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.

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.

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.

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.

The diagnosis of pediatric sepsis still has some controversies.According to the latest guidelines,it is temporarily described as a life-threatening organ dysfunction caused by the host's dysregulated response to infection.Although there is a complete diagnostic and treatment process,its high mortality rate has always been a problem that plagues clinicians.While the diagnosis of adult sepsis is clear,treatment outcomes remain unsatisfactory.The reason lies in the high heterogeneity of sepsis itself,and the same set of diagnostic and treatment methods are not suitable for all patients.Therefore,researchers try to find the rules to classify sepsis.Compared with adults,pediatric sepsis has a more complex pathophysiological mechanism,and the progress of typing research is relatively slow.This review summarized recent advancements in the field by comparing the typing and treatment research of both pediatric and adult sepsis.

Objective To investigate the effects of different inspired oxygen concentrations on periop-erative cerebrovascular function in patients with a history of ischemic stroke.Methods A total of 150 patients scheduled for elective surgery with a history of ischemic stroke were enrolled from Renji Hospital,Shanghai Jiao Tong University School of Medicine,between June 2020 and March 2024.Using a random number table,patients were allocated into two groups:F30 group(intraoperative fraction of inspired oxygen,FiO2=30%)and F80 group(FiO2=80%),with 75 patients in each group.Bilateral middle cerebral artery(MCA)blood flow was continu-ously monitored using transcranial Doppler(TCD),including mean flow velocity(Vm),resistance index(RI),and pulsatility index(PI).Cerebral oxygen saturation(rScO2)was measured using a FORE-SIGHT oximeter.Arterial blood gas analysis was performed preoperatively,1 hour after induction,and before extubation to assess pH,partial pressure of arterial carbon dioxide(PaCO2),oxygenation index(OI),base excess(BE),hematocrit(Hct),and lactate(Lac).Peripheral blood samples were collected 24 hours postoperatively to measure thrombox-ane A2(TXA2)and prostacyclin(PGI2)levels.At 1 month postoperatively,telephone follow-up was conducted to evaluate the risk of recurrent cerebral ischemic events using the ABCD2 score and Essen Stroke Risk Score(ESRS).Results No significant differences were observed in baseline characteristics between the two groups.Perioperative arterial blood gas parameters did not differ significantly between groups(P>0.05).Compared with the F30 group,the F80 group exhibited a smaller reduction in mean flow velocity(Vm)of the affected MCA at the end of surgery(8.18%±3.34%vs.13.57%±5.32%,P<0.05),while no significant intergroup differences were found in RI or PI.At 1 hour after induction and before extubation,rScO2 of the affected hemisphere was signifi-cantly increased in the F80 group as compared with the F30 group(P<0.05),whereas no significant difference was observed in the contralateral hemisphere.Before extubation and on postoperative day 1,TXA2 levels were significantly lower and PGI2 levels higher in F80 group compared with F30 group(P<0.05).The proportion of patients at high risk of cerebral ischemia by ABCD2 and ESRS at 1 month postoperatively did not differ between groups(P>0.05).Conclusion In patients with a history of stroke,intraoperative administration of 80%FiO2under general anesthesia better maintains perioperative cerebral hemodynamic stability and cerebral oxygen satura-tion,improves cerebrovascular endothelial function,but does not significantly affect the short-term incidence of postoperative cerebrovascular events compared with 30%FiO2.

Objective To investigate the effects of different inspired oxygen concentrations on periop-erative cerebrovascular function in patients with a history of ischemic stroke.Methods A total of 150 patients scheduled for elective surgery with a history of ischemic stroke were enrolled from Renji Hospital,Shanghai Jiao Tong University School of Medicine,between June 2020 and March 2024.Using a random number table,patients were allocated into two groups:F30 group(intraoperative fraction of inspired oxygen,FiO2=30%)and F80 group(FiO2=80%),with 75 patients in each group.Bilateral middle cerebral artery(MCA)blood flow was continu-ously monitored using transcranial Doppler(TCD),including mean flow velocity(Vm),resistance index(RI),and pulsatility index(PI).Cerebral oxygen saturation(rScO2)was measured using a FORE-SIGHT oximeter.Arterial blood gas analysis was performed preoperatively,1 hour after induction,and before extubation to assess pH,partial pressure of arterial carbon dioxide(PaCO2),oxygenation index(OI),base excess(BE),hematocrit(Hct),and lactate(Lac).Peripheral blood samples were collected 24 hours postoperatively to measure thrombox-ane A2(TXA2)and prostacyclin(PGI2)levels.At 1 month postoperatively,telephone follow-up was conducted to evaluate the risk of recurrent cerebral ischemic events using the ABCD2 score and Essen Stroke Risk Score(ESRS).Results No significant differences were observed in baseline characteristics between the two groups.Perioperative arterial blood gas parameters did not differ significantly between groups(P>0.05).Compared with the F30 group,the F80 group exhibited a smaller reduction in mean flow velocity(Vm)of the affected MCA at the end of surgery(8.18%±3.34%vs.13.57%±5.32%,P<0.05),while no significant intergroup differences were found in RI or PI.At 1 hour after induction and before extubation,rScO2 of the affected hemisphere was signifi-cantly increased in the F80 group as compared with the F30 group(P<0.05),whereas no significant difference was observed in the contralateral hemisphere.Before extubation and on postoperative day 1,TXA2 levels were significantly lower and PGI2 levels higher in F80 group compared with F30 group(P<0.05).The proportion of patients at high risk of cerebral ischemia by ABCD2 and ESRS at 1 month postoperatively did not differ between groups(P>0.05).Conclusion In patients with a history of stroke,intraoperative administration of 80%FiO2under general anesthesia better maintains perioperative cerebral hemodynamic stability and cerebral oxygen satura-tion,improves cerebrovascular endothelial function,but does not significantly affect the short-term incidence of postoperative cerebrovascular events compared with 30%FiO2.

The diagnosis of pediatric sepsis still has some controversies.According to the latest guidelines,it is temporarily described as a life-threatening organ dysfunction caused by the host's dysregulated response to infection.Although there is a complete diagnostic and treatment process,its high mortality rate has always been a problem that plagues clinicians.While the diagnosis of adult sepsis is clear,treatment outcomes remain unsatisfactory.The reason lies in the high heterogeneity of sepsis itself,and the same set of diagnostic and treatment methods are not suitable for all patients.Therefore,researchers try to find the rules to classify sepsis.Compared with adults,pediatric sepsis has a more complex pathophysiological mechanism,and the progress of typing research is relatively slow.This review summarized recent advancements in the field by comparing the typing and treatment research of both pediatric and adult sepsis.