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.Chinesization of the HEMO-FISS-QoL questionnaire and its reliability and validity
Songpeng SUN ; Shan JIA ; Fangfang XU ; Tianyu LI ; Zhiyun ZHANG ; Qiaorong CAO ; Xinjian LI ; Yao WU ; Weiping WAN ; Bin SHI ; Jianguo WANG ; Hong NI ; Longyu LIANG ; Xingxiao HUO ; Tianqing YANG ; Lei TIAN ; Ying TIAN ; Mei LIN ; Zhanjun WANG ; Yangyang ZHOU ; Hongchuan CHU ; Riyu LIAO ; Kuerban XIEYIDA ; Junhong LONG ; Shuxin ZHANG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(1):75-82
Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.
6.Salidroside Ameliorates Lung Injury Induced by PM2.5 by Regulating SIRT1-PGC-1α in Mice
Hong Xiao LI ; Mei Yu LIU ; Hui SHAN ; Feng Jin TAN ; Jian ZHOU ; Jin Yuan SONG ; Qi Si LI ; Chen LIU ; Qun Dong XU ; Li YU ; Wei Wan LI
Biomedical and Environmental Sciences 2024;37(4):367-376
Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.
7.Clinical characteristics of nephrocalcinosis in preterm infants
Meiying QUAN ; Shan JIAN ; Lijuan GOU ; Linqing ZHONG ; Yu ZHOU ; Weilin WAN ; Zhenghong LI
Chinese Journal of Neonatology 2024;39(2):100-104
Objective:To study the clinical characteristics and risk factors of nephrocalcinosis in preterm infants.Methods:From March 2021 to August 2021, all preterm infants admitted to NICU of our hospital were retrospectively analyzed. The infants were assigned into nephrocalcinosis group and non-nephrocalcinosis group according to urinary tract ultrasound. Clinical data including gestational age, birth weight(BW), nutritional support strategy and complications were reviewed.Results:A total of 40 preterm infants (<34 weeks) were enrolled. 9 cases were in the nephrocalcinosis group and 31 cases in the non-nephrocalcinosis group. The nephrocalcinosis group had lower BW[(1 167±214) g vs.(1 586±215) g], higher calcium [6.9 (5.1, 8.7) g vs.3.3 (2.1, 6.8) g] and vitamin D intake [3.2(2.5, 4.2)×10 4U vs.1.7(1.1, 3.2)×10 4U] during hospitalization. No significant differences existed between the two groups on the following items:blood calcium and phosphate, 25-hydroxyvitamin D, feeding strategy, time to reach full enteral feeding(TFF), furosemide dosage and respiratory support duration ( P>0.05). In the nephrocalcinosis group, the median age of diagnosing nephrocalcinosis was 40.0(30.0, 52.5)d after birth. 5 cases showed bilateral nephrocalcinosis. 5 cases in the nephrocalcinosis group received renal tubule function examination,4 cases had increased urine β2 microglobulin and 2 cases had increased urine α1 microglobulin. 7 cases had elevated urine calcium in the nephrocalcinosis group. Follow-up showed that nephrocalcinosis disappeared 3-9 months after birth. Conclusions:BW, total calcium and vitamin D intake are risk factors for nephrocalcinosis in preterm infants. Increased urine β2 microglobulin and calcium levels are common co-morbidities in preterm infants with nephrocalcinosis.
8.Safety and efficacy of domestically produced novel bioabsorbable vascular scaff old in the treatment of complex coronary artery lesions for 3 years
Deng-Shuang ZHOU ; Qiong YOU ; Hai-Liang MO ; Zi-Jun WU ; Yu-Biao LIN ; Lu-Jun CHEN ; Jun-Yu FAN ; Yong-Jian LIN ; Rui-Sheng ZHANG ; Pei-Shan WAN ; Wei-Guo ZHOU ; Keng WU
Chinese Journal of Interventional Cardiology 2024;32(9):509-515
Objective To investigate the safety and efficacy of novel bioabsorbable vascular scaffold(BVS)in the treatment of patients with complex coronary artery disease.Methods This was a retrospective,matched,single-center observational study.45 patients with coronary atherosclerotic cardiopathy received BVS treatment in the cardiovascular medicine department Department of the Affiliated Hospital of Guangdong Medical University from June 2020 to June 2021(BVS),and 45 patients treated with drug-eluting stents(DES)group were selected according to matching study requirements during the same period.Baseline,surgical,and follow-up data were compared between the two groups to evaluate safety and efficacy.The main measures of safety were:surgical time,intraoperative adverse events,etc.,and the end point of efficacy was target lesion failure(TLF),including cardiac death,target vessel myocardial infarction,and ischa-driven target lesion revascularization.Results A total of 90 patients were enrolled in this study,all of whom were followed up for at least 3 years.There were 20 cases of bifurcation lesions and 25 cases of diffuse long lesions in the two groups,and 50 cases of imaging were reviewed among the 90 patients.The proportion of stable coronary heart disease,history of diabetes,history of hypertension,history of smoking,pre-dilated balloon pressure and postoperative diastolic blood pressure in BVS group was higher than that in DES group,and the proportion of family history was lower than that in DES group(all P<0.05).There were no statistically significant differences in the rates of cardiac death,target vessel myocardial infarction,and ischemia-driven revascularization of target lesions between the two groups(all P>0.05).Binary Logistic regression model analysis showed that the diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis(OR 2.786,95%CI 1.096-7.081,P=0.031).Conclusions Compared with traditional DES,BVS implantation has consistent safety and efficacy in the treatment of complex coronary artery disease within 3 years.The diameter stenosis ratio of target lesions was an independent risk factor for intrastent restenosis.
