Diagnostic value of superb microvascular imaging and color doppler for thyroid nodules: A meta-analysis.

Objective: Superb micro-vascular imaging (SMI) is a new noninvasive modality for the diagnosis of thyroid nodules. However, the performance of SMI in differentiating malignant and benign thyroid nodules has not been systematically evaluated. This meta-analysis was performed to assess the accuracy of SMI in diagnosing thyroid nodules. Methods: PubMed, Cochrane Library, Embase, Web of Science, Sinomed, Scopus were searched. We recorded the characteristics of the included studies and assessed the quality of each study using the QUADAS-2 tool. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated. We also evaluated the publication bias. Results: This meta-analysis included 10 studies with a total of 1083 thyroid nodules. The pooled the sensitivity, specificity, and positive and negative LR were 0.84, 0.86, 6.2, and 0.18, respectively. The DOR and AUC were 33 and 0.91, respectively. Heterogeneity existed between the included studies. No significant publication bias was observed. Conclusion: Compared with CDFI, Superb micro-vascular imaging (SMI) has higher diagnostic sensitivity and specificity, better diagnostic efficiency, and could be used to diagnose benign and malignant nodules in the display of blood flow distribution capabilities of thyroid nodules; at the same time, Fagan plot showed that the SMI technique had a good clinical application value, and it could supplement the deficiencies of color Doppler imaging in the diagnosis of thyroid nodules.

The hepato-cardiac disorders in Tibetan residents with hepatic echinococcosis: A case-control echocardiography study.

BACKGROUND: Clinical guidelines indicate that chronic highland exposure could induce pulmonary hypertension; chronic hepatic disease may affect cardiac structure and functions. However, the simultaneous impact of hepatic echinococcosis (HE) and chronic highland exposure on cardiac structure and function in Tibetan residents are under-investigated. METHODS: One hundred and twenty patients with HE, 23 healthy high-altitude migrants with a mean residence time of 7.15 ± 1.12 years, and 46 healthy Tibetan permanent residents were enrolled in this study. All participants received comprehensive transthoracic echocardiography. RESULTS: High-altitude migrants have a relatively lower pulmonary artery flow velocity (PV) and a slightly higher pulmonary artery mean pressure (PAMP) than the Tibetan permanent residents. Patients with HE presented relatively smaller dimensions of the main pulmonary artery and branches and a bigger right atrium and right ventricular cavity size than the two control groups. PV, PAMP and numbers of detectable tricuspid regurgitation jet velocity (TRJV), right ventricular fractional area change (RV_FAC), tricuspid annular plane systolic excursion (TAPSE), the ratio of tricuspid inflow velocities at early diastole to tricuspid annular early diastolic excursion velocity (RV_E/e') and right ventricular myocardial performance index (RV_MPI) were increased in patients with HE compared to the two control groups. Similarly, decreased LVEF and Impaired left ventricular diastolic function were identified in patients with HE compared to the two control groups. CONCLUSIONS: Patients with HE presented with impaired biventricular contractile performance and diastolic dysfunction.

A global case meta-analysis of three-dimensional speckle tracking for evaluating the cardiotoxicity of anthracycline chemotherapy in breast cancer.

