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. The neuroprotective effects of Haikun Shenxi capsule medicated serum on N2a/APP695 cells based on PINKl-Parkin mitophagy pathway
Yan-Hua SUN ; Jing JI ; Jiao PENG ; Shan HE ; Shan HE ; Xian-Jun FU
Chinese Pharmacological Bulletin 2024;40(3):461-468
Aim To research the neuroprotective effect of Haikun Shenxi (HKSX) medicated serum on N2a/ App695 cells and the underlying mechanism. Methods HKSX medicated serum was prepared and carbohydrate components in it was analyzed using high performance thin layer chromatography (HPTLC) . N2a/ App695 cells were intervened with HKSX medicated serum, the cytotoxicity of HKSX medicated serum was measured by MTT; AP[_
6.Textual analysis of China’s traditional Chinese medicine emergency management policy based on three-dimensional analysis framework
Guowei XIAN ; Hang ZHAO ; Yunna GONG ; Wenfeng HE ; Xiaolin ZHANG ; Chunxiao MA ; Jing ZHANG ; Yong MA
China Pharmacy 2024;35(9):1039-1043
OBJECTIVE To analyze the traditional Chinese medicine (TCM) emergency management policy texts in China, reveal the characteristics, problems and improvement directions of Chinese medicine emergency management policies in China, and provide references and lessons for improving the level of Chinese medicine emergency management. METHODS Twenty-four TCM emergency management policy texts issued at the central level from 2016 to 2023 were coded and analyzed using Nvivo11 software to construct a three-dimensional analysis framework based on policy tools, stakeholders and policy strength. RESULTS In the policy tools dimension, the environmental type was the most (46.74%), the supply type was the second (31.80%), and the demand type was the least (21.46%); in the stakeholder dimension, there were more healthcare institutions (40.63%) and government departments (31.25%), and fewer healthcare workers (14.84%) and residents (13.28%); in the policy strength dimension, the overall policy strength was poor, and the differences in effectiveness across policy instruments and stakeholders were more significant. The cross-cutting results showed that there was a certain degree of mismatch in policy instruments, stakeholders and policy strength. CONCLUSIONS The use of supply-oriented policy tools is slightly lacking, and the use of policy tools should be optimized in a coordinated manner; the distribution of stakeholders is relatively unbalanced, and synergies among stakeholders should be enhanced; the overall strength of policies is poor, and the top-level design of relevant policies should be improved.
7.Direct Determination of 23 Kinds of Per-and Polyfluoroalkyl Substances in Crude Plant Extracts by Liquid Chromatography-Tandem Mass Spectrometry Coupled with Online Solid Phase Extraction
Nan SHEN ; Tong-Zhu HAN ; Can-Can SHENG ; Xiu-Ping HE ; Jun-Hui CHEN ; Chen-Guang LIU ; Xian-Guo LI
Chinese Journal of Analytical Chemistry 2024;52(2):286-295,后插1-后插5
A new method for simultaneous determination of 23 kinds of per-and polyfluoroalkyl substances(PFASs)(13 kinds of perfluoro carboxylic acids,4 kinds of perfluoro sulfonic acids,and 6 kinds of new substitutes)in plant leaf tissue by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)using automatic online solid phase extraction(SPE)to remove the matrix interference components in plant crude extracts was developed.The plant leaf samples were extracted twice with 1%formic acid-methanol solution,then evaporated to dry,redissolved with 70%methanol solution,and directly injected for analysis.After 23 kinds of target PFASs were purified automatically by online SPE with a WAX column,the six-way valve was switched to rinse PFASs onto an alkaline mobile phase system-compatible C18 analytical column.Then,the 23 kinds of target PFASs were separated within 16 min by gradient elution using a binary mobile phase system of methanol/water(Containing 0.4%ammonium hydroxide).Tandem mass spectrometry was performed in multiple reaction monitoring(MRM)mode for online detection of various PFASs,and quantification was carried out by internal standard method.The results of the method validation showed that satisfactory average recoveries of 23 kinds of PFASs in plant leaf samples(64.2%-125.5%),precision(relative standard deviations(RSDs)of 0.7%-12.8%),linearity(R2>0.990),and sensitivity(the detection limits(S/N=3)were in the range of 0.02-0.50 μg/kg)were achieved.Finally,this method was used to detect PFASs in the marine green tide algae(Enteromorpha prolifera)and several tree leaves,and a total of 6 kinds of PFASs were detected,in which PFBA was the main contaminant.Compared with the reported offline SPE methods,the proposed online SPE technique significantly simplified the sample pretreatment process and provided an automatic,simple,and environment-friendly method for the routine monitoring of legacy and emerging PFASs in plant tissues.
