Comparative efficacies and safeties of cylindrical interstitial laser ablation and radiofrequency ablation on swine pancreas.

Laser ablation (LA) has been evaluated for the minimally invasive thermal treatment of various cancers, but conventional unidirectional endoscopic ultrasound (EUS)-guided LA has limitations. Therefore, we developed a cylindrical laser diffuser to overcome the limitations of unidirectional EUS-guided LA. The purpose of this study was to compare the efficacies and safeties of EUS-guided LA using a novel cylindrical laser diffuser and radiofrequency ablation (RFA) in vivo in swine pancreas. EUS-guided RFA (15 W, 30 s, 450 J) and cylindrical interstitial LA (CILA) (5 W, 90 s, 450 J) were applied to normal pancreatic tissue in six anesthetized pigs (three per group). Laboratory tests were performed at baseline, immediately after ablation (day 0), and 2 days after procedures (day 2). Two days after procedures, all pigs were sacrificed, and histopathological safety and efficacy assessments were performed. Technically, EUS-guided RFA and CILA were performed successfully in all cases. No major complications, including perforation or acute pancreatitis, occurred during the experiment in either group. All animals remained in excellent condition throughout the experimental period, and laboratory tests provided no evidence of a major complication. Average necrotic volumes in the RFA and CILA groups were 424.2 mm3 and 3747.4 mm3, respectively, and average necrotic volume was significantly larger in CILA group (p < 0.001). EUS-guided RFA and CILA had acceptable safety profiles in the normal swine pancreas model. Our findings indicate EUS-guided CILA has potential for the effective local treatment of pancreatic cancer as an alternative to EUS-guided RFA.

Natural alleles of CIRCADIAN CLOCK ASSOCIATED1 contribute to rice cultivation by fine-tuning flowering time.

The timing of flowering is a crucial factor for successful grain production at a wide range of latitudes. Domestication of rice (Oryza sativa) included selection for natural alleles of flowering-time genes that allow rice plants to adapt to broad geographic areas. Here, we describe the role of natural alleles of CIRCADIAN CLOCK ASSOCIATED1 (OsCCA1) in cultivated rice based on analysis of single-nucleotide polymorphisms deposited in the International Rice Genebank Collection Information System database. Rice varieties harboring japonica-type OsCCA1 alleles (OsCCA1a haplotype) flowered earlier than those harboring indica-type OsCCA1 alleles (OsCCA1d haplotype). In the japonica cultivar "Dongjin", a T-DNA insertion in OsCCA1a resulted in late flowering under long-day and short-day conditions, indicating that OsCCA1 is a floral inducer. Reverse transcription quantitative PCR analysis showed that the loss of OsCCA1a function induces the expression of the floral repressors PSEUDO-RESPONSE REGULATOR 37 (OsPRR37) and Days to Heading 8 (DTH8), followed by repression of the Early heading date 1 (Ehd1)-Heading date 3a (Hd3a)-RICE FLOWERING LOCUS T 1 (RFT1) pathway. Binding affinity assays indicated that OsCCA1 binds to the promoter regions of OsPRR37 and DTH8. Naturally occurring OsCCA1 alleles are evolutionarily conserved in cultivated rice (O. sativa). Oryza rufipogon-I (Or-I) and Or-III type accessions, representing the ancestors of O. sativa indica and japonica, harbored indica- and japonica-type OsCCA1 alleles, respectively. Taken together, our results demonstrate that OsCCA1 is a likely domestication locus that has contributed to the geographic adaptation and expansion of cultivated rice.

The Rice Basic Helix-Loop-Helix 79 (OsbHLH079) Determines Leaf Angle and Grain Shape.

