Pretreatment CT-based machine learning radiomics model predicts response in unresectable hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors and interventional therapy.

BACKGROUND: Lenvatinib plus PD-1 inhibitors and interventional (LPI) therapy have demonstrated promising treatment effects in unresectable hepatocellular carcinoma (HCC). However, biomarkers for predicting the response to LPI therapy remain to be further explored. We aimed to develop a radiomics model to noninvasively predict the efficacy of LPI therapy. METHODS: Clinical data of patients with HCC receiving LPI therapy were collected in our institution. The clinical model was built with clinical information. Nine machine learning classifiers were tested and the multilayer perceptron classifier with optimal performance was used as the radiomics model. The clinical-radiomics model was constructed by integrating clinical and radiomics scores through logistic regression analysis. RESULTS: 151 patients were enrolled in this study (2:1 randomization, 101 and 50 in the training and validation cohorts), of which three achieved complete response, 69 showed partial response, 46 showed stable disease, and 33 showed progressive disease. The objective response rate, disease control rate, and conversion resection rates were 47.7, 78.1 and 23.2%. 14 features were selected from the initially extracted 1223 for radiomics model construction. The area under the curves of the radiomics model (0.900 for training and 0.893 for validation) were comparable to that of the clinical-radiomics model (0.912 for training and 0.892 for validation), and both were superior to the clinical model (0.669 for training and 0.585 for validation). Meanwhile, the radiomics model can categorize participants into high-risk and low-risk groups for progression-free survival (PFS) and overall survival (OS) in the training (HR 1.913, 95% CI 1.121 to 3.265, p=0.016 for PFS; HR 4.252, 95% CI 2.051 to 8.816, p=0.001 for OS) and validation sets (HR 2.347, 95% CI 1.095 to 5.031, p=0.012 for PFS; HR 2.592, 95% CI 1.050 to 6.394, p=0.019 for OS). CONCLUSION: The promising machine learning radiomics model was developed and validated to predict the efficacy of LPI therapy for patients with HCC and perform risk stratification, with comparable performance to clinical-radiomics model.

FAT10 induces immune suppression by upregulating PD-L1 expression in hepatocellular carcinoma.

The upregulation of programmed death ligand 1 (PD-L1) plays a crucial role in facilitating cancer cells to evade immune surveillance through immunosuppression. However, the precise regulatory mechanisms of PD-L1 in hepatocellular carcinoma (HCC) remain undefined. The correlation between PD-L1 and ubiquitin-like molecules (UBLs) was studied using sequencing data from 20 HCC patients in our center, combined with TCGA data. Specifically, the association between FAT10 and PD-L1 was further validated at both the protein and mRNA levels in HCC tissues from our center. Subsequently, the effect of FAT10 on tumor progression and immune suppression was examined through both in vivo and in vitro experiments. Utilizing sequencing data, qPCR, and Western blotting assays, we confirmed that FAT10 was highly expressed in HCC tissues and positively correlated with PD-L1 expression. Additionally, in vitro experiments demonstrated that the overexpression of FAT10 fostered the proliferation, migration, and invasion of HCC cells. Furthermore, the overexpression of FAT10 in HCC cells led to an increase in PD-L1 expression, resulting in the inhibition of T cell proliferation and the enhancement of HCC cell resistance to T cell-mediated cytotoxicity. Moreover, in vivo experiments utilizing the C57BL/6 mouse model revealed that overexpression of FAT10 effectively suppressed the infiltration of CD8 + GZMB + and CD8 + Ki67 + T cells, as well as reduced serum levels of TNF-α and IFN-γ. Mechanistically, we further identified that FAT10 upregulates PD-L1 expression via activating the PI3K/AKT/mTOR pathway, but not in a ubiquitin-like modification. In conclusion, our findings indicate that FAT10 promotes immune evasion of HCC via upregulating PD-L1 expression, suggesting its potential as a novel target to enhance the efficiency of immunotherapy in HCC.

CircNUP54 promotes hepatocellular carcinoma progression via facilitating HuR cytoplasmic export and stabilizing BIRC3 mRNA.

