The patients with skeletal class Ⅱ malocclusion are often accompanied by structural and functional abnormalities of the upper airway,and obstructive sleep apnea hypopnea syndrome(OSAHS)may occur in severe cases.The morphologic and fluid dynamic changes of the upper airway in one patient with skeletal class Ⅱ malocclusion accompanied by OSAHS after maxillomandibular advancement(MMA)surgery were observed.The patient was a 27-year-old male with skeletal class Ⅱ malocclusion and moderate OSAHS.Combined orthodontic and orthognathic treatment was conducted,involving the anterior movement of the maxilla and mandible.After surgery,the patient's facial and intraoral features showed a satisfactory occlusion relationship with normal overbite,overjet and canine-molar relationships.There was also a significant improvement in the upper airway flow field.Two years after surgery,the cross-sectional area of the nasopharyngeal airway increased by 10.76％with a 55.36％reduction in pressure.The oropharyngeal airway showed a 108.25％increase in cross-sectional area with a 98.14％pressure reduction.The hypopharyngeal airway exhibited a 97.51％increase in cross-sectional area with a 351.03％pressure reduction.The laryngopharyngeal airway demonstrated a 27.54％increase in cross-sectional area with a 95.62％pressure reduction.The apnea-hypopnea index(AHI)decreased by 55.45％,achieving the treatment goal.Morphological measurements combined with fluid dynamic analysis can comprehensively evaluate the condition of the upper airway.The approximate value of the critical closing pressure(Pcrit)obtained from computational fluid dynamics(CFD)analysis may serve as a simple quantitative indicator for assessing the upper airway condition.

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 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.

[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 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 discuss the repairment effect of intra-articular injection of adipose derived stem cells(ADSCs)on articular cartilage destruction in the temporomandibular joint osteoarthritis(TMJOA)model rabbits,and to clarify the possible mechanism.Methods:Twenty-seven rabbits were randomly divided into control group,model group,and ADSCs group.The ADSCs of the rabbits were extracted and cultured.The rabbit TMJOA model was prepared by monosodium-iodoacetate(MIA)injection technique.The temporomandibular joint cavity of the TMJOA model rabbits in ADSCs group was given two continuous intra-articular injections of 1.0×106 mL-1 ADSCs,while the rabbits in control and model group were given sequivalent volume of saline into the temporomandibular joint cavity.After 8 weeks,Micro-CT scan was performed on the temporomandibular joints of the rabbits in various groups;the bone volume fraction(BV/TV),bone surface area/bone volume(BS/BV),trabecular thickness(Tb.Th),trabecular separation(Tb.Sp),and trabecular number(Tb.N)of condyles tissue of the rabbits in various groups were analyzed;HE staining was used to observe the pathomorphology of condyles tissue of the rabbits in various groups;immunohistochemistry was used to detect the localization and expression levels of SRY-related high mobility group box gene 9(SOX9),matrix metalloproteinase-13(MMP-13),and vascular endothelial growth factor(VEGF)proteins in condyles tissue of the rabbits in various groups;Western blotting method was used to detect the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in various groups.Results:The micro-CT scan results showed that compared with control group,the BV/TV,Tb.Th,and Tb.N of condyles tissue of the rabbits in model group were significantly decreased(P<0.05),while the BS/BV and Tb.Sp were significantly increased(P<0.05);compared with model group,the BV/TV,Tb.Th,and Tb.N in condyles tissue of the rabbits in ADSCs group were significantly increased(P<0.05),and the BS/BV and Tb.Sp were significantly decreased(P<0.05).The HE staining results showed that the condylar cartilage surface of the rabbits in control group was smooth with clear layers and intact structure;compared with control group,the surface of condyles tissue of the rabbits in model group was irregular with thickened hypertrophic layer and areas of cell depletion and clustering;compared with model group,the pathological damage of condyles tissue of the rabbits in ADSCs group was significantly decreased.The immunohistochemical staining results showed that compared with control group and ADSCs group,the number of brown granule in condyles tissue of the rabbits in model group was increased,mainly concentrated in the hypertrophic layer,especially in the bone cartilage junction site and the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the number of brown granule in condyles tissue of the rabbits in ADSCs group was significantly decreased,and the expression levels of SOX9,MMP-13,and VEGF proteins were significantly decreased(P<0.05).The Western blotting results showed that compared with control group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in model group were significantly increased(P<0.05);compared with model group,the expression levels of SOX9,MMP-13,and VEGF proteins in condyles tissue of the rabbits in ADSCs group were significantly decreased(P<0.05).Conclusion:Intra-articular injection of ADSCs can effectively repair the cartilage destruction in TMJOA,alleviate the cartilage injury,and mitigate the progression of osteoarthritis.

