The anterior disc displacement (ADD) leads to temporomandibular joint osteoarthritis (TMJOA) and mandibular growth retardation in adolescents. To investigate the potential functional role of fibrocartilage stem cells (FCSCs) during the process, a surgical ADD-TMJOA mouse model was established. From 1 week after model generation, ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis (OA)-like joint cartilage degeneration, manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis. Lineage tracing using Gli1-CreER⁺; Tm^fl/-mice and Sox9-CreER⁺;Tm^fl/-mice showed that ADD interfered with the chondrogenic capacity of Gli1⁺ FCSCs as well as osteogenic differentiation of Sox9⁺ lineage, mainly in the middle zone of TMJ cartilage. Then, a surgically induced disc reposition (DR) mouse model was generated. The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice. And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment. In conclusion, ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage, resulting in cartilage degeneration and loss of subchondral bone homeostasis, finally causing TMJ growth retardation. DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.
Animals ; Mice ; Osteogenesis ; Zinc Finger Protein GLI1 ; Fibrocartilage ; Temporomandibular Joint ; Disease Models, Animal ; Osteoarthritis ; Stem Cells ; Growth Disorders

OBJECTIVE: To analyze the clinical phenotype and MYH7 gene variant in a Chinese pedigree affected with hypertrophic cardiomyopathy (HCM). METHODS: The proband was screened for variant of 96 cardiomyopathy-associated genes by exonic amplification and high-throughput sequencing. Candidate variant was verified by Sanger sequencing among 300 healthy controls as well as family members of the proband. Co-segregation analysis of genotypes and clinical phenotypes was carried out for the pedigree. Clustal X software was used to analyze the sequence conservation of the variant among various species, and its pathogenicity was predicted by using bioinformatics software. RESULTS: 6 out of 12 members from this pedigree were found to harbor heterozygous c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene, among whom five were diagnosed with HCM. The remaining one had failed to meet the diagnostic criteria for HCM, but had abnormal ECG. The same variant was not found in the 300 healthy controls. Amino acid sequence analysis showed that the variant is located in a highly conserved region, and bioinformatics analysis predicted that this variant may affect protein function and has a deleterious effect. Based on the American College of Medical Genetics and Genomics (ACMG) guidelines, the variant was predicted to be likely pathogenic (PM2+ PP1_Moderate+PP3+PP5). CONCLUSION The c.4124A>G (p.Tyr1375Cys) variant of the MYH7 gene probably underlay the pathogenesis in this pedigree. Above finding has important value for the early diagnosis of patients with HCM.
Cardiac Myosins/genetics* ; Cardiomyopathy, Hypertrophic/genetics* ; Genotype ; Humans ; Mutation ; Myosin Heavy Chains/genetics* ; Pedigree ; Phenotype

Objective:To evaluate the 2-dimension and 3-dimension changes of upper airway of patients who were diagnosed with idiopathic condylar resorption (ICR) and anterior open bite as well as received bilateral temporomandibular joint (TMJ) prostheses replacement or bimaxillary orthognathic surgery.Methods:This study is a retrospective study. Seventeen patients diagnosed as ICR and anterior open bite in Department of Orthognathic and TMJ surgery, West China Hospital of Sichuan University were selected (January 2018 to December 2021) and divided into bilateral TMJ protheses replacement group (group R, n=8) and orthognathic group (group O, n=9), according to which surgery they have performed. In order to compare variation of upper airway before and after surgery in different dimensions and sections within the same group or between groups, Spiral computed tomography data were obtained before (1 month) and after operation (10 to 12 months) to measure the total volume of airway (VT), the maximum sagittal area (MSA), the maximum cross-sectional area (MACA), the minimum cross-sectional area (MICA), the area of the most posterior plane(PPA), the area of soft-palate plane (SPA), the area of the most posterior point of tongue base plane (PTA), the area of the root of epiglottis plane (EA), the oropharyngeal airway volume (VO), the glossopharyngeal airway volume (VG) and the laryngeal airway volume (VL). Wilcoxon signed-rank test were used to complete statistical analyses for VO (T2),SPA (T2),ΔMSA,ΔMACA in group R as well as PTA (T1),EA (T2) in group O. Statistical analyses of other items were performed with student′s t test. Results:VT, VO, VG, VL, MSA, MACA, MIC, PPA, PTA and EA of group R (T2) were significantly increased after TMJ prosthesis with Lefort Ⅰ osteotomy ( P<0.05). Meanwhile the VT, VO, VG, MSA, MACA, MICA, PPA and SPA of group O (T2) were significantly increased ( P<0.05). There were significant difference in ΔVT and ΔVL between group R [(6 854.80±3 197.82) mm 3, (2 252.85±1 527.96) mm 3] and group O [(3 367.91±3 124.62) mm 3, (413.21±1 244.44) mm 3]( t=2.27, P=0.038; t=2.74, P=0.015). Conclusions:Bilateral temporomandibular joint (TMJ) prostheses replacement and bimaxillary orthognathic surgery can both enlarge the areas and volumes of upper airway in patients who suffer from ICR and anterior open bite. Compared with bimaxillary orthognathic surgery, bilateral temporomandibular joint prostheses replacement plays a more pronounced role in enlargement and reconstruction of middle-inferior section of upper airway.