Background: Anthracycline cardiotoxicity has become one of the most common complications of anthracycline therapy. Regular follow-up of chemotherapy patients with myocardial deformation parameters might be helpful for early diagnosis of myocardial damage and protective intervention. This study aimed to investigate the value of three-dimensional speckle tracking imaging (3D-STI) in diagnosing and predicting potential cardiotoxicity in breast cancer patients undergoing anthracycline therapy through meta-analysis based on global cases collection. Methods: Relevant case-control studies published prior to November 2021 were extracted to assess cardiotoxicity by 3D-STI in breast cancer patients undergoing chemotherapy. Weighted mean difference (WMD) and 95% confidence interval (CI) were used as pooled statistics. Meta regression and subgroup analysis were employed to identify sources of heterogeneity and publication bias was evaluated by Egger's test and funnel plot. Results: A total of 1,515 breast cancer patients from 14 studies were enrolled and followed up for 4 or 6 cycles of chemotherapy. Following chemotherapy, absolute values of Left ventricular ejection fraction (LVEF) WMD = -1.59, 95% CI (-1.99, -1.20); p < 0.001; global longitudinal strain (GLS) WMD = 2.19, 95% CI (1.87, 2.51); p < 0.001; global circumferential strain (GCS) WMD = 1.69, 95% CI (1.11, 2.26); p < 0.001; global radial strain (GRS) WMD = -1.72,95% CI (-2.44, -1.00); p < 0.001, and global area strain (GAS) WMD = 6.25, 95% CI (4.48, 8.02); p < 0.001 were decreased. A medium degree of heterogeneity was shown for values of LVEF (I 2 = 44.4%, p = 0.037) while values for GLS (I 2 = 59.0%, p = 0.003), GCS (I 2 = 81.3%, p < 0.001) and GRS (I 2 = 57.5%, P = 0.004) showed a large degree of heterogeneity. Egger's test and funnel plot showed no significant publication bias in GLS, GCS and GAS data (all p > 0.05). Conclusion: 3D-STI has utility for the non-invasive and objective evaluation of changes in left ventricular function in breast cancer patients undergoing chemotherapy with anthracyclines. The current findings have clinical potential for the early evaluation of myocardial injury caused by chemotherapy toxicity.

An examination of the protective effects and molecular mechanisms of curcumin, a polyphenol curcuminoid in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and is an enormous burden on both patients and society. There is an urgent need for effective alternative therapeutic strategies for the treatment of DN, as medical treatment is currently limited. The anti-inflammatory, antioxidative, anti-apoptotic, and anti-fibrosis properties of curcumin, a polyphenol curcuminoid, have been demonstrated in research on diabetic nephropathy. The clinical and preclinical trials and mechanisms by which curcumin affects DN have been discussed in this review. A deeper understanding of the pharmacological effects of curcumin on diabetic nephropathy may provide new therapies to improve the development and occurrence of diabetic nephropathy.

Removal of Unusual Foreign Metal Object (Nail) from the Right Ventricle of Human Heart: A Case Report.

Migration of foreign bodies (FB) with the blood flow to the heart is a rare, but very alarming condition as it may lead to life-threatening complications and death. Objects that are larger than 5 mm in diameter and/or irregular in shape are recommended for removal from extra- and intracardiac areas to prevent incurable embolization. Surgical extraction of intracardiac objects is a serious surgical challenge associated with difficulties to operate, during the continuous movement of the heart, and identify the exact FB location. Early diagnosis and timely removal of FBs are crucial treatment factors for this rare case resolution. We report a case of accidental migration of a metal FB object (nail) about 1.0*0.3 cm from the right neck area jugular vein to the right ventricle apex in the heart. The FB localization was accurately detected using Bi-plane transesophageal echocardiography (TEE) with a special comet-tail artifact. TEE provided valuable information before surgery, and the nail was successfully removed through open-heart surgical procedures and cardiopulmonary bypass (CPB). Postoperative tests indicated no complications.

Relationship between living habits and metabolic diseases in community populations based on ultrasound diagnosis of nafld / Relação entre hábitos de vida e doenças metabólicas em comunidades com base na doença hepática gordurosa não alcoólica (dhgna) diagnosticada por ultrassom / Diagnóstico ultrasónico de la relación entre los hábitos de vida de la comunidad nafld y las enfermedades metabólicas

ABSTRACT As a common metabolic disease, non-alcoholic fatty liver disease (NAFLD) is the most common type of liver disease in western developed countries and an important liver disease in the Asia Pacific region. At present, NAFLD lacks targeted conventional therapy and its basic treatment is the correction of bad living habits. In order to verify the effectiveness of the basic treatment of NAFLD, and explore the prevention methods of NAFLD, this study used ultrasound diagnosis, baseline survey and follow-up survey, and conducted a cross-sectional study on the correlation between nighttime and midday sleep duration and NAFLD, and carried out a prospective study on the correlation between sleep duration and NAFLD. The results showed that there was a negative correlation between the length of sleep at night and the prevalence of NAFLD, while the length of midday sleep was positively correlated with the prevalence of NAFLD. The time of night sleep was an independent factor of NAFLD, and the relationship between midday sleep time and NAFLD was not statistically significant. NAFLD-susceptible people can prevent NAFLD by ensuring adequate sleep at night and reducing midday sleep. This study is expected to provide theoretical reference and data support for the prevention and treatment of NAFLD.

