Atherogenic dyslipidaemia and cardiovascular events in patients with diabetes or pre-diabetes and stable coronary artery disease: a prospective, cohort study.

OBJECTIVE: The aim of the study was to investigate the impacts of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) dyslipidaemia on prognosis in coronary artery disease (CAD) patients with different glucose metabolism status. DESIGN: An observational cohort study. SETTING/PARTICIPANTS: A total of 3057 patients with stable CAD were consecutively enrolled and divided into three groups according to different glucose metabolism status. Atherogenic dyslipidaemia (AD) was defined as TG ≥1.7 mmol/L and HDL-C <1.0 mmol/L for men or <1.3 mmol/L for women. The patients were further classified into six subgroups by status of AD. All subjects were followed up for the cardiovascular events (CVEs). PRIMARY OUTCOME MEASURES: The primary endpoints were cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke. RESULTS: During a median follow-up of 6.1 years, 308 (10.1%) CVEs occurred. No significant difference in the occurrence of CVEs was observed between normal glucose regulation (NGR) and pre-diabetes (pre-DM) groups (HR: 1.25, 95% CI 0.89 to 1.76) while DM group presented 1.45-fold higher risk of CVEs (HR: 1.45, 95% CI 1.02 to 2.05). When the participants were categorised according to combined status of two parameters, the cardiovascular risk was significantly elevated in pre-DM or DM plus AD group compared with the NGR plus non-AD group (HR: 1.76, 95% CI 1.10 to 2.80 and HR: 1.87, 95% CI 1.17 to 2.98). CONCLUSIONS: The present study suggested that the presence of AD might affect the prognosis in patients with DM or pre-DM and stable CAD.

The Role of Transient Receptor Potential Channels in Blood-Brain Barrier Dysfunction after Ischemic Stroke.

Stroke is the leading cause of long-term disability, demanding an ever-increasing need to find treatment. Transient receptor potential (TRP) channels are nonselective Ca2+-permeable channels, among which TRPC, TRPM, and TRPV are widely expressed in the brain. Dysfunction of the blood brain barrier (BBB) is a core feature of stroke and is associated with severity of injury. As studies have shown, TRP channels influence various neuronal functions by regulating the BBB. Here, we briefly review the role of TRP channel in the BBB dysfunction after stroke, and explore the therapeutic potential of TRP-targeted therapy.

Lipoprotein(a) as a marker for predicting coronary collateral circulation in patients with acute myocardial infarction.

Aim: The aim of the present study was to examine the predictive value of lipoprotein(a) (Lp[a]) levels for coronary collateral circulation (CCC) in patients with acute myocardial infarction (AMI). Method & methods: A total of 409 consecutive patients with AMI were enrolled for this study. Patients were divided into two groups according to rentrop grades assessed by coronary angiography: bad (n = 277) and good CCC group (n = 132). Result: Patients with bad CCC had a higher level of Lp(a) than that with good CCC (median Lp[a] 219.1 vs 122.0 mg/l). The area under the receiver-operating characteristic curves of Lp(a) in predicting bad CCC was 0.647 (95% CI: 0.592-0.702) with the cut-off value of 199.0 mg/l. Conclusion: Our data firstly suggested that Lp(a) might be a useful marker for CCC after AMI.

The clinical role of contrast enhanced ultrasound in differential diagnosis of BI-RADS 4 breast disease.