9.Scoping review of home-based self-management behaviors assessment tools in patients with lung transplant
Shan WANG ; Yinghua CAI ; Haiqin ZHOU ; Qing ZHAO ; Xia WAN ; Yingxiang ZHANG
Chinese Journal of Modern Nursing 2024;30(16):2218-2227
Objective:To conduct a scoping review of the characteristics, functions, risk of bias and applications of home-based self-management behavior assessment tools for lung transplant patients, so as to provide references for clinical medical staff to conduct further related research.Methods:The relevant literatures were systematically searched in China National Knowledge Infrastructure, Wanfang Database, VIP, China Biology Medicine disc, PubMed, Web of Science Core Collection, Embase, Cochrane Library and CINAHL databases. The search period was from the establishment of the databases to June 30, 2023. The scoping review method framework was used to screen the literature, extract information and standardize the report.Results:A total of 10 167 Chinese and English literatures were searched, and after deduplication and screening, 23 articles that met the criteria were finally included, involving 13 home-based self-management behavior assessment tools for lung transplant patients, including nine specific tools and four universal tools. There were eight kinds of lung transplantation patients whose reliability and validity were not verified. Of the 13 tools, those with single-dimensional assessments and single measures predominate. The level of home self-management behavior of lung transplant patients was reflected mainly through compliance, and medication management was the most frequently assessed content.Conclusions:At present, the measurement of home-based self-management behavior of lung transplant patients is mainly based on questionnaire surveys, and the evaluation tools are mostly single dimensional. The reliability and validity of most evaluation tools in the population of lung transplant patients are not yet clear, and there is a certain risk of bias. It is recommended that researchers pay attention to the reliability and validity verification report of the evaluation tool in the target population when selecting it, and integrate multiple measurement methods to reduce measurement errors.
10.Associations between indoor volatile organic compounds and nocturnal heart rate variability of young female adults: A panel study.
Xue Zhao JI ; Shan LIU ; Wan Zhou WANG ; Ye Tong ZHAO ; Lu Yi LI ; Wen Lou ZHANG ; Guo Feng SHEN ; Fu Rong DENG ; Xin Biao GUO
Journal of Peking University(Health Sciences) 2023;55(3):488-494
OBJECTIVE:
To investigate the association between short-term exposure to indoor total volatile organic compounds (TVOC) and nocturnal heart rate variability (HRV) among young female adults.
METHODS:
This panel study recruited 50 young females from one university in Beijing, China from December 2021 to April 2022. All the participants underwent two sequential visits. During each visit, real time indoor TVOC concentration was monitored using an indoor air quality detector. The real time levels of indoor temperature, relative humidity, noise, carbon dioxide and fine particulate matter were monitored using a temperature and humidity meter, a noise meter, a carbon dioxide meter and a particulate counter, respectively. HRV parameters were measured using a 12-lead Holter. Mixed-effects models were used to evaluate the association between the TVOC and HRV parameters and establish the exposure-response relationships, and two-pollutant models were applied to examine the robustness of the results.
RESULTS:
The mean age of the 50 female subjects was (22.5±2.3) years, and the mean body mass index was (20.4±1.9) kg/m2. During this study, the median (interquartile range) of indoor TVOC concentrations was 0.069 (0.046) mg/m3, the median (interquartile range) of indoor temperature, relative humidity, carbon dioxide concentration, noise level and fine particulate matter concentration were 24.3 (2.7) ℃, 38.5% (15.0%), 0.1% (0.1%), 52.7 (5.8) dB(A) and 10.3 (21.5) μg/m3, respectively. Short-term exposure to indoor TVOC was associated with significant changes in time-domain and frequency-domain HRV parameters, and the exposure metric for most HRV parameters with the most significant changes was 1 h-moving average. Along with a 0.01 mg/m3 increment in 1 h-moving average concentration of indoor TVOC, this study observed decreases of 1.89% (95%CI: -2.28%, -1.50%) in standard deviation of all normal to normal intervals (SDNN), 1.92% (95%CI: -2.32%, -1.51%) in standard deviation of average normal to normal intervals (SDANN), 0.64% (95%CI: -1.13%, -0.14%) in percentage of adjacent NN intervals differing by more than 50 ms (pNN50), 3.52% (95%CI: -4.30%, -2.74%) in total power (TP), 5.01% (95%CI: -6.21%, -3.79%) in very low frequency (VLF) power, and 4.36% (95%CI: -5.16%, -3.55%) in low frequency (LF) power. The exposure-response curves showed that indoor TVOC was negatively correlated with SDNN, SDANN, TP, and VLF when the concentration exceeded 0.1 mg/m3. The two-pollutant models indicated that the results were generally robust after controlling indoor noise and fine particulate matter.
CONCLUSION
Short-term exposure to indoor TVOC was associated with significant negative changes in nocturnal HRV of young women. This study provides an important scientific basis for relevant prevention and control measures.
Humans
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Female
;
Adult
;
Young Adult
;
Air Pollutants/analysis*
;
Heart Rate/physiology*
;
Volatile Organic Compounds/analysis*
;
Carbon Dioxide
;
Particulate Matter/adverse effects*
;
Environmental Pollutants

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