RESUMO Como uma doença metabólica comum, a doença doença hepática gordurosa não alcoólica (DHGNA) é o tipo de doença hepática mais comum nos países desenvolvidos ocidentais e uma doença hepática importante na região Ásia Pacífico. Atualmente, a DHGNA carece de terapia convencional orientada, e seu tratamento básico é a correção de maus hábitos de vida. A fim de verificar a eficácia do tratamento básico da DHGNA e explorar os métodos de prevenção da DHGNA, este estudo, baseado no diagnóstico por ultrassom, através do inquérito de base e do inquérito de acompanhamento, consistiu de estudo transversal sobre a correlação entre a duração do sono à noite e de dia e a DHGNA, e realizou um estudo prospectivo sobre a correlação entre a duração do sono e a DHGNA. Os resultados mostraram que havia uma correlação negativa entre a duração do sono à noite e a prevalência de DHGNA, enquanto a duração do sono de dia estava positivamente correlacionada com a prevalência da DHGNA. A hora do sono noturno foi um fator independente de DHGNA, e a relação entre o sono de dia e DHGNA não foi estatisticamente significativa. As pessoas sensíveis à DHGNA podem prevenir a DHGNA garantindo o sono adequado à noite e reduzindo o sono de dia. Espera-se que este estudo possa fornecer referências teóricas e suporte de dados para a prevenção e tratamento da DHGNA.

RESUMEN Como enfermedad metabólica común, la enfermedad del hígado graso no alcohólico (NAFLD) es el tipo más común de enfermedad hepática en los países desarrollados occidentales y una enfermedad hepática importante en la región de Asia que da al Pacífico. En la actualidad, la EHGNA carece de terapia convencional dirigida y su tratamiento básico es la corrección de los malos hábitos de vida. Con el fin de verificar la efectividad del tratamiento básico y explorar los métodos de prevención de la EHGNA, este estudio utilizó un diagnóstico por ultrasonido, una encuesta de referencia y una encuesta de seguimiento, condujo un estudio transversal sobre la correlación entre la duración del sueño nocturno y la siesta y la EHGNA, y realizó un estudio prospectivo sobre la correlación entre la duración del sueño y la EHGNA. Los resultados mostraron que hubo una correlación negativa entre la duración del sueño por la noche y la prevalencia de EHGNA, mientras que la duración de la siesta se correlacionó positivamente con la prevalencia de EHGNA. El tiempo de sueño nocturno fue un factor independiente de la EHGNA, y la relación entre el tiempo de siesta y la EHGNA no fue estadísticamente significativa. Las personas susceptibles a la EHGNA pueden prevenirla asegurando un sueño adecuado por la noche y reduciendo la siesta. Se espera que este estudio proporcione referencias teóricas y soporte de datos para la prevención y el tratamiento de la EHGNA.

The impact of cigarette smoking in predicting stroke using CHADS2 and CHA2DS2-VASc schemas.

OBJECTIVE: To determine the impact of smoking status in the prediction of stroke using CHADS2 and CHA2DS2-VASc schemes. METHODS: Five hundred twenty-eight consecutive patients with arrhythmic symptoms and without any documented arrhythmia from Queen Mary Hospital, Hong Kong, were followed up to determine the incidence of ischemic stroke, new-onset atrial fibrillation (AF), or all-cause mortality. Smoking status was classified into nonsmokers and smokers. The pairwise comparisons of C-statistics for outcomes were performed. RESULTS: During a median follow-up period of 6.2 years, 65 (12.3%) individuals developed ischemic stroke. Smokers experienced higher annual incidence of stroke, a new-onset AF, and all-cause death compare to nonsmokers, with corresponding hazard ratio (HR) of stroke, AF, and all-cause death being 2.51 (95% confidence intervals, CI 1.36als, CIse death bein 1.15a3.24), and 1.95 (95% CI 1.161.95 (95% CIath being 2.51 (95% confidence corr2 and CHA2DS2-VASc for stroke were 0.60 (95% CI 0.51 for stp = 0.09) and 0.59 (95% CI 0.50 (95%, p = 0.15) respectively, whereas the C-statistics of CHADS2 and CHA2DS2-VASc were 0.66 (95% CI 0.61 were 0p = 0.005), 0.75 (95% CI 0.7 CI 0.7p < 0.0001), respectively among nonsmokers. After incorporating smoking, both the CHADS2-smoking and CHA2DS2-VASc-smoking achieved better C-statistics for new-onset ischemic stroke prediction superior to baseline score systems in male groups. CONCLUSION: Cigarette smoking status has impact on stroke stratification using CHADS2 and CHA2DS2-VASc scheme. The discrimination of the CHADS2 and CHA2DS2-VASc scheme for stroke can be significantly improved if smoking status is additionally considered.