Circular RNAs (circRNAs) have been implicated in tumorigenesis and progression of various cancers. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) have not been fully elucidated. Herein, a new oncogenic circRNA, hsa_circ_0070039 (circNUP54), was identified to be significantly upregulated in HCC through circRNA sequencing. As verified in 68 HCC samples, circNUP54 overexpression was correlated with aggressive cancerous behaviors and poor outcomes. Moreover, the function experiments showed that knockdown of circNUP54 inhibited the malignant progression of HCC in vitro and in vivo, whereas overexpression of circNUP54 had the opposite role. Mechanistic investigations carried out by RNA pull-down, RNA immunoprecipitation, and immunofluorescence revealed that circNUP54 interacted with the RNA-binding protein Hu-antigen R (HuR) and promoted its cytoplasmic export. The cytoplasmic accumulation of HuR stabilized the downstream BIRC3 mRNA through its binding to the 3' UTR region. Consequently, the encoded protein of BIRC3, cellular inhibitor of apoptosis 2 (cIAP2), proceeded to activate the NF-κB signal pathway and ultimately contributed to HCC progression. In addition, depletion of BIRC3 rescued the pro-tumorigenic effect of circNUP54 on HCC cells. Overall, this study demonstrated that circNUP54 facilitates HCC progression via regulating the HuR/BIRC3/NF-κB axis, which may serve as a promising therapeutic target for HCC treatment.

Identification of FOXP1 as a favorable prognostic biomarker and tumor suppressor in intrahepatic cholangiocarcinoma.

BACKGROUND: Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported. METHODS: Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells. RESULTS: FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p < 0.01). The positive rates of FOXP1 were significantly lower in patients with poor differentiation, lymph node metastasis, invasion into surrounding organs, and advanced stages (p < 0.05). Notably, patients with FOXP1 positivity had better outcomes (overall survival) than those with FOXP1 negativity (p < 0.05), as revealed by Kaplan-Meier survival analysis. Moreover, Cox multivariate analysis showed that negative FOXP1 expression, advanced TNM stages, invasion, and lymph node metastasis were independent prognostic risk factors in patients with ICC. Lastly, overexpression of FOXP1 inhibited the proliferation, migration, and invasion of ICC cells and promoted apoptosis, whereas knockdown of FOXP1 had the opposite role. CONCLUSION: Our findings suggest that FOXP1 may serve as a novel outcome predictor for ICC as well as a tumor suppressor that may contribute to cancer treatment.

Response of microplastic occurrence and migration to heavy rainstorm in agricultural catchment on the Loess plateau.

Microplastics have received widespread attention as an emerging pollutant in recent years, but limited studies have explored their response to extreme weather. This study surveyed and analyzed the occurrence and distribution of microplastics in a typical agricultural catchment located on the Loess Plateau, focusing on their response to heavy rainstorms. Microplastics were detected in all soil samples with an abundance of 70-4020 items/kg, and particles less than 0.5 mm accounted for 81.61 % of the total microplastics. The main colors of microplastic were white, yellow, and transparent, accounting for 38.50 %, 32.90 %, and 21.05 % respectively, and the main shapes were film and fragment, accounting for 47.65 % and 30.81 %. Low density polyethylene was the main component of microplastics identified using Fourier transform infrared spectrometry. The extensive use of plastic mulch film is a major contributor to microplastic pollution in this catchment. The differences and connections observed in microplastics imply mutual migration and deposition within the catchment. A check dam at the outlet effectively intercepts microplastics during the rainstorm, reducing the microplastic by at least 6.1 × 1010 items downstream. This study provides a reference for the effects of rainstorms on the sources and pathways of MP pollution in regions prone to severe soil erosion.

Identification of a Novel Ferroptosis-Related Gene Signature for Predicting Prognosis and Responsiveness to Immunotherapy in Hepatocellular Carcinoma.

Purpose: Ferroptosis has been reported to regulate multiple biological behaviors. However, the prognostic and oncologic values of ferroptosis-related genes (FRGs) have not been comprehensively elucidated in hepatocellular carcinoma (HCC). Here, we aimed to construct FRGs-associated signature for stratification of the prognosis of HCC patients. Methods: A list of FRGs was generated from FerrDb. Public databases were used to extract expression matrices and clinical information. TCGA cohort was randomly divided into a training set and a validation set. Prognostic signature for Overall Survival (OS) was established in training set and validated in internal cohorts (TCGA validation set and entire set) and external cohort (ICGC cohort). Additionally, the role of signature in HCC was well investigated by analysis of mutations, gene set enrichment analysis (GSEA), analysis of immune infiltrates, and analysis of response to immune checkpoint blockade (ICB) treatment. The oncogenic effects of ZFP69B on HCC were also investigated in vitro. Results: We identified 12 FRGs-based signature for OS with LASSO regression. Patients were partitioned into different risk groups based on the signature. Overall, patients in different groups had different prognosis. The signature independently predicted OS in multivariate Cox regression analyses. Anti-tumor immune cells including activated CD8 T cells, cytolytic activity, and Th1 cells were negatively correlated with risk score in both TCGC and ICGC cohorts. Furthermore, low-risk patients responded better to ICB than high-risk patients. In addition, knockdown of ZFP69B reduced proliferation, migration, and invasion, and promoted erastin-induced ferroptosis of HCC cells. Conclusion: We developed a prognostic signature based on FRGs to predict OS of HCC patients. And the signature may facilitate clinicians in identifying those who are likely to benefit from ICIs. The results also indicated that ZFP69B might regulate the process of ferroptosis and could be used as a novel potential target for HCC.

