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.

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.

We report a case of adult-onset Still's disease(AOSD)presenting with fever,myalgia,and pleural effusion.The patient exhibited significantly elevated inflammatory markers and exudative pleural effusion with markedly elevated leukocyte count showing neutrophilic predominance.After comprehensive exclusion of infectious etiologies,the diagnosis of AOSD was established.Clinical symptoms resolved following anti-inflam-matory therapy with glucocorticoids and tocilizumab.This case highlights a critical clinical insight:while infec-tion is a common cause of elevated inflammatory markers,it is not an invariable etiology.In such presentations,meticulous clinical observation,thorough diagnostic screening,and systematic inference are es-sential for accurate diagnosis.

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 characteristics and prognostic significance of immunological indexes in patients with hyper-calcemia in multiple myeloma(MM).Methods A retrospective analysis of 241 newly diagnosed multiple myeloma(NDMM)admitted to the Second Hospital of Lanzhou University from January 2017 to September 2024 was conducted to compare the differences of 19 immuno-logical indicators between hypercalcemia and non-hypercalcemia group and in patients with mild,moderate and severe hypercalcemia,so as to explore the influence and significance of immune mechanism on it.Results Compared with patients without hypercalcemia,patients with MM complicated with hypercalcemia had higher levels of serum IL-1β,IL-2,IL-4,IL-5,IL-6,IL-10,IL-12p70,IFN-α and IFN-γ,lower CD4+T lymphocyte ratio and CD4+/CD8+ratio,and statistically significant differences(P＜0.05).Comparative a-nalysis of immune indicators in patients with three different degrees of hypercalcemia revealed that as blood calcium concentration in-creased,the Treg ratio and CD4+/CD8+values gradually decreased,with statistically significant differences(P＜0.05).Conclusion The results of this study showed that the immunological indexes of hypercalcemia patients were more abnormal than patients without in MM,suggesting that patients in this group had more disturbed immune microenvironment,which not only provided new indicators for poor prognosis,but also provided reference for future individualized immunotherapy.

We report a case of adult-onset Still's disease(AOSD)presenting with fever,myalgia,and pleural effusion.The patient exhibited significantly elevated inflammatory markers and exudative pleural effusion with markedly elevated leukocyte count showing neutrophilic predominance.After comprehensive exclusion of infectious etiologies,the diagnosis of AOSD was established.Clinical symptoms resolved following anti-inflam-matory therapy with glucocorticoids and tocilizumab.This case highlights a critical clinical insight:while infec-tion is a common cause of elevated inflammatory markers,it is not an invariable etiology.In such presentations,meticulous clinical observation,thorough diagnostic screening,and systematic inference are es-sential for accurate diagnosis.

