Objective: To evaluate the effects of Catalpa bignonioides fruit extract on the promotion of muscle growth and muscular capacity in vitro and in vivo. Methods: Cell viability was measured using the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay. Cell proliferation was assessed using a 5-bromo-2’-deoxyuridine (BrdU) assay kit. Western blot analysis was performed to determine the protein expressions of related factors. The effects of Catalpa bignonioides extract were investigated in mice using the treadmill exhaustion test and whole-limb grip strength assay. Chemical composition analysis was performed using high-performance liquid chromatography (HPLC). Results: Catalpa bignonioides extract increased the proliferation of C2C12 mouse myoblasts by activating the Akt/mTOR signaling pathway. It also induced metabolic changes, increasing the number of mitochondria and glucose metabolism by phosphorylating adenosine monophosphate-activated protein kinase. In an in vivo study, the extract-treated mice showed improved motor abilities, such as muscular endurance and grip strength. Additionally, HPLC analysis showed that vanillic acid may be the main component of the Catalpa bignonioides extract that enhanced muscle strength. Conclusions: Catalpa bignonioides improves exercise performance through regulation of growth and metabolism in skeletal muscles, suggesting its potential as an effective natural agent for improving muscular strength.

Objective: To measure inter-reader agreement and identify associated factors in interpreting complete response (CR) on magnetic resonance imaging (MRI) following chemoradiotherapy (CRT) for rectal cancer. Materials and Methods: This retrospective study involved 10 readers from seven hospitals with experience of 80–10210 cases, and 149 patients who underwent surgery after CRT for rectal cancer. Using MRI-based tumor regression grading (mrTRG) and methods employed in daily practice, the readers independently assessed mrTRG, CR on T2-weighted images (T2WI) denoted as mrCR T2W, and CR on all images including diffusion-weighted images (DWI) denoted as mrCRoverall. The readers described their interpretation patterns and how they utilized DWI. Inter-reader agreement was measured using multi-rater kappa, and associated factors were analyzed using multivariable regression. Correlation between sensitivity and specificity of each reader was analyzed using Spearman coefficient. Results: The mrCR T2W and mrCRoverall rates varied widely among the readers, ranging 18.8%–40.3% and 18.1%–34.9%, respectively. Nine readers used DWI as a supplement sequence, which modified interpretations on T2WI in 2.7% of cases (36/1341 [149 patients x 9 readers]) and mostly (33/36) changed mrCR T2W to non-mrCRoverall. The kappa values for mrTRG, mrCR T2W, and mrCRoverall were 0.56 (95% confidence interval: 0.49, 0.62), 0.55 (0.52, 0.57), and 0.54 (0.51, 0.57), respectively.No use of rectal gel, larger initial tumor size, and higher initial cT stage exhibited significant association with a higher interreader agreement for assessing mrCRoverall (P ≤ 0.042). Strong negative correlations were observed between the sensitivity and specificity of individual readers (coefficient, -0.718 to -0.963; P ≤ 0.019). Conclusion Inter-reader agreement was moderate for assessing CR on post-CRT MRI. Readers’ varying standards on MRI interpretation (i.e., threshold effect), along with the use of rectal gel, initial tumor size, and initial cT stage, were significant factors associated with inter-reader agreement.

