A novel mutation (c.1010G>T; p.R337L) in TP63 as a cause of split-hand/foot malformation with hypodontia.

BACKGROUND: Tumor protein p63 (TP63)-related disorders can be divided into at least six categories, including ectrodactyly-ectodermal dysplasia-cleft lip/palate syndrome 3 (EEC syndrome 3), ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome), acro-dermo-ungual-lacrimal-tooth syndrome (ADULT syndrome), limb-mammary syndrome (LMS), Rapp-Hodgkin syndrome (RHS) and split-hand/foot malformation 4 (SHFM4), and are all a result of heterozygous mutations of TP63. The phenotypes of TP63-related disorders broadly involve ectodermal dysplasias, acromelic malformation and orofacial cleft. SHFM and hypodontia are prominent clinical manifestations of TP63-related disorders. METHODS: The present study investigated a family with SHFM and hypodontia; determined the sequences of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1 and FGFR1; and performed single nucleotide polymorphism-array analysis. We detected the mutation by multiple sequence alignments and a bioinformatic prediction. RESULTS: We identified a novel missense mutation of TP63 (c.1010G>T; R337L) in the family without mutations of DLX5, WNT8B, WNT10B, BHLHA9, CDH3, DYNC1I1, FGFR1 and copy number variants causing SHFM. CONCLUSIONS: A mutation of TP63 (c.1010G>T; R337L) leads to SHFM with hypodontia. The identification of this mutation expands the spectrum of known TP63 mutations and also may contribute to novel approaches for the genetic diagnosis and counseling of families with TP63-related disorders.

[Clinical characterization of patients with Danon disease].

OBJECTIVE: To analyze the clinical characterization of Danon disease caused by the mutation of lysosome-associated membrane protein-2 (LAMP-2) gene. METHODS: The clinical features, serum biochemical index, electrocardiogram and echocardiography data were retrospectively reviewed in 5 patients with genetically confirmed Danon disease. Mean follow-up period was (56 ± 6) months. RESULTS: Five patients including 2 men and 3 women in 2 unrelated families with 2 novel mutations in the exon 3 (c.189-190TGdel) and 8 (c.1205Cdel) of the LAMP-2 gene were identified. All patients had cardiomyopathy, 1 patient (1/5) had skeletal myopathy, and none of the patients had mental retardation. The two male patients presented cardiac symptoms at the age of 9 and 10 years, respectively, and all female patients were asymptomatic. Biochemical analysis showed that serum creatine kinase and liver transaminase enzyme were increased in 2 patients (2/5). Abnormal electrocardiogram was observed in all patients, and 2 patients (2/5) had ventricular preexcitation. During the follow-up. One male patient died of cardiac failure at the age of 18 years and three months, and the symptoms of the other male patients rapidly developed with the evolution from hypertrophic cardiomyopathy into dilated cardiomyopathy. However, all female patients remained asymptomatic, and repeat echocardiography indicated only mild ventricular hypertrophy during follow up. CONCLUSION: Patients with Danon disease mainly present hypertrophic cardiomyopathy, and sometimes presents with skeletal myopathy. The disorder occurs at early, age and progresses quickly and ends with poor prognosis in male patients. Other clinical features include elevations of serum creatine kinase and liver transaminase enzyme, ventricular preexcitation on electrocardiogram, and ventricular hypertrophy detected by echocardiography. Female patients remain asymptomatic till now in our cohort.

[Relationship between estimated glomerular filtration rate level and clinical characteristics and outcome in patients with angiographic coronary artery disease and normal serum creatinine].

