Circulating plasma galectin-3 predicts new-onset atrial fibrillation in patients after acute myocardial infarction during hospitalization.

BACKGROUND: New-onset atrial fibrillation (NOAF) is a common complication in patients with acute myocardial infarction (AMI) during hospitalization. Galectin-3 (Gal-3) is a novel inflammation marker that is significantly associated with AF. The association between post-AMI NOAF and Gal-3 during hospitalization is yet unclear. OBJECTIVE: The present study aimed to investigate the predictive value of plasma Gal-3 for post-AMI NOAF. METHODS: A total of 217 consecutive patients admitted with AMI were included in this retrospective study. Peripheral venous blood samples were obtained within 24 h after admission and plasma Gal-3 concentrations were measured. RESULTS: Post-AMI NOAF occurred in 18 patients in this study. Patients with NOAF were older (p < 0.001) than those without. A higher level of the peak brain natriuretic peptide (BNP) (p < 0.001) and Gal-3 (p < 0.001) and a lower low-density lipoprotein cholesterol level (LDL-C) (p = 0.030), and an estimated glomerular filtration rate (e-GFR) (p = 0.030) were recorded in patients with post-AMI NOAF. Echocardiographic information revealed that patients with NOAF had a significantly decreased left ventricular eject fraction (LVEF) (p < 0.001) and an increased left atrial diameter (LAD) (p = 0.004) than those without NOAF. The receiver operating characteristic (ROC) curve analysis revealed a significantly higher value of plasma Gal-3 in the diagnosis of NOAF for patients with AMI during hospitalization (area under the curve (p < 0.001), with a sensitivity of 72.22% and a specificity of 72.22%, respectively. Multivariate logistic regression model analysis indicated that age (p = 0.045), plasma Gal-3 (p = 0.018), and LAD (p = 0.014) were independent predictors of post-MI NOAF. CONCLUSIONS: Plasma Gal-3 concentration is an independent predictor of post-MI NOAF.

Left atrial strain for predicting recurrence in patients with non-valvular atrial fibrillation after catheter ablation: a single-center two-dimensional speckle tracking retrospective study.

BACKGROUND: Although catheter ablation (CA) is an effective treatment for non-valvular atrial fibrillation (AF), a good many of patients still have a recurrence following post-operation. Prediction of AF recurrence by evaluating left atrial (LA) phase function with speckle tracking echocardiography (STE) may be helpful for risk stratification and clinical management for AF patients. Therefore, the current study aimed to assess the prognostic value of LA strains in non-valvular AF patients after CA. METHODS: A total of 95 non-valvular AF patients (70.5% paroxysmal AF, 56.8% males, mean age 63.2 ± 9.7 years) were included in this retrospective study between October 2019 and August 2020. Transthoracic echocardiography was performed in all the subjects and STE was used to analyze the LA reservoir strain (LASr), LA conduit strain (LAScd) and LA contractile strain (LASct) during different phases before CA. Patients were followed up with until January 2022. The endpoint was AF recurrence. RESULTS: Over a median follow-up period of 26.0 months (interquartile range, 24.7-26.7 months), 26 patients experienced recurrence and 69 stayed in sinus rhythm. Compared with no-recurrence group, maximum volume of LA (LAVmax), minimum volume of LA (LAVmin) and LA volume index (LAVI) were increased in the recurrence group, while LAEF, LASr and LASct were worsened (P < 0.05). Multivariable logistic regression analysis revealed that LASct was an independent predictor of AF recurrence (odds ratio, 0.89; 95% confidence interval (CI), 0.82-0.97; P = 0.007) and receiver operating characteristic (ROC) curve analysis showed an area under the curve of LASct<8% was 0.70 (95% CI, 0.59-0.79; P = 0.0008). CONCLUSIONS: LASct was of independent predictive value of AF recurrence. LA function assessed by STE may contribute to the risk stratification for AF patients and selection of suitable patients for CA.

Reduced mechanical function of the left atrial predicts adverse outcome in pregnant women with clustering of metabolic risk factors.

