Global, regional, and national burden of gallbladder and biliary diseases from 1990 to 2019.

BACKGROUND: Gallbladder and biliary diseases (GABDs) are a major public health issue. AIM: To analysis the cause-specific incidence, prevalence, and years lived with disability (YLDs) and its temporal trends of GABDs at the global, regional, and national level. Data on GABD were available from the Global Burden of Disease study 2019. METHODS: The estimated annual percentage change (EAPC) was used to quantify temporal trend in GABD age-standardized incidence rates (ASIRs), age-standardized prevalence rate (ASPR), and age-standardized YLD rate (ASYR) by region, sex. We analyzed the relationship between the GABD burden and country development level using the human development index (HDI). RESULTS: In 2019, the incident cases of GABD were 52003772, with an ASIR of 63432/100000 population. Globally, the number of incident cases and ASIR of GABD increased 97% and 58.9% between 1990 and 2019. Although, the ASPR and ASYR decreased from 1990 to 2019, the number of prevalent and YLDs cases increased. The highest ASIR was observed in Italy, and the highest ASPR and ASYR was observed in United Kingdom. The highest burden of GABD was found in low-SDI region, and the burden in female was significantly higher than males. A generally negative correlation (ρ = -0.24, P < 0.05) of GABD with the EAPC and human development index (HDI) (in 2021) were observed for ASIR. What's more, no correlation in ASPR (ρ = -0.06, P = 0.39) and ASYR (ρ = -0.07, P = 0.36) of GABD with the EAPC and HDI (in 2021) were observed, respectively. CONCLUSION: GABD remain a major global public health challenge; however, the burden of GABD varies geographically. Globally, the number of incident cases and ASIR of GABD increased between 1990 and 2019. The results of our study provide insight into the global disease burden of GABD and may assist policymakers in formulating effective policies to mitigate modifiable risk factors.

Vortex formation time as an index of left ventricular filling efficiency: comparison between children volunteers and patients with tetralogy of Fallot.

Background: Vortex formation time (VFT) had been considered a useful marker for assessing diastolic performance. the VFT assessment of diastolic function using four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has not been used in repair of tetralogy of Fallot (rTOF) patient. The aims of this study were as follows: (I) establish reference ranges for VFT measurements in healthy children and adolescents using 4D flow CMR imaging; and (II) analyze VFT parameters to assess diastole dysfunction in rTOF patients group. Methods: We acquired the CMR data was of 62 healthy participants (aged 6-18 years; male: 40, female: 22) and 20 patients with rTOF (aged 10-13 years; male: 15, female: 5) using 4D flow and cine sequence in routine chamber view. The VFT was calculated based on comparison of different algorithms from cine measurements (VFTvolume) and 4D flow measurements (VFTblood). Then, VFT measurements were compared to subject peak filling rate (PFR), age, and cardiac mass using simple linear regression and multiple regression analyses. Data were also categorized according to age for VFT and cardiac functional assessment comparisons between 3 age groups (Group 1: 6-9 years; Group 2: 10-13 years; Group 3: 14-18 years). The correlation of VFT and cardiac function parameters were analyzed in the rTOF group. Results: Normal mean value of VFTvolume and VFTblood were 4.25±0.92 and 3.77±1.11 in healthy children participants. The VFTvolume was correlated with VFTblood (r=0.61, P<0.001). There was a moderately significant correlation between VFTvolume and PFR (r=0.46, P<0.001) and between VFTblood and PFR (r=0.47, P<0.001), age (r=0.41, P=0.002) and left ventricular (LV) mass (r=0.48, P<0.001). Multiple regression analyses demonstrated that VFTvolume was independently associated with PFR (T=2.239; P<0.05) and VFTblood (T=4.361; P<0.001). There was a significant difference in VFTvolume between healthy controls and rTOF patients (5.44±1.93 vs. 4.27±0.88, P=0.018). Conclusions: The VFT measurements showed that the LV that had appropriate space to form the optimal vortex ring in normal children and adolescents aged 6-18 years old. The VFTvolume could potentially be helpful in improving our understanding of LV diastolic dysfunction in rTOF patients.

Cardiac Computed Tomography-Derived Left Atrial Strain and Volume in Pediatric Patients With Congenital Heart Disease: A Comparative Analysis With Transthoracic Echocardiography.