OBJECTIVE: To explore the relationship between estimated glomerular filtration rate level and clinical characteristics and outcome in coronary artery disease (CAD) patients with normal serum creatinine. METHOD: A total of 548 hospitalized and angiographic CAD patients with normal fasting serum creatinine were enrolled. The kidney function was estimated by using the abbreviated modification of diet in renal disease (MDRD) study equation. Patients were divided into three groups according to eGFR tertiles: high eGFR group (eGFR > 88.15 ml×min(-1)×1.73 m(-2), n = 184); intermediate group ZU(70.30 ml× min(-1)×1.73 m(-2) < eGFR ≤ 88.15 ml×min(-1)×1.73 m(-2), n = 187); low eGFR group (eGFR ≤ 70.30 ml × min(-1)×1.73 m(-2), n = 177). Clinical data and cardiovascular risk factors were recorded after admission and during (14.02 ± 8.31) months follow up. The primary end point was combined major adverse cardiovascular and cerebral events (MACCE) including death, targeted vascular revascularization, non-fatal myocardial infarction, rehospitalization due to unstable angina and heart failure, and transient ischemic attack (TIA) and stroke. RESULTS: Patients in intermediate and low eGFR groups were older, more males, had more severe coronary artery disease, higher level of hsCRP, higher incidence of hypertension, and lower smoking rate than those in high eGFR group (all P < 0.05). A total of 89 MACCE were recorded during follow up. The level of eGFR was significantly lower in patients with MACCE than patients without MACCE [(73.76 ± 19.81) ml×min(-1)×1.73 m(-2) vs. (84.97 ± 23.42) ml×min(-1)×1.73 m(-2), P < 0.05]. Univariate and multivariate Cox regression analysis showed that eGFR was an independent predictor of MACCE in patients with CAD (univariate analysis: RR = 0.99, 95%CI:0.973-0.997, P < 0.05; multivariate analysis: RR = 0.98, 95%CI:0.976-0.998, P < 0.05). Kaplan-Meier survival analysis suggested that patients with low eGFR was linked with a decreased event free survival ratio (log-rank χ(2) = 7.271, P < 0.05). CONCLUSIONS: eGFR level in CAD patients with normal serum creatinine is associated with coronary artery severity, inflammation level and serves as an independent predictor for MACCE in this patient cohort.

Identification of A Novel Variant of Filamin A Destroying the Attraction Between Benzene Rings and Sulfhydryl in Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH), characterized by acetabular deformity that manifests from loose ligaments to complete dislocation of the hip, can cause notable pain and dysfunction and lead to hip dislocation, secondary fractures, scoliosis, and osteoarthritis of hip. Variants in FLNA may produce a spectrum of malformations in multiple organs, especially the skeleton. This study aimed to identify the genetic etiologies of DDH patients and provide genetic testing information for further diagnosis and treatment of DDH. We recruited a Chinese woman with DDH and her family members. Whole-exome sequencing was used to identify the patient's genetic etiologies. Protein models were used to analyze the pathogenic mechanism of the identified variants. A novel variant (c.3493T>G, p.C1165G) of FLNA was detected. The structural models of the mutant FLNA protein indicated that the variant would lose its sulfhydryl side chain and destroy the attraction between benzene rings and sulfhydryl. We reported a novel variant (c.3493T>G, p.C1165G) of FLNA in a Chinese woman with DDH. Our research outcome enriches the gene pool for hip dysplasia and emphasizes the pathogenicity of sulfhydryl side chain disruption in FLNA.

Case report: Identification of novel fibrillin-2 variants impacting disulfide bond and causing congenital contractural arachnodactyly.

Background: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder with clinical features of arthrogryposis, arachnodactyly, crumpled ears, scoliosis, and muscular hypoplasia. The heterozygous pathogenic variants in FBN2 have been shown to cause CCA. Fibrillin-2 is related to the elasticity of the tissue and has been demonstrated to play an important role in the constitution of extracellular microfibrils in elastic fibers, providing strength and flexibility to the connective tissue that sustains the body's joints and organs. Methods: We recruited two Chinese families with arachnodactyly and bilateral arthrogryposis of the fingers. Whole-exome sequencing (WES) and co-segregation analysis were employed to identify their genetic etiologies. Three-dimensional protein models were used to analyze the pathogenic mechanism of the identified variants. Results: We have reported two CCA families and identified two novel missense variants in FBN2 (NM_001999.3: c.4093T>C, p.C1365R and c.2384G>T, p.C795F). The structural models of the mutant FBN2 protein in rats exhibited that both the variants could break disulfide bonds. Conclusion: We detected two FBN2 variants in two families with CCA. Our description expands the genetic profile of CCA and emphasizes the pathogenicity of disulfide bond disruption in FBN2.

[The value of SYNTAX score in predicting outcome patients undergoing percutaneous coronary intervention].