OBJECTIVE: To clarify the clinical role of contrast enhanced ultrasound (CEUS) in predicting BI-RADS 4 breast disease. METHODS: A total of 92 sites of BI-RADS 4 breast diseases were reassessed by routine ultrasound and CEUS. The main indicators of routine ultrasound, CEUS and the combination of the two modalities were picked up by binary logistic regression analysis, scoring 0 for benign and 1 for malignant characteristics with pathology as referential standard to generate corresponding score systems of them. Finally, the receiver operating characteristic curves (ROC) were applied to compare the diagnostic efficacy of the three score systems. RESULTS: As pathological results showing, there were 43 malignant and 49 benign sites in total. Binary logistic regression analysis indicated that the margin, micro-calcification, and hyperechoic halo were main indicators for routine ultrasound score system. The scope expansion and pathological vessels in CEUS were main indicators for CEUS score system. The microcalcification, hyperechoic halo, the scope expansion and pathological vessels in CEUS were main indicators for the combination score system of the two modalities. The sensitivity, specificity and the area under ROC curve (AUC) of routine US, CEUS and the combination of the two modalities score systems were 74.4%, 91.8%, 0.885 and 88.4%, 87.8%, 0.901 and 86.0%, 95.9%, 0.937, respectively. CONCLUSION: In summary, CEUS is helpful for us to identify malignant disease and plays a supplementary role in predicting BI-RADS 4 breast disease in some extent. The scope expansion and pathological vessels in CEUS may be the most useful indicators.

Use of cationic microbubbles targeted to P-selectin to improve ultrasound-mediated gene transfection of hVEGF165 to the ischemic myocardium.

Gene therapies have been applied to the treatment of cardiovascular disease, but their use is limited by the need to deliver them to the right target. We have employed targeted contrast ultrasound-mediated gene transfection (TCUMGT) via ultrasound-targeted microbubble destruction (UTMD) to transfer therapeutic genes to specific anatomic and pathological targets. Phospholipid microbubbles (MBs) with pcDNA3.1-human vascular endothelial growth factor 165 (pcDNA3.1-hVEGF165) plasmids targeted to P-selectin (MB+P+VEGFp) were created by conjugating monoclonal antibodies against P-selectin to the lipid shell. These microbubbles were divided into four groups: microbubble only (MB), microbubble+P-selectin (MB+P), microbubble+pcDNA3.1-hVEGF165 plasmid (MB+VEGFp), and microbubble+ P-selectin+pcDNA3.1-hVEGF165 plasmid (MB+P+VEGFp). The reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) results showed that the VEGF gene was successfully transfected by TCUMGT and the efficiency is increased with P-selectin targeting moiety. UTMD-mediated delivery of VEGF increased myocardial vascular density and improved cardiac function, and MB+P+VEGFp delivery showed greater improvement than MB+VEGFp. This study drew support from TCUGMT technology and took advantage of targeted ultrasound contrast agent to identify ischemic myocardium, release pcDNA3.1-hVEGF165 recombinant plasmid, and improve the myocardial microenvironment, so promoting the restoration of myocardial function.

Triglyceride glucose index for predicting cardiovascular outcomes in patients with coronary artery disease.

BACKGROUND: Triglyceride glucose (TyG) index is a novel marker for metabolic disorders and recently it has been reported to be associated with cardiovascular disease (CVD) risk in apparently healthy individuals. However, the prognostic value of TyG index in patients with stable coronary artery disease (CAD) is not determined. METHODS: We conducted a nested case-control study among 3,745 patients with stable CAD. Patients were followed up for 11,235 person-years. The cardiovascular events (CVEs) were defined as all-cause death, non-fatal myocardial infarction (MI), stroke and post-discharge revascularization [percutaneous coronary intervention (PCI) coronary artery bypass grafting (CABG)]. In total, 290 (7.7%) patients with CVEs and 1,450 controls were matched according to age, gender, previous history of PCI or CABG and the duration of follow-up. TyG index was calculated as formula: ln[fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2]. RESULTS: Multivariable Cox proportional hazards models revealed that TyG index was positively associated with CVEs risk (hazard ratio: 1.364, 95% confidence interval: 1.100-1.691, P=0.005). The Kaplan-Meier analysis indicated that patients within the highest quartile of TyG index presented the lowest event-free survival (P=0.029). Moreover, a 1-standard deviation (SD) increment in TyG index was associated with 23.2% [hazard ratio (HR): 1.232, 95% confidence interval (95% CI): 1.084-1.401] higher risk of CVEs, which was superior to other triglyceride or glycemic related markers. CONCLUSIONS: The present study, firstly, showed that TyG index was positively associated with future CVEs, suggesting that TyG may be a useful marker for predicting clinical outcomes in patients with CAD.

