1.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
2.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
3.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
4.Ras Guanine Nucleotide-Releasing Protein-4 Inhibits Erythropoietin Production in Diabetic Mice with Kidney Disease by Degrading HIF2A
Junmei WANG ; Shuai HUANG ; Li ZHANG ; Yixian HE ; Xian SHAO ; A-Shan-Jiang A-NI-WAN ; Yan KONG ; Xuying MENG ; Pei YU ; Saijun ZHOU
Diabetes & Metabolism Journal 2025;49(3):421-435
Background:
In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes.
Methods:
The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments.
Results:
RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice.
Conclusion
RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.
5.Research progress on aspiration in patients with dysphagia after ischemic stroke
Yixian HE ; Gao LIU ; Lu ZHOU ; Muwei YANG ; Qingyuan GUO ; Enli CAI
Chinese Journal of Primary Medicine and Pharmacy 2023;30(4):631-634
Based on the research results of aspiration in patients with dysphagia after ischemic stroke at home and abroad, this paper reviews the definition, detection methods, and risk factors of aspiration and emphasizes the incidence rate and severity of this disease. The authors conclude that preventing aspiration can decrease the incidence rate of aspiration pneumonia, change the clinical outcome of patients, and thereby save medical resources.
6.Machine and deep learning-based clinical characteristics and laboratory markers for the prediction of sarcopenia.
He ZHANG ; Mengting YIN ; Qianhui LIU ; Fei DING ; Lisha HOU ; Yiping DENG ; Tao CUI ; Yixian HAN ; Weiguang PANG ; Wenbin YE ; Jirong YUE ; Yong HE
Chinese Medical Journal 2023;136(8):967-973
BACKGROUND:
Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts.
METHODS:
We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models.
RESULTS:
The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749).
CONCLUSIONS:
The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population.
TRIAL REGISTRATION
Chictr.org, ChiCTR 1800018895.
Humans
;
Aged
;
Sarcopenia/diagnosis*
;
Deep Learning
;
Aging
;
Algorithms
;
Biomarkers
7.Correlation between white matter hyperintensities and the outcomes after reperfusion therapy in patients with acute ischemic stroke
Qijing WANG ; Yixian LIU ; Jing ZENG ; Xingchen LIU ; Feng WANG ; Yufeng HE ; Sisi XU ; Benguo WANG
International Journal of Cerebrovascular Diseases 2021;29(11):812-819
Objective:To investigate the correlation between white matter hyperintensities (WMHs) and the outcomes after reperfusion therapy in patients with acute ischemic stroke (AIS).Methods:Patients with AIS treated with reperfusion therapy (intravenous thrombolysis, endovascular mechanical thrombectomy or bridging therapy) in the Stroke Center of Zhongshan Hospital of traditional Chinese Medicine from January 2014 to December 2019 were retrospectively enrolled. The clinical baseline data of the patients were collected. The Fazekas scale was used to evaluate the severity of WMHs according to the MRI images. At 90 d after discharge, the modified Rankin Scale was used to evaluate the outcomes. A score of ≤ 2 was defined as good outcome, and a score of >2 was defined as poor outcome. Binary multivariate logistic regression analysis was used to determine the independent risk factors for hemorrhagic transformation (HT), symptomatic intracranial hemorrhage (sICH), and poor outcomes. Results:A total of 676 patients with AIS treated with reperfusion therapy were enrolled. Among them, 506 patients (74.9%) were complicated with WMHs, and 80 (11.8%) had severe WMHs. One hundred and thirty-two patients (19.5%) had HT, 34 (5.0%) had sICH, and 306 (45.3%) had a poor outcome. Multivariate logistic regression analysis showed that severe WMHs was an independent risk factor for the occurrence of HT (odds ratio [ OR] 1.890, 95% confidence interval [ CI] 1.047-3.413; P=0.035) and poor outcomes ( OR 3.366, 95% CI 1.567-7.232; P=0.002) after reperfusion treatment in patients with AIS, but there was no independent correlation with sICH ( OR 8.403, 95% CI 0.891-79.294; P=0.063). Conclusion:Severe WMHs is an independent risk factor for the occurrence of HT and poor outcomes in patients with AIS after reperfusion treatment, but it has no independent correlation with sICH.