Objective:To investigate the safety of warfarin for Kawasaki disease (KD) with coronary artery aneurysm (CAA) and its prognosis.Methods:Twenty one children with KD complicated with giant CAA, multiple CAA in one coronary artery or thrombosis in coronary artery were enrolled in this prospective study. Warfarin was used to control the goal international normalized ratio (INR) ranging from 2.0 to 3.0. The CAA diameter, number, location and thrombus in coronary artery were recorded at the beginning of treatment, 1, 2, 3, 4 weeks and 2, 3, 6, 12 months after treatment, as well as the influence on INR, electrocaroliogram, creatine kinase-MB (CK-MB), troponin I. Standardized warfarin bleeding risk training and management was implemented. Children were divided into implementation group and non-implementation group according to the status of actual implementation of their parents. The incidence of bleeding events was compared between the two groups. Comparisons between groups were performed using a Rank sum test and a Fisher exact test.Results:In the 21 patients (15 males and 6 females), the age of onset ranged from 2 months to 6 years. There were 4 cases with grade Ⅱ, 7 cases with grade Ⅲ, 7 cases with grade Ⅳ and 3 cases with grade Ⅴ according to the severity of coronary arterial lesions before treatment. The time of clinical detection of thrombus in 10 children with thrombosis ranged from the fourth day to the fourth month. The dose distribution of warfarin was 0.06-0.10 mg/(kg·d), and the INR was 1.80-2.59. Among the 10 cases with thrombus, 8 cases had disappearance of thrombi and 2 cases with grade Ⅴ had thrombus organization to different degree. After treatment, the coronary artery ectasia of the 4 cases with grade Ⅱ all returned to normal. Among the 7 cases with grade Ⅲ, 3 cases of coronary artery aneurysms returned to normal, and 4 cases did not change. Among the 7 cases with grade Ⅳ , 5 cases of coronary artery aneurysms shrank to grade Ⅲ, and 2 cases remained unchanged. Three cases with grade Ⅴ lesions had no changes in aneurysm. Neither new thrombus nor new CAA was detected during the treatment. There was no significant change in electrocardiogram before and after treatment. No statistically significant difference was found regarding the troponin I (0.07 (0-3.01) vs. 0.04 (0-0.29) μg/L, Z=0.932, P>0.05) and CK-MB (20.6 (11.2-58.2) vs. 29.0 (16.7-47.0) U/L, Z=1.906, P>0.05) before and after treatment. The incidence of bleeding events in the implementation group was significantly lower than that in the non-implementation group (2/15 vs. 4/6, Fisher=5.689, P=0.031). Conclusions:The application of goal INR of 2.0-3.0 and adjustment of warfarin dose according to the severity of CAA combined with standardized and strict warfarin bleeding risk training and management, can increase the safety of warfarin therapy in children with KD, improve the prognosis of coronary artery lesions, promote the dissolution of thrombi, prevent new thrombosis, and effectively reduce the incidence of bleeding complication.