INTRODUCTION: The left atrial (LA) strain and strain rate are sensitive indicators of LA function. However, they are not widely used for the evaluation of pregnant women with metabolic diseases. The aim of this study was to assess the LA strain and strain rate of pregnant women with clustering of metabolic risk factors and to explore its prognostic effect on adverse pregnancy outcomes. MATERIALS AND METHODS: Sixty-three pregnant women with a clustering of metabolic risk factors (CMR group), fifty-seven women with pregnancy-induced hypertension (PIH group), fifty-seven women with gestational diabetes mellitus (GDM group), and fifty matched healthy pregnant women (control group) were retrospectively evaluated. LA function was evaluated with two-dimensional speckle-tracking imaging. Iatrogenic preterm delivery caused by severe preeclampsia, placental abruption, and fetal distress was regarded as the primary adverse outcome. RESULTS: The CMR group showed the lowest LA strain during reservoir phase (LASr), strain during contraction phase (LASct) and peak strain rate during conduit phase (pLASRcd) among the three groups (P < 0.05). LA strain during conduit phase (LAScd) and peak strain rate during reservoir phase (pLASRr) in the CMR group were lower than those in the control and GDM groups (P < 0.05). Multivariable Cox regression analysis demonstrated systolic blood pressure (HR = 1.03, 95% CI 1.01-1.05, p = 0.001) and LASr (HR = 0.86, 95% CI 0.80-0.92, p < 0.0001) to be independent predictors of iatrogenic preterm delivery. An LASr cutoff value ≤ 38.35% predicted the occurrence of iatrogenic preterm delivery. CONCLUSIONS: LA mechanical function in pregnant women with metabolic aggregation is deteriorated. An LASr value of 38.35% or less may indicate the occurrence of adverse pregnancy outcomes.

Risk assessment in interstitial lung disease: the incremental prognostic value of cardiopulmonary ultrasound.

BACKGROUND: The mortality risk of chronic interstitial lung disease (ILD) is currently assessed using the ILD-GAP score. The present study evaluates whether the addition of cardiopulmonary ultrasound parameters to the ILD-GAP score can further improve the predictive value of ILD-GAP. METHODS: Medical records from 91 patients with ILD hospitalized from June 2015 to March 2016 were retrospectively examined. The Lung ultrasound (LUS) score, right ventricular (RV) function, and mechanics were obtained from the cardiopulmonary ultrasound. The ILD-GAP score was calculated from demographic characteristics and pulmonary function parameters. Patients were followed up with until May 2020. The primary endpoint was all-cause death. RESULTS: After exclusions, 74 patients with ILD were included in the analysis. During the follow-up period, 36 patients with ILD survived (ILDs), and 38 patients died (ILDd). Compared to ILDs, the ILDd cases exhibited a higher number of B-lines, LUS score, and RV end-diastolic base dimension (RVD), but lower RV function. In multivariate analysis, the ILD-GAP score (hazard ratio, 2.88; 95% CI 1.38-5.99, P = 0.005), LUS score (hazard ratio 1.13; 95% CI 1.04-1.24, P = 0.006), and RVD (hazard ratio 1.09, 95% CI 1.03-1.16, P = 0.004) were significantly related to the risk of death. Adding the LUS score and RVD to the ILD-GAP score significantly improved the predictive value compared to the ILD-GAP score alone (C statistics 0.90 vs 0.76, P = 0.018). CONCLUSION: We investigated the utility of a new prognostic model for ILD that includes both cardiopulmonary ultrasound parameters (LUS score and RVD) and the ILD-GAP score. This model better reflects the severity of pulmonary fibrosis and cardiac involvement, and has incremental predictive value over the ILD-GAP score alone.

Influence of impaired right ventricular contractile reserve on exercise capacity in patients with precapillary pulmonary hypertension: A study with exercise stress echocardiography.

OBJECTIVES: Right ventricular (RV) contractile reserve reflects the ability of RV to accommodate the increased afterload and may play an essential role in the evaluation of precapillary pulmonary hypertension (PH). This study aimed to assess RV contractile reserve based on exercise stress echocardiography (ESE) and to determine the echocardiographic determinants of exercise capacity in patients with precapillary PH. METHODS: A total of 31 patients with precapillary PH and 15 age- and sex-matched healthy control subjects were prospectively recruited. All subjects underwent ESE to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. Patients with precapillary PH also underwent cardiopulmonary exercise test (CPET), and data pertaining to peak oxygen uptake (peak VO2 ) and minute ventilation/carbon dioxide production (VE/VCO2 ) were collected. RESULTS: Right ventricular contractile reserve including change in tricuspid annular plane systolic excursion (∆TAPSE), change in RV fractional area change (∆RVFAC), and change in Doppler-derived tricuspid lateral annular peak systolic velocity (∆S') was significantly depressed in precapillary PH patients compared with control subjects (P < 0.05). Parameters of RV function and RV contractile reserve were markedly associated with maximal exercise capacity (P < 0.05). ∆RVFAC was an independent predictor of peak VO2 (r2  = 0.601, P < 0.05). CONCLUSIONS: Assessment of RV contractile reserve facilitates identification of subclinical dysfunction and evaluation of clinical status and severity of precapillary PH. ESE as a noninvasive method may provide a comprehensive clinical assessment and facilitate therapeutic decision-making for these patients.