Myocardial Work Measurement With Functional Capacity Evaluation in Primary Systemic Hypertension Patients: Comparison Between Left Ventricle With and Without Hypertrophy.

OBJECTIVE: Noninvasive measurement of myocardial work (MW) incorporates left ventricular (LV) pressure, and, therefore, allows correction of global longitudinal strain for changing afterload conditions. We sought to investigate MW as a tool to detect early signs of LV dysfunction in primary systemic hypertension patients, particularly with different predictive indices. METHODS AND RESULTS: None left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) patients established were all primary systemic hypertension with preserved ejection fraction. Forty in NLVH and forty in LVH according to left ventricular end-diastolic mass index (LVEDmassI) were prospectively enrolled. The following indices of MW were assessed: global work index, global constructive work, global wasted work (GWW), and global work efficiency (GWE). Both global work index (P=0.348) and global constructive work (P=0.225) were increased in NLVH and decreased in LVH, and GWW (P<0.001) was increased significantly in NLVH and increased more in LVH, while GWE (P<0.001) was decreased significantly in NLVH and decreased more in LVH. The clinical utility of GWW (95% CI: 0.802-0.951) and GWE (95% CI: 0.811-0.950) were verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with LVH and control comparisons. In multivariate linear regression analysis, 4-dimenaional LVEDmassI was independently associated with GWE (P=0.018) in systemic hypertension patients. Assessment of intraobserver and interobserver variability in the MW echocardiographic data documented good interclass correlation coefficients (all >0.85). CONCLUSION: GWW and GWE derived from MW are more accurate, sensitive, and reproducible predictors to detect early LV dysfunction in primary systemic hypertension patients, especially in distinguishing the potential functional abnormality of NLVH and LVH, even though the ejection fraction is preserved.

Identification of LSM Family Members as Novel Unfavorable Biomarkers in Hepatocellular Carcinoma.

Background: Smith-like (LSM) family members play critical roles in multiple oncologic processes in several types of malignancies. The study on LSM family members of HCC might provide new insights into the tumorigenesis and therapeutic strategies of HCC. Methods: The clinical significance and oncologic biological functions of LSM family members were assessed through multiple bioinformatics methods and in vitro studies. The potential correlation between LSM family members and tumor immunity was also investigated using single sample gene set enrichment analysis (ssGSEA) and the ESTIMATE algorithm. Results: LSM family member overexpression in HCC was significantly correlated with poor clinical outcomes such as higher TNM stage, advanced histologic grade, and worse prognosis. A risk score system based on LSM5, LSM10, LSM12, and LSM14B showed a reliable predictive ability for OS of HCC patients. Functional enrichment analysis demonstrated that LSM family members overexpressed were all involved in cell cycle related biological processes. Besides, LSM12, LSM14A, and LSM14B were found to be significantly associated with PI3K-Akt-mTOR and T cell receptor signaling pathways. Tumors with LSM12, LSM14A, and LSM14B overexpression exhibited lower infiltration of activated CD8+ T cells with declined cytolytic activity and immune score, but increased infiltration of Th2 cells and Th2/Th1. LSM12, LSM14A, and LSM14B overexpression is also associated with higher tumor-related immune checkpoints (e.g., PD-L1, B7-H3, and PVR) expression and increased therapeutic insensitivity to immune checkpoint blockade (ICB). Moreover, the knockdown of LSM12, LSM14A, and LSM14B significantly inhibited the proliferation and invasion of HCC cells. Conclusion: This study systematically investigated the expression pattern and biological values of LSM family members in HCC and identified LSM family members as novel therapeutic targets in HCC.

CircLIFR suppresses hepatocellular carcinoma progression by sponging miR-624-5p and inactivating the GSK-3ß/ß-catenin signaling pathway.