8.Dosimetric study of two-arc and dual-arc techniques in VMAT program for lower mid-thoracic esophageal cancer
Yong-Fu FENG ; Yu-Song LONG ; Jun-Wen TAN ; Xian-Tao HE ; Gang LI ; Zhan-Yu WANG
Chinese Medical Equipment Journal 2024;45(1):62-66
Objective To compare the effects of two arc(TA)and dual arc(DA)techniques on the dose distribution to the planning target volume(PTV)and organs at risk(OAR)in volumetric modulated arc therapy(VMAT)for lower mid-thoracic esophageal cancer.Methods Ten patients with lower mid-thoracic esophageal cancer who received radiation therapy at some hospital from July 2020 to June 2022 were selected retrospectively.A TA radiation therapy plan and a DA radiation therapy plan were developed for each patient using the Ray Arc module of RayStation 4.7.5.4 planning system,and the two kinds of radiation plans were compared in terms of dosimetric parameters including D2,D5,D50,D95,D98,homogeneity index(HI),conformity index(CI),beam-on time and total monitor unit for PTV and lung V5,V10,V20,V30 and Dmean and heartV30,V40 and Dmean and spine cord Dmax for OAR.SPSS 22.0 was used for statistical analysis.Results TA and DA radiation therapy plans had no significant differences in PTV CI,HI,D2,D5,D50,D95 and beam-on time(P>0.05),and DA plan had D98 and total monitor unit higher obviously than those of TA plan(P<0.05).In terms of OARs protection,DA plan had heart V30,V40 and Dmean slightly lower than those of TA plan with non-significantly differences(P>0.05),while lung V5,V30 and Dmean and spine cordDmax significantly lower(P<0.05).Conclusion DA technique gains advantages over TA technique in PTV dose distribution and dose to OAR,and the involvement of DA technique in preparing the VMAT plan for esophageal cancer contributes to enhancing the treatment efficacy.[Chinese Medical Equipment Journal,2024,45(1):62-66]
9.Effect of high intensity focused ultrasound treatment on ovarian reserve capacity in adenomyosis
Yi-Lin QIAN ; Hui-Xian CHEN ; Qing-Yue CHEN ; Dong-Qin HE ; Shu-Jing CHEN
Chinese Medical Equipment Journal 2024;45(1):67-70
Objective To explore the impact of high intensity focused ultrasound(HIFU)treatment on ovarian reserve capacity in adenomyosis.Methods Clinical data of 106 adenomyosis patients who underwent HIFU treatment from May 2019 to December 2020 at some hospital were analyzed retrospectively.All the patients were treated with HIFU,and color Doppler ultrasonography was performed before and after 6 months of treatment,respectively.The resistance index,pulsatility index,vascularization index,blood flow index,vascularization blood flow index and sinus follicle number were obtained,and serum anti-Mullerian hormone(AMH),follicle-stimulating hormone(FSH)and luteinizing hormone(luteinizing hormone)were measured.The correlation between serum AMH levels and FSH and LH levels was analyzed.SPSS 21.0 statistical software was used for data analysis.Results After 6 months of treatment serum FSH,LH,value of FSH/LH,resistance index and pulsatility index significantly decreased while vascularization index,blood flow index,vascularization blood flow index,number of sinus follicles,and serum AMH level obviously increased when compared with those before treatment,with the differences being statistically significant(P<0.05).Serum AMH levels were negatively correlated with FSH and LH levels(r=-0.448,-0.527,P<0.05)after 6 months of treatment.Conclusion HIFU treatment reduces sex hormone levels,elevates serum AMH levels and sinus follicle number,and may improve ovarian reserve capacity in patients with adenomyosis.[Chinese Medical Equipment Journal,2024,45(1):67-70]
10.Synthesis and antibacterial activity evaluation of octapeptin derivatives
He-xian YANG ; A-long CUI ; Yong-jian WANG ; Shi-bo KOU ; Miao LÜ ; Hong YI ; Zhuo-rong LI
Acta Pharmaceutica Sinica 2024;59(1):152-160
Octapeptin has strong antibacterial activity against Gram-negative bacteria such as

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