Impaired left ventricular mechanics and functional reserve are associated with reduced exercise capacity in patients with hypertrophic cardiomyopathy.

BACKGROUND: Reduced metabolic equivalents (METs) are an indicator of exercise intolerance, which predicts poor prognosis in hypertrophic cardiomyopathy (HCM) patients. We sought to evaluate the changes in left ventricular (LV) mechanics and functional reserves, as well as their association with functional capacity in HCM patients. METHODS: Seventy HCM patients and thirty controls were included in this study. LV mechanics were evaluated at rest and during exercise by echocardiography and two-dimensional speckle-tracking imaging to obtain parameters of functional reserve, LV global longitudinal strain (LVGLS), strain rate (SR), and circumferential strain. RESULTS: Hypertrophic cardiomyopathy (HCM) patients had lower LVGLS, systolic SR, early and late diastolic SR at rest and during exercise, and reduced absolute and relative systolic and diastolic reserve compared to controls. LV circumferential strain was significantly higher at rest but lower during exercise in HCM patients. Exercise capacity was markedly reduced in HCM patients, and peak exercise LVGLS (LVGLS-exe) significantly correlated with exercise capacity. Multivariate regression analyses showed that LVGLS-exe, LV filling pressure during exercise (E/e'-exe), and LV mass index (LVMI) were independent predictors of exercise capacity. Moreover, LVGLS-exe displayed incremental predictive value over E/e'-exe and LVMI for exercise intolerance. Receiver operating characteristic curve analysis showed LVGLS-exe had optimal accuracy for predicting exercise intolerance in HCM patients. CONCLUSIONS: Hypertrophic cardiomyopathy (HCM) patients have reduced LV mechanics at rest and during exercise and impaired mechanical reserve. LVGLS-exe is associated with exercise capacity and is an optimal predictive value for reduced exercise capacity in HCM patients.

High-Resolution Transthoracic Ultrasonography for Assessment of Pleural Lines in Patients With Dyspnea With CT Comparison: An Observational Study.

OBJECTIVES: Detection of B-line in dyspneic patients is often accompanied by abnormal changes of pleural line on transthoracic ultrasonography (TUS). The aim of the study was to evaluate the relevance and diagnostic performance of pleural line abnormalities and B-lines detected on high-resolution TUS against the computed tomography (CT) findings. METHODS: Transthoracic ultrasonography was performed in patients admitted to the emergency department with dyspnea. The pleural line and accompanying B-line were assessed using a linear transducer. The TUS findings were assessed against the corresponding high-resolution CT findings in the same location, which were considered to be the gold standard. RESULTS: Out of a total of 116 patients, 68.1% had changes of the pleural line on TUS. The characteristic changes of the pleural line were classified into four types: slightly rough pleural line with confluent B-lines on TUS corresponded with CT findings of ground-glass opacity; irregular and interrupted pleural line with confluent B-lines corresponded with parenchymal infiltration; fringed pleural line with confluent B-lines corresponded with superimposed ground-glass and irregular reticular opacities; and fringed pleural line with scattered B-lines corresponded with irregularly thickened interlobular septa. Wavy pleural line indicated subpleural emphysema. The coexistence of more than one abnormal pleural line was also found in 31 cases (26.7%). CONCLUSIONS: High-resolution TUS may help in the initial assessment of lung pathology by its ability to identify pleural line abnormalities and B-lines that are shown to be associated with CT, which could add diagnostic value in the emergency evaluation of dyspneic patients.

Vitamin D Level is Associated with Increased Left Ventricular Mass and Arterial Stiffness in Older Patients with Impaired Renal Function.

