Papillary Renal Cell Carcinoma in Transplanted Kidney and Xp11.2 Translocation/Transcription Factor E3-Rearranged Renal Cell Carcinoma in the Native Kidney: A Case Report.

Concomitant renal cell carcinomas (RCC) of both native and allograft kidneys are extremely rare, and only a few cases have been reported in the available English literature. A particularly rare variant within the adult population is the Xp11.2 translocation/transcription factor E3 (TFE3)-rearranged RCC. Although few case reports of TFE3-rearranged RCC have been reported in children who underwent kidney transplantation (KT), no case of adults with TFE3-rearranged RCC following KT has been reported. Herein, we presented the radiological and pathological findings of a rare metachronous papillary RCC in the allograft kidney and TFE3-rearranged RCC in the native kidney. The TFE3-rearranged RCC in the native kidney exhibited slow expansion in size over five years. Radiologically, it appeared as a slightly enhanced, lobulated mass on contrast-enhanced CT. MRI revealed high signal intensity on T1-weighted images and low signal intensity on T2-weighted images.

Comparison of Four Diagnostic Guidelines for Hepatocellular Carcinoma Using Gadoxetic Acid-enhanced Liver MRI.

Background Noninvasive diagnostic guidelines for hepatocellular carcinoma (HCC) vary across different global geographic areas, especially regarding criteria about gadoxetic acid-enhanced MRI. Purpose To compare the diagnostic performance of four different international HCC diagnosis guidelines and readers' judgment in diagnosing HCC using gadoxetic acid-enhanced MRI in patients at high risk for HCC. Materials and Methods This retrospective study included patients who had not undergone treatment, were at risk for HCC, and who underwent gadoxetic acid-enhanced MRI from January 2015 to June 2018 from 11 tertiary hospitals in South Korea. Four radiologists independently reviewed focal liver lesions (FLLs) according to four guidelines: American Association for the Study of Liver Diseases (AASLD)/Liver Imaging Reporting and Data System (LI-RADS), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). Reader judgment (HCC or not HCC) was also recorded. Malignant FLLs were confirmed at pathology, and histologic and clinical follow-up data were used for benign FLLs. The guidelines' diagnostic performance was compared using generalized estimating equations. Additionally, the diagnostic odds ratio was assessed. Results A total of 2445 FLLs (median size, 27.4 mm) were analyzed in 2237 patients (mean age, 59 years ± 11 [SD]; 1666 male patients); 69.3% (1694 of 2445) were HCCs. KLCA-NCC showed the highest accuracy (80.0%; 95% CI: 78.7, 81.2; P = .001), with high sensitivity in Eastern guidelines (APASL, 89.1% [95% CI: 87.8, 90.3]; KLCA-NCC, 78.2% [95% CI: 76.6, 79.7]) and high specificity in Western guidelines (AASLD/LI-RADS, 89.6% [95% CI: 87.8, 91.2]; EASL, 88.1% [95% CI: 86.2, 89.9]) (P = .001). The diagnostic odds ratios were 20.7 (95% CI: 17.0, 25.3) for AASLD/LI-RADS, 18.9 (95% CI: 15.8, 22.6) for KLCA-NCC, 16.8 (95% CI: 13.8, 20.4) for EASL, and 8.9 (95% CI: 7.4, 10.7) for APASL. The readers' judgment demonstrated higher accuracy than that of the guidelines (accuracy, 86.0%; 95% CI: 84.9, 86.9; P = .001). Conclusion Among four different international HCC diagnosis guidelines, Eastern guidelines demonstrated higher sensitivity, whereas Western guidelines displayed higher specificity. KLCA-NCC achieved the highest accuracy, and AASLD/LI-RADS exhibited the highest diagnostic odds ratio. © RSNA, 2024 Supplemental material is available for this article.

Current Status of Anti-Reflux Surgery as a Treatment for GERD.

