Objective:To analyze the clinical characteristics and treatment outcomes of children with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody-mediated necrotizing myopathy, and to explore early identification and management strategies to provide reference for clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data and treatment outcomes of 10 pediatric patients with anti-HMGCR antibody-mediated necrotizing myopathy admitted to the Department of Rheumatology, Children′s Hospital of Fudan University from December 2020 to December 2024. Statistical description was performed using SPSS 22.0.Results:Among the 10 patients, the male-to-female ratio was 1:4, the age of onset was (7.2±4.0) years, and the disease duration at diagnosis was (22.2±19.6) months. None had a history of statin exposure. Six patients presented with muscle weakness, and4 were diagnosed due to asymptomatic elevation of creatine kinase (CK); 4 had dermatomyositis-like rashes. All patients showed significantly elevated CK levels [median 3 291(1 969, 8 776)U/L] and underwent muscle biopsy. Histopathological findings revealed myofiber degeneration, necrosis, and regeneration in all cases, with inflammatory infiltration in 9 cases, MHC-Ⅰ positivity in all, and C5b-9 positivity in 9 cases. The median follow-up duration was (15.7±6.3) months. At the last follow-up, muscle strength was normal or nearly normal, and the CK median value had decreased to 977.5 (211.0, 3 536.0) U/L.Conclusion:For patients with suspected idiopathic inflammatory myopathy and significantly elevated CK, muscle-specific antibody testing-including anti-HMGCR-and muscle biopsy should be performed promptly regardless of the presence of skin rash, to ensure accurate diagnosis and guide treatment, thereby avoiding misdiagnosis or missed diagnosis.

Objective:To analyze the clinical characteristics and treatment outcomes of children with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody-mediated necrotizing myopathy, and to explore early identification and management strategies to provide reference for clinical diagnosis and treatment.Methods:A retrospective analysis was conducted on the clinical data and treatment outcomes of 10 pediatric patients with anti-HMGCR antibody-mediated necrotizing myopathy admitted to the Department of Rheumatology, Children′s Hospital of Fudan University from December 2020 to December 2024. Statistical description was performed using SPSS 22.0.Results:Among the 10 patients, the male-to-female ratio was 1:4, the age of onset was (7.2±4.0) years, and the disease duration at diagnosis was (22.2±19.6) months. None had a history of statin exposure. Six patients presented with muscle weakness, and4 were diagnosed due to asymptomatic elevation of creatine kinase (CK); 4 had dermatomyositis-like rashes. All patients showed significantly elevated CK levels [median 3 291(1 969, 8 776)U/L] and underwent muscle biopsy. Histopathological findings revealed myofiber degeneration, necrosis, and regeneration in all cases, with inflammatory infiltration in 9 cases, MHC-Ⅰ positivity in all, and C5b-9 positivity in 9 cases. The median follow-up duration was (15.7±6.3) months. At the last follow-up, muscle strength was normal or nearly normal, and the CK median value had decreased to 977.5 (211.0, 3 536.0) U/L.Conclusion:For patients with suspected idiopathic inflammatory myopathy and significantly elevated CK, muscle-specific antibody testing-including anti-HMGCR-and muscle biopsy should be performed promptly regardless of the presence of skin rash, to ensure accurate diagnosis and guide treatment, thereby avoiding misdiagnosis or missed diagnosis.

Objective:To investigate the expression of inositol 1, 4, 5-triphate receptor (IP 3R)-glucose-regulated protein 75 (Grp75)-voltage dependent anion channel 1 (VDAC1)-mitochondrial Calcium uniporter (MCU) Calcium axis molecules in proteinuria and to explore its upstream regulator. Methods:Sixteen Sprague Dawley rats were divided into control group (6 rats) and Adriamycin (ADR) group (10 rats). Nephropathy rat model was established by single injection of ADR through tail vein.The glomerular expression of IP 3R, Grp75, VDAC1, MCU and the activation marker of mammalian target of Rapamycin complex 1 (mTORC1) were analyzed by immunohistochemical staining.In cultured mouse podocyte, ADR was used to induce podocyte injury, and the Everolimus of different concentrations was applied for intervention.The expression of the Calcium axis molecules and apoptosis marker was analyzed. Results:Compared with control group, the glomerular expression of IP 3R (0.02±0 vs.0, P<0.001), Grp75 (0.04±0 vs.0, P<0.001), VDAC1 (0.04±0 vs.0.01±0, P<0.001), and MCU (0.05±0.01 vs.0.01±0, P<0.001) were significantly increased in ADR-induced nephropathy rats, and the activation marker of mTORC1 (0.57±0.01 vs.0.18±0, P<0.001) was increased as well.In cultured mouse podocytes, compared with control group, the expression of Grp75 (1.89±1.17 vs.0.16±0.08, P=0.001), VDAC1 (1.59±0.34 vs.0.20±0.07, P=0.006), and MCU (1.56±0.38 vs.0.46±0.35, P=0.014) were obviously increased in ADR induced podocytes, and the activation marker of mTORC1 (2.12±0.08 vs.0.39±0.09, P<0.001) was also increased.Compared with the ADR induced podocytes, the expression of Grp75 (0.26±0.20 vs.1.89±1.17, P=0.001), VDAC1 (0.40±0.26 vs.1.59±0.34, P=0.014) and MCU (0.60±0.32 vs.1.56±0.38, P=0.029) in podocytes treated with ADR and 1.0 nmol/L Everolimus were remarkably decreased, accompanied with the decrease of mitochondrial calcium [(2 664.00±140.57) U vs.(3 025.16±180.92) U, P=0.023] and apoptosis marker cleaved Caspase-3 (0.55±0.28 vs.1.48±0.45, P=0.011). Conclusions:The over-production of IP 3R-Grp75-VDAC1-MCU Calcium axis molecules accompanied with the hyper-activation of mTORC1 was involved in ADR induced nephropathy rats.mTORC1 inhibitor decreased the expression of Calcium axis molecules in mouse podocytes, which might involve in the mechanism of mTORC1 inhibitor′s effects on podocyte.