Expression signature and molecular basis of CDH11 in OSCC detected by a combination of multiple methods.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancy in the oral cancer threatening human health and the survival rate of OSCC has not been effectively improved in recent decades, so more effective biomarkers for the targeted therapy of OSCC are needed. Moreover, the role of CDH11 in OSCC has not been intensively investigated. We here show that the CDH11 protein and mRNA expression levels in the OSCC tissues were all significantly higher than in the non-cancerous tissues using RT-qPCR and western blot. This study also revealed that patients with higher CDH11 levels showed a higher incidence of perineural invasion and lymph node metastasis. By using data available from the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress databases, overexpressed CDH11 in OSCC that associated with patients'history of alcohol, negative Human Papilloma Virus (HPV) status, perineural invasion, infiltration of multiple immune cells, and Single-cell functional states including quiescence and angiogenesis, possessed an excellent discriminatory capability in the OSCC patients. Moreover, the majority of the biological processes or pathways were significantly clustered by co-expressed genes, including extracellular matrix organization, the epithelial to mesenchymal transition, carbon metabolism, and the PI3K-Akt signaling pathway, and the upstream transcriptional regulation mechanism of CDH11 in OSCC was showed on a transcription factor/miRNA-mRNA network with the online tool NetworkAnalyst. Finally, frequent mutation of CDH11 was observed on a mouse OSCC model through whole-genome sequencing. CDH11 might serve as a valuable biomarker in OSCC, as it was identified to be overexpressed in OSCC and related to its clinical progression.

Clinical features of ST-segment elevation myocardial infarction in young Chinese patients.

BACKGROUND: To investigate the clinical characteristics, angiographic findings and clinical outcomes (in-hospital) of young adults with acute myocardium infarction in a Chinese population. METHODS: This was an observational study. Five hundred and forty-nine patients who suffered with ST-segment elevation myocardial infarction (STEMI) firstly between January 2013 and December 2015 were enrolled consecutively. All patients were divided into two groups: "young group" patients were ≤ 50 years old; and "non-young group" patients were > 50 years old. Clinical features were compared, angiographic findings and clinical outcomes were observed between the two groups. RESULTS: There were 131 and 418 patients included in the young group and the non-young group, respectively. Twenty-eight patients suffered deaths during the hospital stay and only one death occurred in the young group. Compared with non-young group, the young group was associated with male, smoke, fewer chronic diseases, Killip class I on admission, lower level of N-terminal pro B-type natriuretic peptide (NT-proBNP), higher level of triglyceride and lower level of high-density lipoprotein cholesterol (HDL-C), single-vessel lesion and intracoronary thrombus (p < 0.005). The average length of hospital stay of non-young group was 1.5 days longer than the young group. Compared with the non-young group, the young group inclined not to use or use only one stent (p = 0.026). Multivariable logistic regression analysis showed that older age, shorter hospital stay, advanced Killip class III/IV, increased white blood cell and NT-proBNP were independent risk factors for survival in acute STEMI patients during hospitalization (p < 0.005). CONCLUSIONS: Compared with non-young group, the young group was associated with male, smoke, higher level of triglyceride and lower level of HDL-C. The condition of patients in young group were relatively mild and the risk of death during hospitalization was lower than the other group.

Diagnostic performance of deep learning-based vascular extraction and stenosis detection technique for coronary artery disease.