Anti-reflux surgery (ARS) is an efficient treatment option for gastroesophageal reflux disease (GERD). Despite growing evidence of the efficacy and safety of ARS, medications including proton pump inhibitors (PPIs) remain the most commonly administered treatments for GERD. Meanwhile, ARS can be an effective treatment option for patients who need medications continuously or for those who are refractory to PPI treatment, if proper candidates are selected. However, in practice, ARS is often regarded as a last resort for patients who are unresponsive to PPIs. Accumulating ARS-related studies indicate that surgery is equivalent to or better than medical treatment for controlling typical and atypical GERD symptoms. Furthermore, because of overall reduced medication expenses, ARS may be more cost-effective than PPI. Patients are selected for ARS based on endoscopic findings, esophageal acid exposure time, and PPI responsiveness. Although there is limited evidence, ARS may be expanded to include patients with normal acid exposure, such as those with reflux hypersensitivity. Additionally, other factors such as age, body mass index, and comorbidities are known to affect ARS outcomes; and such factors should be considered. Nissen fundoplication or partial fundoplication including Dor fundoplication and Toupet fundoplication can be chosen, depending on whether the patient prioritizes symptom improvement or minimizing postoperative symptoms such as dysphagia. Furthermore, efforts to reduce and manage postoperative complications and create awareness of the long-term efficacy and safety of the ARS are recommended, as well as adequate training programs for new surgeons.

Apoptotic Effect of Gallic Acid via Regulation of p-p38 and ER Stress in PANC-1 and MIA PaCa-2 Cells Pancreatic Cancer Cells.

Pancreatic cancer (PC) is currently recognized as the seventh most prevalent cause of cancer-related mortality among individuals of both genders. It is projected that a significant number of individuals will succumb to this disease in the forthcoming years. Extensive research and validation have been conducted on both gemcitabine and 5-fluorouracil as viable therapeutic options for PC. Nevertheless, despite concerted attempts to enhance treatment outcomes, PC continues to pose significant challenges in terms of achieving effective treatment alone through chemotherapy. Gallic acid, an endogenous chemical present in various botanical preparations, has attracted considerable attention due to its potential as an anticancer agent. The results of the study demonstrated that gallic acid exerted a decline in cell viability that was dependent on its concentration. Furthermore, it efficiently suppressed cell proliferation in PC cells. This study observed a positive correlation between gallic acid and the production of reactive oxygen species (ROS). Additionally, it confirmed the upregulation of proteins associated with the protein kinase-like endoplasmic reticulum kinase (PERK) pathway, which is one of the pathways involved in endoplasmic reticulum (ER) stress. Moreover, the administration of gallic acid resulted in verified alterations in the transmission of mitogen-activated protein kinase (MAPK) signals. Notably, an elevation in the levels of p-p38, which represents the phosphorylated state of p38 MAPK was detected. The scavenger of reactive oxygen species (ROS), N-Acetyl-L-cysteine (NAC), has shown inhibitory effects on phosphorylated p38 (p-p38), whereas the p38 inhibitor SB203580 inhibited C/EBP homologous protein (CHOP). In both instances, the levels of PARP have been successfully reinstated. In other words, the study discovered a correlation between endoplasmic reticulum stress and the p38 signaling pathway. Consequently, gallic acid induces the activation of both the p38 pathway and the ER stress pathway through the generation of ROS, ultimately resulting in apoptosis. The outcomes of this study provide compelling evidence to support the notion that gallic acid possesses considerable promise as a viable therapeutic intervention for pancreatic cancer.

Outcomes After Superior Capsular Reconstruction With an Achilles Tendon-Bone Allograft Using the Modified Keyhole Technique: A 2-Year Follow-up of a Novel Technique for Irreparable Rotator Cuff Tears.

Background: Despite improved outcomes, failure or nonhealing of graft materials has been reported after superior capsular reconstruction (SCR) for massive irreparable rotator cuff tears. Purpose: To evaluate the short-term clinical and radiological outcomes of a novel technique for SCR using an Achilles tendon-bone allograft. Study Design: Case series; Level of evidence, 4. Methods: We performed a retrospective review of patients who underwent SCR using an Achilles tendon-bone allograft with the modified keyhole technique and who had a minimum follow-up of 2 years. The visual analog scale score for pain, American Shoulder and Elbow Surgeons score, and Constant score were evaluated as subjective outcomes, while range of motion of the shoulder joint and isokinetic strength were evaluated as objective outcomes. The acromiohumeral interval (AHI), bone-to-bone healing of the allograft and humeral head on computed tomography, and graft integrity on magnetic resonance imaging were evaluated as radiological outcomes. Results: This study included 32 patients with a mean age of 56.8 ± 4.2 years and a mean follow-up of 28.4 ± 6.2 months. A significant improvement from preoperatively to the last follow-up was seen in the mean visual analog scale score for pain (from 6.7 to 1.8), American Shoulder and Elbow Surgeons score (from 42.7 to 83.8), Constant score (from 47.2 to 78.5), and AHI (from 4.8 to 8.2 mm) (P < .001 for all) as well as range of motion in forward elevation and internal rotation (P < .001 for both). Medial-to-lateral graft integrity was good in all patients. Nonunion at the fitting zone of the keyhole on the greater tuberosity was diagnosed in 1 case (3.1%), and failure of incorporation between the allograft and remnant tendon at the site of posterior margin convergence was observed in 4 cases (12.5%). Conclusion: The outcomes after SCR using an Achilles tendon-bone allograft and the keyhole technique improved, with an increased AHI and excellent integrity in the medial and lateral directions compared with preoperatively. This technique is a reasonable option for the surgical treatment of irreparable rotator cuff tears.