OBJECTIVE: To assess the value of SYNTAX score to predict major adverse cardiac and cerebrovascular events (MACCE) among patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention. METHODS: 190 patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention (PCI) with Cypher select drug-eluting stent were enrolled. SYNTAX score and clinical SYNTAX score were retrospectively calculated. Our clinical Endpoint focused on MACCE, a composite of death, nonfatal myocardial infarction (MI), stroke and repeat revascularization. The value of SYNTAX score and clinical SYNTAX score to predict MACCE were studied respectively. RESULTS: 29 patients were observed to suffer from MACCE, accounting 18.5% of the overall 190 patients. MACCE rates of low (≤ 20.5), intermediate (21.0 - 31.0), and high (≥ 31.5) tertiles according to SYNTAX score were 9.1%, 16.2% and 30.9% respectively. Both univariate and multivariate analysis showed that SYNTAX score was the independent predictor of MACCE. MACCE rates of low (≤ 19.5), intermediate (19.6 - 29.1), and high (≥ 29.2) tertiles according to clinical SYNTAX score were 14.9%, 9.8% and 30.6% respectively. Both univariate and multivariate analysis showed that clinical SYNTAX score was the independent predictor of MACCE. ROC analysis showed both SYNTAX score (AUC = 0.667, P = 0.004) and clinical SYNTAX score (AUC = 0.636, P = 0.020) had predictive value of MACCE. Clinical SYNTAX score failed to show better predictive ability than the SYNTAX score. CONCLUSIONS: Both SYNTAX score and clinical SYNTAX score could be independent risk predictors for MACCE among patients with three-vessel or left-main coronary artery disease undergoing percutaneous coronary intervention. Clinical SYNTAX score failed to show better predictive ability than the SYNTAX score in this group of patients.

[Clinical characteristics of coronary artery disease patients with reduced left ventricular ejection fraction and their prognostic analysis].

OBJECTIVE: To explore the relationship between reduced left ventricular ejection fraction (LVEF) and characteristics of coronary artery disease (CAD) and investigate the association between reduced LVEF and cardiovascular prognosis. METHODS: A total of 677 hospitalized patients with angiographic CAD were enrolled. All patients' clinical data were recorded. LVEF were measured, high sensitive C-reactive protein (hs-CRP), white blood cell (WBC) and classic cardiovascular risk factors were recorded after admission. All patients were followed up from admission. The primary end point was combination occurrence of major adverse cardiovascular and cerebral events (MACCE), including death, targeted vascular revascularization, non-fatal myocardial infarction and rehospitalization due to unstable angina or heart failure, transient ischemic attack or stroke. RESULTS: All patients were tracked for (15±12) months, and patients were divided into normal LVEF group (LVEF≥0.50, n=585) and reduced LVEF group (LVEF<0.50, n=92) according to LVEF level. Compared with normal LVEF group, reduced LVEF group had more severe coronary stenosis (Gensini score: 62.85±41.45 vs. 47.68±33.26, P<0.05), a higher level of WBC and hs-CRP (WBC: 7.60±2.71 ×10(9)/L vs. 7.09±2.13 ×10(9)/L, hs-CRP: 5.68±3.97 mg/L vs. 3.97±3.75 mg/L, both P<0.05). A total of 146 MACCE occurred during follow-up periods. Compared with no-MACCE group, LVEF levels were significantly lower in MACCE group (0.576±0.113 vs. 0.603±0.101) and there were a higher level of hs-CRP and Gensini score in MACCE group (hs-CRP: 5.26±3.99 mg/L vs. 3.91±3.72 mg/L, Gensini score: 53.72±35.50 vs. 48.63±34.59, all P<0.05). Moreover, both of univariate and multivariate Cox regression analysis indicated LVEF be an independent predictor of MACCE in patients with CAD [univariate: relative risk (RR)=0.974, 95% confidence interval (95%CI) 0.960 to 0.988, P=0.000; multivariate: RR=0.979, 95%CI 0.961 to 0.998, P=0.033]. Kaplan-Meier analysis suggested that patients with reduced LVEF had an increased MACCE occurrence (χ(2)=14.56, P<0.05). CONCLUSION: LVEF level may be associated with coronary artery severity, and could be independently predict the prognosis of CAD.

[Coronary artery bypass grafting for elderly with unprotected left main coronary artery disease: a clinical analysis].