OBJECTIVE: To investigate the diagnostic performance of deep learning (DL)-based vascular extraction and stenosis detection technology in assessing coronary artery disease (CAD). METHODS: The diagnostic performance of DL technology was evaluated by retrospective analysis of coronary computed tomography angiography in 124 suspected CAD patients, using invasive coronary angiography as reference standard. Lumen diameter stenosis ≥50% was considered obstructive, and the diagnostic performances were evaluated at per-patient, per-vessel and per-segment levels. The diagnostic performances between DL model and reader model were compared by the areas under the receiver operating characteristics curves (AUCs). RESULTS: In patient-based analysis, AUC of 0.78 was obtained by DL model to detect obstructive CAD [sensitivity of 94%, specificity of 63%, positive predictive value of 94%, and negative predictive value of 59%], While AUC by reader model was 0.74 (sensitivity of 97%, specificity of 50%, positive predictive value of 93%, negative predictive value of 73%). In vessel-based analysis, the AUCs of DL model and reader model were 0.87 and 0.89 respectively. In segment-based analysis, the AUCs of 0.84 and 0.89 were obtained by DL model and reader model respectively. It took 0.47 min to analyze all segments per patient by DL model, which is significantly less than reader model (29.65 min) (p < 0.001). CONCLUSION: The DL technology can accurately and effectively identify obstructive CAD, with less time-consuming, and it could be a reliable diagnostic tool to detect CAD. ADVANCES IN KNOWLEDGE: The DL technology has valuable prospect with the diagnostic ability to detect CAD.

The CatLet score: a new coronary angiographic scoring tool accommodating the variable coronary anatomy for the first time.

BACKGROUND: The SYNTAX score for decision makings or outcome predictions in coronary artery disease does not account for the variations in the coronary anatomy, which is a clear fallacy for patients with less typical anatomy than suggested by the SYNTAX score. The current study aimed to derive a new coronary angiographic scoring system accommodating the variability in the coronary anatomy. METHODS: The 17-myocardial segment model and laws of competitive blood supply and flow conservation were utilized to derive this new scoring system. RESULTS: We obtained 6 types of RCA dominance, 3 types of diagonal size and 3 types of left anterior descending artery (LAD) length, which together resulted in a total of 54 patterns of coronary artery circulation to account for the variability in the coronary anatomy among individuals. A Coronary Artery Tree description and Lesion EvaluaTion (CatLet) angiographic scoring system has been designed based on the above-mentioned reclassification scheme (htpp://www.catletscore.com, IE browser is required to run this calculator). CONCLUSIONS: This new CatLet angiographic scoring system accommodated the variability in the coronary anatomy and standardized the collection of the coronary angiographic data, which could facilitate the comparison and exchange of these data between different catheter labs. Its utility for predicting the clinical outcomes and standardizing the angiographic data collection will be investigated in a series of clinical trials enrolling "all-comers" with coronary artery disease (CAD).

Cardiac troponin I elevation with supraventricular tachycardia: two case reports and review of the literature.

BACKGROUND: Although cardiac troponin I gives excellent accuracy in the identification of myocardial necrosis, it can also be elevated in a series of diseases other than acute coronary syndromes. CASE PRESENTATION: We present two cases of Chinese patients with a high serum troponin I level after an acute episode of paroxysmal supraventricular tachycardia with normal coronary arteries via angiography. CONCLUSION: Abnormal troponin elevations can be seen in patients presenting with paroxysmal supraventricular tachycardia and angiographically-normal coronary arteries. Caution is advised with the use of invasive assessments such as coronary angiography in the differential diagnosis of patients with paroxysmal supraventricular tachycardia and elevated troponin levels.

ß-Blockers in heart failure: benefits of ß-blockers according to varying male proportions of study patients.

BACKGROUND: In patients with heart failure (HF), b-blockers reduce mortality. It's not known whether the beneficial effects of the b-blockers were associated with the differing male proportions of study patients. It also remains to be clarified regarding the true beneficial effects of the 3 b-blockers recommended by the guideline on mortality in the real world. HYPOTHESIS: The benefits of b-blockers in HF patients were sex-related different. METHODS: Randomized, placebo controlled clinical trials were included if they evaluated the beneficial effects of the three b-blockers on mortality and on hospital admissions on an intention-to-treat basis, and lasted at least 3 months. RESULTS: Twenty-eighty trials with 14,829 patients were included. The b-blockers significantly reduced all cause mortality by 29.6%, cardiac death by 29.8%, sudden death by 49.4%, respectively. The magnitude of benefits of b-blockers in HF patients was increased with the increased male proportion. A similar magnitude of reduction in all cause mortality was observed among the three b blockers. A trend toward to reduced cardiac death was observed among the three b blockers, but only in bisoprolol was this statistically different (RR, 0.72; 95%CI, [0.59-0.87]). Metoprolol was significantly superior to carvedilol (P = 0.008) or bisoprolol (P = 0.034) in reduced sudden death. CONCLUSIONS: In patients with HF, the 3 commonly used b-blockers significantly reduced mortality. Greater benefits of b-blockers were observed in the higher male proportion studies. The metoprolol was significantly superior to carvedilol or bisoprolol in reduced sudden death. Additional trials are required to determine whether the benefits of b-blockers will be observed in female HF patients.