Objective:To discuss the effect of concentrated growth factor(CGF)on the performance of bone marrow mesenchymal stem cells(BMSCs)sheets,and to clarify the role of CGF-containing composite cell sheets(CS)in the bone defect repairment.Methods:In in vitro experiments,the BMSCs were isolated and cultured from two 3-week-old SD rats;Alizarin Red S and Oil Red O staining were used to identify the osteogenic and adipogenic capabilities of BMSCs;CGF liquid extracts(CGFe)was prepared from three 3-week-old SD rats.The cells were divided into control group,traditional CS(BMSC-CS)group,and CGF-containing composite CS(CGF/BMSC-CS)group.The morphology of the CS in two groups was observed by HE staining.Alizarin Red and alkaline phosphatase(ALP)staining were used to detect the osteogenic differentiation of the CS in various groups;cell scratch assay was used to detect the migration abilities of the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of ALP,collagen are type 1(COL-1),Runt-related transcription factor 2(RUNX2),and osteocalcin(OCN)in the cells in various groups.In in vivo experiments,15 SD rats were randomly divided into control group,BMSC-CS group,and CGF/BMSC-CS group;micro computed tomography(Micro-CT)was used to detect the bone formation parameters in skull defects of the rats in various groups;HE staining and Masson staining were used to observe the morphology of skull defect tissue of the rats in various groups.Results:The third-generation BMSCs were spindle-shaped,closely arranged,and grew in a vortex cluster.The Alizarin red staining results showed obvious calcium nodules,and the Oil red O staining showed red lipid droplets,confirming the cells'ability to undergo osteogenic and adipogenic differentiation.The CS were white and semi-transparent,with slightly curled edges.The peeled CS were irregularly curled and wrinkled.Compared with BMSC-CS group,the CS in CGF/BMSC-CS group were whiter,less transparent,significantly increased in thickness and extensibility,less prone to breakage,and had a certain degree of stickiness and plasticity.The HE staining results showed that compared with BMSC-CS group,the number of the cells of CS in CGF/BMSC-CS group was increased,with denser arrangement and more abundant extracellular matrix(ECM),which wrapped and connected the cells to form an integral sheet-like structure.The Alizarin red and ALP staining results showed that compared with control group,the ALP activity and mineralization uplift value of CS in BMSC-CS group were significantly increased(P<0.05);compared with control group and BMSC-CS group,the number of osteoblasts and red mineralized nodules in the CS in CGF/BMSC-CS group was significantly increased,with obvious deepening of the staining,increased positive area,and the ALP activity and mineralization uplift value were significantly increased(P<0.05).Compared with BMSC-CS group,the ALP activity and mineralization uplif value of the CS in CGF/DMSC-CS group were increased(P<0.05).The cell scratch assay results showed that after 24 of culture,compared with control group,the migration rates of the cells in BMSC-CS group and CGF/BMSC-CS group were significantly increased(P<0.05).Compared with BMSC-CS group,the migration rate of the cells in CGF/BMSC-CS group was significantly increased(P<0.01).After 48 h of culture,compared with control group,the migration rate of the cells in CGF/BMSC-CS group was significantly increased(P<0.05).The RT-qPCR results showed that compared with control group,the expression levels of COL-1 and OCN mRNA in the cells in BMSC-CS group were significantly increased(P<0.01),and the expression levels of ALP,COL-1,OCN,and RUNX2 mRNA in the cells in CGF/BMSC-CS group were significantly increased(P<0.01).Compared with BMSC-CS group,the expression levels of ALP,COL-1,and OCN mRNA in the cells in CGF/BMSC-CS group were significantly increased(P<0.01).The Micro-CT detection results showed that in control group,the boundary of the rat skull defect area was clear,with almost no new bone formation.In BMSC-CS group,a small amount of new bone formed only at the edge of the bone defect in skull of the rats,with a significant gap in the central area of the defect.In CGF/BMSC-CS group,new bone formed along the edge of the bone defect towards the central area in skull of the rats,repairing most of the bone defect.Compared with control group,the bone volume(BV)and trabecular number(Tb.N)of the rats in BMSC-CS group were significantly increased(P<0.05);the bone volume(BV),bone volume fraction[BV/tissue volume(TV)],trabecular thickness(Tb.Th),and trabecular number(Tb.N)in skull of the rats in CGF/BMSC-CS group,were significantly increased(P<0.05).Compared with BMSC-CS group,the BV,BV/TV,Tb.Th,and Tb.N in skull of the rats in CGF/BMSC-CS group were significantly increased(P<0.01).The HE and Masson staining observation showed that in control group,almost no new bone formed in the skull defect tissue of the rats,with only a large amount of collagen fibers connecting the two sides of the bone ends.In BMSC-CS group,a small amount of new bone formed only at the edge of the bone defect in skull tissue of the rats,with the central area of the defect containing dense collagen fibers connected to the newly formed bone at the defect edge.In CGF/BMSC-CS group,new bone tissue could be seen at the edge of the bone defect,and bone islands formed in the central area of the defect,surrounded by osteocytes and a large amount of collagen fibers.The Masson staining observation results showed that the cytoplasm and osteoid were red,and the collagen was blue.In CGF/BMSC-CS group,newly formed osteoid was observed in skull defect tissue of the rats,with the highest amount of new bone formation.Conclusion:CGF can promote the osteogenic differentiation and increase the richness of ECM in BMSCs sheets.CGF-containing composite CS can efficiently repair skull defects of the rats and serve as an ideal and safe material for promoting the bone regeneration.

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.