Objective:To explore the value of three-dimensional speckle tracking imaging (3D-STI) and conventional echocardiography in evaluating left ventricular function characteristics of sarcomere mutation carriers in hypertrophic cardiomyopathy.Methods:Totally 91 subjects with sarcomere mutations in family HCM but without left ventricular hypertrophy (G + /P - group), and 100 normal family members with gender and age matched as the control group (G -/P - group) were enrolled from the center of hypertrophic cardiomyopathy of Xijing Hospital affiliated to the Air Force Military Medical University from February 2013 to April 2017. They all received the comprehensive evaluation of 3D-STI and conventional echocardiography. The ultrasonic paramaters between the two groups were compared. And the diagnostic performance of these paramaters with sarcomere mutations was evaluated. Results:Compared with the G -/P - group, the G + /P -group had larger left atrial diameter (LAD), longer left ventricular isovolumic relaxation time (IVRT), reduced mitral annular systolic velocity (e′), elevated E/e′ ratio, as well as impaired left ventricular global longitudinal and radial strain(GLS and GRS) ( P<0.05). Moreover, the GLS≤19.9%(AUC 0.861, sensitivity 61.4%, specificity 98.5%) and IVRT≥75.5 ms(AUC 0.762, sensitivity 61.4%, specificity 72.6%) showed the best diagnostic performance with sarcomere mutations ( P<0.05). Conclusions:In HCM family members, the sarcomere mutations carriers without left ventricular hypertrophy exhibit impaired left ventricular diastolic function, reduced longitudinal and radial systolic function.Moreover, the GLS and IVRT show the best diagnostic performance for those with sarcomere mutations.

Objective:To explore the value of three-dimensional speckle tracking imaging (3D-STI) in the diagnosis of immunoglobulin light-chain cardiac amyloidosis(AL-CA) patients with normal left ventricular ejection fraction (LVEF).Methods:A total of 92 consecutive patients diagnosed with systemic immunoglobulin light chain amyloidosis(sAL) and with normal LVEF from October 2014 to January 2018 in Xijing Hospital were enrolled.Based on the diagnostic criteria of cardiac involvement, the patients were divided into AL-CA group (52 cases) and immunoglobulin light chain amyloidosis (AL) group (40 cases). The clinical data and serological markers of the patients were collected, the conventional echocardiography and full-volume three dimensional dynamic images were acquired, left ventricular global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), and global area strain (GAS) were analyzed using off-line TomTec software. The differences between the two groups were compared.Results:Compared with the AL group, the NT-proBNP of AL-CA group was significantly higher ( P<0.05) and there were no significant differences of the other serological indexes between the two groups(all P>0.05). Compared with the AL group, the maximal left ventricular wall thickness, left ventricular mass index, left atrial volume index, and E/e′ in the AL-CA group were significantly increased (all P<0.05). There were no significant differences of other conventional echocardiographic measurements between the two groups(all P>0.05). Compared with the AL group, GLS, GAS, and GRS were significantly lower in AL-CA group (all P<0.05); but there was no significant difference of GCS between the two groups( P>0.05). The ROC curve analysis showed that the cut-off values discriminating cardiac involvement were 16.09% for GLS, 36.54% for GAS and 31.90% for GRS. Conclusions:3D-STI measurements of left ventricular myocardial mechanics could detect cardiac involvement in patients with sAL amyloidosis, and provides a new method for diagnosis of AL-CA.

Objective To explore the diagnosis and treatment of poorly differentiated endocardial sarcoma. Method The clinical data of a child with poorly differentiated endocardial sarcoma was retrospectively analyzed. Results One-year-old girl was admitted for diarrhea, polypnea, cyanosis, and cough. Abnormal heart sound was found by auscultation. Leads Ⅱ, Ⅲ, and aVF of ECG showed high peaked P wave. The diagnosis of poorly differentiated endocardial sarcoma was confirmed by echocardiography and pathology after cardiac operation. Three months after discharge from the hospital, the patient suddenly came into coma and died. Conclusion The diagnosis of poorly differentiated endocardial sarcoma is mainly based on clinical manifestations, echocardiography and pathology. Surgical resection is the first choice and chemotherapy and radiotherapy play a supporting role. However, there is no cure for it currently.