OBJECTIVE: To study the correlation between the clinical features and the prognosis in elderly patients with unprotected left main coronary artery disease (ULMCA) after coronary artery bypass grafting (CABG). METHODS: The clinical parameters and prognosis data from 176 patients received CABG for ULM were retrospectively analyzed for comparison of elderly (age≥65) and against non-elderly (age < 65). RESULTS: The elderly patients were found to have significantly higher level of blood high density lipoprotein cholesterin (HDL-C, mmol/L: 28.36 ± 17.20 vs. 13.68 ± 7.78, P < 0.01), lower level of blood low density lipoprotein cholesterin (LDL-C, mmol/L: 1.21 ± 0.77 vs. 2.48 ± 1.27, P < 0.01) and higher level of coronary stenosis [(94.56 ± 8.01)% vs. (87.96 ± 11.10)%, P < 0.01]. The incidence of multi-vessel disease (75.9% vs. 58.1%, P < 0.05) and chronic total occlusion (55.4% vs. 29.0%, P < 0.05) were both significantly higher in the elderly. No significant difference was found between the two groups in major adverse cardiac and cerebral events (MACCE), cerebral infarction, myocardial infarction, cardiac mortality, and total mortality (16.9% vs 17.2%, 3.6% vs 3.2%, 3.6% vs 5.4%, 6.0% vs 9.7%, and 12.0% vs 8.6%, all P > 0.05). CONCLUSION: In the elderly ULMCA patients the coronary lesions are more severe, but CABG is still a safe and efficient therapy for these patients.

Identification of Two Novel Frameshift Mutations in Exostosin 1 in Two Families with Multiple Osteochondromas.

Multiple osteochondromas (MO) is an autosomal dominant hereditary disorder, which typically manifests as skeletal dysplasia, mainly involving long bones and knees, ankles, elbows, wrists, shoulders, and pelvis. Previous studies have demonstrated that mutations in exostosin glycosyl transferase-1 (EXT1) and exostosin glycosyl transferase-2 (EXT2) were the main cause of MO. In this study, we enrolled 2 families with MO. Sanger sequencing revealed 2 novel frameshift mutations - c.1432_1433insCCCCCCT; p.Lys479Profs*44 and c.1431_1431delC; p.S478PfsX10 - in the EXT1 gene detected in 2 families, respectively. Both novel mutations, located in the conserved domain of EXT1 and predicted to be disease causing by informatics programs, were absent in our 200 control cohorts and other public databases. Our study expanded the spectrum of EXT1 mutations and contributed to genetic diagnosis and counseling of patients with MO.

Simvastatin inhibited cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice fed a "Western-style diet" by increasing PPAR α and γ expression and reducing TC, MMP-9, and Cat S levels.

AIM: The examine the cardiac hypertrophy and fibrosis in apolipoprotein E-deficient mice (ApoE-/- mice) fed a "Western-style diet" and the effect of simvastatin intervention. METHODS: Male ApoE-/- mice (n=36) were fed a "Western-style diet" from the age of 8 weeks. After 16 weeks, they were randomly given either simvastatin (25 mg·kg⁻¹·d⁻¹) or normal saline (control group) by gavage for 8, 16, or 24 weeks. The left ventricular (LV) wall thickness and diameter of the myocardial cells were determined with Hematoxylin-Eosin stain, and the level of fibrosis of the myocardial matrix was assessed with Masson stain. Real-time quantitative polymerase chain reaction and Western blotting analysis were used to determine the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9), Cathepsin S (Cat S), and the peroxisome proliferator-activated receptors (PPARs) in the myocardium of ApoE-/- mice. RESULTS: ApoE-/- mice fed a "Western-style diet" showed an significant age-dependent increase in total cholesterol (TC), LV wall thickness, myocardial cell diameter and LV collagen content (P<0.05). The simvastatin treatment group showed significantly reduced LV wall thickness, myocardial cell diameters and LV collagen content at 40 weeks when compared with the control group (P<0.05). Furthermore, treatment with simvastatin also significantly inhibited the mRNA and protein expressions of MMP-9 and Cat S as well as increased the mRNA and protein expressions of PPAR alpha and PPAR gamma at 32 and 40 weeks compared with the control group (P<0.05). CONCLUSION: ApoE-/- mice fed a "Western-style diet" had cardiac hypertrophy and fibrosis, which worsened with age. Simvastatin treatment inhibits the development of cardiac hypertrophy and fibrosis, and this effect may be mediated through increased levels of PPAR alpha and PPAR gamma and reduced levels of TC, MMP-9, and Cat S.