Purpose: This study aimed at exploring the feasibility and reproducibility of CCT for the measurement of Left Atrial (LA) strain and volume compared with transthoracic echocardiography (TTE) in pediatric patients with congenital heart disease (CHD). Materials and Methods: The present study included 43 postoperative patients with CHD (7.39 ± 3.64 years, 56% male) who underwent clinically indicated CCT, and all patients underwent additional TTE on the same day. LA strain and volume parameters were measured by dedicated software. The correlation and agreement of LA strain and volume parameters were assessed using Pearson's correlation coefficient and Bland-Altman analysis. Intra-class correlation coefficients (ICC) were used to assess CCT intra-observer and inter-observer reproducibility. Results: All strain parameters of CCT were lower compared to TTE (reservoir strain: 28.37 ± 6.92 vs. 32.15 ± 8.15, respectively; conduit strain: 21.33 ± 6.46 vs. 24.23 ± 7.75, respectively; booster strain: 7.04 ± 2.74 vs. 7.92 ± 3.56). While the volume parameters of CCT were higher compared to TTE (LAV: 29.60 ± 19.01 vs. 25.66 ± 17.60, respectively; LAVi: 30.36 ± 22.31 vs. 28.63 ± 19.25, respectively). Both LA strain and volume measurements showed good correlation and agreement between the two modalities (r = 0.63-0.87, p < 0.001). CT-derived LA strain and volume measurements showed good intra- and inter-observer reproducibility using prototype software (ICC = 0.78-0.96). Conclusions: CCT was feasible for measuring LA strain and volume with good correlation and high reproducibility as compared with TTE. As a complementary modality, CCT can regard as an accepted method in the evaluation of LA function in pediatric patients with CHD.

Fatty Acid-Binding Protein 4 in Patients with and without Diabetic Retinopathy.

BACKGROUND: Fatty acid-binding protein 4 (FABP4) has been demonstrated to be a predictor of early diabetic nephropathy. However, little is known about the relationship between FABP4 and diabetic retinopathy (DR). This study explored the value of FABP4 as a biomarker of DR in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 238 subjects were enrolled, including 20 healthy controls and 218 T2DM patients. Serum FABP4 levels were measured using a sandwich enzyme-linked immunosorbent assay. The grade of DR was determined using fundus fluorescence angiography. Based on the international classification of DR, all T2DM patients were classified into the following three subgroups: non-DR group, non-proliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Multivariate logistic regression analyses were employed to assess the correlation between FABP4 levels and DR severity. RESULTS: FABP4 correlated positively with DR severity (r=0.225, P=0.001). Receiver operating characteristic curve analysis was used to assess the diagnostic potential of FABP4 in identifying DR, with an area under the curve of 0.624 (37% sensitivity, 83.6% specificity) and an optimum cut-off value of 76.4 µg/L. Multivariate logistic regression model including FABP4 as a categorized binary variable using the cut-off value of 76.4 µg/L showed that the concentration of FABP4 above the cut-off value increased the risk of NPDR (odds ratio [OR], 3.231; 95% confidence interval [CI], 1.574 to 6.632; P=0.001) and PDR (OR, 3.689; 95% CI, 1.306 to 10.424; P=0.014). CONCLUSION: FABP4 may be used as a serum biomarker for the diagnosis of DR.

Ventricular flow analysis and its association with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovascular magnetic resonance study.

BACKGROUND: Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows quantification of biventricular blood flow by flow components and kinetic energy (KE) analyses. However, it remains unclear whether 4D flow parameters can predict cardiopulmonary exercise testing (CPET) as a clinical outcome in repaired tetralogy of Fallot (rTOF). Current study aimed to (1) compare 4D flow CMR parameters in rTOF with age- and gender-matched healthy controls, (2) investigate associations of 4D flow parameters with functional and volumetric right ventricular (RV) remodelling markers, and CPET outcome. METHODS: Sixty-three rTOF patients (14 paediatric, 49 adult; 30 ± 15 years; 29 M) and 63 age- and gender-matched healthy controls (14 paediatric, 49 adult; 31 ± 15 years) were prospectively recruited at four centers. All underwent cine and 4D flow CMR, and all adults performed standardized CPET same day or within one week of CMR. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes. Four flow components were analyzed: direct flow, retained inflow, delayed ejection flow and residual volume. Additionally, three phasic KE parameters normalized to end-diastolic volume (KEiEDV), were analyzed for both LV and RV: peak systolic, average systolic and peak E-wave. RESULTS: In comparisons of rTOF vs. healthy controls, median LV retained inflow (18% vs. 16%, P = 0.005) and median peak E-wave KEiEDV (34.9 µJ/ml vs. 29.2 µJ/ml, P = 0.006) were higher in rTOF; median RV direct flow was lower in rTOF (25% vs. 35%, P < 0.001); median RV delayed ejection flow (21% vs. 17%, P < 0.001) and residual volume (39% vs. 31%, P < 0.001) were both greater in rTOF. RV KEiEDV parameters were all higher in rTOF than healthy controls (all P < 0.001). On multivariate analysis, RV direct flow was an independent predictor of RV function and CPET outcome. RV direct flow and RV peak E-wave KEiEDV were independent predictors of RV remodelling index. CONCLUSIONS: In this multi-scanner multicenter 4D flow CMR study, reduced RV direct flow was independently associated with RV dysfunction, remodelling and, to a lesser extent, exercise intolerance in rTOF patients. This supports its utility as an imaging parameter for monitoring disease progression and therapeutic response in rTOF. Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier: NCT03217240.