Radiologic Findings of Mesonephric-Like Adenocarcinoma of the Uterine Corpus: A Case Report.

According to the 2020 World Health Organization classification, mesonephric-like adenocarcinoma (MLA) is newly categorized as a subtype of endometrial carcinoma and remains a relatively unknown disease owing to its rarity. To the best of our knowledge, radiological findings of MLA have not been reported in the English literature. The uterine MLAs show a worse clinical prognosis and a more aggressive biological behavior than the usual endometrial carcinoma. Herein, we present the imaging findings of a 65-year-old female with a MLA in the uterine corpus. The tumor was a solid endometrial mass with deep myometrial invasion, poor contrast enhancement, and moderate diffusion restriction.

Comparing rapid rule-learning strategies in humans and monkeys.

Inter-species comparisons are key to deriving an understanding of the behavioral and neural correlates of human cognition from animal models. We perform a detailed comparison of macaque monkey and human strategies on an analogue of the Wisconsin Card Sort Test, a widely studied and applied multi-attribute measure of cognitive function, wherein performance requires the inference of a changing rule given ambiguous feedback. We found that well-trained monkeys rapidly infer rules but are three times slower than humans. Model fits to their choices revealed hidden states akin to feature-based attention in both species, and decision processes that resembled a Win-stay lose-shift strategy with key differences. Monkeys and humans test multiple rule hypotheses over a series of rule-search trials and perform inference-like computations to exclude candidates. An attention-set based learning stage categorization revealed that perseveration, random exploration and poor sensitivity to negative feedback explain the under-performance in monkeys.

Abbreviated MRI with second shot arterial phase for HCC evaluation: modified version of LI-RADS and recall reduction strategy.

OBJECTIVES: To evaluate the feasibility of simulated abbreviated MRI (AMRI) with second shot arterial phase (SSAP) for HCC surveillance and diagnosis. METHODS: A total of 129 consecutive patients (age, 58.8 ± 11.4 years; male, 71.3%) underwent gadoxetic acid-enhanced MRI using a modified injection protocol for HCC evaluation from July 2017 to February 2018. The modified injection protocol consisted of routine dynamic imaging (6 mL) and SSAP imaging (4 mL). Two radiologists independently reviewed two AMRI sets: AMRI without SSAP (surveillance set) and AMRI with SSAP (diagnosis set). A modified version of the Liver Imaging Reporting and Data System (LI-RADS) for the diagnosis set was devised by referring to contrast-enhanced ultrasound LI-RADS. RESULTS: Sixty-seven patients with HCC and 62 patients without HCC were included. In the surveillance set, sensitivity and specificity for the detection of patients with HCC were 95.5% and 96.8%, and 94.0% and 96.8% in reviewers 1 and 2, respectively. In the diagnosis set, the scores of most HCCs (76/78, 97.4%) were consistent between LI-RADS of full-protocol and modified LI-RADS of AMRI with SSAP protocol. When the HCC surveillance and diagnosis strategy was changed from strategy 1 (AMRI without SSAP) to strategy 2 (AMRI with SSAP), the recall rate significantly decreased from 52.7 to 3.9% (p < 0.001). CONCLUSIONS: The modified LI-RADS score of the AMRI with SSAP protocol showed high agreement with the LI-RADS score of the full protocol. The HCC surveillance and diagnosis strategy using the AMRI with SSAP protocol reduced the recall rate. These results may enable to diagnose HCC simultaneously with surveillance. KEY POINTS: • A modified version of LI-RADS was devised for the diagnostic algorithm using AMRI with the second shot arterial phase (SSAP) by referring to CEUS LI-RADS. • The modified LI-RADS scores using AMRI with SSAP showed a high concordance rate with the conventional LI-RADS score using full-protocol MRI. • The recall rate significantly decreased when the HCC surveillance and diagnosis strategy was changed from strategy 1 (AMRI without SSAP; surveillance then recall test) to strategy 2 (AMRI with SSAP; simultaneous surveillance and diagnosis).