BACKGROUND Impaired renal function is common among older patients. Deficiency of vitamin D is a frequent phenomenon among patients with impaired renal function, who are likely to develop cardiovascular diseases. This study aimed to explore the association of 25 (OH) D levels with left ventricular mass and arterial stiffness in older patients with impaired renal function. MATERIAL AND METHODS Based on their admission estimate glomerular filtration rate (eGFR), 273 inpatients (≥65 years) were allocated into a normal eGFR group (≥60 ml/min) and an impaired eGFR group (<60 ml/min). The 25 (OH) D levels were measured and the left ventricular mass index (LVMI) was estimated. Pulse wave velocity (PWV) was used to explore arterial stiffness. RESULTS The 25 (OH) D levels of patients in the impaired eGFR group were significantly lower than in the normal eGFR group [(11.92±6.01) µg/L vs. (18.14±8.07) µg/L, p<0.05). LVMI and PWV were both significantly higher in the impaired eGFR group than in the normal eGFR group [(104.89±33.50) g/m2 vs. (92.95±18.95) g/m2, P<0.05; (15.99±3.10) m/s vs. (13.62±2.90) m/s, P<0.05]. After adjusting for age, sex, eGFR, cardiovascular risk factors, serum calcium, and iPTH levels, the inverse association between LVMI and 25 (OH) D, PWV, and 25 (OH) D were statistically significant. CONCLUSIONS Vitamin D level is lower in older patients with impaired renal function. Lower vitamin D levels were correlated with higher left ventricular mass and increased arterial stiffness in older patients.

[Pharmacoeconomic evaluation of treatments based on antiretrovirals for HBeAg-negative chronic hepatitis B].

OBJECTIVE: To evaluate long-term cost-effectiveness of nucleoside analogues and peg-interferon alfa-2a (peg-IFNa2a) for the treatment of chronic hepatitis B (CHB) in hepatitis B e antigen (HBeAg)-negative patients. METHODS: A multi-health slate Markov model was developed based on the disease progression pattern to estimate the long-term effect and medical expense of different treatments for HBeAg-negative CHB.Incremental cost-effectiveness analysis was then carried out. RESULTS: In comparison with no antiretroviral treatment, all of the antiretroviral treatments were capable of prolonging CHB patients' life years.In particular, entecavir plus adefovir dipivoxil combination therapy showed the best 2 year survival, with expected life-years and quality-adjusted life-years (QALYs) being 19.59 years and 10.12 years, respectively, which were 1.46 years and 1.12 years better than with no antiretroviral treatment. The most cost-effective treatment for HBeAg-negative CHB was lamivudine plus adefovir dipivoxil rescue therapy, as it prolonged survival by 0.95 QALYs with an additional 15459 yuan; the incremental medical cost for gaining 1 QALY was 16273 yuan. CONCLUSION: Among the antiretroviral medicines applied as therapy for HBeAg-negative CHB in China, the most effective treatment is entecavir plus adefovir dipivoxil rescue therapy and the most cost-effective treatment is lamivudine plus adefovir dipivoxil rescue therapy.

Transcatheter Edge-to-Edge Repair for Severe Mitral Regurgitation With Double-Orifice Mitral Valve.

Double-orifice mitral valve (DOMV), a rare congenital heart disease, is the inspiration behind the transcatheter edge-to-edge repair (TEER). Here we report a successful TEER case in a patient with DOMV with severe regurgitation. The patient's symptoms were greatly improved after the procedure.

Hepatitis C virus cure with direct acting antivirals: Clinical, economic, societal and patient value for China.

About 10 million people in China are infected with hepatitis C virus (HCV), with the seroprevalence of anti-HCV in the general population estimated at 0.6%. Delaying effective treatment of chronic hepatitis C (CHC) is associated with liver disease progression, cirrhosis, hepatocellular carcinoma, and liver-related mortality. The extrahepatic manifestations of CHC further add to the disease burden of patients. Managing CHC-related advanced liver diseases and systemic manifestations are costly for both the healthcare system and society. Loss of work productivity due to reduced well-being and quality of life in CHC patients further compounds the economic burden of the disease. Traditionally, pegylated-interferon plus ribavirin (PR) was the standard of care. However, a substantial number of patients are ineligible for PR treatment, and only 40%-75% achieved sustained virologic response. Furthermore, PR is associated with impairment of patient-reported outcomes (PROs), high rates of adverse events, and poor adherence. With the advent of direct acting antivirals (DAAs), the treatment of CHC patients has been revolutionized. DAAs have broader eligible patient populations, higher efficacy, better PRO profiles, fewer adverse events, and better adherence rates, thereby making it possible to cure a large proportion of all CHC patients. This article aims to provide a comprehensive evaluation on the value of effective, curative hepatitis C treatment from the clinical, economic, societal, and patient experience perspectives, with a focus on recent data from China, supplemented with other Asian and international experiences where China data are not available.