Objective To explore the clinical value of the monitoring of electronic cardiac index (CI) in the evaluation of neonatal congenital heart disease complicated with heart failure. Methods Sixty neonates with congenital heart disease treated in neonatal department from March 1, 2016 to December 30, 2016 were selected, and divided into severe group (n=11), moderate group (n=15), mild group (n=34), and no heart failure group (n=10) according to the modified Ross heart failure score. CI was measured by electronic force measurement. Left ventricular ejection fraction (LVEF) and pulmonary arterial pressure (PAP) were measured by echocardiography. Venous blood sampling was collected to detect the N-terminal type B brain natriuretic peptide (NT-proBNP). Results The neonates in the severe group were mainly under 2-week-old, while those in the mild group and the moderate group were more than 2-week-old. The differences of CI, LVEF, NT-proBNP, and PAP among the groups were statistically different. The CI and LVEF values were lowest in the severe group, followed by moderate group and mild group, and the highest in no heart failure group. The NT-proBNP and PAP values were the highest in the severe group, followed by moderate group and mild group, and the lowest in no heart failure group. Correlation analysis showed that CI was positively correlated with LVEF (r=0.845, P<0.001), and negatively correlated with NT-proBNP (r=-0.886, P<0.001); CI and PAP were weakly negatively correlated (r=-0.595, P<0.001). Conclusions CI reflects the degree of heart failure to some extent and has some clinical value.

Objective To test the levels of enterovirus 71 (EV71) antibody among children of different ages in Shanghai in 2011,and to investigate the relationship between antibody levels and virus infection.Methods EV71 antibody was detected by microneutralization assay from the serum specimens of healthy children of different ages collected during July to August,2011.The results were analyzed by t test for quantitative data with normal distribution,and by x2 test for count data.Results The positive rate of EV71 antibody among the 93 serum specimens was 58.1％ (54/93).The geometric mean titer (GMT) of EV71-specific neutralizing antibody was 1 ∶ 14.48.The positive rate of EV71 antibody in infants less than 6 months old was 87.5％ (21/24),and the GMT was 1∶29.56.In children aged 2 to 3 years,the positive rate of EV71 antibody decreased to 3.7％ (1/27),and GMT decreased to 1∶4.21,which were both statistically significantly lower than those less than 6 months old (x2 =36.37,t=7.58; both P＜0.01).The positive rate of EV71 antibody increased to 83.3％ (20/24) in children aged 5 to 6 years,with GMT reaching 1∶21.74.Whereas in children aged 7 to 8 years,the positive rate was 66.7％ (12/18) and GMT was 1∶20.76,without statistically significant difference compared with those aged 5 to 6 years (x2 =1.58,t=0.597; both P＞0.05).No statistically significant difference was found between boys and girls in positive rate of EV71 antibody [62.7 ％ (32/51) vs 52.4 ％ (22/42),x2 =1.02,P＞0.05] or GMT (1 ∶ 16.23 vs 1 ∶ 12.61,t=0.881,P＞0.05).Conclusions Children aged 2 to 3 years were at higher risk for EV71 infection,with EV71 antibody level significantly lower than other age groups.

Objective To understand the genetic and antigenic variations of influenza A (H1N1) isolates in Shanghai area in winter of 2010.Methods A total of 137 throat swabs were collected from patients with influenza-like illness in the sentinel hospital in Shanghai area from December 2010 to January 2011,then inoculated into Madin-Darby canine kidney (MDCK) cells.The types of influenza were identified by direct immunofluorescence assay (DIF) and influenza A (H1N1) subtype was determined by reverse transcriptase-polymerase chain reaction (RT-PCR).The mutations of gene and amino acid locus were analyzed through the whole genome sequencing of hemagglutinin (HA),neuraminidase (NA) and polymerase (PB2) segments from some influenza A (H1N1) isolates.Results Total of 53 human influenza virus strains were isolated including 48 influenza A (H1N1) virus strains.Nineteen strains were selected for sequencing by simple random sampling.The phylogenetic tree of HA gene revealed that the latest isolates and most of influenza A (H1N1) viruses isolated before June 2010 were not in the same stem.Analysis of amino acid residues in HA protein showed that mutations were found in antigenic determinant region in some strains.Residues at the enzyme active sites of NA protein were strictly conservative,no change was observed in amino acid residues which were related to drug resistance against oseltamivir and zanamivir.The 627 and 701 residues in PB2 protein were glutamic acid and aspartic acid,respectively,which was still the feature of avian influenza virus,but E677G mutation was detected.Conclusion Compared to influenza A (H1N1) strains isolated in spring and summer,some variations have been detected in the strains isolated in Shanghai area in winter of 2010,some antigen drift and adaptive evolution in mammalian hosts have appeared.