1.Immunological Characteristics of Multiple Myeloma Patients with Hypercalcemia
Zilu MENG ; Hanxue ZHENG ; Xiaowan LI
Journal of Medical Research 2025;54(7):36-41
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.
2.Comparative study of rat models of pulmonary hypertension induced by normobaric hypoxia and hypobaric oxygen
Hanxue LI ; Jinlian SUN ; Dingyu ZHENG ; Ruixin LIU ; Meiduo HUAYU ; Yan MA
Chinese Journal of Comparative Medicine 2025;35(9):37-49
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.
3.Comparative study of rat models of pulmonary hypertension induced by normobaric hypoxia and hypobaric oxygen
Hanxue LI ; Jinlian SUN ; Dingyu ZHENG ; Ruixin LIU ; Meiduo HUAYU ; Yan MA
Chinese Journal of Comparative Medicine 2025;35(9):37-49
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.
4.Immunological Characteristics of Multiple Myeloma Patients with Hypercalcemia
Zilu MENG ; Hanxue ZHENG ; Xiaowan LI
Journal of Medical Research 2025;54(7):36-41
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.
5.Drug resistance factors in postoperative gemcitabine chemotherapy after radical resection of pancreatic cancer
Shuai WU ; Jiaqiang REN ; Hanxue WU ; Feng XUE ; Jiantao MO ; Zheng WANG ; Qingyong MA ; Zheng WU
Chinese Journal of Digestive Surgery 2023;22(5):616-622
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.

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