FGF21 attenuates high uric acid­induced endoplasmic reticulum stress, inflammation and vascular endothelial cell dysfunction by activating Sirt1.

Uric acid (UA) is the final oxidation product of purine metabolism. Hyperuricemia has been previously reported to contribute to vascular endothelial dysfunction and the development of cardiovascular diseases, metabolic syndrome and chronic kidney diseases. In addition, it has been reported that fibroblast growth factor 21 (FGF21) can exert regulatory effects on UA­induced lipid accumulation. Therefore, the present study aimed to investigate the possible role of FGF21 in HUVEC cell injury induced by UA. The study used UA to induce HUVEC cell injury, inhibited sirtuin 1 (Sirt1) expression using EX527 and overexpressed FGF21 by transfection. Subsequently, reverse transcription­quantitative PCR was performed to measure the mRNA expression levels of FGF21, Sirt1 and inflammatory cytokines TNF­α, IL­1ß and IL­6, whereas western blotting was performed to measure their corresponding protein expression levels including FGF21, Sirt1, NLR family pyrin domain containing 3, pro­caspase1, apoptosis­associated speck­like protein containing a CARD, activating transcription factor 4, C/EBP homologous protein and eukaryotic initiation factor 2. Furthermore, dichloro­dihydro­fluorescein diacetate staining was performed to measure intracellular reactive oxygen species (ROS) generation in HUVECs. The levels of ROS and nitric oxide were also quantified using commercial assay kits. The results demonstrated that overexpression of FGF21 significantly inhibited UA treatment­induced endoplasmic reticulum (ER) stress, inflammation and oxidative stress in HUVECs. Furthermore, overexpression of FGF21 significantly activated Sirt1. The sirt1 inhibitor, EX527, significantly abrogated the suppressive effects of FGF21 overexpression on ER stress, inflammation and oxidative stress in UA­stimulated HUVECs. To conclude, results of the present study suggested that FGF21 may attenuate UA­induced ER stress, inflammation and vascular endothelial cell dysfunction by activating Sirt1. Therefore, FGF21 may be a potential effective target for the future treatment of vascular endothelial cell dysfunction.

Feasibility of Cardiac Computed Tomography for the Evaluation of Ventricular Function in Postoperative Children With Congenital Heart Disease: Comparison With Cardiac Magnetic Resonance Imaging.

OBJECTIVE: We explored the feasibility of cardiac computed tomography (CCT) to evaluate postoperative ventricular function in children with congenital heart disease (CHD) and evaluated the accuracy and reproducibility of CCT using cardiac magnetic resonance (CMR) as a reference. METHODS: Thirty-two postoperative children with CHD (20 boys and 12 girls) who underwent CMR and CCT were enrolled. Left and right ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, and cardiac index were measured using cardiac function analysis software. Cardiac function data were compared between CMR and CCT. The agreement between the 2 modalities was assessed using a Bland-Altman analysis. Intraclass correlation coefficients were used to assess intraobserver and interobserver reproducibility in CCT functional measurements. RESULTS: All functional parameters showed no significant difference (P > 0.05) and were well-correlated (r > 0.5, P < 0.05) between CMR and CCT. The mean values of all ventricular function parameters in CCT were higher compared with CMR. As indicated by 95% limits of agreement, left ventricular function parameters showed a better level of agreement compared with right ventricular function parameters between the 2 modalities. Intraobserver and interobserver reproducibility were excellent in CCT measurements for all functional parameters (intraclass correlation coefficient > 0.9). CONCLUSIONS: Compared with the criterion standard of CMR, CCT is feasible for assessing postoperative ventricular function with sufficient diagnostic accuracy and reproducibility in children with CHD. In addition to its important role regarding anatomical characterization, CCT is a suitable alternative and convenient follow-up tool that can be used to functional evaluation in children who are intolerant with CMR or have contraindications to CMR.

Shift of Glucose Peak Time During Oral Glucose Tolerance Test is Associated with Changes in Insulin Secretion and Insulin Sensitivity After Therapy with Antidiabetic Drugs in Patients with Type 2 Diabetes.