Mutation of Arg723Gly in beta-myosin heavy chain gene in five Chinese families with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a form of cardiomyopathy with an autosomal dominant inherited disease, which is caused by mutations in at least one of the sarcomeric protein genes. Mutations in the beta-myosin heavy chain (beta-MHC) are the most common cause of HCM. This study was to reveal the disease-causing gene mutations in Chinese population with HCM, and to analyze the correlation between the genotype and phenotype. METHODS: The exons 3 to 26 of MYH7 were amplified by PCR, and the PCR products were sequenced in five non-kin HCM patients. A 17-year-old patient was detected to be an Arg723Gly mutation carrier. Then his family was gene-screened, and the correlation between genotype and phenotype was analyzed. RESULTS: The mutation of Arg723Gly in a Chinese family with HCM was detected for the first time. With a C-G transversion in nucleotide 13,619 of the MYH7 gene, located at the essential light chain interacting region in S1, the replacement of arginine by glycine took place at amino acid residue 723. A two-dimensional echocardiogram showed moderate asymmetrical septal hypertrophy with left atria enlargement. There was no obstruction in the left ventricular outflow tract. In his family, a total of 13 individuals were diagnosed HCM and 5 of them were dead of congestive heart failure at a mean age of 66-year-old. Eight living members were all detected to carry the mutation, in which 3 developed progressive heart failure. Moreover, the heart function of the people evidently deteriorates when their age are older than 50. The mutation and the disease show co-separated. CONCLUSION: The Arg723Gly mutation is a malignant type. In Chinese the mutation has the similar characters to the former report but has low degree malignant.

[Malignant hypertrophic cardiomyopathy caused by the Arg723Gly mutation in beta-myosin heavy chain gene in a Chinese pedigree].

OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease and an Arg723Gly mutation in beta-myosin heavy chain (beta-MHC) gene was found in 3 Spanish families with malignant HCM. We detected this gene mutation in 5 Chinese pedigrees with hypertensive cardiomyopathy. METHODS: Five Chinese pedigrees with HCM and 80 age-matched normal control subjects were chosen for the study. The exons in the functional regions of the beta-MHC gene were amplified with PCR and the products were sequenced, genotype and phenotype analyzed. RESULTS: Arg723Gly mutation was identified in exon 20 in one pedigree. In this pedigree, 13 out of 25 family members were diagnosed as HCM, 5 died of heart failure, all HCM patients in this pedigree had Arg723Gly mutation and 3 of them had NYHA III and 2 of them were diagnosed as HCM before the age of 20. CONCLUSIONS: Arg723Gly mutation was also one of the main disease-causing genes in Chinese familial HCM. The mutation of Arg723Gly is a malignant phenotype as shown by early progressive heart failure development and poor prognosis in this pedigree with Arg723Gly mutation.

[The acute electrophysiological effects of amiodarone on normal and hypertrophied rat myocytes].