Objective: We aimed to assess and validate the radiologic and clinical factors that were associated with recurrence and survival after curative surgery for heterogeneous targetoid primary liver malignancies in patients with chronic liver disease and to develop scoring systems for risk stratification. Materials and Methods: This multicenter retrospective study included 197 consecutive patients with chronic liver disease who had a single targetoid primary liver malignancy (142 hepatocellular carcinomas, 37 cholangiocarcinomas, 17 combined hepatocellular carcinoma-cholangiocarcinomas, and one neuroendocrine carcinoma) identified on preoperative gadoxetic acid-enhanced MRI and subsequently surgically removed between 2010 and 2017. Of these, 120 patients constituted the development cohort, and 77 patients from separate institution served as an external validation cohort. Factors associated with recurrence-free survival (RFS) and overall survival (OS) were identified using a Cox proportional hazards analysis, and risk scores were developed. The discriminatory power of the risk scores in the external validation cohort was evaluated using the Harrell C-index. The Kaplan–Meier curves were used to estimate RFS and OS for the different risk-score groups. Results: In RFS model 1, which eliminated features exclusively accessible on the hepatobiliary phase (HBP), tumor size of 2–5 cm or > 5 cm, and thin-rim arterial phase hyperenhancement (APHE) were included. In RFS model 2, tumors with a size of > 5 cm, tumor in vein (TIV), and HBP hypointense nodules without APHE were included. The OS model included a tumor size of > 5 cm, thin-rim APHE, TIV, and tumor vascular involvement other than TIV. The risk scores of the models showed good discriminatory performance in the external validation set (C-index, 0.62–0.76). The scoring system categorized the patients into three risk groups: favorable, intermediate, and poor, each with a distinct survival outcome (all log-rank p < 0.05). Conclusion Risk scores based on rim arterial enhancement pattern, tumor size, HBP findings, and radiologic vascular invasion status may help predict postoperative RFS and OS in patients with targetoid primary liver malignancies.

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

Purpose: To systematically compare the performance of liver imaging reporting and data system treatment response (LR-TR) with the modified Response Evaluation Criteria in Solid Tumors (mRECIST) for diagnosing viable hepatocellular carcinoma (HCC) treated with locoregional therapy (LRT). Materials and Methods: Original studies of intra-individual comparisons between the diagnostic performance of LR-TR and mRECIST using dynamic contrast-enhanced CT or MRI were searched in MEDLINE and EMBASE, up to August 25, 2021. The reference standard for tumor viability was surgical pathology. The meta-analytic pooled sensitivity and specificity of the viable category using each criterion were calculated using a bivariate random-effects model and compared using bivariate meta-regression. Results: For five eligible studies (430 patients with 631 treated observations), the pooled per-lesion sensitivities and specificities were 58% (95% confidence interval [CI], 45%–70%) and 93% (95% CI, 88%–96%) for the LR-TR viable category and 56% (95% CI, 42%–69%) and 86% (95% CI, 72%–94%) for the mRECIST viable category, respectively. The LR-TR viable category provided significantly higher pooled specificity (p < 0.01) than the mRECIST but comparable pooled sensitivity (p = 0.53). Conclusion The LR-TR algorithm demonstrated better specificity than mRECIST, without a significant difference in sensitivity for the diagnosis of pathologically viable HCC after LRT.

Objective: We aimed to evaluate the usefulness of arterial subtraction images for predicting the viability of hepatocellular carcinoma (HCC) after locoregional therapy (LRT) using gadoxetic acid-enhanced MRI and the Liver Imaging Reporting and Data System treatment response (LR-TR) algorithm. Materials and Methods: This study included 90 patients (mean age ± standard deviation, 57 ± 9 years) who underwent liver transplantation or resection after LRT and had 73 viable and 32 nonviable HCCs. All patients underwent gadoxetic acid-enhanced MRI before surgery. Two radiologists assessed the presence of LR-TR features, including arterial phase hyperenhancement (APHE) and LR-TR categories (viable, nonviable, or equivocal), using ordinary arterial-phase and arterial subtraction images. The reference standard for tumor viability was surgical pathology. The sensitivity of APHE for diagnosing viable HCC was compared between ordinary arterial-phase and arterial subtraction images. The sensitivity and specificity of the LR-TR algorithm for diagnosing viable HCC was compared between the use of ordinary arterial-phase and the use of arterial subtraction images.Subgroup analysis was performed on lesions treated with transarterial chemoembolization (TACE) only. Results: The sensitivity of APHE for viable HCCs was higher for arterial subtraction images than ordinary arterial-phase images (71.2% vs. 47.9%; p < 0.001). LR-TR viable category with the use of arterial subtraction images compared with ordinary arterial-phase images showed a significant increase in sensitivity (76.7% [56/73] vs. 63.0% [46/73]; p = 0.002) without significant decrease in specificity (90.6% [29/32] vs. 93.8% [30/32]; p > 0.999). In a subgroup of 63 lesions treated with TACE only, the use of arterial subtraction images showed a significant increase in sensitivity (81.4% [35/43] vs. 67.4% [29/43]; p = 0.031) without significant decrease in specificity (85.0% [17/20] vs. 90.0% [18/20]; p > 0.999). Conclusion Use of arterial subtraction images compared with ordinary arterial-phase images improved the sensitivity while maintaining specificity for diagnosing viable HCC after LRT using gadoxetic acid-enhanced MRI and the LR-TR algorithm.