INTRODUCTION: Delay in peak blood glucose during an oral glucose tolerance test (OGTT) predicts declining ß-cell function and poor ability to regulate glucose metabolism. Glucose peak time has not been used as a comparative indicator of the improvement in islet function after treatment with exenatide, insulin, or oral antidiabetic drugs (OADs). We evaluated the efficacy of three types of antidiabetic drugs on the basis of blood glucose peak time in patients with non-newly diagnosed type 2 diabetes. METHODS: The data from 100 patients with diabetes who completed two OGTTs within 6 months were collected. Thirty-seven of them with type 2 diabetes were treated with Humalog Mix25, 28 patients with OADs (metformin, acarbose, and gliclazide), and 35 patients with exenatide. RESULTS: Glycated hemoglobin improved in all three groups after treatment (P < 0.05). Subcutaneous adipose tissue (P < 0.01) and visceral adipose tissue (P < 0.0001) significantly decreased in the exenatide group. The insulinogenic index (IGI) (P = 0.01) and IGI × oral glucose insulin sensitivity (OGIS) (P = 0.01) improved in the exenatide group only. Homeostatic assessment of ß-cell function (HOMA-ß) and OGIS were greater in the exenatide and OAD groups than in the Humalog Mix25 group (all P < 0.05). A shift to an earlier peak was observed in 57.1%, 35.7%, and 27.0% of patients in the exenatide, OAD, and Humalog Mix25 groups, respectively (P = 0.029). OGIS (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.33-0.89, P = 0.026) and IGI × OGIS (OR 1.72, 95% CI 0.44-6.68, P = 0.012) were independently related to shifts in glucose peak time. CONCLUSION: Exenatide, Humalog Mix25, and OADs improved glycemic metabolism. However, exenatide exhibited superior efficacy in shifting blood glucose peak time to an earlier point, while it improved insulin secretion and insulin sensitivity. Hence, the shift of glucose peak time may be considered an indicator for the evaluation of the effect of hypoglycemic drugs.

Postoperative evaluation of left ventricular global strain using cardiac computed tomography in pediatric patients with congenital heart disease: A comparison with echocardiography.

PURPOSE: We explored the feasibility and reproducibility of cardiac computed tomography (CCT)-derived left ventricular (LV) global strain in postoperative childrenwith congenital heart disease (CHD) and compared its correlation and agreement with transthoracic echocardiography (TTE). METHODS: Fifty-one patients (28 males, 23 females) were included who underwent clinically indicated retrospective electrocardiography-triggered CCT. and all patients underwent additional TTE on the same day. LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured. Correlations of global strains between CCT and TTE were assessed using Pearson's correlation coefficient. Intra-class correlation coefficients (ICC) were used to assess CCT intra-observer and inter-observer reproducibility. RESULTS: GLS and GCS were not significantly different between CCT and TTE (GLS: -23.54 ± 3.24 vs. -23.85 ± 3.72, respectively, p = 0.415; GCS: -28.21 ± 3.55 vs. -28.79 ± 3.69, respectively, p = 0.155). GRS was significantly different between CCT and TTE (60.79 ± 15.11 vs. 41.73 ± 4.27, respectively, p < 0.001). There was good correlation between CCT- and TTE-derived GLS (r = 0.70, p < 0.001) and GCS (r = 0.68, p < 0.001), but GRS showed no correlation between CCT and TTE (r = 0.09, p = 0.54). CCT-derived global strain showed good intra- and inter-observer reproducibility (ICC = 0.86-0.92), except the inter-observer reproducibility for GRS (ICC = 0.77). CONCLUSIONS: CCT was feasible for postoperative evaluation of LV global strain in pediatric patients with CHD with sufficient reproducibility. CCT-derived global strain can provide additional information in selected CHD patients with poor acoustic windows and who are intolerant to or have contraindications for cardiac magnetic resonance.

Feasibility of using a non-sedation protocol for evaluation of neonatal congenital heart disease by using a 16-cm wide-detector computed tomography with a low radiation dose: preliminary experience from a single pediatric medical center.

The aim of this study is to explore the feasibility of using a non-sedation protocol for the evaluation of neonatal congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Thirty-four neonates (group 1) were enrolled to undergo cardiac CT without sedation between August 2018 and March 2019. The control group (group 2) comprising 20 inpatient neonates was sedated. Cardiac CT was performed using 16-cm area detector 320-row CT with free breathing and prospective ECG-triggering scan mode. The examination completion time, radiation dose, and image quality were compared between the groups. The results of cardiac CT for patients in group 1 who underwent surgery were compared with surgical findings. Intergroup differences in body weight, age, examination completion time, radiation dose, and image quality evaluation were not significant. There was no significant difference in oxygen saturation before and after the examination in group 1. In all, 98 separate cardiovascular abnormalities in 27 group 1 patients were confirmed using surgical reports. The overall sensitivity, specificity, positive predictive value, and negative predictive value of cardiac CT were 94.90%, 100.0%, 100.0%, and 98.53%. The non-sedation protocol can be applied in neonates with congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Based on the image quality obtained, non-sedative examination did not extend the examination completion time and helped avoid the possible side effects of sedative drugs.

