1.Plateau hypoxia improves tumor immune microenvironment and inhibits subcutaneous tumor growth of colorectal cancer
Sijie ZHAO ; Meng WANG ; Yuan GAO ; Fang YANG ; Shaofan HU ; Hongming MIAO
Journal of Army Medical University 2025;47(1):38-50
Objective To investigate the effects of plateau hypoxia on the growth and tumor microenvironment of colorectal carcinoma in vivo.Methods A total of 16 male BALB/C mice(6 weeks old,weight 18-20 g)were randomly divided into plateau hypoxic group and plain normoxic group,with 8 mice in each group,while 14 male C57BL/6 mice were grouped in same way,with 7 mice in each group.The mice in the plateau hypoxic group were housed in a low-pressure oxygen(10%)chamber to simulate an altitude of approximately 5 600 m,while the mice of the other group was maintained in SPF-grade normal atmospheric conditions(21%oxygen,at an altitude of about 300 m).Colorectal tumor MC38 cells and colon adenocarcinoma CT26 cells were subcutaneously implanted into C57BL/6 mice and BALB/C mice,respectively to construct subcutaneous tumor-bearing mouse models.Then the tumor size and weight were measured in 4 groups of mice.After the tumor tissues,spleen and blood samples were collected in the C57BL/6 mice.Flow cytometry was used to determine the percentages of macrophages,T lymphocytes,IFN-γ+T lymphocytes,and myeloid-derived suppressor cells(MDSC).The differences in these immune cells were compared between the cells from the plateau hypoxic group and those from the plain normoxic group.Results The weight of subcutaneous tumor mass was significantly inhibited in both C57BL/6 and BALB/C mice from the plateau hypoxic group than those from the 2 plain normoxic groups(0.17 vs 0.09 g,1.38 vs 0.51 g,P<0.01).When compared with the immune cells from the tumor mass of the plain normoxic C57BL/6 mice,the percentage of M2-type macrophages was reduced in the tumor tissue from the plateau hypoxic mice(22.13%vs 15.90%,P<0.05),so was that of MDSC(2.06%vs 1.05%,P<0.01),particularly in the monocytic(M)-MDSC subgroup(60.97%vs 41.13%,P<0.01).While,no significant change was observed in the proportion of the polymorphonuclear(PMN)-MDSC subgroup(10.97%vs 9.70%,P>0.05).Additionally,the percentage of CD4+T cells was significantly reduced(48.70%vs 41.93%,P<0.05),whereas that of CD8+T cells was obviously increased(41.25%vs 51.18%,P<0.05),along with a notable rise in the proportions of IFN-γ+T,IFN-γ+CD4+T and IFN-γ+CD8+T cells(28.58%vs 59.65%,23.33%vs 53.65%,36.9%vs 66.48%,P<0.01).However,between the peripheral blood samples of the 2 groups of C57BL/6 mice,the proportions of M1-type macrophages and CD4+T cells were reduced(84.98%vs 78.43%,5.86%vs 4.01%,P<0.01),and those of MDSC and PMN-MDC were increased(4.47%vs 16.43%,36.56%vs 62.97%,P<0.01).In the spleen tissues,notable decreases were observed in the proportions of CD8+T cells and IFN-γ+CD8+T cells between the 2 groups(33.05%vs 27.68%,5.13%vs 1.58%,P<0.01).Conclusion Plateau hypoxia improves the immune response within the tumor microenvironment,and inhibits subcutaneous tumor growth of colorectal cancer,but suppresses systemic immune response.
2.Analysis of correlation between clinical manifestations and immunofluorescence in children with primary IgA nephropathy
Xiaojie PENG ; Rui FU ; Weimin ZHENG ; Shanshan TAO ; Shaofan HU ; Tingjie WANG
Chinese Journal of Applied Clinical Pediatrics 2020;35(17):1329-1335
Objective:To investigate the correlation among clinical manifestations, pathological changes and immunofluorescence in children with primary IgA nephropathy (IgAN).Methods:The data of a total of 222 cases diagnosed with IgAN by the Department of Nephrology, Jiangxi Children′s Hospital in recent 10 years were collected for the analysis of clinical and pathological features and their correlation.Results:(1)Immunofluorescence showed that 115 cases (51.8%) IgA patients had only mesangial deposition, and 107 cases (48.2%) IgA patients had both mesangial deposition and capillary loop deposition.Most IgA patients (122 cases, 55.0%) had immunofluorescence intensity+ + .In IgA patients, IgM deposition was the most common [168 cases (75.7%)], followed by C 3 deposition [160 cases (72.1%)]. Patients with C 4 deposition were the least[7 cases (3.2%)]. (2) Hypertension were positively correlated with IgM, C 3 deposition, IgA deposition intensity and IgA with vascular loop deposition(all P<0.05). Hyperuricemia was positively correlated with IgM deposition, IgG deposition, C 3 deposition and IgA with vascular loop deposition(all P<0.05); hypoalbuminemia was negatively correlated with IgM deposition, C 3 deposition, IgA deposition intensity and IgA with vascular loop deposition(all P<0.05). Hypercholesterolemia were positively correlated with C 3 deposition and IgA with vascular loop deposition(all P<0.05). Urine protein quantification were positively related to IgM, IgG and IgA with vascular loop deposition (all P<0.05). The estimated glomerular filtration rate(eGFR)was negatively related to IgA with vascular loop deposition( P<0.05). (3) Lee′s grade were positively correlated with IgM and C 3 deposition, IgA deposition intensity and IgA with capillary loop deposition(all P<0.05). (4) Oxford type mesangial hypercellularity(M1)were positively correlated with C 3 deposition and IgA deposition intensity(all P<0.001). Endocapillary hypercellularity(E1)lesions were positively correlated with IgA deposition intensity and IgA with capilla-ry loop deposition(all P<0.05). Segmental glomerulosclerosis(S1)lesions had no correlation with immunofluorescence pathology.Tubular atrophy and interstitial fibrosis(T1)was positively correlated with IgG and C 3 deposition(all P<0.05). (5) There was no correlation between glomerulosclerosis and immunofluorescence pathology.Crescent was positively correlated with IgM deposition, IgG deposition, C 3 deposition, IgA deposition intensity and IgA capillary loop deposition(all P<0.05). Renal artery thickening was positively correlated with IgG deposition and IgA capillary loop deposition(all P<0.05). Conclusions:IgA intensity of + + and IgM deposition are most commonly found in immunofluorescence of children with primary IgAN.IgA patients with capillary loops or C 3 deposition have more severe clinical manifestations and light microscopy results.