Objective: We aimed to evaluate the usefulness of arterial subtraction images for predicting the viability of hepatocellular carcinoma (HCC) after locoregional therapy (LRT) using gadoxetic acid-enhanced MRI and the Liver Imaging Reporting and Data System treatment response (LR-TR) algorithm. Materials and Methods: This study included 90 patients (mean age ± standard deviation, 57 ± 9 years) who underwent liver transplantation or resection after LRT and had 73 viable and 32 nonviable HCCs. All patients underwent gadoxetic acid-enhanced MRI before surgery. Two radiologists assessed the presence of LR-TR features, including arterial phase hyperenhancement (APHE) and LR-TR categories (viable, nonviable, or equivocal), using ordinary arterial-phase and arterial subtraction images. The reference standard for tumor viability was surgical pathology. The sensitivity of APHE for diagnosing viable HCC was compared between ordinary arterial-phase and arterial subtraction images. The sensitivity and specificity of the LR-TR algorithm for diagnosing viable HCC was compared between the use of ordinary arterial-phase and the use of arterial subtraction images.Subgroup analysis was performed on lesions treated with transarterial chemoembolization (TACE) only. Results: The sensitivity of APHE for viable HCCs was higher for arterial subtraction images than ordinary arterial-phase images (71.2% vs. 47.9%; p < 0.001). LR-TR viable category with the use of arterial subtraction images compared with ordinary arterial-phase images showed a significant increase in sensitivity (76.7% [56/73] vs. 63.0% [46/73]; p = 0.002) without significant decrease in specificity (90.6% [29/32] vs. 93.8% [30/32]; p > 0.999). In a subgroup of 63 lesions treated with TACE only, the use of arterial subtraction images showed a significant increase in sensitivity (81.4% [35/43] vs. 67.4% [29/43]; p = 0.031) without significant decrease in specificity (85.0% [17/20] vs. 90.0% [18/20]; p > 0.999). Conclusion Use of arterial subtraction images compared with ordinary arterial-phase images improved the sensitivity while maintaining specificity for diagnosing viable HCC after LRT using gadoxetic acid-enhanced MRI and the LR-TR algorithm.

BACKGROUND/OBJECTIVES: To assess the longitudinal associations of the antioxidant capacity of zinc and body mass index (BMI) with serum uric acid (SUA) in South Korean children. SUBJECTS/METHODS: Using follow-up data from the Ewha Birth and Growth Cohort, we included subjects who were seen at 3 and 7 years of age (n = 183; 90 boys, 93 girls). Daily zinc intake and BMI were assessed at 3 and 7 years of age. SUA measured at 7 years was used as the outcome variable. Using a general linear model, the effects of dietary zinc intake and BMI on SUA were assessed. We also assessed the combined effect of early dietary zinc intake and BMI on SUA in children. RESULTS: The dietary zinc intake at 3 years of age was negatively correlated (ρ = −0.18, P = 0.04), whereas the BMI at 7 years of age was positively correlated (r = 0.18, P = 0.01), with the SUA level at 7 years of age. The dietary zinc intake level at 3 years of age and the BMI level at 7 years of age were, together, significantly related to SUA in children at 7 years of age. SUA was lower in group 1 (normal-weight, high-zinc group) than in the other two groups (group 2: normalweight, low-zinc and overweight, high-zinc group; and group 3: overweight, low-zinc group). Our results demonstrate the combined effect of zinc intake and BMI on SUA. The combined association remained significant in both the crude and adjusted models (P < 0.01). CONCLUSIONS SUA was related to combined BMI and dietary zinc intake, and increased zinc intake and normal body weight had a beneficial effect on reducing SUA in children.