Exploration of the relationship between tumor mutation burden and immune infiltrates in colon adenocarcinoma.

Background: Tumor mutation burden (TMB) was correlated with the immunotherapeutic response in various malignancies. We aimed to evaluate the TMB immune signature in colon adenocarcinoma (COAD). Methods: Gene expression profile, mutation and clinical data of COAD patients were obtained from The Cancer Genome Atlas (TCGA) database. The samples were divided into high and low TMB level groups to identify differentially expressed genes (DEGs). Functional enrichments analyzes were performed to identify the biological functions of the DEGs. Then, immune cell infiltration signatures were calculated by the CIBERSORT algorithm. Finally, Cox proportional hazard model was constructed to estimate the prognostic value of the identified immune-related genes. Results: Gene set enrichment analysis in the high-TMB level group showed that DEGS were enriched in immune-related pathways, such as antigen processing and presentation, Toll-like receptor signaling and natural killer cell-mediated cytotoxicity. A higher infiltration level of CD8+ T cells, CD4+ T cells, activated NK cells , M1 Macrophages and T follicular helper cells was observed in the high-TMB level group. Furthermore, a Cox regression model combined with survival analysis based on the expression level of four identified prognostic genes was constructed, validated anf revealed that higher risk-score levels conferred poor survival outcomes in COAD patients. Conclusions: Our data demonstrate that the high TMB levels are associated with an immune signature in COAD and deepen the molecular understanding of TMB function in tumor immunotherapy.

Identification of hub genes in colon cancer via bioinformatics analysis.

OBJECTIVES: This study aimed to investigate hub genes and their prognostic value in colon cancer via bioinformatics analysis. METHODS: Differentially expressed genes (DEGs) of expression profiles (GSE33113, GSE20916, and GSE37364) obtained from Gene Expression Omnibus (GEO) were identified using the GEO2R tool and Venn diagram software. Function and pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were verified based on The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. RESULTS: We identified 207 DEGs, 62 upregulated and 145 downregulated genes, enriched in Gene Ontology terms "organic anion transport," "extracellular matrix," and "receptor ligand activity", and in the Kyoto Encyclopedia of Genes and Genomes pathway "cytokine-cytokine receptor interaction." The PPI network was constructed and nine hub genes were selected by survival analysis and expression validation. We verified these genes in the TCGA database and selected three potential predictors (ZG16, TIMP1, and BGN) that met the independent predictive criteria. TIMP1 and BGN were upregulated in patients with a high cancer risk, whereas ZG16 was downregulated. The immunostaining results from HPA supported these findings. CONCLUSION: This study indicates that these hub genes may be promising prognostic indicators or therapeutic targets for colon cancer.

The Cancer Genome Atlas (TCGA) based m6A methylation-related genes predict prognosis in hepatocellular carcinoma.

The current study aims to investigate the significance of N6-methyladenosine (m6A) methylation-related genes in the clinical prognosis of hepatocellular carcinoma (HCC) using bioinformatics analyses based on The Cancer Genome Atlas (TCGA) database. Transcriptome data and corresponding clinical data on m6A methylation-related genes (including 15 genes) were obtained from TCGA database. Differential expression of 15 genes was identified. Survival curves of subgroups based on m6A methylation-related gene expression levels were plotted. We selected potential predictive genes and analyzed their prognostic values using bioinformatics methods. Eleven genes (METTL3, YTHDF1, YTHDF2, YTHDF3, YTHDC1, YTHDC2, FTO, KIAA1429, HNRNPC, HNRNPA2B1, and RBM15) were found to be overexpressed in HCC. Of these, five genes had worse survival (P < 0.05). There was a significant difference in the survival rate between subgroups with different expression levels of m6A. We selected five potential predictors (METTL3, KIAA1429, ZC3H13, YTHDF1, and YTHDF2) that met the independent predictive value. ZC3H13 was upregulated in patients with high cancer risk, whereas METTL3, KIAA1429, YTHDF1, and YTHDF2 were downregulated. In summary, we found that the expression levels of m6A methylation-related genes were different in patients with HCC and correlated with survival and prognosis. This implies that m6A methylation-related genes may be promising prognostic indicators or therapeutic targets for HCC.

Efficacy and Safety of Peripherally Acting Mu-Opioid Receptor Antagonists for the Treatment of Opioid-Induced Constipation: A Bayesian Network Meta-analysis.