Evaluation of Scapula and Humerus Bone Change after Repair of Small- to Medium-Sized Rotator Cuff Tears: Comparison between Healing and Retear Groups Using Three-Dimensional Computed Tomography.

Background: Rotator cuff tendon retears after rotator cuff repair cause glenohumeral joint instability, which results in changes in the glenoid and humerus head. However, limited data are available on the bone change after repair of small- to medium-sized rotator cuff tears. The aim of this study was to evaluate the difference of glenoid and humerus bone changes between healing and retear groups after repair of small- to medium-sized rotator cuff tears. Methods: Among patients who had arthroscopic repair due to small- to medium-sized rotator cuff tears from January 2009 to January 2017, 49 patients who underwent both preoperative and postoperative (at least 3 years after surgery) shoulder computed tomography were enrolled. Using three-dimensional reconstruction program (3D Slicer) and shape analysis program (SlicerSALT), we compared the occurrence and degree of glenoid bone change, glenoid inclination change, retroversion change, and glenoid center, as well as the degree of humerus head change, between the healing and retear groups. Results: The occurrence of glenoid bone change was significantly more common in the retear group than in the healing group (p = 0.026). The degree of bone change in the 11-1 o'clock axial plane and 10-8 o'clock, 11-7 o'clock, and 12-6 o'clock coronal plane and the degree of glenoid inclination change were significantly larger in the retear group than the healing group (p = 0.026, p = 0.026, p = 0.026, p = 0.026, and p = 0.014, respectively), but the average value of glenoid bone change in the retear group was within the range of 0.14 to 1.01 mm for each plane. The mean humeral head change was 5.69 ± 3.67 mm increase in the retear group and 1.27 ± 2.02 mm increase in the healing group. Compared with the healing group, the retear group showed statistically significantly increased humeral head change (p < 0.001). Conclusions: There was difference in glenoid and humerus bone change between the healing and retear groups at midterm follow-up after repair of small- to medium-sized tears. However, considering the measurement bias, the difference between the two groups was within the measurement error range.

Co-Responses of Soil Organic Carbon Pool and Biogeochemistry to Different Long-Term Fertilization Practices in Paddy Fields.

Long-term application of soil organic amendments (SOA) can improve the formation of soil organic carbon (SOC) pool as well as soil fertility and health of paddy lands. However, the effects of SOA may vary with the input amount and its characteristics. In this work, a descriptive field research was conducted during one cropping season to investigate the responses of various SOC fractions to different long-term fertilization practices in rice fields and their relationships with soil biogeochemical properties and the emission of greenhouse gases (GHG). The field sites included two conventional paddies applied with chemical fertilizer (CF) or CF + rice straw (RS) and six organic agriculture paddies applied with oilseed cake manure (OCM) + wheat straw (WS), cow manure (CM) + WS, or CM + RS. The two paddy soils treated with CM + RS had significantly higher concentrations of recalcitrant to labile C forms, such as loss-on-ignition C (LOIC; 56-73 g kg-1), Walkley-Black C (WBC; 20-25 g kg-1), permanganate oxidizable C (POXC; 835-853 mg kg-1), and microbial biomass carbon (MBC; 133-141 mg kg-1), than soils treated with other SOA. Likewise, long-term application of CM + RS seemed to be the best for regulating soil fertility parameters, such as ammonium (11-141 mg kg-1); phosphate (61-106 mg kg-1); and soluble Ca, K, and Mg (7-10, 0.5-1.2, and 1.9-3.8 mg kg-1, respectively), although the results varied with the location and soil properties of rice fields. Additionally, the two paddy sites had the largest cumulative methane emission (754-762 kg ha-1), seemingly attributed to increased microbial biomass and labile C fractions. The significant correlations of most SOC fractions with soil microbial biomass, trophic factors, and methane emissions were confirmed with multivariate data analysis. It was also possible to infer that long-term SOA application, especially with CM + RS, enhanced interaction in belowground paddy fields, contributing to soil fertility and rice production sustainability. Based on our findings, we suggest the need for analysis of various types of SOC fractions to efficiently manage soil fertility and quality of paddy fields, C sequestration, and GHG emissions.