Purpose: Isoform 2 of tight junction protein claudin-18 (CLDN18.2) is a potential target for gastric cancer treatment. A treatment targeting CLDN18.2 has shown promising results in gastric cancer. We investigated the clinical significance of CLDN18.2 and other cell-adherens junction molecules (Rho GTPase-activating protein [RhoGAP] and E-cadherin) in metastatic diffuse-type gastric cancer (mDGC). Materials and Methods: We evaluated CLDN18.2, RhoGAP, and E-cadherin expression using two-plex immunofluorescence and quantitative data analysis of H-scores of 77 consecutive mDGC patients who received first-line platinum-based chemotherapy between March 2015 and February 2017. Results: CLDN18.2 and E-cadherin expression was significantly lower in patients with peritoneal metastasis (PM) than those without PM at the time of diagnosis (P=0.010 and 0.013, respectively), whereas it was significantly higher in patients who never developed PM from diagnosis to death than in those who did (P=0.001 and 0.003, respectively). Meanwhile, CLDN18.2 and E-cadherin expression levels were significantly higher in patients with bone metastasis than in those without bone metastasis (P=0.010 and 0.001, respectively).Moreover, we identified a positive correlation between the expression of CLDN18.2 and E-cadherin (P<0.001), RhoGAP and CLDN18.2 (P=0.004), and RhoGAP and E-cadherin (P=0.001). Conversely, CLDN18.2, RhoGAP, and E-cadherin expression was not associated with chemotherapy response and survival. Conclusions CLDN18.2 expression was reduced in patients with PM but significantly intactin those with bone metastasis. Furthermore, CLDN18.2 expression was positively correlated with other adherens junction molecules, which is clinically associated with mDGC and PM pathogenesis.

BACKGROUND/AIMS: Computed tomography (CT) hepatic volumetry is currently accepted as the most reliable method for preoperative estimation of graft weight in living donor liver transplantation (LDLT). However, several factors can cause inaccuracies in CT volumetry compared to real graft weight. The purpose of this study was to determine the frequency and degree of resection plane-dependent error in CT volumetry of the right hepatic lobe in LDLT. METHODS: Forty-six living liver donors underwent CT before donor surgery and on postoperative day 7. Prospective CT volumetry (VP) was measured via the assumptive hepatectomy plane. Retrospective liver volume (VR) was measured using the actual plane by comparing preoperative and postoperative CT. Compared with intraoperatively measured weight (W), errors in percentage (%) VP and VR were evaluated. Plane-dependent error in VP was defined as the absolute difference between VP and VR. % plane-dependent error was defined as follows: |VP–VR|/W∙100. RESULTS: Mean VP, VR, and W were 761.9 mL, 755.0 mL, and 696.9 g. Mean and % errors in VP were 73.3 mL and 10.7%. Mean error and % error in VR were 64.4 mL and 9.3%. Mean plane-dependent error in VP was 32.4 mL. Mean % plane-dependent error was 4.7%. Plane-dependent error in VP exceeded 10% of W in approximately 10% of the subjects in our study. CONCLUSIONS: There was approximately 5% plane-dependent error in liver VP on CT volumetry. Plane-dependent error in VP exceeded 10% of W in approximately 10% of LDLT donors in our study. This error should be considered, especially when CT volumetry is performed by a less experienced operator who is not well acquainted with the donor hepatectomy plane.
Cone-Beam Computed Tomography ; Hepatectomy ; Humans ; Liver Transplantation ; Liver* ; Living Donors ; Methods ; Organ Size ; Prospective Studies ; Retrospective Studies ; Tissue Donors* ; Transplants