[This corrects the article DOI: 10.1016/j.apsb.2024.03.030.].

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 protective effect of Akebia saponin D(ASD)on non-alcoholic fatty liver disease(NAFLD)in rats by regulating IL-6/STAT3 axis.Methods:Fifty SD rats were separated into control group,model group,low dose ASD group(ASD 20 mg/kg),high dose ASD group(ASD 40 mg/kg)and inhibitor group(ASD 40 mg/kg+IL-6/STAT3 signal pathway inhibitor LMT-28 3 mg/kg),with 10 rats in each group.Rats in control group were fed with standard diet,while the other four groups were fed with high fat and high sugar diet.All rats were fed for 6 consecutive weeks,and the corresponding dose of drugs was injected intraperitoneally from the 7th week,which were given drugs for 8 consecutive weeks.All rats were weighed to calculate liver index;levels of serum total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)were mea-sured by automatic biochemical analyzer;HE staining was used to observe pathological changes of rats liver;oil red staining was used to observe lipid accumulation in rats liver;expressions of IL-6,JAK1,STAT3 in rats liver were detected by qRT-PCR;Western blot was used to detect expressions of IL-6,JAK1,p-JAK1,STAT3 and p-STAT3 proteins.Results:Compared with control group,hepatocytes in liver tissue of model group were swollen,accompanied by many ballooning changes,severe cytoplasmic vacuolization,the structure of hepatic lobule was unclear,and accompanied by inflammatory cell infiltration,and obvious red granular lipid droplets occupied most of the cytoplasm,body mass,liver index,levels of serum TC,ALT,AST,TG,expressions of IL-6,JAK1,STAT3 mRNAs,and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue of rats were obviously increased(P<0.05);compared with model group,damage of hepatic lobule structure in low and high doses ASD groups were reduced,swelling and vacuolization of liver cells were reduced,and accumulation of lipid droplets in liver tissue was obviously reduced.Body mass,liver index,levels of serum TC,ALT,AST and TG in rats were obviously decreased(P<0.05),while expressions of IL-6,JAK1,STAT3 mRNAs and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue were further increased(P<0.05);LMT-28,an inhibitor of IL-6/STAT3 signaling pathway,attenuated the liver protective effect of ASD on NAFLD rats.Conclusion:ASD can protect liver of NAFLD rats by activating IL-6/STAT3 signaling pathway.

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 clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective:To investigate the clinical characteristics and independent risk factors of severe disease in patients with anti-nuclear matrix protein (NXP) 2 antibody-positive juvenile dermatomyositis (JDM).Methods:A retrospective cohort study was conducted, including 219 anti-NXP2 antibody-positive JDM patients admitted to 23 children′s hospitals across China from July 2011 to July 2023. Patients were classified into severe and non-severe groups based on classification criteria for severe dermatomyositis. Demographic characteristics, clinical manifestations, and laboratory parameters were compared between the 2 groups using independent sample t-test, Mann-Whitney U test, or χ2 test. Univariate and multivariate Logistic regression analyses were performed to identify risk factors for severe disease. The receiver operating characteristic curve was employed to calculate optimal cut-off values. Results:Among the 219 patients, 108 were male and 111 were female, with an age at onset of 6.3 (3.5, 9.4) years. The severe group comprised 69 patients, and the non-severe group 150 patients. The severe group had significantly higher rates of fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, as well as elevated levels of ferritin-to-albumin ratio (FAR), creatine kinase (CK), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (all P<0.05). Multivariate analysis identified anti-Ro52 antibody positivity ( OR=13.26, 95% CI 1.37-128.29) and elevated FAR ( OR=1.90, 95% CI 1.09-2.31) as independent risk factors for severe anti-NXP2 antibody-positive JDM (both P<0.05). Receiver operating characteristic curve analysis revealed that a FAR cutoff value of 6.82 predicted severe disease with an area under the curve of 0.87 (95% CI 0.81-0.94, P<0.001), sensitivity of 0.85, and specificity of 0.70. All patients received glucocorticoid therapy, and the severe group received higher proportions of steroid pulse therapy, cyclophosphamide, mycophenolate mofetil, intravenous immunoglobulin, biologics, and adjuvant treatments compared to the non-severe group (all P<0.05). In terms of outcomes, 2 patients (2.9%) in the severe group died (due to neurological involvement and intestinal perforation, respectively), while the remaining patients achieved complete clinical response or remission. All patients in the non-severe group achieved remission. Conclusions:The primary clinical features of anti-NXP2 antibody-positive JDM included fever, heliotrope rash, subcutaneous edema, periorbital edema, anti-Ro52 antibody positivity, and elevated levels of CK, AST, LDH, and FAR. Furthermore, anti-Ro52 antibody positivity and a FAR>6.82 were identified as independent risk factors.