The spectrum of magnetic resonance imaging proton density fat fraction (MRI-PDFF), magnetic resonance spectroscopy (MRS), and two different histopathologic methods (artificial intelligence vs. pathologist) in quantifying hepatic steatosis.

Background: The grade of hepatic steatosis is assessed semi-quantitatively and graded as a discrete value. However, the proton density fat fraction (PDFF) measured by magnetic resonance imaging (MRI) and FF measured by MR spectroscopy (FFMRS) are continuous values. Therefore, a quantitative histopathologic method may be needed. This study aimed to (I) provide a spectrum of values of MRI-PDFF, FFMRS, and FFs measured by two different histopathologic methods [artificial intelligence (AI) and pathologist], (II) to evaluate the correlation among them, and (III) to evaluate the diagnostic performance of MRI-PDFF and MRS for grading hepatic steatosis. Methods: Forty-seven patients who underwent liver biopsy and MRI for nonalcoholic steatohepatitis (NASH) evaluation were included. The agreement between MRI-PDFF and MRS was evaluated through Bland-Altman analysis. Correlations among MRI-PDFF, MRS, and two different histopathologic methods were assessed using Pearson correlation coefficient (r). The diagnostic performance of MRI-PDFF and MRS was assessed using receiver operating characteristic curve analyses and the area under the curve (AUC) were obtained. Results: The means±standard deviation of MRI-PDFF, FFMRS, FF measured by pathologist (FFpathologist), and FF measured by AI (FFAI) were 12.04±6.37, 14.01±6.16, 34.26±19.69, and 6.79±4.37 (%), respectively. Bland-Altman bias [mean of MRS - (MRI-PDFF) differences] was 2.06%. MRI-PDFF and MRS had a very strong correlation (r=0.983, P<0.001). The two different histopathologic methods also showed a very strong correlation (r=0.872, P<0.001). Both MRI-PDFF and MRS demonstrated a strong correlation with FFpathologist (r=0.701, P<0.001 and r=0.709, P<0.001, respectively) and with FFAI (r=0.700, P<0.001 and r=0.690, P<0.001, respectively). The AUCs of MRI-PDFF for grading ≥S2 and ≥S3 were 0.846 and 0.855, respectively. The AUCs of MRS for grading ≥S2 and ≥S3 were 0.860 and 0.878, respectively. Conclusions: Since MRS and MRI-PDFF demonstrated a strong correlation with each other and with the two different histopathologic methods, they can be used as an alternative noninvasive reference standard in nonalcoholic fatty liver disease (NAFLD) patients. However, these preliminary results should be interpreted with caution until they are validated in further studies.

Potential Therapeutic Implication of Herbal Medicine in Mitochondria-Mediated Oxidative Stress-Related Liver Diseases.

Mitochondria are double-membrane organelles that play a role in ATP synthesis, calcium homeostasis, oxidation-reduction status, apoptosis, and inflammation. Several human disorders have been linked to mitochondrial dysfunction. It has been found that traditional therapeutic herbs are effective on alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) which are leading causes of liver cirrhosis and hepatocellular carcinoma. The generation of reactive oxygen species (ROS) in response to oxidative stress is caused by mitochondrial dysfunction and is considered critical for treatment. The role of oxidative stress, lipid toxicity, and inflammation in NAFLD are well known. NAFLD is a chronic liver disease that commonly progresses to cirrhosis and chronic liver disease, and people with obesity, insulin resistance, diabetes, hyperlipidemia, and hypertension are at a higher risk of developing NAFLD. NAFLD is associated with a number of pathological factors, including insulin resistance, lipid metabolic dysfunction, oxidative stress, inflammation, apoptosis, and fibrosis. As a result, the improvement in steatosis and inflammation is enough to entice researchers to look into liver disease treatment. However, antioxidant treatment has not been very effective for liver disease. Additionally, it has been suggested that the beneficial effects of herbal medicines on immunity and inflammation are governed by various mechanisms for lipid metabolism and inflammation control. This review provided a summary of research on herbal medicines for the therapeutic implementation of mitochondria-mediated ROS production in liver disease as well as clinical applications through herbal medicine. In addition, the pathophysiology of common liver disorders such as ALD and NAFLD would be investigated in the role that mitochondria play in the process to open new therapeutic avenues in the management of patients with liver disease.