Circular RNAs have been reported to play essential roles in the tumorigenesis and progression of various cancers. However, the biological processes and mechanisms involved in hepatocellular carcinoma (HCC) remain unclear. Initial RNA-sequencing data and qRT-PCR results in our cohort showed that hsa_circ_0072309 (also called circLIFR) was markedly downregulated in HCC tissues. Kaplan-Meier analysis indicated that higher levels of circLIFR in HCC patients correlated with favorable overall survival and recurrence-free survival rates. Both in vitro and in vivo experiments indicated that circLIFR inhibited the proliferation and invasion abilities of HCC cells. We therefore conducted related experiments to explore the mechanism of circLIFR in HCC. Fluorescence in situ hybridization results revealed that circLIFR was mainly located in the cytoplasm, and RNA immunoprecipitation assays indicated that circLIFR was significantly enriched by Ago2 protein. These results suggested that circLIFR may function as a sponge of miRNAs to regulate HCC progression. We further conducted bioinformatics prediction as well as dual-luciferase reporter assays, and the results of which showed that circLIFR could sponge miR-624-5p to stabilize glycogen synthase kinase 3ß (GSK-3ß) expression. Loss and gain of function experiments demonstrated that regulation of the expression of miR-624-5p or GSK-3ß markedly affected HCC progression induced by circLIFR. Importantly, we also proved that circLIFR could facilitate the degradation of ß-catenin and prevent its translocation to the nucleus in HCC cells. Overall, our study demonstrated that circLIFR acts as a tumor suppressor in HCC by regulating miR-624-5p and inactivating the GSK-3ß/ß-catenin signaling pathway.

SLC39A1 Overexpression is Associated with Immune Infiltration in Hepatocellular Carcinoma and Promotes Its Malignant Progression.

BACKGROUND: Solute carrier family 39 member 1 (SLC39A1) has been identified as a zinc ion transport protein that possesses oncogenic properties in various types of cancers. However, its potential function in hepatocellular carcinoma (HCC) remains unknown. This study aimed to investigate the expression profile and potential mechanisms of SLC39A1 in HCC. METHODS: SLC39A1 expression was analyzed using multiple databases. The clinical significance and associated biological pathways of SLC39A1 were investigated using bioinformatics analysis. Potential correlations between SLC39A1 expression and tumor immunity in HCC were also evaluated using single-sample gene set enrichment analysis (GSEA). Sixty paired HCC samples were used to verify the expression pattern of SLC39A1. In vitro studies were performed to investigate the oncogenic effects of SLC39A1 in HCC. Western blot analysis was conducted to further investigate the possible involved signaling pathways. RESULTS: The overexpression of SLC39A1 in HCC was determined by bioinformatics analysis and was confirmed in tissues from our center. SLC39A1 overexpression was also significantly correlated with worse prognosis, advanced TNM stage, and histological grade. GSEA analysis demonstrated that SLC39A1 overexpression was involved in various tumor-related pathways, such as the cell cycle and Wnt signaling pathway. SLC39A1 knockdown repressed the proliferation, invasion, and migration abilities of HCC cells. Furthermore, SLC39A1 knockdown decreased the expression of the tumor progression-related proteins (eg, cyclin D1 and MMP2) and Wnt signaling pathway-related proteins (eg, Wnt3A and ß-catenin). In addition, SLC39A1 overexpression may be associated with impaired tumor immunity in HCC, as evidenced by the increased infiltration of Th2 cells and reduced infiltration of cytotoxic cells. CONCLUSION: These findings preliminarily suggested the crucial effect of SLC39A1 overexpression on HCC tumor progression and immunosuppression, suggesting its potential as a novel prognostic and therapeutic target in HCC.

Quantitative Differentiation of Left Atrial Performance in Hypertrophic Cardiomyopathy: Comparison Between Nonobstruction and Occult Obstruction With 4-dimensional Volume-strain.

OBJECTIVE: The objective of this study was to describe the different components of left atrial (LA) dysfunction predictors in nonobstructive and occult obstructive hypertrophy cardiomyopathy (HCM) patients especially with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (D) longitudinal and circumferential strains. METHODS: Twenty-eight nonobstructive HCM patients and 30 occult obstructive HCM patients according to LV outflow tract gradient at rest and after exercise were prospectively enrolled. 4D echocardiographic evaluation was performed in 58 HCM patients, both nonobstructive and occult obstructive, and 38 control subjects. LA reservoir, conduit, contractile functions were performed by 4D volume-strain with volumes and longitudinal, circumferential strains. RESULTS: Optimal correlation coefficients obtained between LV 4D mass (index) and LA 4D longitudinal/circumferential strain (r=-0.860 to 0.518, all P<0.001). Both nonobstructive and occult obstructive HCM patients had increased volumes and significantly decreased longitudinal, circumferential strain values with lower reservoir, conduit, contractile functions than the controls (all P<0.001). Occult obstructive HCM patients presented incremented volumes compared with nonobstructive ones (P<0.001 to 0.003). Lower conduit function and higher contractile function indicated with lower reservoir function revealed by circumferential strain in occult obstructive HCM patients than nonobstructive ones (P<0.001 to 0.017). Interclass correlation coefficients of intraobserver and interobserver in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. CONCLUSIONS: LA volumes were significantly increased and LA reservoir, conduit, and contractile functions were significantly impaired in HCM patients. Furthermore, different performances of LA functional analyses in nonobstruction and occult obstruction patients with 4D volume-strain echocardiography may facilitate the recognition of subtle LA dysfunctional differentiation in HCM patients.