[Value of ultrasonography in diagnosis of xanthogranulomatous cholecystitis].

OBJECTIVE: To assess the value of ultrasonography in differential diagnosis of xanthogranulomatous cholecystitis (XGC) and wall-thickening type of gallbladder cancer (GBC). METHODS: The clinical features and sonographic finding of 31 patients with XGC and 36 patients with wall-thickening type of GBC were retrospectively reviewed. The diagnosis of all cases was confirmed by pathological examination, and the ultrasonographic manifestations of the thickening of the gallbladder wall, intramural hypoechoic nodules, gallbladder mucosa line, gallbladder stones, biliary dilatation and gallbladder-liver boundary were compared between two groups. RESULTS: There were significant differences in the intramural hypoechoic nodules, the continuous gallbladder wall mucosal line and dilatation of bile duct between XGC and GBC groups (all P<0.05), while no statistically significant differences in the other sonographic features(all P>0.05). In the six positive sonographic features of the XGC patients, the intramural hypoechoic nodules and the continuous mucosa line of the gallbladder wall had highest accuracy in the diagnosis of XGC(64.2% and 65.7%). CONCLUSIONS: Intramural hypoechoic nodule and the continuous mucosal line are characteristic sonographic features of XGC, which can be used for the diagnosis of XGC.

Hysterosalpingo-Contrast Sonography With Four-Dimensional Technique for Screening Fallopian Tubal Patency: Let's Make an Exploration.

STUDY OBJECTIVE: To evaluate the practicability of transvaginal 4-dimensional (4D) hysterosalpingo-contrast sonography (HyCoSy) using SonoVue for screening of fallopian tube patency in infertile females. DESIGN: Prospective observational study (Canadian Task Force classification II-2). SETTING: The Second Affiliated Hospital of Zhejiang University. PATIENTS: 204 infertile females who underwent 4D-HyCoSy between July 2015 and June 2016. INTERVENTION: 4D-HyCoSy was performed to acquire dynamic images. If any of the fallopian tubes was not developing during the process, the procedure was repeated promptly, to exclude false-positive outcomes. Subsequently, tube status was confirmed by traditional 2-dimensional (2D)-HyCoSy. Finally, the results of the 4D-HyCoSy and the final 2D-HyCoSy were compared. MEASUREMENTS AND MAIN RESULTS: A total of 204 patients (408 tubes) were evaluated ith 4D-HyCoSy followed by 2D-HyCoSy. Of these 408 tubes, 385 demonstrated the same status on 4D-HyCoSy and 2D-HyCoSy, for an agreement rate of 94.4%. CONCLUSION: A 4D technique combined with HyCoSy is a practicable screening method for assessing fallopian tube patency. It overcomes the disadvantages of 2D-HyCoSy and has a relatively high degree of agreement with the more difficult 2D-HyCoSy technique.

Microarray analysis unmasked two siblings with pure hereditary spastic paraplegia shared a run of homozygosity region on chromosome 3q28-q29.

Hereditary spastic paraplegia (HSP) is a clinical and genetic heterogeneity group of neurodegenerative disorders which is characterized by progressive weakness and spasticity of the lower limbs. More than 70 genetic types of HSP have been described so far. Here we describe a Chinese non-consanguineous family with two affected siblings manifesting early-onset autosomal recessive HSP in pure forms. To identify genotype and characterize phenotype, CytoScan HD array analysis was performed on the two siblings. A run of homozygosity (ROH) shared by the two patients was detected on chromosome 3q28-q29. The ROH region, about 7.7Mb on the chromosome 3:190172058-197851260 partially overlapped with the ROH region of SPG14 previously reported. Subsequently, microsatellite analysis confirmed this ROH and whole-exome sequencing was carried out while no causative mutations were found in the exons of known HSP genes and 68 candidate genes in that region. In conclusion, our data suggest the ROH in this region may play a pivotal role in SPG14 pathogenesis. This is the first clinical description of a pure form spastic paraplegia in a non-consanguineous family associated with the SPG14 locus.