3.Correlations of serum prealbumin and albumin with the short-term outcomes in patients with acute ischemic stroke in different age groups
Wenyuan LIU ; Aiying LI ; Xiaoxiao SUN ; Zheng ZHANG ; Jianye XIE ; Song HU ; Chengxiu LYU ; Shaofan WANG
International Journal of Cerebrovascular Diseases 2017;25(7):626-632
Objective To investigate the correlations of serum prealbumin and albumin with the shortterm outcome in patients with acute cerebral infarction in different age groups.Methods Patients with acute ischemic stroke admitted to hospital with 48 h were prospectively enrolled in the study.The modified Rankin Scale was used to assess the functional outcomes at 14 d after onset,0-2 was defined as a good outcome.According to the age of the patients,they were divided into either a young and middle-aged group (< 60 years) or an elderly group (≥60 years).The demography,baseline clinical data and laboratory findings of the patients were compared in the overall patients and the different age groups between the good outcome group and the poor outcome group.Multivariate logistic regression analysis was used to determine the independent influencing factors of short-term outcomes.Results A total of 622 patients with acute ischemic stroke were enrolled,including 402 (64.6%) males and 220 (35.4%) females;206 (33.1%) were in the young and middle-aged group,and 416 (66.9%) were in the elderly group;310 (49.8%) had good outcomes and 312 (50.2%) had poor outcomes.There were significant differences in the proportions of patients in male,old people,hyperlipidemia,diabetes mellitus,history of previous stroke or transient ischemic attack (TIA),as well as age,body mass index,levels of prealbumin,albumin,triglyceride,high-density lipoprotein cholesterol low-density lipoprotein cholesterol total bilirubin,direct bilirubin,indirect bilirubin,urea nitrogen,and uric acid between the good outcome group and the poor outcome group (all P <0.05).Multivariate logistic regression analysis showed that the female (odds ratio [OR] 1.522,95% confidence interval [CI] 1.023-2.266;P =0.038),diabetes (OR 1.789,95% CI 1.171-2.735;P =0.007) and higher low-density lipoprotein cholesterol (OR 1.251,95% CI 1.017-1.539;P =0.034),total bilirubin (OR 1.054,95% CI 1.029-1.081;P<0.001),urea nitrogen (OR 1.245,95% CI 1.100-1.409;P=0.001),and baseline National Institutes of Health Stroke Scale (NIHSS) score (OR 2.854,95% CI 1.027-3.628;P =0.019) were the independent risk factors for poor outcomes,and higher prealbumin (OR 0.798 95% CI 0.633-0.979;P =0.034) and albumin (OR 0.741,95% CI 0.693-0.988;P =0.020) were the independent predictors of good outcomes.In the young and middle-aged patients,there were significant differences in the proportions of patients with small artery occlusion as well as age,triglyceride,and high-density lipoprotein cholesterol levels between the good outcome group and the poor outcome group (all P <0.05);multivariate logistic regression analysis showed that diabetes (OR 2.343 95% CI 1.127-4.871;P=0.023) and higher baseline NIHSS scores (OR 2.041,95% CI 1.304-4.125;P =0.027) were the independent risk factors for poor outcome,and higher high-density lipoprotein cholesterol (OR 0.742 95% CI 0.639-0.937;P =0.044)was an independent predictor for good outcome.In the elderly patients,there were significant differences in the proportions of patients in male,previous stroke or TIA,and cardiogenic embolism,as well as prealbumin,low-density lipoprotein cholesterol,total bilirubin,direct bilirubin,indirect bilirubin,and uric acid levels between the good outcome group and the poor outcome group (all P < 0.05);multivariate logistic regression the analysis showed that diabetes (OR 2.797,95% CI 1.153-4.756;P =0.039),higher baseline NIHSS score (OR 2.586,95% CI 1.033-3.435;P =0.035) and higher low-density lipoprotein cholesterol (OR 1.304,95% CI 1.027-1.656;P =0.029) were the independent risk factors for poor outcome,and higher prealbumin was an independent predictor for good outcome (OR 0.795,95% CI 0.691-0.998;P =0.002).Conclusions Prealbumin and albumin are the independent predictors for short-term good outcome in patients with acute ischemic stroke.The protective effect of serum prealbumin is more obvious in the elderly population (≥60 years).

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