Association of Cholecystectomy With Liver Fibrosis and Cirrhosis Among Adults in the USA: A Population-Based Propensity Score-Matched Study.

Background and Aims: Cholecystectomy is the "gold standard" for treating diseases of the gallbladder. In addition, non-alcoholic fatty liver disease (NAFLD), liver fibrosis or cirrhosis, are major causes of morbidity and mortality across the world. However, the association between cholecystectomy and these diseases is still unclear. We assessed the association among US adults and examined the possible risk factors. Methods: This cross-sectional study used data from 2017 to 2018 National Health and Nutrition Examination Survey, a population-based nationally representative sample of US. Liver fibrosis and cirrhosis were defined by median stiffness, which was assessed by transient elastography. Furthermore, patients who had undergone cholecystectomy were identified based on the questionnaire. In addition, Propensity Score Matching (PSM, 1:1) was performed based on gender, age, body mass index (BMI) and diabetes. Results: Of the 4,497 included participants, cholecystectomy was associated with 60.0% higher risk of liver fibrosis (OR:1.600;95% CI:1.278-2.002), and 73.3% higher risk of liver cirrhosis (OR:1.733, 95% CI:1.076-2.792). After PSM based on age, gender, BMI group and history of diabetes, cholecystectomy was associated with 139.3% higher risk of liver fibrosis (OR: 2.393;95% CI: 1.738-3.297), and 228.7% higher risk of liver cirrhosis (OR: 3.287, 95% CI: 1.496-7.218). Conclusions: The present study showed that cholecystectomy is positively associated with liver fibrosis and cirrhosis in US adults. The discovery of these risk factors therefore provides new insights on the prevention of NAFLD, liver fibrosis, and cirrhosis.

Sevoflurane inhibits ferroptosis: A new mechanism to explain its protective role against lipopolysaccharide-induced acute lung injury.

Sevoflurane (Sev) has protective effects in acute lung injury (ALI), but the relevant mechanisms are still not fully understood. The present study aimed to determine whether Sev exerts a protective effect on lipopolysaccharide (LPS)-induced ALI by regulating ferroptosis. In this study, we found that Sev could protect mice from lung injury caused by LPS stimulation, including extenuating lung histological damage, pulmonary edema and pulmonary vascular permeability, and the content of inflammatory factors in Bronchoalveolar lavage fluid (BALF), as well as improving the survival rate of ALI mice, which was in line with the effects of ferroptosis inhibitor ferrostatin-1. Simultaneously, Sev could eliminate the worsening effects of ferroptosis inducer Fe-citrate on LPS-induced ALI to a certain extent. Additionally, the administration of Sev could inhibit ferroptosis caused by LPS, which was manifested by reducing the accumulation of MDA and Fe2+, and increasing the levels of GSH and GPX4 in the lung tissues of ALI mice. It was also observed in BEAS-2B cells that the increased MDA and Fe2+ levels and the decreased GSH and GPX4 levels caused by LPS could be rescued by ferrostatin-1 and Sev. LPS stimulation compensatory up-regulated heme oxygenase-1 (HO-1) expression in mouse lung tissues and BEAS-2B cells, which could be enhanced by Sev. Moreover, HO-1 depletion could offset the inhibitory effect of Sev on LPS-induced ferroptosis and inflammation in BEAS-2B cells. Taken together, Sev inhibited ferroptosis by up-regulating HO-1 expression to reduce LPS-induced ALI, which may provide a possible mechanism for the application of Sev in clinical anesthesia.

Association of Serum Vitamin C With NAFLD and MAFLD Among Adults in the United States.