Thyroid imaging reporting and data system (TIRADS) for ultrasound features of nodules: multicentric retrospective study in China.

PURPOSE: To establish a practical and simplified Chinese thyroid imaging reporting and data system (C-TIRADS) based on the Chinese patient database. METHODS: A total of 2141 thyroid nodules that were neither cystic nor spongy were used in the current study. These specimens were derived from 2141 patients in 131 alliance hospitals of the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound. The ultrasound features, including location, orientation, margin, halo, composition, echogenicity, echotexture, echogenic foci and posterior features were assessed. Univariate and multivariate analyses were performed to investigate the association between ultrasound features and malignancy. The regression equation, the weighting, and the counting methods were used to determine the malignant risk of the thyroid nodules. The areas under the receiver operating characteristic curve (Az values) were calculated. RESULTS: Of the 2141 thyroid nodules, 1572 were benign, 565 were malignant, and 4 were borderline. Vertical orientation, ill-defined, or irregular margin (including extrathyroidal extension), microcalcifications, solid, and markedly hypoechoic were positively associated with malignancy, while comet-tail artifacts were negatively associated with malignancy. The logistic regression equation yielded the highest Az value of 0.913, which was significantly higher than that obtained using the weighting method (0.893) and the counting method (0.890); however, no significant difference was found between the latter two. The C-TIRADS, based on the counting method, was designed following the principle of balancing the diagnostic performance and sensitivity of the risk stratification with the ease of use. CONCLUSIONS: A relatively simple C-TIRADS was established using the counting value of positive and negative ultrasound features.

Tibetan patients with hepatic hydatidosis can tolerate hypoxic environment without incident increase of pulmonary hypertension: an echocardiography study.

Use of echocardiography to evaluate the characteristics of right heart and pulmonary artery of Tibetans with hepatic hydatidosis living in a high plateau area. We recruited 222 Tibetan adults diagnosed with hydatidosis from June 2016 to June 2017 in Shiqu and Seda areas of Tibet; 40 healthy control from the same area, denoted as the high plateau group. We also include 755 Healthy adults of Han nationality living in the plain from the EMINCA study as the low altitude group. Compared to high plateau group, hydatidosis individuals showed decreased RVADed, RVTDed, increased E(T)/A(T) and reduced RVFAC and TAPSE (p < 0.05). The 2 groups did not differ in the incidence rate of tricuspid regurgitation (TR) and pulmonary regurgitation (PR) (63.9% vs. 55.0%, p = 0.281 and 15.3% vs. 5.0%, p = 0.135, respectively) or incidence of pulmonary hypertension (PH) (13.9% vs. 20.5%, p = 0.167). PH risk did not differ between hydatidosis individuals and high plateau controls (OR 0.559, 95% CI 0.243-1.287). The RVADed and TAPSE were higher and E(T)/A(T) was lower for high plateau group than low altitude group (p < 0.05). The decreased right ventricular size and reduced diastolic and systolic function were found in Tibetans with hydatidosis. Hepatic hydatidosis had no significant effect on the incidence of pulmonary hypertension in Tibetans. Healthy Tibetans showed increased right ventricular size, decreased diastolic function, and increased systolic function compared to the Han counterparts.

2020 Chinese guidelines for ultrasound malignancy risk stratification of thyroid nodules: the C-TIRADS.

Thyroid nodules are very common all over the world, and China is no exception. Ultrasound plays an important role in determining the risk stratification of thyroid nodules, which is critical for clinical management of thyroid nodules. For the past few years, many versions of TIRADS (Thyroid Imaging Reporting and Data System) have been put forward by several institutions with the aim to identify whether nodules require fine-needle biopsy or ultrasound follow-up. However, no version of TIRADS has been widely adopted worldwide till date. In China, as many as ten versions of TIRADS have been used in different hospitals nationwide, causing a lot of confusion. With the support of the Superficial Organ and Vascular Ultrasound Group of the Society of Ultrasound in Medicine of the Chinese Medical Association, the Chinese-TIRADS that is in line with China's national conditions and medical status was established based on literature review, expert consensus, and multicenter data provided by the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound.

