Hypertrophic cardiomyopathy(HCM)is a primary myocardial disease characterized by myocardial hypertrophy,excluding other cardiovascular or systemic/metabolic causes of ventricular wall thickening.Apical hypertrophic ca...Hypertrophic cardiomyopathy(HCM)is a primary myocardial disease characterized by myocardial hypertrophy,excluding other cardiovascular or systemic/metabolic causes of ventricular wall thickening.Apical hypertrophic cardiomyopathy(ApHCM)represents a special form of ventricular hypertrophy predominantly affecting the left ventricular apex below the papillary muscles,typically without significant left ventricular outflow tract obstruction.[1,2]ApHCM often coexists with mild coronary artery abnormalities,[3]and reports of acute myocardial infarction with coronary artery stenosis in ApHCM or HCM patients are uncommon.展开更多
BACKGROUND Diabetes mellitus(DM)is a significant risk factor for cardiovascular diseases and can worsen the risk of cardiovascular events among patients with hypertrophic cardiomyopathy(HCM).However,strong evidence is...BACKGROUND Diabetes mellitus(DM)is a significant risk factor for cardiovascular diseases and can worsen the risk of cardiovascular events among patients with hypertrophic cardiomyopathy(HCM).However,strong evidence is needed to show the impact of DM on all-cause mortality(ACM)and atrial fibrillation(AF),which we explored in this systematic review and meta-analysis.AIM To determine the impact of DM on ACM and AF in patients with HCM.METHODS PubMed,Google Scholar,and EMBASE databases were searched for studies showing the effect of DM on ACM and AF in HCM.A binary random effects model with a 95%confidence interval(CI)was used to pool odds ratios(ORs)for ACM and AF outcomes.Study quality was assessed using the Joanna Briggs Institute’s critical appraisal tool and leave-one-out sensitivity analysis.P<0.05 was considered statistically significant.RESULTS Fourteen studies(n=106138)with a mean age of 61.76±19.84 years and 61.55%males were included in our systematic review;ten studies(n=102882)were eligible for meta-analysis.In the unadjusted analysis,DM was not significantly associated with ACM(OR=0.96;95%CI:0.43-2.15;P=0.93).However,after adjustment,DM showed a significant association with higher ACM risk(adjusted OR=1.37;95%CI:1.16-1.61;P<0.01).DM was significantly associated with AF in both unadjusted(OR=2.02;95%CI:1.14-3.58;P=0.04)and adjusted analyses(adjusted OR=2.68;95%CI:1.68-4.27;P=0.01).The Joanna Briggs Institute tool revealed a low risk of bias.Leaveone-out sensitivity analysis,performed by sequentially excluding each study,demonstrated no significant change in the overall effect estimates,indicating the robustness and stability of our results.CONCLUSION DM significantly increased the risk of ACM and AF,highlighting the importance of tighter glycemic control and cardiovascular risk factor modification among patients with HCM.展开更多
Hypertrophic chondrocytes(HCs)could transform into osteoblastic lineage cells while the pathophysiological implications of HC transformation remain largely unknown.Here,we generated a mouse line utilizing Col10a1-Cre ...Hypertrophic chondrocytes(HCs)could transform into osteoblastic lineage cells while the pathophysiological implications of HC transformation remain largely unknown.Here,we generated a mouse line utilizing Col10a1-Cre to induce DTA expression to genetically ablate HCs and their descendants.Col10a1-Cre;R26^(DTA/+)mice displayed dwarf phenotype,abnormal spongy bone,and significantly delayed drill-hole injuries healing,suggesting an indispensable role of HC lineage extension in bone growth and injury repair.Intriguingly,single-cell RNA sequencing analysis revealed the most significant loss of a cell cluster expressing multiple angiogenic factors(Pro-Angiogenic Descendants of HCs,PADs)among cells derived from Col10a1-Cre;R26^(DTA/+)and control femurs.In silico analysis of cell-cell communication supported Thrombospondin 4(THBS4)as a specific angiogenic factor mediating the crosstalk between PADs and vascular endothelial cells.Concordantly,analyses using immunostaining combined with tissue clearing revealed that PADs physically contacted with endothelial cells,whereas Col10a1-Cre;R26^(DTA/+)mice showed defective metaphyseal and cortical vessel formation and post-injury angiogenesis along with a significant loss of THBS4.Moreover,in vitro assays showed that supplying THBS4 was sufficient to promote proliferation and tube formation of endothelial cells and rescue defective angiogenesis of Col10a1-Cre;R26D TA/+metatarsal explants.Collectively,these findings demonstrate a critical role of PADs in bone growth and injury repair by secreting THBS4 to regulate angiogenesis.展开更多
Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating ...Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.展开更多
Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The ...Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The prevalence rate in the population is 1:500-1:200.This article mainly introduces the diagnostic criteria,pathological manifestations,and genetic basis of HCM,which is the leading cause of sudden death in adolescents and athletes due to exercise,with 60%-70%showing familial clustering.It also discusses the latest progress in the relationship between different genotypes and clinical phenotypes of HCM pa-tients.展开更多
Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Mole...Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.HCM has a relatively wide phenotypic heterogeneity,varying from asymptomatic to sudden cardiac death,because of the many different mutations and pathogenic genes underlying it.Many studies have explored the clinical symptoms and prognosis of HCM,emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM.To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease.Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients.As sequencing technology advances,the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer.HCM is a widespread inherited disease with a highly variable clinical phenotype.The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.展开更多