Objective To evaluate pulmonary vascular remodeling,right ventricular function,intestinal barrier integrity,and inflammatory factor expression in rat models of pulmonary hypertension(PH)induced by normobaric hypoxia(NH)and hypobaric hypoxia(HH).We also aimed to compare modeling method and establish an experimental basis for understanding the pathogenesis of PH and for developing appropriate treatment strategies.Methods From June 2024 to December 2024,eighteen 6-week-old male SPF Sprague-Dawley rats were assigned randomly to three groups:normobaric normoxia(Control),NH,and HH groups.Mean pulmonary artery pressure(mPAP)was measured by right heart catheterization.Right ventricular function was assessed using echocardiography and right ventricular hypertrophy index(RVHI).Pulmonary vascular remodeling and intestinal mucosal barrier damage were evaluated via hematoxylin/eosin staining.Colon permeability was quantified by colon ligation followed by fluorescein isothiocyanate-dextran injection.Expression levels of inflammatory factors in lung and colon tissues were analyzed by enzyme-linked immunosorbent assays.Results Right heart function assessment revealed that mPAP was significantly increased(P＜0.05),pulmonary artery acceleration time(PAAT)was shortened,and RVHI and right ventricular free wall thickness(RVFW)were significantly elevated(P＜0.05)in rats in NH and HH groups compared with Control group.Rats in NH group demonstrated a prolonged pulmonary ejection time(PET)and reduced PAAT/PET ratio compared with HH group,indicating more pronounced right heart dysfunction.Pulmonary vascular morphology demonstrated that percentage of medial area percentage(MA％)and percentage of wall thickness percentage(WT％)of pulmonary vessels were significantly higher in NH and HH groups compared with Control group(P＜0.05).Moreover,MA％was markedly increased in the NH group relative to the HH group(P＜0.05),suggesting more severe pulmonary vascular remodeling in NH group.Regarding intestinal injury,rats in NH and HH groups exhibited shorter colon length,increased mucosal damage,and significantly increased permeability compared with Control group(P＜0.05),while rats in HH group showed more prominent inflammatory cell infiltration compared with NH group,confirming intestinal mucosal barrier damage in both groups.In terms of inflammation,expression levels of interleukin(IL)6,IL1β,and IL 17a were significantly elevated in lung and colon tissues from rats in NH and HH groups compared with Control group(P＜0.05).Notably,expression levels of IL6 and IL1 β in lung tissue and IL17a in colon tissue were significantly higher in NH group compared with HH group(P＜0.05),while IL6 expression in colon tissue was relatively lower(P＜0.05),indicating local inflammation in lung and colon tissues in both groups.Conclusions There are phenotypic differences between PH rat models induced by NH and HH,with respect to pulmonary vascular remodeling,right heart function,intestinal mucosal barrier injury,and the expression of inflammatory factors in lung and intestinal tissues.These result demonstrate that air pressure contributes to the pathogenesis and progression of PH.Different air pressures may affect the development of PH via distinct mechanisms,thereby offering critical insights into the pathological changes of PH,potential therapeutic strategies to mitigate disease progression,and the elucidation of inflammatory mechanisms underlying PH based on the lung-intestine axis.

Objective To evaluate pulmonary vascular remodeling,right ventricular function,intestinal barrier integrity,and inflammatory factor expression in rat models of pulmonary hypertension(PH)induced by normobaric hypoxia(NH)and hypobaric hypoxia(HH).We also aimed to compare modeling method and establish an experimental basis for understanding the pathogenesis of PH and for developing appropriate treatment strategies.Methods From June 2024 to December 2024,eighteen 6-week-old male SPF Sprague-Dawley rats were assigned randomly to three groups:normobaric normoxia(Control),NH,and HH groups.Mean pulmonary artery pressure(mPAP)was measured by right heart catheterization.Right ventricular function was assessed using echocardiography and right ventricular hypertrophy index(RVHI).Pulmonary vascular remodeling and intestinal mucosal barrier damage were evaluated via hematoxylin/eosin staining.Colon permeability was quantified by colon ligation followed by fluorescein isothiocyanate-dextran injection.Expression levels of inflammatory factors in lung and colon tissues were analyzed by enzyme-linked immunosorbent assays.Results Right heart function assessment revealed that mPAP was significantly increased(P＜0.05),pulmonary artery acceleration time(PAAT)was shortened,and RVHI and right ventricular free wall thickness(RVFW)were significantly elevated(P＜0.05)in rats in NH and HH groups compared with Control group.Rats in NH group demonstrated a prolonged pulmonary ejection time(PET)and reduced PAAT/PET ratio compared with HH group,indicating more pronounced right heart dysfunction.Pulmonary vascular morphology demonstrated that percentage of medial area percentage(MA％)and percentage of wall thickness percentage(WT％)of pulmonary vessels were significantly higher in NH and HH groups compared with Control group(P＜0.05).Moreover,MA％was markedly increased in the NH group relative to the HH group(P＜0.05),suggesting more severe pulmonary vascular remodeling in NH group.Regarding intestinal injury,rats in NH and HH groups exhibited shorter colon length,increased mucosal damage,and significantly increased permeability compared with Control group(P＜0.05),while rats in HH group showed more prominent inflammatory cell infiltration compared with NH group,confirming intestinal mucosal barrier damage in both groups.In terms of inflammation,expression levels of interleukin(IL)6,IL1β,and IL 17a were significantly elevated in lung and colon tissues from rats in NH and HH groups compared with Control group(P＜0.05).Notably,expression levels of IL6 and IL1 β in lung tissue and IL17a in colon tissue were significantly higher in NH group compared with HH group(P＜0.05),while IL6 expression in colon tissue was relatively lower(P＜0.05),indicating local inflammation in lung and colon tissues in both groups.Conclusions There are phenotypic differences between PH rat models induced by NH and HH,with respect to pulmonary vascular remodeling,right heart function,intestinal mucosal barrier injury,and the expression of inflammatory factors in lung and intestinal tissues.These result demonstrate that air pressure contributes to the pathogenesis and progression of PH.Different air pressures may affect the development of PH via distinct mechanisms,thereby offering critical insights into the pathological changes of PH,potential therapeutic strategies to mitigate disease progression,and the elucidation of inflammatory mechanisms underlying PH based on the lung-intestine axis.