BACKGROUND AND AIMS: Despite the remarkable progress of metabolic dysfunction-associated fatty liver disease (MAFLD), formerly named non-alcoholic fatty liver disease (NAFLD), the disease remains poorly improved. Since increased oxidative stress and inflammation contribute to the initiation and progression of fatty liver disorders, vitamin C (VC), an antioxidant agent, might be a suitable treatment option for MAFLD. However, the lack of clinically confirmed benefits makes clinicians challenging to recommend antioxidant supplements for MAFLD individuals. METHODS: Herein, the nationally representative National Health and Nutrition Examination Survey 2017-2018 data were collected to evaluate the potential association between the serum VC levels with the risk of different categories of NALFD and the newly proposed MAFLD terminology. Hepatic steatosis was defined as controlled attenuated parameter scores ≥ 263 dB/m, whereas liver fibrosis (LF) status was defined as F0-F4, with the cutoff values of median liver stiffness being 6.3, 8.3, 10.5, and 12.5 (KPa), respectively. A cross-sectional analysis was performed to calculate the odds rate and determine the potential beneficial effects of VC. RESULTS: A total of 4,494 participants aged more than 18 years and conducted transient elastography examinations were included. Our findings demonstrated that participants with increased serum VC status were more likely to be female predominant, more educated, and moderate drinkers. Interestingly, female participants tended to have a lower prevalence of NAFLD, MAFLD, LF, and liver cirrhosis (LC) after stratification by gender. Moreover, our results revealed that participants from the quartile three group (quartile 3: 50.5-67.0 µmol/L) experienced a slightly lower risk of MAFLD than the risk of NAFLD. Of note, the serum concentration of VC (quartile 2: 30.9-50.5 µmol/L) inversely associated with LF and LC was lower than the serum VC level (quartile 3) associated with NAFLD and MAFLD. Notably, individuals from the quartile 3 group experienced a statistically significant 32.5, 42.0, 45.7, and 71% decrease in risk of NAFLD, MAFLD, LF, and LC, respectively. CONCLUSION: In summary, our findings suggested an inverse association between serum VC levels and NAFLD, MAFLD, LF, or LC. Additionally, adjustment of VC supplementation according to age, gender, and ethnicity may be a promising candidate for these diseases.

Heart transplantation ten-year follow-ups: Deformation differentiation comparison of myocardial performance in left ventricle and right ventricle.

BACKGROUND: We try to investigate whether the values of three-dimensional principal longitudinal strain present differently between the left and right ventricles in patients with long-time follow-ups after heart transplantation (HTx). METHODS AND RESULTS: Transthoracic echocardiography with three-dimensional speckle tracking was performed at one-, five- and ten-year follow-ups in 62 "healthy" HTx patients together with routine echocardiographic evaluation in 32 control group (CG) individuals. Longitudinal strain was applied in all subjects assessing without myocardium wall motion abnormality. Firstly, left ventricular ejection fraction preserved in HTx and had no significant difference in comparison with the controls (p > .05). 3D measurement showed obvious reduction in global (%: CG: -20.5 ± 3.5 vs. HT1y: -13.7 ± 4.6, HT5y: -14.4 ± 4.5, HT10y: -14.6 ± 4.7. p < .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p < .01) strain values of the left compared HTx with control subjects. Secondly, tissue Doppler imaging s' velocity and tricuspid annular plane systolic excursion reduced in HTx as compared to the controls in right ventricle (p < .01). Longitudinal strain presented a more distinctive reduction in global (%: CG: -24.5 ± 4.6 vs. HT1y:-14.8 ± 7.5, HT5y: -15.5 ± 6.4, HT10y: -15.9 ± 6.8. p < .01) and horizontal segmental (basal, mid, apical, CG vs. HTx: all p < .01) average values of the right compared HTx with control subjects. Thirdly, there weren't any significant changes between one-, five- and ten-year of all the values with HTx inter-group comparison in both the left and right ventricles (p > .05). Fourthly, the global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, with the global decreased differentiation rates of 7%, 7%, 6%, respectively. CONCLUSIONS: Compared HTx with control subjects in both ventricles, conventional evaluation showed preserved or decreased functions in the left and right separately. Myocardial function evaluating by 3D longitudinal strain reduced after HTx, but the deformation of the right ventricle reduced more than those of the left ventricle. Additionally, 3D strain values almost remained with stable decreased differentiation rates during the long-time follow-ups.

Four-Dimensional Volume-Strain Expression in Asymptomatic Primary Hypertension Patients Presenting with Subclinical Left Atrium-Ventricle Dysfunction.

OBJECTIVE: The purpose of this study was to evaluate the different components of left atrial (LA) dysfunction predictors in asymptomatic primary systemic hypertension patients with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (4D) longitudinal and circumferential strain values. METHODS AND RESULTS: Patients with no left ventricular hypertrophy (NLVH) and left ventricular hypertrophy (LVH) are all asymptomatic regarding primary blood hypertension. Thirty NLVH patients and 30 LVH patients according to LV mass index and 40 controls analyzed by 4D echocardiography were prospectively enrolled. LA volumes and longitudinal and circumferential strains were measured using 4D volume-strain echocardiography with a Vivid E95 Version 203 instrument. Correlation analysis indicated a significant relation between LV 4D mass index and LA 4D longitudinal/circumferential strain (r = -0.446 to 0.381, p = 0.000-0.042). LVH patients had a reduced LA emptying fraction compared with NLVH patients and control subjects (p < 0.01). NLVH patients had an impaired LA conduit function and increased contractile function compared with the control group (p < 0.01). LVH patients had increased LA volumes and significantly decreased reservoir, conduit and contractile functions compared with the controls (p < 0.01). LVH patients had increased LA volumes and decreased reservoir and contractile functions compared with NLVH patients (p < 0.01). The clinical utility of LA 4D volume-strain measurement was verified by receiver-operating characteristic curve analysis showing larger net benefits as evaluated with NLVH, LVH and control group comparisons. Interclass correlation coefficients of interobserver and intraobserver assessments in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. CONCLUSIONS: LVH patients showed increased LA volumes and decreased LA emptying fractions. LA reservoir, conduit and contractile functions were significantly impaired in LVH patients. Decreased LA conduit function and increased contractile function were revealed in NLVH patients. LA volumetric and functional analyses with 4D volume-strain echocardiography may facilitate the recognition of subtle LA and LV dysfunctions in asymptomatic systemic hypertension patients.