Significant radiologic factors related to clinical outcomes after arthroscopic rotator cuff retear repair.

BACKGROUND: Healing of the tendon itself is not always related to successful clinical outcomes after rotator cuff repair. It was hypothesized that certain radiologic factors affecting clinical outcomes could exist in case of the retear after arthroscopic rotator cuff repair (ARCR) and the radiologic factors could help predict clinical process. The purpose of this study was to identify the radiologic factors associated with clinical outcomes of the retear after ARCR. METHODS: Between January 2012 and December 2019, among patients with sufficient footprint coverage for ARCR, 96 patients with Sugaya classification 4 or higher retear on follow-up magnetic resonance imaging were included. The association between clinical outcomes such as American Shoulder and Elbow Surgeons (ASES) score, Constant score and range of motion and radiologic variables such as initial tear dimension, retear dimension, variance of tear dimension, critical shoulder angle, acromial index, and acromiohumeral distance was analyzed. RESULTS: Preoperatively, the ASES and Constant scores were 59.81±17.02 and 64.30±15.27, respectively. And at the last follow-up, they improved to 81.56±16.29 and 78.62±14.16, respectively (p<0.01 and p<0.01). In multiple linear regression analysis, the variance of the mediolateral dimension of tear had statistically significant association with the ASES and Constant scores (p<0.01 and p=0.01). CONCLUSIONS: In patients with the retear after ARCR, the variance in the mediolateral dimension of tear had significantly negative association with the clinical outcomes. This could be considered to be reference as relative criteria and needed more sample and mechanical study.

Ectopic lesions in the abdomen and pelvis: a multimodality pictorial review.

Various ectopic lesions occur in the abdomen and pelvis and affect multiple organs including liver, gallbladder, pancreas, spleen, and organs of the genitourinary system. Ectopic organs may be present outside their normal positions, or ectopic tissues may develop while the original organ exists in its normal position. Both benign and malignant lesions can occur in ectopic organs and tissues. Owing to their unusual location, they can often be misdiagnosed as other lesions or even malignant lesions, such as metastasis or seeding. This multimodality pictorial review provides various cases of ectopic lesions in the abdomen and pelvis, which will help narrow the differential diagnosis and guide clinical decision-making.

Ultrasonographic index for the diagnosis of non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease.

Background: Liver biopsy is a gold standard for the diagnosis of non-alcoholic steatohepatitis (NASH), but has several disadvantages including invasiveness, high cost, and sampling error. Ultrasonography (US) is a noninvasive imaging modality widely used in non-alcoholic fatty liver disease (NAFLD) patients. This study aimed: (I) to assess the feasibility of US in the prediction of NASH and (II) to develop various US indices combining US parameters and laboratory data for the detection of NASH in NAFLD patients and to compare the diagnostic performance of them. Methods: Sixty patients who underwent liver biopsy, gray-scale US [hepatorenal index (HRI) and shear-wave elastography (SWE)], and Fibroscan [controlled attenuation parameter (CAP) and transient elastography (TE)] for the evaluation of NASH were included. Patients were classified according to the NAFLD Activity Score (NAS) into the NASH (NAS ≥5) and non-NASH (NAS <5) groups. The diagnostic performance of HRI, CAP, SWE, TE, and laboratory data for grading steatosis, lobular inflammation, ballooning degeneration, and fibrosis was evaluated. After the identification of laboratory data that were independently associated with NASH through univariable and multivariable logistic regression analyses, various US indices were developed by combining US parameters with or without these laboratory data. The diagnostic performance of the US indices was assessed with obtaining area under the curve (AUC) and compared using DeLong test. Results: Twenty-five NASH and 35 non-NASH patients were included. The mean AUCs for grading steatosis were 0.871 using HRI and 0.583 using CAP. The mean AUCs for grading fibrosis and ballooning degeneration were 0.777 and 0.729 using SWE and 0.830 and 0.708 using TE, respectively. Aspartate aminotransferase (AST) was the only significant laboratory data associated with NASH (OR, 1.019; P=0.032). Using AST, the mean AUCs for grading lobular inflammation and ballooning degeneration were 0.712 and 0.775, respectively. Among various US indices, the index consisting of gray-scale US parameters (SWE and HRI) and AST showed the best diagnostic performance for the detection of NASH in NAFLD patients (AUC =0.806). Conclusions: The index combining gray-scale US parameters and AST is useful for the detection of NASH and may be used to exclude the need for liver biopsy in NAFLD patients.