Objective:To investigate the protective effect of Akebia saponin D(ASD)on non-alcoholic fatty liver disease(NAFLD)in rats by regulating IL-6/STAT3 axis.Methods:Fifty SD rats were separated into control group,model group,low dose ASD group(ASD 20 mg/kg),high dose ASD group(ASD 40 mg/kg)and inhibitor group(ASD 40 mg/kg+IL-6/STAT3 signal pathway inhibitor LMT-28 3 mg/kg),with 10 rats in each group.Rats in control group were fed with standard diet,while the other four groups were fed with high fat and high sugar diet.All rats were fed for 6 consecutive weeks,and the corresponding dose of drugs was injected intraperitoneally from the 7th week,which were given drugs for 8 consecutive weeks.All rats were weighed to calculate liver index;levels of serum total cholesterol(TC),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and triglyceride(TG)were mea-sured by automatic biochemical analyzer;HE staining was used to observe pathological changes of rats liver;oil red staining was used to observe lipid accumulation in rats liver;expressions of IL-6,JAK1,STAT3 in rats liver were detected by qRT-PCR;Western blot was used to detect expressions of IL-6,JAK1,p-JAK1,STAT3 and p-STAT3 proteins.Results:Compared with control group,hepatocytes in liver tissue of model group were swollen,accompanied by many ballooning changes,severe cytoplasmic vacuolization,the structure of hepatic lobule was unclear,and accompanied by inflammatory cell infiltration,and obvious red granular lipid droplets occupied most of the cytoplasm,body mass,liver index,levels of serum TC,ALT,AST,TG,expressions of IL-6,JAK1,STAT3 mRNAs,and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue of rats were obviously increased(P<0.05);compared with model group,damage of hepatic lobule structure in low and high doses ASD groups were reduced,swelling and vacuolization of liver cells were reduced,and accumulation of lipid droplets in liver tissue was obviously reduced.Body mass,liver index,levels of serum TC,ALT,AST and TG in rats were obviously decreased(P<0.05),while expressions of IL-6,JAK1,STAT3 mRNAs and IL-6,p-JAK1/JAK1,p-STAT3/STAT3 proteins in liver tissue were further increased(P<0.05);LMT-28,an inhibitor of IL-6/STAT3 signaling pathway,attenuated the liver protective effect of ASD on NAFLD rats.Conclusion:ASD can protect liver of NAFLD rats by activating IL-6/STAT3 signaling pathway.

Objective:To discuss the therapeutic effect of resveratrol on the temporomandibular joint osteoarthritis(TMJOA),and to clarify the related mechanism.Methods:Forty-five SD rats were randomly divided into control group,model group,and resveratrol group,and there were 15 rats in each group.The rats in model group and resveratrol group were intra-articularly injected with 50 μL of 20 g·L-1 monosodium iodoacetate(MIA)to set TMJOA rat models,while the rats in control group were injected with an equal volume of normal saline.Three weeks after modeling,the rats in resveratrol group received an injection of 80 μL resveratrol solution,once a week for three weeks,while the rats in control and model groups were injected with an equal volume of normal saline.Micro-computed tomography(Micro-CT)system was used to detect the condyle structure and the bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular spacing(Tb.Sp),and trabecular number(Tb.N)of the rats in various groups were calculated;HE staining and toluidine blue staining were used to observe the pathomorphology of temporomandibular joint(TMJ)tissue of the rats in various groups;immunohistochemistry was used to detect the expression levels of SRY-related HMG box(SOX)-9,matrix metalloproteinase(MMP)-13,silent information regulator(Sirt)1,phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-Akt),and phosphorylated mammalian target of rapamycin(p-mTOR)in TMJ tissue of the rats in various groups;real-time quantitative PCR(RT-qPCR)method was used to detect the expression levels of SOX-9,MMP-13,Sirt1,PI3K,mTOR,and Akt mRNA in TMJ tissue of the rats in various groups.Results:Three weeks after modeling,condylar bone was destructed,the surface was roughness,and continuity interruption were observed,indicating TMJOA model of the rats was established successfully.The Micro-CT system results showed that the condylar surface of the rats in control group was smooth and regularly shaped,with continuous bone texture;the rats in model group had significant condylar destruction,disrupted continuity,surface roughness,and varying degrees of bone defects;the rats in resveratrol group showed alleviated condylar lesions and improved appearance.Compared with control group,the BV/TV and Tb.Th of the rats in model group were significantly decreased(P<0.05),and Tb.Sp was significantly increased(P<0.05);compared with model group,the BV/TV and Tb.Th of the rats in resveratrol group were significantly increased(P<0.05),and the Tb.Sp was significantly decreased(P<0.05).The HE staining results showed clear layers and orderly chondrocyte arrangement in condyle of the rats in control group;the rats in model group showed rough uneven surface,obvious defects,and typical TMJOA features;the rats in resveratrol group showed slightly rough surface with generally clear layers and orderly arranged cells.The toluidine blue staining results showed distinct blue-purple staining of chondrocytes in hypertrophic layer of the rats in control group;pale staining or even loss of staining in some areas of the rats in model group;and distinct and relatively uniform staining in hypertrophic layer of the rats in resveratrol group.The immunohistochemistry results showed that compared with control group,the expression levels of MMP-13,PI3K,p-Akt,and p-mTOR proteins in TMJ tissue of the rats in model group were significantly increased(P<0.05),while the expression levels of SOX-9 and Sirt1 proteins in TMJ tissue of the rats were significantly decreased(P<0.05);compared with model group,the expression levels of SOX-9 and Sirt1 proteins in TMJ tissue of the rats in resveratrol group were significantly increased(P<0.05),whereas the expression levels of MMP-13,PI3K,p-Akt,and p-mTOR proteins were significantly decreased(P<0.05).The RT-qPCR results showed that compared with control group,the expression levels of MMP-13,PI3K,Akt,and mTOR mRNA in TMJ tissue of the rats in model group were significantly increased(P<0.05),while the expression levels of SOX-9 and Sirt1 mRNA were significantly decreased(P<0.05);compared with model group,the expression levels of SOX-9 and Sirt1 mRNA in TMJ tissue of the rats in resveratrol group were significantly increased(P<0.05),whereas the expression levels of MMP-13,PI3K,Akt,and mTOR mRNA were significantly decreased(P<0.05).Conclusion:Resveratrol has therapeutic effect on TMJOA,and its mechanism may be related to the activation of Sirt1 and inhibition of the PI3K-Akt-mTOR signaling pathway.