[The value of transesophageal echocardiography to guide the implantation of 2 pieces of MitraClip during transcatheter mitral valve repair operation].

OBJECTIVE: To investigate the value of transesophageal echocardiography to guide the implantation of 2 pieces of MitraClip during transcatheter mitral valve repair operation. METHODS: From October 2013 to June 2014, 6 transcatheter mitral valve repair operations were performed in our hospital for symptomatic patients with severe functional mitral regurgitation (MR), transesophageal echocardiography was applied to guide the implantation of 2 pieces of MitraClip. Clinical data are retrospectively analyzed to evaluate implantation timing and approach of the 2nd piece of MitraClip, as well as the immediate effect of the interventional therapy. RESULTS: After implantation of 1st piece of MitraClip, transesophageal echocardiography evidenced MR ≥ grade 2 with central regurgitation and immediate mitral average transvalvular pressure gradient < 3 mmHg (1 mmHg = 0.133 kPa) in these 6 patients and 2nd piece of MitraClip was implanted in these patients. After implantation of 2nd piece of MitraClip, it is observed via transesophageal echocardiography that mitral regurgitations were reduced by ≥ 2 grades for all 6 patients. For 3 patients, MR was reduced to grade 1. For the other 3 patients, MR is reduced to grade 2. Among the 3 patients whose MR was reduced to grade 2, 2 operations were stopped because immediate mitral average transvalvular pressure gradient equaled to 3 mmHg, and the rest 1 operation was stopped because MR was too diverse and not able to select proper position to implant the next MitraClip. All 6 operations are completed successfully.There were no myocardial infarction, death or complications requiring mitral valve surgery after the MitraClip procedure. There were also no MitraClip detachment, thrombus embolism, mitral valve apparatus injuries, mitral stenosis, pericardial tamponade post procedure. CONCLUSIONS: Transesophageal echocardiography plays an important role to guide the implantation of 2 pieces of MitraClip in transcatheter mitral valve repair operation. Mitral average transvalvular pressure gradient and initial position of regurgitation after implantation of the previous MitraClip are critical determinants for decision making if the next piece of MitraClip can be implanted or not.

Association between the NFKB1-94ins/del ATTG polymorphism and cancer risk: an updated meta-analysis.

To assess the effect of the NFKB1 -94ins/del polymorphism on cancer, we conducted a meta-analysis based on 25 studies including 8,750 cases and 9,170 controls. Overall, the -94ins/del polymorphism was associated with cancer risk in the pooled analysis and in Asian population, whereas no association was observed in Caucasian population. Stratified analysis by subtypes of cancer showed that the -94ins/del polymorphism was associated with oral squamous cell carcinoma and ovarian cancer risk, but had no association with colorectal cancer, bladder cancer, and renal cell cancer. Our meta-analysis suggests the NFKB1 -94ins/del polymorphism affects cancer susceptibility, and the association is ethnic-specific.

Relationship between enhanced intensity of contrast enhanced ultrasound and microvessel density of aortic atherosclerostic plaque in rabbit model.