BACKGROUND Managing left ventricular outflow tract obstruction(LVOTO)and systolic anterior motion(SAM)of the mitral valve can be challenging,especially in the context of circulatory shock and pulmonary edema post card...BACKGROUND Managing left ventricular outflow tract obstruction(LVOTO)and systolic anterior motion(SAM)of the mitral valve can be challenging,especially in the context of circulatory shock and pulmonary edema post cardiac surgery.CASE SUMMARY We describe a case of an 80-year-old female patient with a history of severe aortic stenosis and hypertrophic obstructive cardiomyopathy that underwent aortic valve replacement and myectomy.The patient presented with acute pulmonary edema and low blood pressure due to LVOTO and SAM post cardiac surgery in the intensive care unit.She was paced with an epicardial dual-chamber pacing system due to complete atrioventricular block and treated initially with norepinephrine,furosemide,and esmolol infusion and continuous positive pressure ventilation.The patient remained hypoxemic and kept deteriorating hemodynamically despite titrating up norepinephrine.The addition of vasopressin infusion and tapering of norepinephrine finally stabilized the patient with significant reduction of LVOTO,confirmed by transthoracic echocardiography assessment,improved oxygenation and increased urine output.CONCLUSION Vasopressin seems to be the preferred vasopressor for managing LVOTO and SAM post-cardiac surgery,because of its absence of inotropic effects.Echocardiography is crucial for early diagnosis and therapeutic management.展开更多
BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress ...BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress to a dilated phase of HCM(DPHCM),which is associated with a poor prognosis;however,the underlying pathogenesis remains inadequately understood.CASE SUMMARY In this study,we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations.Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy,a heterozygous missense mutation(c.746G>A,p.Arg249Glu)in the MYH7 gene was identified in the proband(III-5).Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members(II-4,III-4,and IV-3).A total of 26 well-documented patients with DPHCM were identified in the literature.Patients with DPHCM are commonly middle-aged and male.The mean age of patients with DPHCM was 53.43±12.79 years.Heart failure,dyspnoea,and atrial fibrillation were the most prevalent symptoms observed,accompanied by an average left ventricular end-diastolic size of 58.62 mm.CONCLUSION Our findings corroborate the pathogenicity of the MYH7(c.746G>A,p.Arg249Glu)mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.展开更多
BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac m...BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac magnetic resonance(CMR)imaging is commonly used to detect myocardial fibrosis,circulating microRNAs(miRNAs)have emerged as promising noninvasive biomarkers for this condition due to their stability in blood plasma and resistance to pH and temperature variance.AIM To explore the role of specific circulating miRNAs in identifying myocardial fibrosis in patients with HCM.METHODS Using PubMed/MEDLINE and Google Scholar,we reviewed studies from 2014 to 2024 examining the link between circulating miRNAs and myocardial fibrosis in HCM.We included studies measuring miRNA expression in blood samples from HCM patients and assessing fibrosis via imaging,mostly CMR.Data extraction concentrated on the population,methodology,and findings related to the correlation between miRNA levels and fibrosis.RESULTS Seven studies involving 365 HCM patients with a mean age of 49.37±10.5 years,116(31.78%)females,and one animal study identified miR-21,miR-29a,miR-133,miR-4454,and miR-221 as frequently dysregulated markers associated with fibrosis.Elevated levels of miR-21 and miR-29a correlated with more extensive fibrosis,as assessed by late gadolinium enhancement in CMR imaging,with miR-29a consistently linked to both fibrosis and hypertrophy across the studies.CONCLUSION Circulating miRNAs,particularly miR-21,miR-29a,and miR-221,show significant potential as biomarkers for myocardial fibrosis in HCM.Further research should validate these findings and investigate the clinical application of miRNA-based diagnostics in HCM.展开更多
Hypertrophic scars(HS)are fibrotic proliferative diseases that develop after deep skin injuries caused by trauma,burns,and surgery.Traditional treatment methods include both surgical and nonsurgical therapies.Early in...Hypertrophic scars(HS)are fibrotic proliferative diseases that develop after deep skin injuries caused by trauma,burns,and surgery.Traditional treatment methods include both surgical and nonsurgical therapies.Early intervention and combination therapy tailored to the individual needs of the patients are crucial for achieving optimal results.Three-dimensional(3D)printing technology,a rapid prototyping technique,is increasingly being applied in the medical field.The customization and precise functionality of 3D printing technology are particularly important for the rehabilitation of HS.This review provides an overview of HS and the role of 3D printing technology in medical applications,analyses the application of 3D-printed rehabilitation aids for HS,and discusses the use of 3D printing technology to improve HS treatment outcomes,thereby providing clinical guidance for effective HS rehabilitation.展开更多