Impaired Right Ventricular Mechanics at Rest and During Exercise Are Associated With Exercise Capacity in Patients With Hypertrophic Cardiomyopathy.

Background Impaired right ventricular ( RV ) function indicates RV involvement in patients with hypertrophic cardiomyopathy ( HCM ). We aimed to assess RV function at rest and during exercise in HCM patients and to examine the association between impaired RV mechanics and exercise capacity. Methods and Results A total of 76 HCM patients (48 without and 28 with RV hypertrophy) and 30 age- and sex-matched controls were prospectively recruited. RV function was evaluated at rest and during semisupine bicycle exercise by conventional echocardiography and 2-dimensional speckle-tracking imaging. Exercise capacity was measured by metabolic equivalents. RV functional reserve was calculated as the difference of functional parameters between peak exercise and rest. Compared with controls, HCM patients had significantly higher RV free wall thickness, lower RV global longitudinal strain and RV free wall longitudinal strain at rest and during exercise, and reduced RV systolic functional reserve. Compared with those with HCM without RV hypertrophy, patients with HCM with RV hypertrophy had lower metabolic equivalents. Among HCM patients, an effective correlation was seen between exercise capacity and peak exercise RV global longitudinal strain and peak exercise RV free wall longitudinal strain. A binary logistic regression model revealed several independent predictors of exercise intolerance in HCM patients, but receiver operating characteristic curve analysis indicated exercise RV global longitudinal strain had the highest area under the curve for the prediction of exercise intolerance in HCM patients. Conclusions HCM patients have RV dysfunction and reduced contractile reserve. Exercise RV global longitudinal strain correlates with exercise capacity and can independently predict exercise intolerance. In addition, patients with HCM with RV hypertrophy exhibit more reduced exercise capacity, suggesting more severe disease and poorer prognosis.

Decreased biventricular mechanics and functional reserve in nonobstructive hypertrophic cardiomyopathy patients: implications for exercise capacity.

The present study investigated the changes of biventricular mechanics at rest and during exercise and examined the association between exercise capacity and biventricular mechanics and functional reserve in nonobstructive hypertrophic cardiomyopathy (NHCM) patients. A total of 50 NHCM patients and 25 controls were consecutively recruited for this study. Using echocardiography and two-dimensional speckle-tracking imaging, an experienced echocardiographer determined the following indices: RV free wall longitudinal strain (RVFWLS), LV global longitudinal strain (LVGLS), strain rate (SR), and functional reserve of strain values. We also investigated the relationships between biventricular mechanics and exercise capacity using metabolic equivalents (METs). NHCM patients had lower RVFWLS, LVGLS, systolic SR, early diastolic SR, and systolic and diastolic reserve during exercise compared to controls. An association of biventricular mechanics (LVGLS, RVFWLS) with exercise capacity at rest and during exercise was established. Multivariable logistic regression revealed that RVFWLS and LVE/e' during exercise (RVFWLS-exe, E/e'-exe) were independent predictors of exercise intolerance. Receiver operating characteristic curve analysis indicated that LVE/e'-exe had a higher area under the curve for predicting exercise intolerance in NHCM patients. In hierarchical analysis, RVFWLS-exe provided an incremental predictive value of exercise intolerance over LVGLS during exercise (LVGLS-exe) and LVE/e'-exe. LVE/e'-exe also changed incrementally compared to LVGLS-exe and RVFWLS-exe. NHCM patients have decreased biventricular mechanics at rest and during exercise and impaired biventricular functional reserve, and biventricular mechanics are associated with functional capacity. We propose that simultaneous evaluation of biventricular function should provide incremental predictive value for exercise intolerance.

A Simplified Ultrasound Comet Tail Grading Scoring to Assess Pulmonary Congestion in Patients with Heart Failure.