BK002 Induces miR-192-5p-Mediated Apoptosis in Castration-Resistant Prostate Cancer Cells via Modulation of PI3K/CHOP.

BK002 consists of Achyranthes japonica Nakai (AJN) and Melandrium firmum Rohrbach (MFR) that have been used as herbal medicines in China and Korea. AJN and MFR have been reported to have anti-inflammatory, anti-oxidative, and anti-cancer activities, although the synergistic targeting multiple anti-cancer mechanism in castration-resistant prostate cancer (CRPC) has not been well reported. However, the drug resistance and transition to the androgen-independent state of prostate cancer contributing to CRPC is not well studied. Here, we reported that BK002 exerted cytotoxicity and apoptosis in CRPC PC3 cell lines and prostate cancer DU145 cell lines examined by cytotoxicity, western blot, a LIVE/DEAD cell imaging assay, reactive oxygen species (ROS) detection, quantitative real-time polymerase chain reaction (RT-PCR), and transfection assays. The results from our investigation found that BK002 showed more cellular cytotoxicity than AJN and MFR alone, suggesting that BK002 exhibited potential cytotoxic properties. Consistently, BK002 increased DNA damage, and activated p-γH2A.X and depletion of survivin-activated ubiquitination of pro-PARP, caspase9, and caspase3. Notably, live cell imaging using confocal microscopy found that BK002 effectively increased DNA-binding red fluorescent intensity in PC3 and DU145 cells. Also, BK002 increased the anti-proliferative effect with activation of the C/EBP homologous protein (CHOP) and significantly attenuated PI3K/AKT expression. Notably, BK002-treated cells increased ROS generation and co-treatment of N-Acetyl-L-cysteine (NAC), an ROS inhibitor, significantly preventing ROS production and cellular cytotoxicity, suggesting that ROS production is essential for initiating apoptosis in PC3 and DU145 cells. In addition, we found that BK002 significantly enhanced miR-192-5p expression, and co-treatment with BK002 and miR-192-5p inhibitor significantly reduced miR-192-5p expression and cellular viability in PC3 and DU145 cells, indicating modulation of miR-192-5p mediated apoptosis. Finally, we found that BK002-mediated CHOP upregulation and PI3K downregulation were significantly reduced and restrained by miR-192-5p inhibitor respectively, suggesting that the anti-cancer effect of BK002 is associated with the miR-192-5p/PI3K/CHOP pathway. Therefore, our study reveals that a combination of AJN and MFR might be more effective than single treatment against apoptotic activities of both CRPC cells and prostate cancer cells.

MRE-based NASH score for diagnosis of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: As the prevalence of nonalcoholic fatty liver disease (NAFLD) is approximately 30% in the general population, it is important to develop a non-invasive biomarker for the diagnosis of nonalcoholic steatohepatitis (NASH). This prospective cross-sectional study aimed to develop a scoring system for NASH diagnosis through multiparametric magnetic resonance (MR) and clinical indicators. METHODS: Medical history, laboratory tests, and MR parameters of patients with NAFLD were assessed. A scoring system was developed using a logistic regression model. In total, 127 patients (58 with nonalcoholic fatty liver [NAFL] and 69 with NASH) were enrolled. After evaluating 23 clinical characteristics of the patients (4 categorical and 19 numeric variables) for the NASH diagnostic model, an equation for MR elastography (MRE)-based NASH score was obtained using 3 demographic factors, 2 laboratory variables, and MRE. RESULTS: The MRE-based NASH score showed a satisfactory accuracy for NASH diagnosis (c-statistics, 0.841; 95% CI 0.772-0.910). At a cut-off MRE-based NASH score of 0.68 for NASH diagnosis, its sensitivity was 0.68 and specificity was 0.91. When an MRE-based NASH score of 0.37 was used as a cut-off for NASH exclusion, the sensitivity was 0.91 and specificity was 0.55. Overall, 35% (44/127) of patients were in the gray zone (between 0.37 and 0.68). Internal validation via bootstrapping also indicated the satisfactory accuracy of NASH diagnosis (optimism-corrected statistics, 0.811). CONCLUSION: MRE-based NASH score is a useful and accurate non-invasive biomarker for diagnosis of NASH in patients with NAFLD.