Left and right ventricular function detection and myocardial deformation analysis in heart transplant patients with long-time follow-ups.

OBJECTIVE: We try to investigate whether the values of longitudinal strain present differences between the left and right ventricles in long-time follow-ups after heart transplantation (HTx) with dynamic changes in function. METHODS AND RESULTS: Follow-up transthoracic echocardiography was performed in 1- and 3-month and 1- and 5-year follow-ups in 50 "healthy" HTx patients and compared with 26 control subjects. The left ventricle with preserved ejection fraction evaluated by biplane Simpson (control group [CG] vs HT; P > .05) had an obvious reduction in global (CG: -20.49 ± 2.38 vs heart transplant 1 month [HT1m]: -13.06 ± 2.86, heart transplant 3 month [HT3m]: -13.61 ± 2.61, heart transplant 1 year [HT1y]: -13.69 ± 4.56, heart transplant 5 year [HT5y]: -14.41 ± 4.54; P < .001) and horizontal segmental (basal, mid, apical) (P < .001) together with chamber segmental (apical 4-chamber, apical 3-chamber, apical 2-chamber) (P < .001) average strain values. The right ventricle with reduced ventricular function measured by tissue Doppler imaging S' and tricuspid annular plane systolic excursion had a more distinctive reduction in global (CG: -24.53 ± 4.20 vs HT1m: -12.94 ± 5.03, HT3m: -13.68 ± 4.35, HT1y: -14.95 ± 7.50, HT5y: -15.20 ± 6.15; P < .001) with segmental lateral (P < .001) strain values. There were not any significant changes between 1- and 3-month follow-ups of all the values (P > .05). But it could be seen that values increased in 1- and 5-year follow-ups compared with the baseline of 1- and 3-month follow-ups (P < .05). The global and segmental strain of the right ventricle decreased more than that of the left ventricle in all HTx groups, and the strain values were decreased in the HTx groups compared with the CG, with the global decreased change rates being 11%, 10%, 6%, and 8%, respectively. CONCLUSIONS: The strain values decreased after HTx and almost remained stable in the long-time follow-ups. Compared with the CG in both ventricles, they were with preserved or reduced functions. In addition, the deformation values of the right ventricle decreased more than those of the left.

[Clinical trial of electroacupuncture at Neimadian-point for cancer pain].

OBJECTIVE: To observe the clinical efficacy and safety of electroacupuncture (EA) at Neimadian-point for cancer pain. METHODS: A total of 140 cancer patients with pain were randomly divided into EA and control groups, with 70 cases in each group. The patients of the EA group received EA at Neimadian-point plus analgesia pump (all prepared with normal saline). The patients of the control group were treated by Sufentanil patient-controlled intravenous analgesia plus sham EA (without stimulation). The treatment was conducted once daily for two days at 8 o'clock every morning. Respectively, in 1 h before treatment (T0), 1 h (T1), 8 h (T2), 24 h (T3) after treatment of the first day, 1 h (T4), 8 h (T5), 24 h (T6) after treatment of the second day, the visual analogue scale (VAS) score of pain, and the plasma levels of norepinephrine, 5-HT, leucine enkephalin, ß-endorphin and dynorphin A1-13 were tested. The security level (1-4 grade) was assessed during the treatment. RESULTS: Compared with their own pre-treatment, in T1 to T6, the VAS scores, and the contents of plasma norepinephrine and 5-HT obviously decreased in both groups （P<0.05）, and the contents of leucine enkephalin, ß-endorphin and dynorphin A1-13 all increased (P<0.05) in the EA group. The analgesia effects were significantly higher in the EA group than in the control group in T1, T2, T4 and T5 (P<0.05,P<0.01). The therapeutic effect of EA at Neimadian-point was significantly superior to that of the Sufentanil in down-regulating plasma norepinephrine and 5-HT levels, and in up-regulating leucine enkephalin, ß-endorphin and dynorphin A1-13 levels (P<0.05,P<0.01). CONCLUSION: EA at Neimadian-point can effectively relieve the pain of cancer patients and improve their quality of daily life.