To improve the treatment effect of obstructive hypertrophic cardiomyopathy,this article focuses on the treatment of obstructive hypertrophic cardiomyopathy and conducts a comprehensive analysis of the disease.It highl...To improve the treatment effect of obstructive hypertrophic cardiomyopathy,this article focuses on the treatment of obstructive hypertrophic cardiomyopathy and conducts a comprehensive analysis of the disease.It highlights the limitations of traditional treatment methods and elaborates on interventional and surgical treatments.Additionally,this article compares the indications,risks,treatment effects,and costs of the two different treatment methods,providing a reference for doctors and patients in selecting clinical treatment plans.展开更多
BACKGROUND Apical hypertrophic cardiomyopathy(AHCM)is a subtype of hypertrophic cardiomyopathy.Due to its location,the thickening of the left ventricular apex can be missed on echocardiography.Giant negative T waves(G...BACKGROUND Apical hypertrophic cardiomyopathy(AHCM)is a subtype of hypertrophic cardiomyopathy.Due to its location,the thickening of the left ventricular apex can be missed on echocardiography.Giant negative T waves(GNTs)in left-sided chest leads are the hallmark electrocardiogram(ECG)change of AHCM.CASE SUMMARY The first patient was a 68-year-old woman complaining of recurrent chest tightness persisting for more than 3 years.The second was a 59-year-old man complaining of spasmodic chest tightness persisting for more than 2 years.The third was a 55-year-old woman complaining of recurrent chest pain persisting for 4 mo.In all three cases,GNTs were observed several years prior to apical cardiac hypertrophy after other causes of T-wave inversion were ruled out.CONCLUSION Electrophysiological abnormalities of AHCM appear earlier than structural abnormalities,confirming the early predictive value of ECG for AHCM.展开更多
BACKGROUND Immunoglobulin G4 related disease(Ig G4-RD)is a fibroinflammatory disease with markedly elevated serum Ig G4 levels and fibrous tissue proliferation,accompanied by numerous plasma cells.Ig G4 related hypert...BACKGROUND Immunoglobulin G4 related disease(Ig G4-RD)is a fibroinflammatory disease with markedly elevated serum Ig G4 levels and fibrous tissue proliferation,accompanied by numerous plasma cells.Ig G4 related hypertrophic pachymeningitis(Ig G4-RHP)is relatively rare and indistinguishable from other phymatoid diseases before the operation.The risk of long-term immunosuppression needs to be balanced with disease activity.CASE SUMMARY A 40-year-old man presented with headache and bilateral abducent paralysis.He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same.Before the operation and steroid therapy,the patient was suspected of having tubercular meningitis at a local hospital.A clivus lesion was found via brain magnetic resonance imaging(MRI)at this presentation.He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery.Transnasal endoscopic resection was performed to treat deterioration of nerve function.Postoperative pathologic examination suggested Ig G4-RD.Moreover,the serum Ig G4 was elevated at 1.90 g/L(reference range:0.035-1.500 g/L).After steroid therapy for 2 mo,the lesion size diminished on MRI,and the function of bilateral abducent nerves recovered.CONCLUSION Ig G4-RHP is relatively rare and indistinguishable before the operation.Elevated serum Ig G4 levels and imaging examination help in the diagnosis of Ig G4-RHP.Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.展开更多
Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein...Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。展开更多
Background Hypertrophic obstructive cardiomyopathy(HOCM)is one of the main reasons for sudden cardiac death(SCD)in young people.Researches has revealed that immune-related genes are closely relevant to HOCMprogression...Background Hypertrophic obstructive cardiomyopathy(HOCM)is one of the main reasons for sudden cardiac death(SCD)in young people.Researches has revealed that immune-related genes are closely relevant to HOCMprogression.Therefore,it is important to explore the key immuneregulatory mechanisms and biomarkersof HOCM progression.Methods The bioinformatics methods,including linear models for microarray analysis(LIMMA),protein-protein interaction(PPI)network,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)and CIBERSORT,were used to assess the key pathways and hub genes involved in HOCM.Furthermore,expression levels of hub genes were validatedin human tissue.Results Our results showed that the degree of infiltration of five immune cells was linked to HOCM progression,including monocytes,macrophages M2,natural killer(NK)cell resting,B cells native,and T cells regulatory(Tregs).A total of 7 hub genes(CCL2,CXCL8,FOS,MAP2K1,NFKBIA,STAT3,and TNFRSF1A)were identified and validated by quantitative real-time polymerase chain reaction(qt-PCR).The core genes including CCL2,MAP2K1,NFKBIA,STAT3,and TNFRSF1A are closely related to monocytes infiltration during HOCM progression.Conclusions Taken together,our research provided useful information to explore the immune mechanisms underlying HCM progression and to provide a potential therapeutic target for therapy in HOCM.The interactional relationship of GATA5,BCL3,and ATF1 complex-regulation CCL2,MAP2K1,NFKBIA,STAT3,and TNFRSF1A was involved in the regulation of monocytes tissue infiltration,which was closely related to the progression of HOCM.展开更多
Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand wh...Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed （about 15 d post wounding）. For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results： Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 （p〈0.05）. Scar thickness, measured by scar elevation index （SEI） at Day 35 post wounding, was significantly reduced in the intervention group （1.09±0.19） compared with the controls （1.36±0.28）. Microvessel density （MVD） observed in the intervention group （1.73±0.94） was significantly lower than that of the control group （5.63±1.78） on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions： Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-dedved growth factor （PDGF） and fibroblast growth factor （FGF）, thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.展开更多
Hypertrophic cardiomyopathy(HCM),the most variable cardiac disease in terms of phenotypic presentation and clinical outcome,represents the most common inherited cardiomyopathic process with an autosomal dominant trait...Hypertrophic cardiomyopathy(HCM),the most variable cardiac disease in terms of phenotypic presentation and clinical outcome,represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance.To date,more than 1400 mutations of myofilament proteins associated with the disease have been identified,most of them "private" ones.This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations.Additionally,topics pertaining to patients' everyday lives,such as sudden cardiac death(SCD)risk stratification and prevention,along with disease prognosis,are grossly related to the genetic variation of HCM.This review incorporates contemporary research findings and addresses major aspects of HCM,including preclinical diagnosis,genetic analysis,left ventricular outflow tract obstruction and SCD.More specifically,the spectrum of genetic analysis,the selection of the best method for obstruction alleviation and the need for a unique and accuratefactor for SCD risk stratification are only some of the controversial HCM issues discussed.Additionally,future perspectives concerning HCM and myocardial ischemia,as well as atrial fibrillation,are discussed.Rather than enumerating clinical studies and guidelines,challenging problems concerning the disease are critically appraised by this review,highlighting current speculations and recommending future directions.展开更多
Apical hypertrophic cardiomyopathy(AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to other...Apical hypertrophic cardiomyopathy(AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to others mimic coronary artery disease including acute coronary syndrome, thus resulting in inappropriate hospitalization. Transthoracic echocardiography is the firstline imaging technique for the diagnosis of hypertrophic cardiomyopathies. However, when the hypertrophy of the myocardium is localized in the ventricular apex might results in missed diagnosis. Aim of this paper is to review the different imaging techniques used for the diagnosis of AHCM and their role in the detection and comprehension of this uncommon disease.展开更多
AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patient...AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patients(mean age 53 ± 16 years,range:18-81 years,10 were male),with apical HCM. We measured global longitudinal peak systolic strain(GLPSS) in the midwall and endocardium of the left ventricle. RESULTS The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolicfunction with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular(LV) systolic function,midwall GLPSS was decreased in all patients,more in the apical(-7.3% ±-8.8%) than in basal segments(-15.5% ±-6.93%),while endocardial GLPPS was significantly greater and reached normal values(apical:-22.8% ±-7.8%,basal:-17.9% ±-7.5%). CONCLUSION This study shows that two-dimensional strain was decreased mainly confined to the mesocardium,while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.展开更多
Objective To identify the osteogenesis genes whose expression is altered in hypertrophic chondrocytes treated with H2 O2.Methods Murine chondrogenitor cells(ATDC5) were differentiated into hypertrophic chondrocytes by...Objective To identify the osteogenesis genes whose expression is altered in hypertrophic chondrocytes treated with H2 O2.Methods Murine chondrogenitor cells(ATDC5) were differentiated into hypertrophic chondrocytes by InsulinTransferrin-Selenium(ITS) treatment, and then treated with H2 O2. Suitable conditions(concentration, time) were determined by using the MTT assay. After total RNA isolation and cD NA synthesis, the levels of 84 genes were determined using the PCR array, whereas quantitative RT-PCR was carried out to validate the PCR array data. Results We identified 9 up-regulated genes and 12 down-regulated genes, encoding proteins with various functions, such as collagen proteins, transcription factors, proteins involved in skeletal development and bone mineral metabolism, as well as cell adhesion molecules. Quantitative RT-PCR confirmed the altered expression of 5 down-regulated genes(Smad2, Smad4, transforming growth factor β receptor 1, transforming growth factor β receptor 3, and matrix metalloproteinase 10). Conclusions H2 O2 significantly changed the expression of several genes involved in a variety of biological functions. Because of the link between oxidative damage and Kashin-Beck disease, these genes may also be involved in the deep-zone necrosis of the cartilage observed in Kashin-Beck disease.展开更多
文摘Hypertrophic cardiomyopathy(HCM)is a primary myocardial disease characterized by myocardial hypertrophy,excluding other cardiovascular or systemic/metabolic causes of ventricular wall thickening.Apical hypertrophic cardiomyopathy(ApHCM)represents a special form of ventricular hypertrophy predominantly affecting the left ventricular apex below the papillary muscles,typically without significant left ventricular outflow tract obstruction.[1,2]ApHCM often coexists with mild coronary artery abnormalities,[3]and reports of acute myocardial infarction with coronary artery stenosis in ApHCM or HCM patients are uncommon.