Ultrasound lung comets (ULCs) are a nonionizing bedside approach to assess extravascular lung water. We evaluated a protocol for grading ULC score to estimate pulmonary congestion in heart failure patients and investigated clinical and echocardiographic correlates of the ULC score. Ninety-three patients with congestive heart failure, admitted to the emergency department, underwent pulmonary ultrasound and echocardiography. A ULC score was obtained by summing the ULC scores of 7 zones of anterolateral chest scans. The results of ULC score were compared with echocardiographic results, the New York Heart Association (NYHA) functional classification, radiologic score, and N-terminal pro-b-type natriuretic peptide (NT-proBNP). Positive linear correlations were found between the 7-zone ULC score and the following: E/e', systolic pulmonary artery pressure, severity of mitral regurgitation, left ventricular global longitudinal strain, NYHA functional classification, radiologic score, and NT-proBNP. However, there was no significant correlation between ULC score and left ventricular ejection fraction, left ventricle diameter, left ventricular volume, or left atrial volume. A multivariate analysis identified the E/e', systolic pulmonary artery pressure, and radiologic score as the only independent variables associated with ULC score increase. The simplified 7-zone ULC score is a rapid and noninvasive method to assess lung congestion. Diastolic rather than systolic performance may be the most important determinant of the degree of lung congestion in patients with heart failure.

Expressions of Orphan Nuclear Receptor TR3/Nur77 in Chronic Hepatopathy and Its Clinical Significance.

OBJECTIVE: Although great success has been achieved in cancer treatment, current cancer therapies, including anti-tumorigenesis and anti-angiogenesis, still face the problems of insufficient efficacy, resistance and intrinsic refractoriness, in addition to their toxic side effects. There is a demand to identify additional targets that can be blocked to turn off the downstream effects of most, if not all, pathways. Our studies suggest that orphan nuclear receptor TR3 (human)/Nur77 (mouse) is such a target. Most recently, we reported that TR3/Nur77 expression in human hepatic cancer tissues correlates well with tumor progress, suggesting that TR3 is a specific therapeutic target for hepatic cancers. However, the correlation of TR3/Nur77 expression in hepatocellular carcinoma (HCC) with chronic hepatitis has not been studied. METHODS: The expression of TR3/Nur77 was analyzed in human primary hepatic cancer specimens from patients that have complete medical records with Immunohistochemically staining. The statistical analysis was used to access the significance of TR3 expression in tumor tissues, cirrhosis tissues and chronic hepatitis tissues with and without hepatitis B virus infection (HBV(+) and HBV(-)), which were obtained from para-tumor tissues. RESULTS: The positive rates of TR3/Nur77 expression in hepatocellular carcinoma, cancerous liver cirrhosis and chronic hepatitis are 66.67%, 30%, and 20%, respectively, which are statistic significant (p<0.05). The positive rates of TR3/Nur77 expression in hepatocellular carcinoma are statistic significant (p<0.05) with 81.25% and 20% in HBV (+) or HBV (-), respectively. CONCLUSION: The positive expression rate of TR3/Nur77 in hepatocellular carcinoma is higher than that in chronic hepatitis and cirrhosis. The positive rate of TR3/Nur77 expression in hepatocellular carcinoma is higher with HBV infection than that without infection. Our results suggest that TR3/Nur77 plays an important role in the progression of chronic hepatitis, and the occurrence and development of HCC.

Orphan Nuclear Receptor TR3/Nur77 is a Specific Therapeutic Target for Hepatic Cancers.