Can Combined Screening of Ultrasound and Elastography Improve Breast Cancer Identification Compared with MRI in Women with Dense Breasts-a Multicenter Prospective Study.

Objectives: To assess the performance of elastography (ES) and ultrasound (US) in predicting the malignancy of breast lesions and to compare their combined diagnostic value with that of magnetic resonance imaging (MRI). Materials and Methods: The study prospectively enrolled 242 female patients with dense breasts treated in 35 heath care facilities in China between November 2018 and October 2019. Based on conventional US and elastography, radiologists classified the degree of suspicion of breast lesions according to the US Breast Imaging Reporting and Data System (BI-RADS) criteria. The diagnostic value was compared between US BI-RADS and MRI BI-RADS, with pathological results used as the reference standard. Results: The results demonstrated that irregular tumor shape, a nonparallel growth orientation, indistinct margins, angular contours, microcalcifications, color Doppler flow and ES score on US imaging were significantly related to breast cancer in dense breasts (P=0.001; P=0.001; P=0.008; P<0.001; P=0.019; P=0.008; P=0.002, respectively). The sensitivity, specificity, PPV, NPV, accuracy and AUC of US BI-RADS category were 94.7%, 90.7%, 95.8%, 88.0%, 93.4% and 0.93 (95%CI, 0.88-0.97), respectively, while those of MRI BI-RADS category were 98.2%, 57.5%, 84.3%, 83.3%, 86.0% and 0.78 (95%CI, 0.71-0.85), respectively. MRI BI-RADS showed a significantly higher sensitivity than US BI-RADS (98.2% vs 94.7%, P=0.043), whereas US BI-RADS showed significantly higher specificity (90.7% vs 57.5%, P<0.001). US BI-RADS showed better diagnostic efficiency in differentiating nodules in dense breasts than MRI BI-RADS (AUC 0.93 vs 0.78, P<0.001). Conclusion: By combining the use of ES and conventional US, US BI-RADS had better diagnostic efficiency in differentiating nodules in dense breasts than MRI. For the diagnosis of malignant tumors in patients with dense breasts, MRI and US BI-RADS can be used as supplemental diagnostic tools to detect lesions, with US BI-RADS considered the preferred adjunctive resource.

Outcomes of Asian-Americans Implanted With Left Ventricular Assist Devices: An Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Analysis.

BACKGROUND: Studies have indicated differences between Asians and Whites in their propensity for stroke, coronary artery disease, heart failure, bleeding and thrombosis. We investigated whether Asian-Americans on durable left ventricular assist devices (LVADs) exhibit differential morbidity and mortality when compared to Whites. METHODS: We analysed prospectively collected data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database to compare the outcomes after LVAD implantation of Asians versus Whites. RESULTS: In total, 7,018 patients were included, 130 were identified as Asian-Americans. Asian-Americans were younger, had lower body mass index, higher serum bilirubin and lower albumin levels. In a multivariable regression model, there was no difference in survival between the two groups. Asian-Americans had lower incidence of device malfunction and after adjusting for multiple factors this remained lower. The adjusted risk of a major safety composite outcome, including major bleeding, major infection, stroke and device malfunction, revealed no difference between the two groups. CONCLUSIONS: Although prior studies have reported worse cardiac surgery outcomes in Asians, in this INTERMACS analysis Asian-Americans appear to have similar survival and risk of adverse events as their White counterparts. The incidence of device malfunction was lower in the Asian-Americans, both in a univariate model and after adjusting for multiple clinical factors. Future, larger studies of Asian-Americans with end-stage heart failure and LVAD support are warranted to confirm these results.

PAK1 promotes proliferation, migration and invasion of hepatocellular carcinoma by facilitating EMT via directly up-regulating Snail.