OBJECTIVE: To assess the efficacy and safety of peripherally acting mu-opioid receptor antagonists (PAMORAs) for the treatment of opioid-induced constipation (OIC). METHODS: Randomized controlled trials (RCTs) were searched for OIC therapy comparing PAMORAs with placebo. Both a pairwise and network meta-analysis were performed. The surface under the cumulative ranking area (SUCRA) was used to determine the efficacy and safety of OIC treatment using different PAMORAs. RESULTS: The primary target outcome was a response that achieves an average of three or more bowel movements (BMs) per week. In the network meta-analysis, four PAMORAs (naldemedine, naloxone, methylnaltrexone, and alvimopan) showed a better BM response than the placebo. Naldemedine was ranked first (odds ratio [OR] = 2.8, 95% credible interval [CrI] = 2-4.5, SUCRA = 89.42%), followed by naloxone (OR = 2.9, 95% CrI = 1.6-5.3, SUCRA = 87.44%), alvimopan (OR = 2.2, 95% CrI = 1.3-3.5, SUCRA = 68.02%), and methylnaltrexone (OR = 1.7, 95% CrI = 1.0-2.8, SUCRA = 46.09%). There were no significant differences in safety found between the PAMORAs and the placebo. CONCLUSIONS: We found that PAMORAs are effective and can be safely used for the treatment of OIC. In network meta-analysis, naldemedine and naloxone appear to be the most effective PAMORAs for the treatment of OIC.

Effects of Exenatide and Humalog Mix25 on Fat Distribution, Insulin Sensitivity, and ß-Cell Function in Normal BMI Patients with Type 2 Diabetes and Visceral Adiposity.

In China, most normal BMI (body mass index of ≥18.5 to <25 kg/m2) adults with type 2 diabetes (T2DM) exhibit visceral adiposity. This study compared the effects of exenatide and humalog Mix25 on normal BMI patients with T2DM and visceral adiposity. A total of 95 patients were randomized to receive either exenatide or humalog Mix25 treatment for 24 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were quantified by magnetic resonance imaging (MRI) and liver fat content (LFC) by liver proton magnetic resonance spectroscopy (1H MRS). Each patient's weight, waist circumference, BMI, blood glucose, insulin sensitivity, pancreatic ß-cell function, and fibroblast growth factor 21 (FGF-21) levels were measured. Data from 81 patients who completed the study (40 and 41 in the exenatide and humalog Mix25 groups, respectively) were analysed. The change in 2 h plasma blood glucose was greater in the exenatide group (P = 0.039). HOMA-IR and MBCI improved significantly after exenatide therapy (P < 0.01, P = 0.045). VAT and LFC decreased in both groups (P < 0.01 for all) but to a greater extent in the exenatide group, while SAT only decreased with exenatide therapy (P < 0.01). FGF-21 levels declined more in the exenatide group (P < 0.01), but were positively correlated with VAT in the entire cohort before (r = 0.244, P = 0.043) and after (r = 0.290, P = 0.016) the intervention. The effects of exenatide on glycaemic metabolism, insulin resistance, pancreatic ß-cell function, and fat deposition support its administration to normal BMI patients with T2DM and visceral adiposity.

Systemic ventricular strain and torsion are predictive of elevated serum NT-proBNP in Fontan patients: a magnetic resonance study.

BACKGROUND: This study aimed to investigate the associations between cardiac strain, cardiac torsion, ventricular volumes, and ventricular ejection fraction, with N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in Fontan patients who were age- and gender-matched with healthy control subjects. METHODS: Cardiovascular magnetic resonance (CMR) studies performed in 22 (15 male, 7 female) patients with single-ventricle physiology (all morphological left ventricles) palliated with Fontan and 17 (10 male, 7 female) age- and gender-matched healthy children volunteers were retrospectively analyzed. Serum NT-proBNP levels were obtained in Fontan subjects. Standard post-processing of CMR images included systemic ventricular end-diastolic and end-systolic volumes, stroke volume, cardiac mass, atrioventricular regurgitation, and ejection fraction. CMR tissue tracking (TT) software was used to quantify global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) and torsion of the systemic ventricle. Pearson and Spearman correlation coefficients were used in comparisons of correlations between NT-proBNP and functional parameters in repair Fontan patients. Intra-observer and inter-observer variability of CMR strain and torsion values were determined from 10 randomly selected Fontan subjects and 10 randomly selected control subjects. RESULTS: GLS was significantly lower in Fontan patients than in control subjects (-15.19±2.94 vs. -19.97±1.70; P<0.001). GLS was not significantly different between normal NT-proBNP levels and high NT-proBNP levels in Fontan patients (-15.59±2.72 vs. -14.62±3.32; P=0.462). The GCS of repair Fontan patients was not significantly lower than that of the control group (-16.76±3.27 vs. -17.88±2.26; P=0.235). GCS was significantly different between normal and high NT-proBNP levels group in Fontan patients (-17.95±2.43 vs. -15.04±3.67; P=0.036). The peak systolic torsion and peak systolic torsion rates were significantly lower in Fontan patients than in control subjects (0.81±0.41 vs. 1.07±0.36, P=0.044; 7.36±3.41 vs. 9.85±2.61, P=0.017). Peak systolic torsion was significantly lower in Fontan patients with normal NT-proBNP levels than in high NT-proBNP subjects (0.67±0.43 vs. 1.01±0.29; P=0.036). GCS and torsion were more strongly correlated with NT-proBNP in the patient group (r=0.541 for GCS; r=0.588 for torsion, P<0.01). The parameters of strain and torsion could be reproduced with sufficient accuracy by intra-observer agreement(biases =0.04 for GLS; biases =0.66 for GCS; biases =1.03 for GRS; biases =0.04 for torsion) and inter-observer agreement (biases =0.32 for GLS; biases =0.85 for GCS; biases =1.52 for GRS; biases =0.18 for torsion). CONCLUSIONS: GLS is an earlier marker of contractile dysfunction in repair Fontan patients. Peak systolic torsion may be a biomarker for determining subclinical dysfunction, as it is more strongly correlated with serum biomarkers of ventricular function than ventricular size or ejection fraction.