OBJECTIVE: Although great success has been achieved in cancer treatment, current cancer therapies, including anti-tumorigenesis and anti-angiogenesis, still face the problems of insufficient efficacy, resistance and intrinsic refractoriness, in addition to their toxic side effects. There is a demand to identify additional targets that can be blocked to turn off the downstream effects of most, if not all, pathways. Our previous studies suggest that orphan nuclear receptor TR3 (human) / Nur77 (mouse) is such a target. However, the correlation of TR3 expression and clinical tumor progression has not been studied. METHODS: The expression of TR3 was analysed in human primary hepatic cancer specimens from patients that have complete medical records with Immunohistochemical staining. The statistical analysis was used to assess the significance of TR3 expression in tumor tissues, paratumor tissues and normal tissues, and to investigate the correlation of TR3 expression and clincopathologic characteristics. RESULTS: TR3 is highly expressed in human hepatic cancer tissues, but not in normal liver tissues. The positive expression yields of TR3 are 67.67% (14/21), 19.05% (4/21) and 0% (0/10) in cancer tissues, para cancer tissues, and normal liver tissue, respectively, which are statistic significant (χ2=17.07, p<0.005). The expression of TR3 is significantly higher in cancer tissues than in para cancer tissues χ2=9.722, p<0.005) and in normal tissues (p<0.0005). The levels of TR3 expression in human hepatic cancer tissues correlates well with tumors that are at low/middle degree of tumor differentiation and have portal vein thrombosis, metastasis and recurrence, but not with age, gender, tumor number and Alpha-fetal protein (AFP) volume. CONCLUSION: The results indicate that TR3 is a specific therapeutic target for hepatic cancers.

Integrative Cardiopulmonary Ultrasound for Interstitial Lung Disease Assessment: Correlation between Lung Ultrasound Performance and Cardiac Involvement.

The aims of this study were to apply integrative cardiopulmonary ultrasound (thoracic ultrasound) to the evaluation of patients with interstitial lung disease (ILD) and to determine the relationship between lung ultrasound signs and echocardiographic parameters such as systolic pulmonary artery pressure (SPAP) and various right ventricular parameters. ILD patients and healthy controls underwent lung ultrasound (LUS) and echocardiographic tests. In addition to traditional echocardiographic parameters, right ventricular free wall longitudinal strain (RVLS_FW) was measured using 2-D speckle-tracking echocardiography. The degree of pulmonary fibrosis or the disease severity of each ILD patient was scored with a semiquantitative scoring method, taking into account multiple LUS signs. Statistical analyses were performed to compare various parameters between ILD patients with and those without pulmonary hypertension. Correlations between the different parameters were then evaluated, and the LUS scores were used to predict pulmonary hypertension using a receiver operating characteristic curve analysis. Among the 90 patients who qualified for entry into this study, 30% (n = 27) had pulmonary hypertension. The patients with pulmonary hypertension had larger right ventricular dimensions, lower RVLS_FW and higher LUS scores. An effective correlation was found between ILD LUS scores and echocardiographic parameters, especially SPAP (r = 0.735, p < 0.001). The groups were comparable with respect to most echocardiographic parameters, with mild, moderate and severe pulmonary fibrosis, whereas SPAP was significantly higher in the moderate and severe groups. RVLS_FW was obviously reduced in the group with severe pulmonary fibrosis. Although RVLS_FW in the mild pulmonary fibrosis group was in the normal range, it was slightly reduced compared with that of the controls. A cutoff of more than 16 LUS points had 85.2% sensitivity and 80.3% specificity in predicting elevated SPAP (>36 mm Hg). Thoracic ultrasound is useful in the assessment of ILD. As ILD progresses, the structure or function of the right ventricle gradually deteriorates. LUS not only detects lung conditions in ILD, but also indirectly reflects SPAP and right ventricular function. Integrated use of LUS and echocardiography will provide an invaluable point-of-care imaging modality to facilitate the diagnosis, management and treatment of patients with ILD.

Effect of switching from treatment with nucleos(t)ide analogs to pegylated interferon α-2a on virological and serological responses in chronic hepatitis B patients.