BACKGROUND: Hepatocellular carcinoma (HCC) is a primary cause of cancer mortality. PAK1 plays key roles in many types of cancers. However, the role of PAK1 in HCC is not clear. METHODS: qRT-PCR and Western blotting were used to determine expressions of PAK1, Snail and epithelial mesenchymal transition (EMT)-related proteins. Luciferase reporter assay was used to measure the interaction between PAK1 and Snail. Wound healing, transwell, colony formation assays and flow cytometry were used to assess cell migration, invasion, proliferation and apoptosis. Mouse tumor xenograft model was used to determine the effect of PAK1 on tumor growth in vivo. RESULTS: PAK1 and Snail were up-regulated in HCC cells. PAK1 knockdown suppressed cell proliferation, migration and invasion, and increased apoptosis of HCC cells. PAK1 knockdown also inhibited tumor growth in vivo. Mechanistically, PAK1 promoted EMT by targeting Snail. Knockdown of PAK1 could up-regulate pro-apoptotic proteins but down-regulate proliferation-related proteins via suppressing ß-catenin signaling pathway. CONCLUSION: PAK1 promotes EMT process by increasing Snail, and facilitates progression of HCC by activating ß-catenin pathway.

Cell penetrating peptide-modified nanoparticles for tumor targeted imaging and synergistic effect of sonodynamic/HIFU therapy.

BACKGROUND: Theranostics based on multifunctional nanoparticles (NPs) is a promising field that combines therapeutic and diagnostic functionalities into a single nanoparticle system. However, the major challenges that lie ahead are how to achieve accurate early diagnosis and how to develop efficient and noninvasive treatment. Sonodynamic therapy (SDT) utilizing ultrasound combined with a sonosensitizer represents a novel noninvasive modality for cancer therapy. Different ultrasound frequencies have been used for SDT, nevertheless, whether the effect of SDT can enhance synergistic HIFU ablation remains to be investigated. MATERIALS AND METHODS: We prepared a nanosystem for codelivery of a sonosensitizer (methylene blue, MB) and a magnetic resonance contrast agent (gadodiamide, Gd-DTPA-BMA) based on hydrophilic biodegradable polymeric NPs composed of poly (lactic-co-glycolic acid) (PLGA). To enhance accumulation and penetration of the NPs at the tumor site, the surface of PLGA NPs was decorated with a tumor-homing and penetrating peptide-F3 and polyethylene glycol (PEG). The physicochemical, imaging and therapeutic properties of F3-PLGA@MB/Gd and drug safety were thoroughly evaluated both in vitro and in vivo. F3-PLGA@MB/Gd was evaluated by both photoacoustic and resonance imaging. RESULTS: F3-PLGA@MB/Gd NPs exhibited higher cellular association than non-targeted NPs and showed a more preferential enrichment at the tumor site. Furthermore, with good drug safety, the apoptosis triggered by ultrasound in the F3-PLGA@MB/Gd group was greater than that in the contrast group. CONCLUSION: F3-PLGA@MB/Gd can work as a highly efficient theranostic agent, and the incorporation of targeted multimodal and combined therapy could be an encouraging strategy for cancer treatment.

miR-122 enhances sensitivity of hepatocellular carcinoma to oxaliplatin via inhibiting MDR1 by targeting Wnt/ß-catenin pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the primary causes of cancer-related death and resistance to cytotoxic chemotherapy is the major cause of mortality in HCC patients. miR-122 is a liver specific miRNA and is found to be reduced in HCC, however, the function of miR-122 in HCC chemosensitivity remains elusive. METHODS: We used qRT-PCR to measure expressions of miR-122, ß-catenin and MDR1 in four HCC cell lines. And we assessed the effects of miR-122 or ß-catenin on cell viability and apoptosis upon oxaliplatin (OXA) treatment by MTT assay and flow cytometry. In addition, we validated the interactions of miR-122/ß-catenin and ß-catenin/MDR1 by dual luciferase reporter assay and chromatin immunoprecipitation (ChIP). Western blotting was used to determine the protein levels of ß-catenin, Wnt1 and MDR1. In the end, we verified the anti-tumor effect of miR-122 in vivo by using mouse tumor xenograft model. RESULTS: We found that miR-122 was down-regulated in HCC cells. Up-regulation of miR-122 or inhibition of Wnt/ß-catenin signaling promoted HCC cells apoptosis and increased the sensitivity of HCC cells to OXA. On the molecular level, we showed that miR-122 directly targeted and suppressed Wnt/ß-catenin pathway while ß-catenin bound with MDR1 promoter and activated its transcription. Overexpression of miR-122 inhibited MDR1 expression via directly suppressing Wnt/ß-catenin pathway. CONCLUSION: Our study fully demonstrated that miR-122 inhibits MDR1 expression via suppression of Wnt/ß-catenin pathway, thereby enhancing HCC sensitivity to OXA. Therefore, miR-122 could serve as a novel potential therapeutic target for HCC.