文摘BACKGROUND Diabetes mellitus(DM)is a significant risk factor for cardiovascular diseases and can worsen the risk of cardiovascular events among patients with hypertrophic cardiomyopathy(HCM).However,strong evidence is needed to show the impact of DM on all-cause mortality(ACM)and atrial fibrillation(AF),which we explored in this systematic review and meta-analysis.AIM To determine the impact of DM on ACM and AF in patients with HCM.METHODS PubMed,Google Scholar,and EMBASE databases were searched for studies showing the effect of DM on ACM and AF in HCM.A binary random effects model with a 95%confidence interval(CI)was used to pool odds ratios(ORs)for ACM and AF outcomes.Study quality was assessed using the Joanna Briggs Institute’s critical appraisal tool and leave-one-out sensitivity analysis.P<0.05 was considered statistically significant.RESULTS Fourteen studies(n=106138)with a mean age of 61.76±19.84 years and 61.55%males were included in our systematic review;ten studies(n=102882)were eligible for meta-analysis.In the unadjusted analysis,DM was not significantly associated with ACM(OR=0.96;95%CI:0.43-2.15;P=0.93).However,after adjustment,DM showed a significant association with higher ACM risk(adjusted OR=1.37;95%CI:1.16-1.61;P<0.01).DM was significantly associated with AF in both unadjusted(OR=2.02;95%CI:1.14-3.58;P=0.04)and adjusted analyses(adjusted OR=2.68;95%CI:1.68-4.27;P=0.01).The Joanna Briggs Institute tool revealed a low risk of bias.Leaveone-out sensitivity analysis,performed by sequentially excluding each study,demonstrated no significant change in the overall effect estimates,indicating the robustness and stability of our results.CONCLUSION DM significantly increased the risk of ACM and AF,highlighting the importance of tighter glycemic control and cardiovascular risk factor modification among patients with HCM.
基金financial support from the National Natural Science Foundation of China(grants 82394442,82422043,82272442)the Key Industrial Chain Program of Shaanxi,China(No.2022ZDLSF02-12)。
文摘Hypertrophic chondrocytes(HCs)could transform into osteoblastic lineage cells while the pathophysiological implications of HC transformation remain largely unknown.Here,we generated a mouse line utilizing Col10a1-Cre to induce DTA expression to genetically ablate HCs and their descendants.Col10a1-Cre;R26^(DTA/+)mice displayed dwarf phenotype,abnormal spongy bone,and significantly delayed drill-hole injuries healing,suggesting an indispensable role of HC lineage extension in bone growth and injury repair.Intriguingly,single-cell RNA sequencing analysis revealed the most significant loss of a cell cluster expressing multiple angiogenic factors(Pro-Angiogenic Descendants of HCs,PADs)among cells derived from Col10a1-Cre;R26^(DTA/+)and control femurs.In silico analysis of cell-cell communication supported Thrombospondin 4(THBS4)as a specific angiogenic factor mediating the crosstalk between PADs and vascular endothelial cells.Concordantly,analyses using immunostaining combined with tissue clearing revealed that PADs physically contacted with endothelial cells,whereas Col10a1-Cre;R26^(DTA/+)mice showed defective metaphyseal and cortical vessel formation and post-injury angiogenesis along with a significant loss of THBS4.Moreover,in vitro assays showed that supplying THBS4 was sufficient to promote proliferation and tube formation of endothelial cells and rescue defective angiogenesis of Col10a1-Cre;R26D TA/+metatarsal explants.Collectively,these findings demonstrate a critical role of PADs in bone growth and injury repair by secreting THBS4 to regulate angiogenesis.
文摘Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.
基金Supported by National Natural Science Foundation of China,No.82230065,No.82371974 and No.82272009.
文摘Hypertrophic cardiomyopathy(HCM)is the most common genetic cardiovascular disease,mostly inherited in an autosomal dominant manner.It is a global heart disease with complex clinical phenotypes and gene expression.The prevalence rate in the population is 1:500-1:200.This article mainly introduces the diagnostic criteria,pathological manifestations,and genetic basis of HCM,which is the leading cause of sudden death in adolescents and athletes due to exercise,with 60%-70%showing familial clustering.It also discusses the latest progress in the relationship between different genotypes and clinical phenotypes of HCM pa-tients.
基金Supported by National Natural Science Foundation of China,No.81770379 and 81470521.
文摘Hypertrophic cardiomyopathy(HCM)is an autosomal dominant inherited cardiomyopathy characterized by left ventricular hypertrophy.It is one of the chief causes of sudden cardiac death in younger people and athletes.Molecular-genetic studies have confirmed that the vast majority of HCM is caused by mutations in genes encoding sarcomere proteins.HCM has a relatively wide phenotypic heterogeneity,varying from asymptomatic to sudden cardiac death,because of the many different mutations and pathogenic genes underlying it.Many studies have explored the clinical symptoms and prognosis of HCM,emphasizing the importance of genotype in evaluating patient prognosis and guiding the clinical management of HCM.To elaborate the main pathogenic genes and phenotypic prognosis in HCM to promote a better understanding of this genetic disease.Retrospective analysis of literature to evaluate the association between underlying gene mutations and clinical phenotypes in HCM patients.As sequencing technology advances,the pathogenic gene mutation spectrum and phenotypic characteristics of HCM are gradually becoming clearer.HCM is a widespread inherited disease with a highly variable clinical phenotype.The precise mechanisms linking known pathogenic gene mutations and the clinical course of this heterogeneous condition remain elusive.