OBJECTIVE: The aim of the present study was to investigate the acute action of amiodarone (AM) on the inward currents I(Na), I(Ca-L) and outward currents I(k), I(k1), I(to) in hypertrophied and normal rat ventricular myocytes. METHODS: The pressure overload hypertrophy rat model was established by partial ligation of ascending aorta for 4 weeks. Ventricular myocytes were exposed to 0.01, 0.1, 1, 10 and 50 micromol/L AM and whole cell patch clamp technique was used to study the acute effects of AM on the inward currents I(Na), I(Ca-L) and outward currents I(k), I(k1), I(to). RESULTS: (1) Compared with the normal ventricular myocytes, the current density of I(k), I(ks), I(to) and I(k1) were all decreased in hypertrophied myocytes, but I(Na) and I(Ca-L) remained unchanged. (2) I(Ca-L) was blocked by 59.0% +/- 4.4% in normal myocytes but only blocked by 16.7% +/- 8.0% in hypertrophied myocytes after 50 micromol/L AM application; IC(50) of I(Na) were 9.2 micromol/L and 5.9 micromol/L in normal and in hypertrophied myocytes, respectively; I(to) was blocked by 55.9% +/- 5.5% in normal myocytes and 23.0% +/- 2.8% in hypertrophied myocytes after 50 micromol/L AM application. I(k1) was not affected by AM in both normal and hypertrophied myocytes; I(ks) was blocked by 21.6% +/- 5.6% in normal myocytes and 42.7% +/- 9.2% in hypertrophied myocytes after 10 micromol/L AM application. CONCLUSION: Our results show that the sensitivity of hypertrophied myocytes to AM on I(Na), I(ks) were higher than that of normal myocytes, while the sensitivity on I(Ca-L), I(k1), I(to) were lower than that of normal myocytes favoring the use of AM on hypertrophied myocardium for antiarrhythmic therapy.

[Pacemaker current gene expression of rat mesenchymal stem cells and identification of mesenchymal stem cells expressing human pacemaker current gene (hHCN2)].

OBJECTIVE: To study pacemaker current gene expression of mesenchymal stem cells (MSCs) and the electrophysiological property of MSCs expressing human pacemaker current gene. METHODS: Pacemaker current gene expression of MSCs were studied by real-time quantitative polymerase chain reaction (real-time PCR) and pcDNA3-hHCN2 was transfected with Lipofectin 2000 into MSCs. hHCN2 expression at mRNA and at protein levels in the transfected cells were identified by real-time PCR and Western blot, respectively. The ionic currents of cloned hHCN2 (IhHCN2) were recorded and the current characteristics were studied through the whole-cell patch clamp technique. RESULTS: mHCN1, mHCN2, mHCN3, mHCN4 represent (0.08+/-0.01)%, (77.16+/-0.03)%, (0.24+/-0.01)%, (22.53+/-0.02)% of total HCN mRNA in MSCs as determined by real-time PCR. Transfected hHCN2 ionic currents were recorded by whole-cell patch clamp and current density-voltage curves were obtained. The threshold for activation of IhHCN2 was approximately -80 mV and this current could be blocked by Cs+ (4 mmol/L). hHCN2 expression in transfected MSCs was detected both at mRNA and protein levels. CONCLUSIONS: 1. mHCN2 and mHCN4 represent the major populations of total HCN mRNA in MSCs. 2. Plasmid pcDNA3-hHCN2 by Lipofectin could be successfully transfected into MSCs with IhHCN2 recorded by whole-cell patch clamp technique, this study provides a basis for future antiarrhythmic gene therapy.

[Establishment of a HEK293 cell line stably expressing human HCN2 gene].

AIM: To create a model for studying ionic channels by means of the expressing human HCN2 and G418-resistant HEK293 cell lines established. METHODS: pcDNA3-hHCN2 was transfected with Lipofectin2000 into HEK293 cell line. The transfected cells would be survived in the further culture medium containing G418 antibiotic as the hHCN2 gene could express a G418 resistant products. Whole-cell patch clamp investigated that hHCN2 gene was transfected into HEK293 cells. RESULTS: The G418 resistant (600 ug/ml) HEK293 cell line was established successfully and whole-cell patch clamp recorded ionic currents of transfected hHCN2. CONCLUSION: The G418 resistant HEK293 cell line was successfully established with transfection of plasmid pcDNA3-hHCN2 by Lipofectin, which might be useful for studying the relationship between the structure and function of cloned ionic channels.