Inflammation is the pathological basis of many diseases,which can infect locally or act on the whole body,and is closely related to the pathogenesis of many diseases.In recent years,in the background of more and more traditional anti-inflammatory drugs showing adverse reactions,scholars have been exploring the use of traditional Chinese medicine in the ascendant.As an herb in the Asteraceae(daisy)family,Artemisia dracunculus possesses low toxicity and a wide range of uses and can be applied to the regulation of metabolism,analgesia,antidepressant,antioxidant,immune regulation,antibacterial,anti-inflammatory,antiparasitic,and other treatment of a variety of diseases.In-depth studies have revealed that the therapeutic effects and potential of Artemisia dracunculus for a variety of diseases are closely related to its anti-inflammatory mechanism.This article will summarize the relevant literature in recent years and review the research progress of the mechanism of Artemisia dracunculus on the regulation of immune cells and inflammatory factors,as well as its mediation of inflammation-related signaling pathways,intending to provide theoretical references for future application of Artemisia dracunculus in clinical trials and treatments.

Objective To explore the relationship between lactate dehydrogenase to albumin ratio(LAR)and short-term prognosis in patients with sepsis-associated acute kidney injury(AKI).Methods A retrospective analysis was conducted on 463 sepsis patients treated in the intensive care unit(ICU)of Beijing Shijitan Hospital,Capital Medical University,from January 2018 to June 2022.The patients were divided into two groups:a group with secondary AKI(AKI group)and the one without acute kidney injury(non-AKI group).Acute Physiology and Chronic Health Evaluation Ⅱ(APACHEⅡ),Sequential Organ Failure Assessment(SOFA),and levels of procalcitonin(PCT),C-reactive protein(CRP),serum creatinine(SCr),lactate dehydrogenase(LDH),and albumin(ALB)were compared between the two groups.Multivariate logistic regression analysis was used to determine prognostic factors for sepsis-associated acute kidney injury,and Receiver Operating Characteristic(ROC)analysis was performed to assess the predictive value of APACHE Ⅱ score,SOFA score,PCT,SCr,and lactate dehydrogenase to albumin ratio(LAR)for short-term prognosis of sepsis-associated acute kidney injury.Results The 28-day mortality rate in the non-AKI group was lower than that in the AKI group,and the length of stay in ICU was shorter in the non-AKI group than in the AKI group(P<0.05).APACHE Ⅱ score,SOFA score,PCT,SCr and LAR were independent influencing factors for 28-days death in patients with sepsis-associated acute kidney injury.The ROC curve analysis showed that LAR level had a higher predictive value for short-term prognosis in patients with sepsis-associated AKI as compared with APACHE Ⅱ score,SOFA score,PCT,and SCr.Conclusions LAR is an independent risk factor for sepsis-associated AKI and is associated with 28-day mortality in patients.