Serum Fibroblast Growth Factor 19 and Total Bile Acid Concentrations Are Potential Biomarkers of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus.

PURPOSE: Type 2 diabetes mellitus (T2DM) carries a high risk of hepatocellular carcinoma (HCC). Both serum fibroblast growth factor 19 (FGF19) and bile acid concentrations are associated with T2DM and HCC. We aimed at evaluating the relationships between FGF19 and bile acid concentrations and HCC in patients with T2DM. METHODS: Twenty-seven healthy volunteers (control group), 27 patients with T2DM (T2DM group), 16 patients with newly diagnosed HCC (HCC group), and 10 T2DM patients with newly diagnosed HCC (T2DM-HCC group) were studied at the Affiliated Hospital of Nantong University between June 2016 and June 2017. The serum concentrations of serum FGF19 and total bile acids (TBA) were measured in all the participants. Correlation analysis and multiple stepwise regression analysis of the FGF19 and TBA concentrations were performed in all the participants and in the four groups. RESULTS: The concentrations of FGF19 were 220.5 pg/ml, 185.1 pg/ml, 115.8 pg/ml, and 70.4 pg/ml in the HCC, T2DM-HCC, control, and T2DM groups, respectively (p < 0.001), and the TBA concentrations were 21.75 µmol/l, 14.25 µmol/l, 14.25 µmol/l, 14.25 µmol/l, 14.25 p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 . CONCLUSIONS: Simultaneous increase of serum FGF19 and TBA levels may be used as indicators of HCC screening at early stage in patients with T2DM.

Quantitative comparison of two-dimensional and three-dimensional strain measurement using MRI feature tracking in repair Fontan patients and normal child volunteers.

BACKGROUND: The accuracy of 2D and 3D strain analyses was evaluated by comparing strain and cardiac function parameters in Fontan repair patients and normal child volunteers. METHODS: We retrospectively enrolled 32 patients with Fontan circulation and 32 child volunteers who had undergone clinical cardiac magnetic resonance (CMR) assessment of the dominant ventricle with a 1.5-Tesla MRI scanner. Global and regional strain (2D and 3D) of the dominant ventricle in both groups was assessed using CMR feature-tracking. Correlations between cardiac function and strain data were assessed using Pearson's correlation coefficient values. The intraclass correlation coefficient (ICC) and coefficient of variation (CoV) were determined to evaluate repeatability and agreement. RESULTS: The 2D GLS showed significant differences between the Fontan repair patients and volunteers (- 16.49 ± 5.00 vs. -19.49 ± 2.03; p = 0.002). The 2D GRS and 2D GCS showed no significant differences between two groups. 2D GRS: 38.96 ± 14.48 vs. 37.46 ± 7.77; 2D GCS: - 17.64 ± 5.00 vs. -16.89 ± 2.96, respectively; p > 0.05). The 3D global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS) showed significant differences between the Fontan repair patients and volunteers (3D GRS: 36.35 ± 16.72 vs. 44.96 ± 9.98; 3D GLS: - 8.86 ± 6.84 vs. -13.67 ± 2.44; 3D GCS: - 13.70 ± 7.84 vs. -18.01 ± 1.78; p < 0.05, respectively). The ejection fraction (EF) and 3D GCS were significantly associated (r = - 0.491, p = 0.004). The 3D GCS showed correlations with the indexed end-diastolic volume (EDV) (r = 0.523, p = 0.002) and indexed end-systolic volume (ESV) (r = 0.602, p < 0.001). 3D strain showed good reproducibility, with GCS showing the best inter-observer agreement (ICC = 0.87 and CoV = 5.15), followed by GLS (ICC = 0.84 and CoV = 5.36). CONCLUSIONS: 3D GCS is feasible, highly reproducible, and strongly correlated with conventional cardiac function measures. 3D GCS assessments may be useful for monitoring abnormal myocardial motion in patients with Fontan circulation.