AIM: To investigate the efficacy of switching to pegylated interferon-α-2a (PegIFNα-2a) treatment in nucleos(t)ide analog (NA)-treated chronic hepatitis B (CHB) responder patients. METHODS: A 48-wk prospective and retrospective treatment trial of NA-treated CHB patients who had received entecavir (ETV) for at least 48 wk and had serum hepatitis B virus (HBV)-DNA < 500 IU/mL, serum hepatitis B envelope antigen (HBeAg) < 100 S/CO, serum alanine aminotransferase, and aspartate aminotransferase levels < 2 × the upper limit of normal of 40 IU/L was performed. The effects on virological and serological responses and adverse reactions to 0.5 mg daily ETV for 48 wk vs switching to PegIFNα-2a were compared. Forty-four patients were randomized to be switched from NA treatment to the PegIFNα-2a group, and 44 patients were simultaneously randomized to the ETV group. RESULTS: After 48 wk of therapy, the decrease in hepatitis B surface antigen (HBsAg) levels was greater in the PegIFNα-2a group than in the ETV group (3.1340 log10 IU/mL vs 3.6950 log10 IU/mL, P = 0.00). Seven patients who were anti-HBs-positive at baseline achieved HBsAg loss when switched to PegIFNα-2a (15.91% vs 0%, P = 0.018). The HBeAg serological conversion rate was higher in the PegIFNα-2a group than in the ETV group; however, the difference was not significant because of the small sample sizes (34.38% vs 21.88%, P = 0.232). In the PegIFNα-2a group, patients with HBsAg levels < 1500 IU/mL at baseline had higher HBeAg seroconversion and HBsAg loss rates at week 48 than those with HBsAg levels ≥ 1500 IU/mL (HBeAg seroconversion: 17.86% vs 62.5%, P = 0.007; HBsAg loss: 41.67% vs 6.25%, P = 0.016). Moreover, patients with HBsAg levels < 1500 IU/mL at week 24 had higher HBsAg loss rates after therapy than those with HBsAg levels ≥ 1500 IU/mL (36.84% vs 0%, P = 0.004). However, there were no statistically significant differences in HBeAg seroconversion rates (47.06% vs 25.93%, P = 0.266). CONCLUSION: NA-treated CHB patients switched to sequential PegIFNα-2a achieved highly potent treatment termination safely.

Clinical study of right ventricular longitudinal strain for assessing right ventricular dysfunction and hemodynamics in pulmonary hypertension.

This study aimed to appraise the application of right ventricular longitudinal strain for assessing right ventricular dysfunction and severe hemodynamic changes in pulmonary hypertension. The study included 53 patients clinically diagnosed with PH. Tissue Doppler-derived tricuspid lateral annular systolic velocity (s'), early diastolic peak velocity (e'), late diastolic peak velocity (a'), tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), and right ventricular fractional area change (FAC) were determined. The STI parameter was RV free wall longitudinal peak systolic strain (RV LPSS). The patients were assigned into two groups based on a RV LPSS value of - 19%.RV LPSS, s', TAPSE, RIMP, FAC, a' and e'/a' showed significant differences. PH patients with an RV LPSS≥ -19% exhibited a lower RV function (P < 0.05). RV LPSS was negatively correlated with TAPSE (r = -0.326, P < 0.05) and FAC (r = -0.495, P < 0.001) and positively correlated with RIMP (r = 0.508, P < 0.001). The optimal cut-off value of RV LPSS to reveal an mPAP ≥ 45 mmHg defined based on the receiver operating characteristic curve analysis was - 19.26% with a sensitivity of 83.9% and a specificity of 73.4%.Distinguishing the degree of RV dysfunction by 2D-STI may help physicians to determine the state of cardiac function and degree of PH in patients and offer a basis for subsequent clinical diagnosis and therapy. Our study demonstrates the superiority of RV LPSS for uncovering severe PH over the traditional echocardiographic parameters.

In vitro characterization and inhibition of the interaction between ciprofloxacin and berberine against multidrug-resistant Klebsiella pneumoniae.

Ciprofloxacin is a quinolone antibiotic used to treat Klebsiella pneumoniae infections in the clinic. Previous studies have demonstrated that berberine exhibits antibacterial activity and less acquired resistance related to efflux pumps. The multidrug efflux pump acrAB-tolC can be stimulated to expel as much toxic material as possible from the cells, but a detrimental effect can be produced owing to an overcrowded periplasm with excess expression products, which inhibits bacterial growth. In this study, the in vitro antibacterial activities of ciprofloxacin in combination with berberine were evaluated and compared with those of ciprofloxacin and berberine alone by evaluating the MIC, MBC and summation fractional IC against 20 clinical multidrug-resistant K. pneumoniae isolates, 1 quality control bacterium and 1 induced-resistance bacterium. Susceptibility tests showed that the MIC for the combination of berberine and ciprofloxacin was 1/2 that of the individual agents or less. Antimicrobial activities of 18.18% synergy and 77.27% additivity were found. Furthermore, synergism was verified through a time-kill assay, which suggested that the synergistic antibacterial effect of the two-drug combination may, to some extent, be related to the high expression of the acrAB-tolC and acrR multidrug efflux pumps. Indeed, the expression of these genes was increased >14-fold in the isolates affected by ciprofloxacin-berberine combination synergism.