Twelve-year outcomes after revascularization for ostial/shaft lesions in unprotected left main coronary artery.

OBJECTIVE: To evaluate a very long-term clinical outcomes of patients treated with coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with drug-eluting stents (DES) for ostial/shaft lesions in unprotected left main coronary artery (ULMCA). METHODS & RESULTS: A total of 472 patients with isolated ostial/shaft lesions in ULMCA were enrolled, who received DES implantation or underwent CABG between January 2003 and July 2009 in Beijing Anzhen Hospital. The major endpoints of this study were death, repeat revascularization, non-procedural myocardial infarction (MI) and stroke. The median follow-up was twelve years (interquartile range: 9.4-14.0 years) in the overall patients. There were no significant differences of incidence of death (23.3% vs. 25.6%, P = 0.227), repeat revascularization (27.3% vs. 28.4%, P = 0.423), non-procedural MI (20.0% vs. 14.5%, P = 0.561), and stroke (6.1% vs. 9.3%, P = 0.255) between PCI and CABG groups before multivariate adjusting. After adjusting covariates with multivariate Cox hazard regression model, there were still no significant differences between PCI and CABG groups. CONCLUSIONS: During the median follow-up of twelve years, we found that PCI with DES was as effective and safe as CABG in patients with left main ostial/shaft lesion in this observational study.

Novel Compound Heterozygous DST Variants Causing Hereditary Sensory and Autonomic Neuropathies VI in Twins of a Chinese Family.

Background: Hereditary sensory and autonomic neuropathies (HSANs) are a rare and severe group of sensory axonal neuropathies. HSANs have been classified into eight groups based on mode of inheritance, clinical features, and the involved genes. HSAN-VI, perhaps the most notable type, is an autosomal recessive disease, which manifests as the severely impaired pain sensitivity, autonomic disturbances, distal myopathy, spontaneous or surgical amputations, and sometimes early death. Mutations in DST have been identified as the cause of HSAN-VI. DST encodes dystonin, a member of the plakin protein family that is involved in cytoskeletal filament networks. Dystonin has seven major isoforms in nerve, muscle, and epithelium. Material and Methods: The present study investigated a Chinese family with HSAN and explored potential pathogenic variants using whole-exome sequencing (WES). Variants were screened and filtered through bioinformatics analysis and prediction of variant pathogenicity. Co-segregation analysis was subsequently conducted. Results: We identified compound heterozygous variants of DST (c.3304G>A, p.V1102I and c.13796G>A, p.R4599H) in two patients. Conclusion: We reported on a Chinese family with HSAN-VI family and detected the disease-causing variants. Our description expands the spectrum of known DST variants and contributes to the clinical diagnosis of HSAN-VI.

[The clinical characteristics of 5 patients with inherited hypertrophic cardiomyopathy].

OBJECTIVE: To explore the clinical characteristics of patients with inherited hypertrophic cardiomyopathy. METHODS: The clinical characteristics, electrocardiogram, serum chemistry and diagnostic methods were retrospectively investigated in 5 patients with inherited hypertrophic cardiomyopathy. RESULTS: The electrocardiograms of all patients were abnormal, with prominent left ventricular voltage and ST-T changes. One male patient with clinicopathological features of early onset, muscle weakness, ventricular preexcitation, elevations of two serum proteins and intracytoplasmic vacuoles containing autophagic material and glycogen in biceps brachial muscle cells was diagnosed Danon's disease. Mitochondrial cardiomyopathy was diagnosed in one male patient with early onset, short PR interval and biopsy findings of ragged-red fibers in biceps brachial muscle. Three patients were diagnosed as Fabry's disease with clinical characteristics including pain and acroparesthesias, angiokeratoma and decrease of alpha-galactosidase A activity. CONCLUSION: Some of the rare inherited hypertrophic cardiomyopathy might easily be clinically misdiagnosed as hypertrophic cardiomyopathy, systemic and careful case history inquiring and specific relevant examinations would help to make the right diagnosis in these patients.

[Angiographic characteristics and long term clinical outcomes post coronary stenting in non-diabetic and type 2 diabetic patients with coronary artery disease].