8.Effect of collateral circulation on hemorrhagic transformation or short-term prognoses in patients with acute ischemia stroke after different reperfusion therapies
Yixian LIU ; Qijing WANG ; Xingchen LIU ; Yufeng HE ; Feng WANG ; Sisi XU ; Benguo WANG
Chinese Journal of Neuromedicine 2021;20(11):1108-1116
Objective:To investigate the correlations of collateral circulation with hemorrhagic transformation (HT) and short-term prognoses in patients with acute ischemic stroke (AIS) after different reperfusion therapies.Methods:Four hundred and forty-nine patients with AIS after different reperfusion therapies, admitted to our hospital from January 2016 to December 2019, were chosen in our study. These patients were divided into HT group ( n=90) and non-HT group ( n=359) according to whether HT presented or not. The baseline data, clinical characteristics, and prognoses of patients between the 2 groups were compared. And the variables of P<0.05 in univariate analysis were re-analyzed by multivariate Logistics regression to identify the independent influencing factors for HT in patients with AIS; the correlations between cerebral collateral circulation grading (American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology [ASITN/SIR], and modified Thrombolysis in Cerebral Infarction [mTICI]) and modified Rankin scale (mRS) scores at discharge were explored. Results:(1) There were significant differences between patients in the two groups in terms of age, percentages of patients with atrial fibrillation, baseline National Institutes of Health Stroke Scale (NIHSS) scores, emergency blood glucose, platelet count, and percentages of patients used dual antiplatelet agents and statin ( P<0.05). (2) Results of multivariate Logistics analysis: moderate stroke (NIHSS scores of 9-15), severe stroke (NIHSS scores≥16), elevated emergency glucose, atherosclerotic cerebral infarction and bridging therapy were independent risk factors for HT, and good collateral circulation status and dual antiplatelet therapy were independent protective factors for HT. (3) Correlation of collateral circulation with short-term prognosis: mRS scores of patients at discharge were negatively correlated with ASITN/SIR grading of collateral circulation and mTICI grading ( rs=-0.201, P=0.003; rs=-0.222, P=0.001). Further grouping by different reperfusion therapies showed that ASITN/SIR grading in the intravenous thrombolysis group and mTICI grading in the bridging therapy group were negatively correlated with mRS scores of these patients at discharge ( rs=-0.176, P=0.016; rs=-0.271, P=0.010). Conclusion:AIS patients with poor collateral circulation who receive reperfusion therapies are more likely to develop HT than patients with good collateral circulation, enjoying a relatively poor short-term prognosis.
9.Expression of NONHSA1254644 in lung adenocarcinoma and its clinical significance
Yixian ZHOU ; Jun WANG ; Dan HE ; Chaojun DUAN ; Qun XIE
Journal of Chinese Physician 2018;20(5):664-666
Objective To investigate the expression of long non-coding RNA NONHSA1254644 in lung adenocarcinoma and its clinical significance.Methods 99 cases of lung adenocarcinoma and the adjacent tissues as well as clinical data was collected.The expression level was detected by quantitative realtime polymerase chain reaction (qRT-PCR).Then the relationship between the expression level and the clinical parameters was analyzed.Cell counting kit-8 (CCK8) was used to investigate its effect of lung adenocarcinoma cell line A549 on proliferation.Results The expression of NONHSA1254644 was down-regulated in lung adenocarcinoma,and its expression was positively correlated with the differentiation of patients.The overexpression of NONHSA1254644 could inhibit the proliferation of A549 cells.Conclusions NONHSA1254644 is involved in the development and progression of lung adenocarcinoma.
10.The clinical value of neutrophil to lymphocyte ratio in postmenopausal patients with type 2 diabetes
Yixian PENG ; Yin YANG ; Wengao LI ; Zhiyong WU ; Peng LUO ; Ru TANG ; Lei HE
Tianjin Medical Journal 2017;45(1):68-71
Objective To investigate the clinical value of neutrophil-lymphocyte ratio (NLR) in postmenopausal patients with type 2 diabetes mellitus (T2DM). Methods A total of 128 newly diagnosed T2DM female patients were randomly recruited from the Zhujiang Hospital of Southern Medical University from March to September 2015. According to the physiological state, the patients were divided into menopausal group (n=66) and non-menopausal group (n=62). Fifty-six healthy females were chosen as the control group. The values of blood pressure, blood lipid, fasting plasma glucose (FPG), fasting insulin (FINS) and white blood count (WBC), neutrophil count, percentage of neutrophils,lymphocytes count, and percentage of lymphocytes were detected and compared between three groups. The NLR and the HOMA insulin resistance index (HOMA-IR) were calculated. Results Age, systolic blood pressure (SBP), triglyceride (TG), FINS, percentage of neutrophil, NLR, HOMA-IR were significantly higher in menopause group than those of control group and non-menopause group (P<0.05). There were no significant differences in diastolic blood pressure (DBP) and FPG between menopause group and non-menopause group, but both were significantly higher than those of control group (P < 0.05). There were no significant differences in total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), WBC and HbA1c between three groups (P>0.05). There was no linear correlation between NLR and HOMA-IR (rs=0.015, P > 0.05), HbA1c (r=0.030, P > 0.05). Conclusion NLR is of a certain significance in the assessment of inflammatory status and IR levels in postmenopausal women with T2DM, which may be related to the changes of autonomic nervous system.

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