Smoking is associated with depletion of circulating endothelial progenitor cells and elevated pulmonary artery systolic pressure in patients with coronary artery disease.

Smoking is associated with depletion of endothelial progenitor cells (EPCs) and may subsequently contribute to the development of vascular dysfunction. The aim of this study was to investigate the relation between circulating EPCs and pulmonary artery systolic pressure (PASP) as determined by flow cytometry and echocardiography in 174 patients (mean age 69 ± 9 years, 95 smokers) with established coronary artery disease. Smokers had significantly lower circulating log CD34/KDR(+) (0.86 ± 0.03 vs 0.96 ± 0.03 × 10⁻³/ml, p = 0.032) and log CD133/KDR(+) (0.68 ± 0.03 vs 0.82 ± 0.03 × 10⁻³/ml, p = 0.002) EPCs and a higher prevalence of elevated PASP >30 mm Hg (52% vs 30%, p = 0.001) than nonsmokers. Smokers with elevated PASP also had significantly lower circulating log CD34/KDR(+) (0.74 ± 0.04 vs 0.88 ± 0.06 × 10⁻³/ml, p <0.001) and log CD133/KDR(+) (0.61 ± 0.04 vs 0.78 ± 0.05 × 10⁻³/ml, p <0.001) EPCs, higher pulmonary vascular resistance, and larger right ventricular dimensions with impaired function (all p values <0.05). Log CD34/KDR(+) and log CD133/KDR(+) EPC counts were significantly and negatively correlated with PASP (r = -0.30, p <0.001, and r = -0.34, p <0.001, respectively) and pulmonary vascular resistance (r = -0.29, p = 0.002, and r = -0.18, p = 0.013, respectively). In conclusion, this study demonstrated that in patients with coronary artery disease, smoking was associated with a reduced number of EPCs and elevated PASP. This suggests that in smokers, depletion of circulating EPCs might be linked to the occurrence of pulmonary vascular dysfunction.

Intracardiac echocardiography-guided his bundle pacing and atrioventricular nodal ablation.

BACKGROUND: His bundle pacing (HBP) results in rapid synchronous ventricular activation, but has been associated with long procedure times and compromised pacing and sensing performance. This study sought to reduce procedure time and radiation exposure, and improve electrical performance through more accurate lead placement. METHODS: Intracardiac echocardiography (ICE) was used to guide ablation and lead implantation at the His bundle, right atrial appendage (RAA), and right ventricular apex (RVA), and to assess cardiac function. Custom bipolar screw-in leads with steerable delivery sheaths and an ablation catheter were navigated using ICE (local detailed imaging) and fluoroscopy (global imaging) in anesthetized closed-chest canines (N = 6). RESULTS: HBP (N = 1) or His + ventricular septal pacing (N = 5) was achieved in all canines. The QRS width was 59.7 +/- 5.3 ms for canines in sinus rhythm (SR) and 82.8 +/- 16.6 ms for canines with HBP (P = 0.0086). The QRS width for RVA pacing was 106.3 +/- 18.4 ms (P = 0.042 vs HBP; P = 0.00013 vs SR). HBP thresholds were 3.0 +/- 1.0 volts at 0.5 ms (N = 5 due to a late exit block in one canine). The average procedure duration for His lead placement was 40 +/- 28 minutes (range of 3-81 minutes) and the total procedural X-ray exposure was 12 +/- 12 minutes (range of 2-30 minutes). Hemodynamic performance was similar for HBP and RAA pacing. CONCLUSIONS: Feasibility of ICE guidance for His pacing and precision ablation of the atrioventricular (AV) node has been shown. This anatomic approach improved accuracy, limited X-ray exposure, and might allow His pacing in patients with preexisting AV nodal block.