Objective To investigate the characteristics and prognostic significance of immunological indexes in patients with hyper-calcemia in multiple myeloma(MM).Methods A retrospective analysis of 241 newly diagnosed multiple myeloma(NDMM)admitted to the Second Hospital of Lanzhou University from January 2017 to September 2024 was conducted to compare the differences of 19 immuno-logical indicators between hypercalcemia and non-hypercalcemia group and in patients with mild,moderate and severe hypercalcemia,so as to explore the influence and significance of immune mechanism on it.Results Compared with patients without hypercalcemia,patients with MM complicated with hypercalcemia had higher levels of serum IL-1β,IL-2,IL-4,IL-5,IL-6,IL-10,IL-12p70,IFN-α and IFN-γ,lower CD4+T lymphocyte ratio and CD4+/CD8+ratio,and statistically significant differences(P＜0.05).Comparative a-nalysis of immune indicators in patients with three different degrees of hypercalcemia revealed that as blood calcium concentration in-creased,the Treg ratio and CD4+/CD8+values gradually decreased,with statistically significant differences(P＜0.05).Conclusion The results of this study showed that the immunological indexes of hypercalcemia patients were more abnormal than patients without in MM,suggesting that patients in this group had more disturbed immune microenvironment,which not only provided new indicators for poor prognosis,but also provided reference for future individualized immunotherapy.

Objective:To analyze the association between healthy lifestyle and mortality among Henan Province 35-74 years old individuals.Methods:Data from the programme of screening and intervention subjects with high-risk cardiovascular disease 99 133 adults were analyzed in a provincial cohort study of 16 counties. Four healthy lifestyle behaviors were assessed based on a questionnaire survey. Information on mortality endpoints was retrieved from the national death surveillance system. Cox proportional hazards regression models were used to estimate the associations between healthy lifestyles, mortality risk and population attributable fraction (PAF).Results:Out of the adult participants in Henan, 50.6% adhered to a healthy lifestyle, and only 0.1% adhered to 4 healthy lifestyle behaviours. During a mean of 4.5 years, 2 685 all-cause death and 1 283 cardiovascular deaths were documented. The decreased risk of mortality among individuals with non-smoking, moderate drinking, adequate exercise and healthy diet were 0.85 (95% CI: 0.77-0.94), 0.75 (95% CI: 0.63-0.89), 0.73 (95% CI: 0.67-0.79) and 0.86 (95% CI: 0.77-0.96), while the adjusted PAF for all-cause deaths were 5.2% (95% CI: 2.5%-7.9%), 24.0% (95% CI: 10.7%-36.4%), 19.4% (95% CI: 13.8%-24.8%) and 12.3% (95% CI: 3.4%-20.9%), respectively. A combined healthy lifestyle can bring more health benefits. Adherence to 4 healthy lifestyle behaviours could avoid 49.1% of all-cause death. Conclusion:Adherence to a healthy lifestyle can reduce the risk of death, and participants with a healthy lifestyle had a lower mortality risk.