The aim of this study was to evaluate the relationship between enhanced intensity of contrast enhanced ultrasound and microvessel density of aortic atherosclerotic plaque in rabbit model. The abdominal aortas of thirty-six male New Zealand rabbits were damaged by balloon expansion and the animals were then fed a high fat diet for 12 weeks. Twenty-seven plaques on the near aortic wall were detected using conventional ultrasound examination. The maximum thickness of each plaque was recorded. CEUS was performed on these 27 plaques and the time-intensity curves (TICs) were analyzed offline. Using the quantitative ACQ software, features such as the arrival time (AT), time to peak (TTP), baseline intensity (BI), peak intensity (PI) and enhanced intensity (EI) (EI = PI-BI) were assessed. Inter- and intra-observer agreement of EI were assessed using the Bland-Altman test. After CEUS examination, the rabbits were sacrificed for pathological examination and CD34 monoclonal antibody immunohistochemical detection. Microvessel density (MVD) was counted under the microscope. The relationship between indexes of CEUS and the level of MVD was analyzed. There was a good positive linear correlation between EI and MVD (γ = 0. 854, P<0. 001), the intraclass correlations for inter- and intra-observer agreement for EI were 0.73 and 0.82 respectively, suggesting that EI may be act as a useful index for plaque risk stratification in animal models.

A novel therapeutic strategy using ultrasound mediated microbubbles destruction to treat colon cancer in a mouse model.

The goal of this study was to determine whether ultrasound mediated microbubbles destruction (UMMD) could inhibit colon cancer growth in a mouse model. Six-week-old balb/c female nude mice were subcutaneously inoculated with HT29-GFP cells (HT29 cells labeled with green fluorescent dye) in axilla to establish a xenograft mouse model of colon carcinoma, which were randomly divided into five groups (n=10 each): group A (blank group): no treatment; group B (saline only); group C (saline+ultrasound exposure); group D (intravenous microbubbles only); and group E (intravenous microbubbles+ultrasound exposure). Treatment of each group was performed on days 20, 21, and 22 after inoculation. Tumor growth and metastatic spread were monitored by the whole-body fluorescent imaging, tumor volume growth and body weight growth curve were obtained as well. The mice were euthanized 30 days after treatment. Specimens of the tumor tissues were evaluated pathologically using light microscopy and transmission electron microscopy. Necrosis percentages, microvascular density and tumor cells damage of each tumor were assessed histologically. Our data indicate that: (1) tumor growth in group E (intravenous microbubbles+ultrasound exposure) was significantly decreased after four weeks post inoculation, compared with other control treatments (P<0.05); (2) the tumor weight at sacrifice in group E was significantly lower than that in other groups; (3) The intravenous microbubbles combined with ultrasound exposure treated mice showed significantly decreased expression levels of CD31. (4)The pathological changes of absence of nucleus membrane, chromatin condensation, mitochondrial vacuolation and hemorrhagic damage of microvessel were observed in the tumors of group E only, whereas these changes occurred rarely in other groups; and (5) no metastatic lesion was found in any group throughout this study using whole-body fluorescent imaging, and the skin of the mouse in group E was intact after UMMD treatment. Our results suggest that UMMD can be used as a promising novel therapeutic strategy to treat colon cancer.

[Exploration on an ultrasonographic imaging reporting and data system in malignancy grading of thyroid nodules].

OBJECTIVE: To explore the values of ultrasonographic features in differentially diagnosing benign and malignant thyroid nodules, and attempt to establish a quantitative ultrasound classification system. METHODS: We retrospectively analyzed 20 ultrasound features of 926 thyroid nodules in 527 patients. Using logistic regression analysis, we obtained the probability function for predicting the malignancy in thyroid nodules and established a preliminary ultrasound classification system. RESULTS: The ages of patients with thyroid nodules was older than that of the patients with thyroid carcinoma (t = 6.496, P < 0.001). The correctness rate of ultrasonic diagnosis was 80.1%. The logistic multivariate regression analysis showed that among all ultrasonographic features, aspect ratio ≥ 1, obscure boundary, irregular margin, significant internal hypoecho, internal hypoecho, internal micro-calcifications, posterior echo attenuation, thyroid capsule invasion, abnormal adjacent lymph nodes, and ultrasonic elastography 5-point evaluation scores > 3 were contributing factors for thyroid carcinoma. The equation was P (us) = 1 /[1+e(-)Z], where z is the logit of malignant thyroid nodule, and taking P (us) > 0.50 as boundary value, the prediction accuracy rate was 84.1%. Using this model, 92.2% of the thyroid nodules were predicted as nodular goiter, and 69.4% of the thyroid carcinomas were correctly predicted. P (us) was stratified into four levels: Level 1: 0-16% malignancy; Level 2: 17%-50% malignancy; Level 3: 51%-70% malignancy; and level 4: 71%-100% malignancy. CONCLUSIONS: The quantitative thyroid imaging reporting and data system developed in this study makes ultrasound reports more objective, normalized and standardized. It can be used to evaluate the malignancy risk of thyroid nodules and help to make right decision in clinics.