OBJECTIVE: To observe the angiographic characteristics and the long-term clinical outcomes following coronary stenting in non-diabetic (non-DM) and type 2 diabetic (DM) patients with coronary artery disease. METHODS: This cohort study enrolled 1172 consecutive patients with coronary heart disease underwent elective coronary stenting (249 type 2 DM and 923 non-DM). The angiographic characteristics and the long-term clinical follow-up results were compared between non-DM and DM patients. RESULTS: The follow-up period was (39.2 +/- 6.4) months (6 - 83 months), follow-up rate was 90.3% in DM and 91.0% in non-DM group (P > 0.05). Compared with non-diabetic patients, there were significantly higher incidences of 2-vessel (P = 0.029) and 3-vessel (P = 0.013) diseases of coronary artery, severe stenosis lesion (P = 0.012), chronic total obstructive lesion (P = 0.044) and long lesion (P = 0.001), in-stent restenosis (ISR, P = 0.000) and revascularization (P = 0.000) and MACE (P = 0.000) in DM patients. COX multiple factorial analysis showed that DM is independent risk factor for ISR (P = 0.000), revascularization (P = 0.001) and MACE (P = 0.003). CONCLUSIONS: CHD patients with type 2 DM are associated with multi- and more severe vessel lesions. Type 2 DM is also an independent risk factor for increased ISR, revascularization and MACE post stenting.

Compound heterozygous GNPTAB mutations cause mucolipidosis II or III alpha/beta in two Chinese families.

OBJECTIVE: Mucolipidosis II and III alpha/beta (ML II & ML III alpha/beta) are rare autosomal recessive lysosomal storage disorders. ML II is clinically evident from birth with a progressive course and fatal outcome in childhood. The typical phenotypes of ML II include limited statural growth, craniofacial abnormality, skeletal malformation, intelligence developmental deficiency and visceral organ abnormality. ML III is milder than ML II. Mutations in GNPTAB cause the ML II/III. METHODS: Two families with ML II/III (initially undiagnosed) were recruited. We applied whole-exome sequencing (WES) and filtered mutations by genes causing lysosomal storage diseases with skeletal involvement. Mutational analysis and co-segregation confirmation were then performed. RESULTS: We presented two families with ML II or ML III alpha/beta. By WES, the compound heterozygosity of GNPTAB (c.2404C>T, p.Q802* and c.2590dup, p.E864Gfs*4) is identified in a family with ML II, and c.1364C>T, p.A455V and c.2715+1G>A are detected in a family with ML III alpha/beta. CONCLUSION: We detected the causative mutations in two ML II/III families by WES and confirmed their diagnosis of the diseases. The present identification of mutations expands the spectrum of known GNPTAB mutations and it may contribute to novel approaches to genetic diagnosis and counseling for patients with ML II/III.

[Clinical features of late stent thrombosis after successful sirolimus-eluting stent implantation].

OBJECTIVE: To analyze the potential risk factors for patients developing late stent thrombosis (LST) after successful sirolimus-eluting stents (SES) implantation. METHODS: The clinical, angiographic, procedural as well as antiplatelet therapy data were retrospectively analyzed in 8 patients with LST after successful SES implantation. RESULTS: The patient's mean age was (51 +/- 10) years old and indication for SESs was mostly acute coronary syndrome with multiple risk factors of cardiovascular diseases. There was 1 chronic heart failure patient and renal function was normal in all patients. Multivessel diseases and complex coronary lesions including total occlusion lesions, bifurcation lesions and long lesions were seen in these patients. The mean release pressure of stents was (11.60 +/- 1.65) atm and with no high-pressure dilation after the procedure. The median time of dual antiplatelet therapy was (157.5 +/- 41.7) days. The mean duration from SESs implantation to thrombosis was (450.3 +/- 344.7) days. LST developed in 2 patients with active dual antiplatelet therapy, 1 patient at 7 days and 5 patients at 6 months after clopidogrel withdraw, 5 patients presented nonfatal acute myocardial infarction, 1 patient died of acute myocardial infarction after coronary artery bypass grafting. Five patients were successfully treated with second SESs implantations and another one was treated medically. CONCLUSIONS: LST could be safe and effective treated with re-SESs. The development of LST after successful SESs implantation were probably associated with the following factors: (1) acute coronary syndrome with multiple risk factors of cardiovascular diseases and multivessel diseases with complex coronary lesions. (2) Low-pressure deployment without high-pressure dilation after the release. (3) Dual antiplatelet therapy withdraw.