Leonurus japonicus Houttuyn induces reactive oxygen species-mediated apoptosis via regulation of miR-19a-3p/PTEN/PI3K/AKT in U937 and THP-1 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houttuyn is a medicinal ingredient in more than 300 prescriptions in traditional Korean medicine. It is especially important for women's health and blood-related diseases. Recent research revealed that Leonurus japonicus Houttuyn extracts have antioxidative, anticancer, analgesic, anti-inflammatory, and neuroprotective properties. AIM OF THE STUDY: However, its underlying anti-cancerous mechanisms remain unclear. This study elucidated the anticancer mechanism of Leonurus japonicus Houttuyn in U937 and THP-1 cancer cells. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used for detecting main compound of Leonurus japonicus Houttuyn, rutin. EZ-Cytox cell viability assay, Western blot analysis, live and dead cell assay, 2', 7' dichlorofluorescin diacetate (DCFDA) assay, quantitative real-time PCR (qRT-PCR) analysis, and microRNA (miR) mimic transfection assay were applied to further investigate anti-cancer efficacies and underlying mechanism in U937 and THP-1 cells. RESULTS: The main compound of Leonurus japonicus Houttuyn, rutin was detected using HPLC. The cytotoxic effect of Leonurus japonicus Houttuyn was exerted in U937 and THP-1 cancer cells but not in MDBK and IEC-6 normal cells. Leonurus japonicus Houttuyn decreased mitochondria membrane potential (ΔΨm). Consistently, Leonurus japonicus Houttuyn reduced the expression of survivin and cleaved caspase-9, caspase-3, and poly (ADP-ribose) polymerase (PARP). Cell death was increased in Leonurus japonicus Houttuyn treated groups. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and CCAAT-enhancer-binding protein homologous protein (CHOP) was increased and phosphatidylinositol-3-kinase (PI3K) and Protein kinase B (AKT) were decreased by Leonurus japonicus Houttuyn. Reactive oxygen speices generation was elevated by Leonurus japonicus Houttuyn and its cytotoxicity was reversed by N-acetyl-l-cysteine (NAC) pretreatment. Moreover, onco-microRNA (miR), miR-19a-3p was suppressed by Leonurus japonicus Houttuyn and transfection of miR-19a-3p mimic reversed the regulated PTEN, p-AKT, CHOP expression, attenuating Leonurus japonicus Houttuyn induced apoptosis. CONCLUSIONS: These findings indicated that Leonurus japonicus Houttuyn has anti-cancer effects by regulation of PTEN/PI3K/AKT signal pathway and ROS-related ER stress-induced apoptosis via regulation of miR-19a-3p. Leonurus japonicus Houttuyn may be an effective candidate for triggering PTEN-dependent apoptosis of cancer cells related to acute myeloid leukemia.

Clinical outcomes of bending versus non-bending of the plate hook in acromioclavicular joint dislocation.

BACKGROUND: We aimed to assess the effect of plate hook bending in treatment of acromioclavicular (AC) dislocation by analyzing clinical and radiological results according to the angle of the plate hook (APH). METHODS: This was a retrospective, observational, case-control study including 76 patients with acute AC joint dislocation that were divided into two groups according to treatment with bent or unbent plate hook. The visual analog scale (VAS), the American Shoulder and Elbow Surgeons (ASES) shoulder score, and range of motion (ROM) were evaluated as clinical outcomes. Comparative coracoclavicular distance (CCD) was measured to evaluate radiological outcomes. RESULTS: While the VAS and ASES of the bending group at 4 months after surgery were significantly higher (p=0.021 and p=0.019), the VAS and ASES of the bending group at other periods and ROM of the bending group showed no significant difference. The initial CCD decreased from 183.2%±25.4% to 114.3%±18.9% at the final follow-up in the bending group and decreased from 188.2%±34.4% to 119.1%±16.7% in the non-bending group, with no statistical difference (p=0.613). The changes between the initial and post-metal removal CCD were 60.2%±11.2% and 57.3%±10.4%, respectively, with no statistical difference (p=0.241). The non-bending group showed greater subacromial osteolysis (odds ratio, 3.87). Pearson's coefficients for the correlation between APH and VAS at 4 months after surgery and for that between APH and ASES at 4 months after surgery were 0.74 and -0.63 (p=0.027 and p=0.032), respectively. CONCLUSIONS: The APH was associated with improved postoperative pain and clinical outcomes before implant removal and with reduced complications; therefore, plate hook bending is more useful clinically during plate implantation.