Right and left ventricular interactions, strain, and remodeling in repaired pulmonary stenosis patients with preserved right ventricular ejection fraction: A cardiac magnetic resonance study.

BACKGROUND: Right ventricular dilation and dysfunction is a common long-term complication in patients with repaired pulmonary stenosis (rPS). Additionally, abnormal right and left ventricular interactions have been reported in right-sided heart defect after intervention, including in pulmonary stenosis. PURPOSE: To analyze ventricular strain, remodeling, and left and right ventricular interactions in rPS patients with preserved right ventricular ejection fraction (RVEF) compared with healthy children using cardiac magnetic resonance. STUDY TYPE: A cross-sectional study. POPULATION: In all, 34 rPS patients and 10 healthy children volunteers (controls). FIELD STRENGTH/SEQUENCE: 3.0T/2D balanced steady-state free precession (2D b-SSFP) cine, late gadolinium enhancement (LGE), and 2D phase contrast (2D-PC). ASSESSMENT: Pulmonary regurgitation (PR) fractions of the main pulmonary artery, biventricular volumes, masses, function, and cardiac strain. STATISTICAL TESTS: Mann-Whitney U-test, t-test, Pearson correlation coefficients, Spearman's correlation coefficients, and intraclass correlation coefficients analysis were performed. RESULTS: For group analysis, the right ventricular (RV) global circumferential strain and radial strain were significantly increased in patients when compared with controls (-13.57 ± 2.69 vs. -5.91 ± 3.16, P < 0.001; 25.31 ± 8.12 vs. 9.87 ± 5.32, P < 0.001, respectively). The fraction of PR displayed moderate correlation with right ventricular end-diastolic volume index (RVEDVi) (r = 0.452, P = 0.022). RVEDVi and mass index were larger in patients vs. control (104.92 ± 27.46 vs. 85.15 ± 11.98, P = 0.016; 18.28 ± 4.95g/m2 vs. 11.67 ± 2.14 g/m2 , P < 0.001, respectively). Patients presented with preserved left ventricular ejection function, but was lower than healthy controls (60.89% ± 4.89% vs. 65.95% ± 4.56%, P = 0.006). Regional circumferential strain of segment 3 of left ventricle (LV) were significantly decreased in patients (-7.79 ± 6.52 vs. -13.56 ± 3.22, P = 0.003). DATA CONCLUSION: Compensated increased RV strain, myocardial remodeling of RV, and adverse right and left ventricular interactions occur in rPS patients with preserved RVEF. The decreased interventricular septum strain may lead to impaired LV function due to RV dilation as a result of PR. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;52:129-138.

Knockdown of collagen α-1(III) inhibits glioma cell proliferation and migration and is regulated by miR128-3p.

As a member of the collagen family, collagen α-1(III) (COL3A1) is an important protein in the development and progression of several tumors. However, the role of COL3A1 in glioma is not yet clear. The present study examined the expression and function of COL3A1 in glioma cell behavior and identified microRNA (miRNA) regulators. It was demonstrated that COL3A1 expression was upregulated in glioma and directly correlated with the tumor grade. Analysis of the GSE4290 and GSE7696 profiles acquired from the Gene Expression Omnibus database also revealed an increased COL3A1 expression in malignant gliomas compared with the lower grade gliomas and non-tumor brain tissue, which was directly correlated with glioma grade. To explore the functional role of COL3A1 in glioma cell growth, small interfering RNA interference was applied to inhibit COL3A1 expression in Hs683 and U251 cells. The relative COL3A1 mRNA and protein expression levels were significantly reduced in the knockdown cells as determined by western blot analysis. In addition, decreased COL3A1 expression in Hs683 and U251 glioma cells resulted in a delay in cell growth and colony disruption as determined by MTS and colony formation assays. Wound healing analysis indicated that cells with suppressed expression of COL3A1 had a reduced ability to migrate. COL3A1 mRNA levels were inversely correlated with the miR128-3p level in glioma, suggesting that miR128-3p expression is associated with COL3A1 inhibition as verified by reverse transcription-quantified polymerase chain reaction. These results suggest that COL3A1 may be a novel regulator of glioblastoma cell behavior and may represent a novel target for gene therapies against glioma.