle fat content and its correlation with muscle strength in middle-aged and elderly volunteers.Methods:From December 2020 to April 2021, 30 volunteers aged 45 to 70 were recruited prospectively, including 15 males and 15 females with 52.5 (49.0, 56.3) years old. All subjects were scanned at 3.0 T MR, including axial T 1WI, IDEAL-IQ and coronal T 2WI of the left thigh. The region of interest of the knee extensors (quadriceps femoris) and knee flexors (hamstrings) in the left mid-thigh were delineated, and muscle cross-sectional area (CSA), skeletal muscle index (SMI), intermuscular fat fraction (FF) and intramuscular FF were obtained. In addition, isokinetic muscle strength measurement was performed on the left knee joint of all subjects at angular speeds of 60°/s and 180°/s to obtain peak torque (PT) and total work (TW) of knee flexors and extensors. Independent sample t-test, paired t-test or Mann-Whitney U test were used to compare the differences of CSA, SMI, intermuscular FF, intramuscular FF, PT and TW between different genders and muscle groups. Pearson or Spearman correlation analysis, and multiple linear regression analysis were used to analyze the correlation between CSA, SMI, intermuscular FF, intramuscular FF and PT, TW of thigh muscles. Results:The CSA, PT and TW of thighs in males were higher than those in females ( P<0.05), while the intermuscular FF in males was lower than that in females ( P=0.005). The CSA, SMI and PT of the thigh extensors were higher than those of the flexors ( P<0.001), while the intramuscular FF and intermuscular FF were lower than those of the flexors ( P<0.001). Intramuscular FF of flexors and extensors were moderately negatively correlated with PT ( r=-0.635, P<0.001; r=-0.546, P<0.001), and highly, moderately negatively correlated with TW ( r=-0.718, P<0.001; r=-0.616, P<0.001). Intermuscular FF of flexors and extensors were moderately negatively correlated with PT ( r=-0.519, P=0.003; r=-0.443, P=0.014), and negatively correlated with TW ( r=-0.363, P=0.049; r=-0.552, P=0.002). There was no significant correlation between CSA, SMI and PT, TW in flexors and extensors of thigh ( P>0.05). Multiple linear regression analysis showed that intramuscular FF was still significantly correlated with PT and TW of flexors and extensors (flexors: R 2adj=0.505, P=0.001; R 2adj=0.540, P<0.001; extensors: R 2adj=0.351, P=0.006; R 2adj=0.470, P=0.002). Conclusion:FF based on IDEAL-IQ technology can accurately quantify the intramuscular and intermuscular fat content of thighs, and there are negative correlations between intramuscular FF, intermuscular FF and isokinetic muscle strength measurements including PT and TW. Among them, intramuscular FF is more significant.

Objective:To establish a risk prediction model for hospital acute heart failure in elderly patients with chronic heart failure (CHF) .Methods:From January 2018 to December 2020, 619 elderly CHF patients admitted to the Cardiovascular Department of Peking University Third Hospital were selected as the research object by convenience sampling. The patients were divided into the occurrence group ( n=55) and the non-occurrence group ( n=564) according to whether the patients had acute heart failure in hospital. Binomial Logistic regression was used to explore the independent risk factors of acute heart failure in elderly CHF patients. The nomogram model was constructed by R software, and its prediction effect was verified. Results:Binomial Logistic regression showed that high heart rate at admission [ OR=1.021, 95% CI (1.003, 1.039) ], history of cerebrovascular disease [ OR=2.253, 95% CI (1.197, 4.240) ], constipation [ OR=10.382, 95% CI (1.376, 78.308) ], arrhythmia [ OR=2.051, 95% CI (1.079, 3.898) , taking aspirin [ OR=2.741, 95% CI (1.447, 5.193) ], intravenous diuretics [ OR=6.326, 95% CI (2.629, 15.220) ]and high level of N-terminal forebrain natriuretic peptide [ OR=3.511, 95% CI (1.890, 6.521) ]were independent risk factors for hospital onset of acute heart failure in elderly patients with CHF, and the use of vasodilator was a protective factor. The nomogram model was validated. The area under the receiver operating characteristic curve ( AUC) of the subject was 0.808 [95% CI (0.753, 0.864) ], the AUC of internal validation was 0.821 [95% CI (0.764, 0.871) ], and the calibration curve was a straight line with a slope close to 1. Conclusions:There are many risk factors of hospital acute heart failure in elderly CHF patients. The prediction model based on risk factors has good discrimination and calibration, and can predict the risk of acute heart failure in elderly CHF patients in hospital.

Objective:To assess the association between blood pressure and the risks of diabetes mellitus.Methods:Screening and intervention were conducted from 2015 to 2019 for high-risk subjects of cardiovascular diseases in eight counties of Henan. Information on demographic characteristics, lifestyle behaviors, and anthropometric measurements were obtained via a questionnaire. Fasting blood samples were collected for blood glucose and serum lipids. The R 3.6.3 software was used to analyze the relationship between blood pressure and diabetes mellitus.Results:The detection rate of diabetes mellitus was 23.5% among 120 040 participants aged 35-75 years. The mean fasting blood glucose level was significantly different among normotensive, prehypertensive, and hypertensive patients. Compared to normotensive patients, prehypertension and hypertension had adjusted ORs of 34%( OR=1.34, 95 CI%: 1.30-1.37) and 85%( OR=1.85, 95 CI%: 1.81-1.89). The corresponding ORs were 1.81(1.77-1.85) in controlled and 2.17(2.06-2.28) in uncontrolled patients. A subgroup analysis showed the same trend, where the risk of diabetes increased with blood pressure ( P<0.05). Conclusions:People with elevated BP may increase their risk of diabetes, while the risk declines when BP is under control. Therefore, targeted measures should be taken to reduce the risk.