文摘BACKGROUND Managing left ventricular outflow tract obstruction(LVOTO)and systolic anterior motion(SAM)of the mitral valve can be challenging,especially in the context of circulatory shock and pulmonary edema post cardiac surgery.CASE SUMMARY We describe a case of an 80-year-old female patient with a history of severe aortic stenosis and hypertrophic obstructive cardiomyopathy that underwent aortic valve replacement and myectomy.The patient presented with acute pulmonary edema and low blood pressure due to LVOTO and SAM post cardiac surgery in the intensive care unit.She was paced with an epicardial dual-chamber pacing system due to complete atrioventricular block and treated initially with norepinephrine,furosemide,and esmolol infusion and continuous positive pressure ventilation.The patient remained hypoxemic and kept deteriorating hemodynamically despite titrating up norepinephrine.The addition of vasopressin infusion and tapering of norepinephrine finally stabilized the patient with significant reduction of LVOTO,confirmed by transthoracic echocardiography assessment,improved oxygenation and increased urine output.CONCLUSION Vasopressin seems to be the preferred vasopressor for managing LVOTO and SAM post-cardiac surgery,because of its absence of inotropic effects.Echocardiography is crucial for early diagnosis and therapeutic management.
基金Supported by National Natural Science Foundation of China,No.81770379.
文摘BACKGROUND Hypertrophic cardiomyopathy(HCM)is one of the most prevalent inherited myocardial disorders and is charac-terized by considerable genetic and phenotypic heterogeneity.A subset of patients with HCM progress to a dilated phase of HCM(DPHCM),which is associated with a poor prognosis;however,the underlying pathogenesis remains inadequately understood.CASE SUMMARY In this study,we present a case involving a pedigree with familial DPHCM and conduct a retrospective review of patients with DPHCM with identified gene mutations.Through panel sequencing targeting the coding regions of 312 genes associated with inherited cardiomyopathy,a heterozygous missense mutation(c.746G>A,p.Arg249Glu)in the MYH7 gene was identified in the proband(III-5).Sanger sequencing subsequently confirmed this pathogenic mutation in three additional family members(II-4,III-4,and IV-3).A total of 26 well-documented patients with DPHCM were identified in the literature.Patients with DPHCM are commonly middle-aged and male.The mean age of patients with DPHCM was 53.43±12.79 years.Heart failure,dyspnoea,and atrial fibrillation were the most prevalent symptoms observed,accompanied by an average left ventricular end-diastolic size of 58.62 mm.CONCLUSION Our findings corroborate the pathogenicity of the MYH7(c.746G>A,p.Arg249Glu)mutation for DPHCM and suggest that the Arg249Gln mutation may be responsible for high mortality.
文摘BACKGROUND Hypertrophic cardiomyopathy(HCM)is characterized by left ventricular hypertrophy and interstitial fibrosis,which contribute to adverse outcomes such as heart failure and sudden cardiac death.While cardiac magnetic resonance(CMR)imaging is commonly used to detect myocardial fibrosis,circulating microRNAs(miRNAs)have emerged as promising noninvasive biomarkers for this condition due to their stability in blood plasma and resistance to pH and temperature variance.AIM To explore the role of specific circulating miRNAs in identifying myocardial fibrosis in patients with HCM.METHODS Using PubMed/MEDLINE and Google Scholar,we reviewed studies from 2014 to 2024 examining the link between circulating miRNAs and myocardial fibrosis in HCM.We included studies measuring miRNA expression in blood samples from HCM patients and assessing fibrosis via imaging,mostly CMR.Data extraction concentrated on the population,methodology,and findings related to the correlation between miRNA levels and fibrosis.RESULTS Seven studies involving 365 HCM patients with a mean age of 49.37±10.5 years,116(31.78%)females,and one animal study identified miR-21,miR-29a,miR-133,miR-4454,and miR-221 as frequently dysregulated markers associated with fibrosis.Elevated levels of miR-21 and miR-29a correlated with more extensive fibrosis,as assessed by late gadolinium enhancement in CMR imaging,with miR-29a consistently linked to both fibrosis and hypertrophy across the studies.CONCLUSION Circulating miRNAs,particularly miR-21,miR-29a,and miR-221,show significant potential as biomarkers for myocardial fibrosis in HCM.Further research should validate these findings and investigate the clinical application of miRNA-based diagnostics in HCM.
基金supported by the Cross-Disciplinary Research Fund Project of the Shanghai Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine(grant no.JYJC202236)the Shanghai Plastic Surgery Research Center of Shanghai Priority Research Center(grant no.2023ZZ02023)the Shanghai Healthcare System Key Supporting Disciplines Program(grant no.2023ZDFC0303).
文摘Hypertrophic scars(HS)are fibrotic proliferative diseases that develop after deep skin injuries caused by trauma,burns,and surgery.Traditional treatment methods include both surgical and nonsurgical therapies.Early intervention and combination therapy tailored to the individual needs of the patients are crucial for achieving optimal results.Three-dimensional(3D)printing technology,a rapid prototyping technique,is increasingly being applied in the medical field.The customization and precise functionality of 3D printing technology are particularly important for the rehabilitation of HS.This review provides an overview of HS and the role of 3D printing technology in medical applications,analyses the application of 3D-printed rehabilitation aids for HS,and discusses the use of 3D printing technology to improve HS treatment outcomes,thereby providing clinical guidance for effective HS rehabilitation.
文摘To improve the treatment effect of obstructive hypertrophic cardiomyopathy,this article focuses on the treatment of obstructive hypertrophic cardiomyopathy and conducts a comprehensive analysis of the disease.It highlights the limitations of traditional treatment methods and elaborates on interventional and surgical treatments.Additionally,this article compares the indications,risks,treatment effects,and costs of the two different treatment methods,providing a reference for doctors and patients in selecting clinical treatment plans.