[Aortic elastic properties and its clinical significance in intracranial aneurysms].

OBJECTIVE: To investigate the aortic elastic properties and its clinical significance in intracranial aneurysms (IAs). METHODS: One hundred and seven IAs patients (57 with hypertension) and 108 healthy subjects were recruited. The internal aortic diameters in systole and diastole were measured by the M-mode echocardiography, the aortic elasticity indexes were calculated and compared. RESULTS: The aortic distensibility (DIS) was lower and the aortic stiffness index (SI) was higher in IAs patients than those in controls (both P <0.001). DIS was lower and SI was higher in IAs patients with hypertension (IAs-HP) than those in IAs with no hypertension (P <0.001). Similar results were obtained when the aortic elasticity index were adjusted for body surface area and body mass index. CONCLUSION: Abnormal aortic elasticity is a common finding in IAs patients and hypertension is closely related to the severity of aortic elasticity.

Protein expression of mesenchymal stem cells after transfection of pcDNA3.1⁻-hVEGF165 by ultrasound-targeted microbubble destruction.

Ultrasound-targeted microbubble destruction (UTMD) has been proposed as a new technique for organ-specific gene transfer and drug delivery. This study was performed to investigate the effect of UTMD on marrow mesenchymal stem cells (MSCs) transfected with pcDNA3.1⁻-hVEGF165.pcDNA3.1⁻-hVEGF165 were transfected into the third passage of MSCs, with or without UTMD under different ultrasound conditions. Protein expression was quantified by hVEGF165-ELISA kit after transfection for 24, 48, and 72 hours. UTMD-mediated transfection of MSCs yielded a significant protein expression. UTMD of mechanic index (MI) 0.6 for 90 seconds led to the highest level of protein expression.

Giant left atrial thrombus associated with ablation for atrial tachycardia.

We report a very rare case of giant left atrial thrombus (size: 7.2 x 4.5 mm(2)) associated with radiofrequency catheter ablation for atrial tachycardia in a 72-year-old man. After 4 weeks of anticoagulation with warfarin, a repeat echocardiogram demonstrated partial resolution of the thrombus (size: 4.5 x 2.6 mm(2)) without systemic embolization.

Biventricular pacemaker implantation in a patient with isolated noncompaction of the right ventricular myocardium.

Isolated noncompaction of the ventricular myocardium is an unclassified cardiomyopathy and is thought to be due to arrest of myocardial morphogenesis. Fetal arrhythmias may occur in approximately half of the patients and account for the death in this disorder. We describe a patient with isolated noncompaction of the right ventricular myocardium in whom implantation of biventricular pacemaker was thought to be effective to prevent the risk of sudden cardiac death and complications.

Cerebral infarction in an adult patient with right ventricular hypertrabeculation/noncompaction.

Ventricular hypertrabeculation/noncompaction (VHT) is a rare congenital anomaly, and usually involves the left ventricle (LVHT), with the right ventricle (RVHT) being infrequently involved. Clinical manifestations are highly variable, ranging from no symptoms to disabling congestive heart failure, arrhythmias, systemic thromboemboli and sudden death. We report a case of right ventricular hypertrabeculation/noncompaction (RVHT) presenting as cerebral infarction.