AIM To study the chemical constituents from the buds of Aralia chinensis L.var.nuda Nakai and their in vitro anti-inflammatory activities.METHODS The 70％ethanol extract from the buds of A.chinensis var.nuda was isolated and purified by silica gel,Sephadex LH-20,ODS and semi-preparative HPLC,then the structures of compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities in vitro were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as 4-(2,2-dibutoxyethyl)phenol(1),trans-linalool-3,7-oxide-6-O-β-D-glucopyranoside(2),2'-O-(9Z,12Z,15Z-octadecatrienoyl)glyceryl β-D-galactopyranoside(3),quercetin-3-O-β-D-glucopyranoside(3'→ O-3''')quercetin-3-O-β-D-galactopyranoside(4),syringaresinol-4'-O-β-D-glucopyranoside(5),p-hydroxybenzaldehyde(6),7α-hydroxystigmasterol 3-O-β-D-glucopyranoside(7),trans-p-hydroxy cinnamic acid methyl ester(8),funingensin A(9),3,4-dihydroxy-acetophenone(10),N-acetyltyramine(11),3,4-di-O-caffeoyl quinic acid(12),chlorogenic acid(13),aralia cerebroside(14),caffeic acid methyl ester(15),tetradecanoic acid(16).The IC50values of compounds 8,10,12 and 13 were(22.19±1.59),(35.25±1.30),(13.38±0.72),(15.73±1.16)μmol/L,respectively.CONCLUSION Compound 1 is a new compound,2-13 are isolated from genus Aralia for the first time.Compounds 8,10,12,13 exhibit significant in vitro anti-inflammatory activities.

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.

Doxorubicin is a commonly used antitumor drug for the treatment of various cancers.How-ever,its clinical application is greatly restricted by its severe cardiotoxicity.At present,doxorubicin-induced cardiotoxicity is categorized into acute and chronic forms,depending on the dosage and dura-tion of exposure,which may eventually lead to the occurrence of heart failure.The pathogenesis of doxorubicin cardiotoxicity is associated with oxidative stress,mitochondrial damage,calcium overload,dysregulation of autophagy,and apoptosis.In forensic medical practice,cases of poisoning or even car-diac death caused by doxorubicin showed no obvious changes in cardiac morphology through routine forensic pathological examinations.The paper aims to summarize the research on the mechanisms of action of doxorubicin-induced cardiotoxicity in recent years,analyze and discuss the possible pathways of cardiomyocyte injury caused by doxorubicin,and provide references for research on the mechanisms of doxorubicin-induced cardiotoxicity and forensic application.

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.

To report 3 cases of acute generalized exanthematous pustulosis (AGEP) caused by hydroxychloroquine. All the 3 patients were females, aged 23, 30, and 28 years respectively. In cases 1 and 3, the rashes appeared 4 days and 12 days respectively after the treatment with hydroxychloroquine for systemic lupus erythematosus; case 2, who was 8 weeks pregnant, developed rashes 10 days after starting hydroxychloroquine treatment for antiphospholipid syndrome. All the 3 patients had high fever, and clinically presented with generalized round or oval-shaped edematous erythema on the face, neck, trunk and limbs, covered with a large number of pinhead-sized pustules, and with multiple erythema multiforme-like lesions on the trunk and both upper limbs, including targetoid lesions. Mutations in the IL36RN gene were identified in all the 3 patients: a homozygous mutation c.115+6T>C in the IL36RN gene was found in case 1, and her parents were heterozygous carriers; case 2 inherited the heterozygous mutation c.115+6T>C in the IL36RN gene from her mother; the heterozygous mutation c.115+6T>C found in case 3 was a de novo mutation. A diagnosis of AGEP was made in all the 3 cases. Cases 1 and 2 received subcutaneous injections of adalimumab in addition to the treatment of their underlying diseases, and skin lesions markedly regressed after 1 week of treatment; case 3 was treated with high-dose glucocorticoids, and lesions subsided after 4 weeks; no significant adverse reactions were observed in cases 1 and 2, however, femoral head necrosis was noted in case 3. During a follow-up period of 42 months, none of the patients experienced recurrence, and case 2 gave birth to a healthy baby boy after 8-month treatment.

Generalized pustular psoriasis (GPP) is a rare and life-threatening autoinflammatory disorder. Recent advances in genetics, immunology, and targeted therapies have made its pathogenesis increasingly clear and led to refinements in diagnostic criteria and treatment strategies. Nonetheless, several challenges remain unresolved, including the heterogeneity of clinical phenotypes and therapeutic responses, as well as the prediction and control of disease relapse. Future research will focus on dissecting the immune mechanisms and pivotal inflammatory signaling pathways underlying GPP, identifying novel therapeutic targets, and developing more effective and durable treatment regimens based on research findings.

To report 3 cases of acute generalized exanthematous pustulosis (AGEP) caused by hydroxychloroquine. All the 3 patients were females, aged 23, 30, and 28 years respectively. In cases 1 and 3, the rashes appeared 4 days and 12 days respectively after the treatment with hydroxychloroquine for systemic lupus erythematosus; case 2, who was 8 weeks pregnant, developed rashes 10 days after starting hydroxychloroquine treatment for antiphospholipid syndrome. All the 3 patients had high fever, and clinically presented with generalized round or oval-shaped edematous erythema on the face, neck, trunk and limbs, covered with a large number of pinhead-sized pustules, and with multiple erythema multiforme-like lesions on the trunk and both upper limbs, including targetoid lesions. Mutations in the IL36RN gene were identified in all the 3 patients: a homozygous mutation c.115+6T>C in the IL36RN gene was found in case 1, and her parents were heterozygous carriers; case 2 inherited the heterozygous mutation c.115+6T>C in the IL36RN gene from her mother; the heterozygous mutation c.115+6T>C found in case 3 was a de novo mutation. A diagnosis of AGEP was made in all the 3 cases. Cases 1 and 2 received subcutaneous injections of adalimumab in addition to the treatment of their underlying diseases, and skin lesions markedly regressed after 1 week of treatment; case 3 was treated with high-dose glucocorticoids, and lesions subsided after 4 weeks; no significant adverse reactions were observed in cases 1 and 2, however, femoral head necrosis was noted in case 3. During a follow-up period of 42 months, none of the patients experienced recurrence, and case 2 gave birth to a healthy baby boy after 8-month treatment.

Generalized pustular psoriasis (GPP) is a rare and life-threatening autoinflammatory disorder. Recent advances in genetics, immunology, and targeted therapies have made its pathogenesis increasingly clear and led to refinements in diagnostic criteria and treatment strategies. Nonetheless, several challenges remain unresolved, including the heterogeneity of clinical phenotypes and therapeutic responses, as well as the prediction and control of disease relapse. Future research will focus on dissecting the immune mechanisms and pivotal inflammatory signaling pathways underlying GPP, identifying novel therapeutic targets, and developing more effective and durable treatment regimens based on research findings.