文摘BACKGROUND Apical hypertrophic cardiomyopathy(AHCM)is a subtype of hypertrophic cardiomyopathy.Due to its location,the thickening of the left ventricular apex can be missed on echocardiography.Giant negative T waves(GNTs)in left-sided chest leads are the hallmark electrocardiogram(ECG)change of AHCM.CASE SUMMARY The first patient was a 68-year-old woman complaining of recurrent chest tightness persisting for more than 3 years.The second was a 59-year-old man complaining of spasmodic chest tightness persisting for more than 2 years.The third was a 55-year-old woman complaining of recurrent chest pain persisting for 4 mo.In all three cases,GNTs were observed several years prior to apical cardiac hypertrophy after other causes of T-wave inversion were ruled out.CONCLUSION Electrophysiological abnormalities of AHCM appear earlier than structural abnormalities,confirming the early predictive value of ECG for AHCM.
基金Supported by 1·3·5 Project for Disciplines of Excellence–Clinical Research Incubation Project,West China Hospital,Sichuan University,No.2019HXFH018。
文摘BACKGROUND Immunoglobulin G4 related disease(Ig G4-RD)is a fibroinflammatory disease with markedly elevated serum Ig G4 levels and fibrous tissue proliferation,accompanied by numerous plasma cells.Ig G4 related hypertrophic pachymeningitis(Ig G4-RHP)is relatively rare and indistinguishable from other phymatoid diseases before the operation.The risk of long-term immunosuppression needs to be balanced with disease activity.CASE SUMMARY A 40-year-old man presented with headache and bilateral abducent paralysis.He was also diagnosed with pulmonary tuberculosis 10 years ago and was on regular treatment for the same.Before the operation and steroid therapy,the patient was suspected of having tubercular meningitis at a local hospital.A clivus lesion was found via brain magnetic resonance imaging(MRI)at this presentation.He was preliminarily diagnosed with meningioma and underwent Gamma Knife Surgery.Transnasal endoscopic resection was performed to treat deterioration of nerve function.Postoperative pathologic examination suggested Ig G4-RD.Moreover,the serum Ig G4 was elevated at 1.90 g/L(reference range:0.035-1.500 g/L).After steroid therapy for 2 mo,the lesion size diminished on MRI,and the function of bilateral abducent nerves recovered.CONCLUSION Ig G4-RHP is relatively rare and indistinguishable before the operation.Elevated serum Ig G4 levels and imaging examination help in the diagnosis of Ig G4-RHP.Surgery is necessary when lesions progress and patients start to develop cranial nerve function deficit.
基金the National Natural Science Foundation of China(grant no.81872219)Science and Technology Project of Hunan Provincial Health Commission(grant no.B2015-040)+2 种基金Major Scientific and Technological Projects in Hunan Province(grant no.2019SK1010)2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant(grant nos.2020LKSFG18B,2020LKSFG02E)Guangdong University Innovation Team Project(grant no.2021KCXTD047).
文摘Background:The role of autophagy in the formation of hypertrophic scars(HS)remains unclear.This study aimed to explore the role and potential mechanism of autophagy during the development of HS.Methods:RNA and protein expression levels of Beclin-1,p62,and LC3II in normal skin tissues and HS specimens from different patients were examined.Autophagy inducers and inhibitors were used to cure established HS in rabbit ears,and the expression of Beclin-1,p62,and LC3II at the RNA and protein level was determined.Lastly,the effects of autophagy inducers and inhibitors on HS development were analyzed.Results:Compared to normal skin tissues,the expression of LC3II and Beclin-1 was higher(P<0.05),while that of p62 was lower(P<0.05)in HS tissues.In addition,the LC3II/LC3I ratio was increased during HS formation,and the altered expression of the three proteins stabilized after one year.Administration of autophagy inducers enhanced the formation of HS as well as the expression levels of LC3II and Beclin-1 but decreased p62 expression.Meanwhile,administration of autophagy inhibitors increased the expression of LC3II,Beclin-1,and p62,along with reduced HS formation.Conclusion:Autophagic activity increased during HS initiation and subsequent stabilization.In addition,autophagy inhibitors were able to inhibit HS formation by suppressing autophagy,whereas autophagy inducers promoted scar hyperplasia by enhancing autophagy。
基金National Natural Science Foundation of China(No.82102955)Guangzhou Basic Research Project(No.02201011326)。
文摘Background Hypertrophic obstructive cardiomyopathy(HOCM)is one of the main reasons for sudden cardiac death(SCD)in young people.Researches has revealed that immune-related genes are closely relevant to HOCMprogression.Therefore,it is important to explore the key immuneregulatory mechanisms and biomarkersof HOCM progression.Methods The bioinformatics methods,including linear models for microarray analysis(LIMMA),protein-protein interaction(PPI)network,Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)and CIBERSORT,were used to assess the key pathways and hub genes involved in HOCM.Furthermore,expression levels of hub genes were validatedin human tissue.Results Our results showed that the degree of infiltration of five immune cells was linked to HOCM progression,including monocytes,macrophages M2,natural killer(NK)cell resting,B cells native,and T cells regulatory(Tregs).A total of 7 hub genes(CCL2,CXCL8,FOS,MAP2K1,NFKBIA,STAT3,and TNFRSF1A)were identified and validated by quantitative real-time polymerase chain reaction(qt-PCR).The core genes including CCL2,MAP2K1,NFKBIA,STAT3,and TNFRSF1A are closely related to monocytes infiltration during HOCM progression.Conclusions Taken together,our research provided useful information to explore the immune mechanisms underlying HCM progression and to provide a potential therapeutic target for therapy in HOCM.The interactional relationship of GATA5,BCL3,and ATF1 complex-regulation CCL2,MAP2K1,NFKBIA,STAT3,and TNFRSF1A was involved in the regulation of monocytes tissue infiltration,which was closely related to the progression of HOCM.