[Evaluation of changes in right ventricular myocardial mechanical properties in breast cancer patients receiving pirarubicin using three-dimensional speckle tracking imaging].

OBJECTIVE: To evaluate the changes in the mechanical properties of the right ventricular myocardium (RVM) after chemotherapy using three-dimensional speckle tracking echocardiography (3D-STI). METHODS: Thirty-six breast cancer patients receiving chemotherapy with pirarubicin underwent examinations with 3D-STI to test the mechanical properties of the RVM before chemotherapy and at the end of the second, fourth, and sixth cycles of chemotherapy (C2, C4, and C6, respectively). Blood levels of hs-cTnI and NT-proBNP were also examined at the same time points. Thirty-one of these patients also underwent 99mTc-MIBI and 18F-FDG myocardial perfusion/metabolism imaging at C6. Myocardial perfusion abnormalities and survival outcomes of the patients were analyzed according to radionuclide imaging results. RESULTS: Compared with that before chemotherapy, RVGLS at C2 was significantly lowered, and both RVGLS and RVGAS were significantly decreased at C4 and further decreased at C6 (P < 0.05) in relation with the cumulative drug dose. The RVGLS and RVGAS differed significantly among patients with different levels of TAPSE, hs-cTnI, and RV-FAC decline after chemotherapy. RVGLS and RVGAS were found to significantly correlate with FAC (r=0.37, 0.26), TAPSE (r=0.43, 0.51), and S' (r=0.21, 0.36) (P < 0.01), and showed a high sensitivity and specificity for identifying RV-FAC decline by > 5%. Myocardial perfusion/metabolic imaging showed normal myocardial perfusion in 17 patients, and abnormal myocardial segments of the RVM were detected in 14 patients, but 18F-FDG imaging showed that these myocardial segments were all viable; these 14 patients showed significantly decreased RVGLS and RVGAS and significantly increased hs-cTnI level compared with the patients with normal ventricular myocardial perfusion (P < 0.05). ROC curve analysis showed that an absolute value of RVGLS less than 18.2% had a sensitivity of 92.9% for diagnosis of RV impairment with a diagnostic specificity of 88.2% and an area under the curve of 0.87. RVGAS less than 26.8% had a sensitivity of 94.8% and a specificity of 86.6% for diagnosis of RV damage with an area under the curve of 0.86. CONCLUSIONS: 3D-STI can provide a reliable new approach to early diagnosis of changes in the mechanical properties of the RVM related with chemotherapy with pirarubicin in breast cancer patients.

Assessment of Left Ventricular Myocardial Viability by 3-Dimensional Speckle-Tracking Echocardiography in Patients With Myocardial Infarction.

OBJECTIVES: To determine whether 3-dimensional (3D) speckle-tracking echocardiography could provide a new way to assess myocardial viability in patients with myocardial infarction (MI). METHODS: Forty-five patients with MI underwent routine echocardiography, 2-dimensional (2D) speckle-tracking echocardiography, and 3D speckle-tracking echocardiography. Radionuclide myocardial perfusion/metabolic imaging was used as a reference standard to define viable and nonviable myocardia. RESULTS: Among 720 myocardial segments in 45 patients, 368 showed abnormal motion on routine echocardiography; 204 of 368 were categorized as viable on single-photon emission computed tomography/positron emission tomography (SPECT/PET), whereas 164 were defined as nonviable; 300 normal segments on SPECT/PET among 352 segments without abnormal motion on routine echocardiography were categorized as a control group. The radial, longitudinal, 3D, and area strain on 3D speckle-tracking echocardiography had significant differences between control and nonviable groups (P < .001), whereas none of the parameters had significant differences between control and viable groups. There were no significant differences in circumferential, radial, and longitudinal peak systolic strain from 2D speckle-tracking echocardiography between viable and nonviable groups. Although there was no significant difference in circumferential strain between the groups, radial and longitudinal strain from 3D speckle-tracking echocardiography decreased significantly in the nonviable group. Moreover, 3D and area strain values were lower in the nonviable segments than the viable segments. By receiver operating characteristic analysis, radial strain from 3D speckle-tracking echocardiography with a cutoff of 11.1% had sensitivity of 95.1% and specificity of 53.4% for viable segments; longitudinal strain with a cutoff of 14.3% had sensitivity of 65.2% and specificity of 65.7%; 3D strain with a cutoff of 17.4% had sensitivity of 70.6% and specificity of 77.2%; and area strain with a cutoff of 23.2% had sensitivity of 91.5% and specificity of 82.8%. CONCLUSIONS: Three-dimensional speckle-tracking echocardiography might have potential for detection of myocardial viability in patients with cardiac dysfunction due to MI.