[Short and long-term therapeutic efficacy of drug-eluting stents (Firebird) for the treatment of coronary artery disease].

OBJECTIVE: To evaluate the short and long-term therapeutic efficacy of drug-eluting stents (Firebird) for the treatment of coronary artery disease. METHODS: From Nov. 2003 to Jan. 2005, 501 Firebird stents were implanted in 410 patients with 460 lesions. All patients were administered with aspirin and clopidogrel before and after the procedures. Follow-up was made by telephone or interview, 102 out of 410 patients were followed up by angiography. RESULTS: The procedure success rate was 99.5%. Stent thrombosis occurred in one patient during the procedure and one sudden death developed 10 hours after the procedure in hospital. The major adverse cardiac event (MACE, including death, acute myocardial infarction and target lesion revascularization) rate during hospitalization was 0.2% (1/410). The MACE rate was 4.3% (16/376) and the stent thrombosis rate was 1.1% (4/376) during clinical follow-up of 376 patients (12.8 +/- 3.2 months). The angiographic restenosis rate in 102 patients with 122 lesions was 9.8% (12/122). CONCLUSION: Firebird drug-eluting stent could be used safely and effectively in patient with coronary heart disease.

A novel splice-site mutation of WRN (c.IVS28+2T>C) identified in a consanguineous family with Werner Syndrome.

Werner Syndrome (WS) is a rare, adult­onset progeroid syndrome that is associated with multiple age­associated complications and relatively short life expectancy. The characteristics of WS include a 'bird­like' appearance, canities, cataracts and ulcerations around the ankles. In addition, certain patients develop hypogonadism with atrophic genitalia and infertility. The average life span of affected individuals is 54 years. Previous studies have demonstrated that mutations in the Werner syndrome RecQ like helicase gene (WRN) may contribute to WS. The present study investigated a consanguineous family with WS, comprising of 4 generations from Northwest China (Gansu province). A novel homozygous splice­site mutation in WRN (c.IVS28+2T>C) was identified in this family and was predicted to be deleterious. No further relevant mutations were identified by direct sequencing of the genes lamin A/C, barrier to autointegration factor 1, zinc metallopeptidase STE24 and DNA polymerase Δ1. cDNA sequencing and alignments were performed to further confirm the pathogenicity of this mutation. The results support the important role of WRN in WS and expand the spectrum of known WRN mutations. In addition, it may provide novel approaches in genetic diagnosis and counseling of families with WS.

Long-term outcomes of PCI vs. CABG for ostial/midshaft lesions in unprotected left main coronary artery.

BACKGROUND: There are limited data on long-term (> 5 years) outcomes of drug-eluting stent (DES) implantation compared with coronary artery bypass grafting (CABG) for ostial/midshaft left main coronary artery (LMCA) lesions. METHODS: Of the 259 consecutive patients in Beijing Anzhen Hospital with ostial/midshaft LMCA lesions, 149 were treated with percutaneous coronary intervention (PCI) with DES and 110 were with CABG. The endpoints of the study were death, repeat revascularization, myocardial infarction (MI), stroke, the composite of cardiac death, and major adverse cardiac and cerebrovascular events (MACCE, the composite of cardiac death, MI, stroke or repeat revascularization).The duration of follow-up is 7.1 years (interquartile range 5.3 to 8.2 years). RESULTS: There is no significant difference between the PCI and CABG group during the median follow-up of 7.1 years (interquartile range: 5.3-8.2 years) in the occurrence of death (HR: 0.727, 95% CI: 0.335-1.578; P = 0.421), the composite endpoint of cardiac death, MI or stroke (HR: 0.730, 95% CI: 0.375-1.421; P = 0.354), MACCE (HR: 1.066, 95% CI: 0.648-1.753; P = 0.801), MI (HR: 1.112, 95% CI: 0.414-2.987; P = 0.833), stroke (HR: 1.875, 95% CI: 0.528-6.659; P = 0.331), and repeat revascularization (HR: 1.590, 95% CI: 0.800-3.161; P = 0.186). These results remained after multivariable adjusting. CONCLUSION: During a follow-up up to 8.2 years, we found that DES implantation had similar endpoint outcomes compared with CABG.