基金supported by the National Natural Science Foundation of China (No.81272120)the Health Department of the Zhejiang Province (No.2007B086),China
文摘Objective： The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods： Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed （about 15 d post wounding）. For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results： Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 （p〈0.05）. Scar thickness, measured by scar elevation index （SEI） at Day 35 post wounding, was significantly reduced in the intervention group （1.09±0.19） compared with the controls （1.36±0.28）. Microvessel density （MVD） observed in the intervention group （1.73±0.94） was significantly lower than that of the control group （5.63±1.78） on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions： Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-dedved growth factor （PDGF） and fibroblast growth factor （FGF）, thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.
文摘Hypertrophic cardiomyopathy(HCM),the most variable cardiac disease in terms of phenotypic presentation and clinical outcome,represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance.To date,more than 1400 mutations of myofilament proteins associated with the disease have been identified,most of them "private" ones.This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations.Additionally,topics pertaining to patients' everyday lives,such as sudden cardiac death(SCD)risk stratification and prevention,along with disease prognosis,are grossly related to the genetic variation of HCM.This review incorporates contemporary research findings and addresses major aspects of HCM,including preclinical diagnosis,genetic analysis,left ventricular outflow tract obstruction and SCD.More specifically,the spectrum of genetic analysis,the selection of the best method for obstruction alleviation and the need for a unique and accuratefactor for SCD risk stratification are only some of the controversial HCM issues discussed.Additionally,future perspectives concerning HCM and myocardial ischemia,as well as atrial fibrillation,are discussed.Rather than enumerating clinical studies and guidelines,challenging problems concerning the disease are critically appraised by this review,highlighting current speculations and recommending future directions.
文摘Apical hypertrophic cardiomyopathy(AHCM) is a relatively rare morphologic variant of HCM in which the hypertrophy of myocardium is localized to the left ventricular apex. Symptoms of AHCM might vary from none to others mimic coronary artery disease including acute coronary syndrome, thus resulting in inappropriate hospitalization. Transthoracic echocardiography is the firstline imaging technique for the diagnosis of hypertrophic cardiomyopathies. However, when the hypertrophy of the myocardium is localized in the ventricular apex might results in missed diagnosis. Aim of this paper is to review the different imaging techniques used for the diagnosis of AHCM and their role in the detection and comprehension of this uncommon disease.
文摘AIM To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy(HCM).METHODS We prospectively assessed 20 patients(mean age 53 ± 16 years,range:18-81 years,10 were male),with apical HCM. We measured global longitudinal peak systolic strain(GLPSS) in the midwall and endocardium of the left ventricle. RESULTS The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolicfunction with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular(LV) systolic function,midwall GLPSS was decreased in all patients,more in the apical(-7.3% ±-8.8%) than in basal segments(-15.5% ±-6.93%),while endocardial GLPPS was significantly greater and reached normal values(apical:-22.8% ±-7.8%,basal:-17.9% ±-7.5%). CONCLUSION This study shows that two-dimensional strain was decreased mainly confined to the mesocardium,while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.
基金Supported by the National Natural Science Foundation of China(81573102 and 81273006)the Natural Science Fund Projects of Shaanxi Province(2017JM812)
文摘Objective To identify the osteogenesis genes whose expression is altered in hypertrophic chondrocytes treated with H2 O2.Methods Murine chondrogenitor cells(ATDC5) were differentiated into hypertrophic chondrocytes by InsulinTransferrin-Selenium(ITS) treatment, and then treated with H2 O2. Suitable conditions(concentration, time) were determined by using the MTT assay. After total RNA isolation and cD NA synthesis, the levels of 84 genes were determined using the PCR array, whereas quantitative RT-PCR was carried out to validate the PCR array data. Results We identified 9 up-regulated genes and 12 down-regulated genes, encoding proteins with various functions, such as collagen proteins, transcription factors, proteins involved in skeletal development and bone mineral metabolism, as well as cell adhesion molecules. Quantitative RT-PCR confirmed the altered expression of 5 down-regulated genes(Smad2, Smad4, transforming growth factor β receptor 1, transforming growth factor β receptor 3, and matrix metalloproteinase 10). Conclusions H2 O2 significantly changed the expression of several genes involved in a variety of biological functions. Because of the link between oxidative damage and Kashin-Beck disease, these genes may also be involved in the deep-zone necrosis of the cartilage observed in Kashin-Beck disease.