Changes in plant architecture, such as leaf size, leaf shape, leaf angle, plant height, and floral organs, have been major factors in improving the yield of cereal crops. Moreover, changes in grain size and weight can also increase yield. Therefore, screens for additional factors affecting plant architecture and grain morphology may enable additional improvements in yield. Among the basic Helix-Loop-Helix (bHLH) transcription factors in rice (Oryza sativa), we found an enhancer-trap T-DNA insertion mutant of OsbHLH079 (termed osbhlh079-D). The osbhlh079-D mutant showed a wide leaf angle phenotype and produced long grains, similar to the phenotypes of mutants with increased brassinosteroid (BR) levels or enhanced BR signaling. Reverse transcription-quantitative PCR analysis showed that BR signaling-associated genes are largely upregulated in osbhlh079-D, but BR biosynthesis-associated genes are not upregulated, compared with its parental japonica cultivar 'Dongjin'. Consistent with this, osbhlh079-D was hypersensitive to BR treatment. Scanning electron microscopy revealed that the expansion of cell size in the adaxial side of the lamina joint was responsible for the increase in leaf angle in osbhlh079-D. The expression of cell-elongation-associated genes encoding expansins and xyloglucan endotransglycosylases/hydrolases increased in the lamina joints of leaves in osbhlh079-D. The regulatory function of OsbHLH079 was further confirmed by analyzing 35S::OsbHLH079 overexpression and 35S::RNAi-OsbHLH079 gene silencing lines. The 35S::OsbHLH079 plants showed similar phenotypes to osbhlh079-D, and the 35S::RNAi-OsbHLH079 plants displayed opposite phenotypes to osbhlh079-D. Taking these observations together, we propose that OsbHLH079 functions as a positive regulator of BR signaling in rice.

A major QTL and candidate genes for capsaicinoid biosynthesis in the pericarp of Capsicum chinense revealed using QTL-seq and RNA-seq.

KEY MESSAGE: A major QTL and candidate genes controlling capsaicinoid content in the pericarp were identified by QTL-seq and RNA-seq in Capsicum chinense. Capsaicinoid biosynthesis was previously thought to be restricted to the placental tissue; however, the recent discovery of their biosynthesis in the pericarp provides new opportunities to increase the capsaicinoid content in pepper fruits. Currently, the genetic mechanisms regulating capsaicinoid biosynthesis in the pericarp remain unknown. Here, we performed quantitative trait loci (QTL) mapping and RNA sequencing (RNA-seq) to reveal the genes controlling capsaicinoid biosynthesis in the pericarp. A whole-genome sequencing-based QTL-seq strategy was employed, identifying a major QTL on chromosome 6. To validate the QTL on chromosome 6, we performed traditional QTL mapping using the same population in QTL-seq with an additional biparental population. A total of 15 QTLs for capsaicinoid content distributed on chromosomes 3, 6, and 11 were newly identified. Among these QTLs, the genetic loci on the lower arm of chromosome 6 were commonly detected in the two mapping populations, corresponding to the location of the major QTL detected using whole-genome sequencing-based QTL-seq. Our RNA-seq analysis identified candidate genes within the common QTL that were differentially expressed in the pungent and non-pungent pericarp tissues. Our results are expected to contribute to the elucidation of the regulation of capsaicinoid biosynthesis. We also demonstrated that a combination of QTL mapping and RNA-seq is helpful for refining the candidate genes of a complicated trait of interest.

Rice ONAC106 Inhibits Leaf Senescence and Increases Salt Tolerance and Tiller Angle.

NAM/ATAF1/ATAF2/CUC2 (NAC) is a plant-specific transcription factor (TF) family, and NACs participate in many diverse processes during the plant life cycle. Several Arabidopsis thaliana NACs have important roles in positively or negatively regulating leaf senescence, but in other plant species, including rice, the senescence-associated NACs (senNACs) remain largely unknown. Here we show that the rice senNAC TF ONAC106 negatively regulates leaf senescence. Leaves of onac106-1D (insertion of the 35S enhancer in the promoter region of the ONAC106 gene) mutants retained their green color under natural senescence and dark-induced senescence conditions. Genome-wide transcriptome analysis revealed that key senescence-associated genes (SGR, NYC1, OsNAC5, OsNAP, OsEIN3 and OsS3H) were differentially expressed in onac106-1D during dark-induced senescence. In addition to delayed senescence, onac106-1D also showed a salt stress-tolerant phenotype; key genes that down-regulate salt response signaling (OsNAC5, OsDREB2A, OsLEA3 and OsbZIP23) were rapidly up-regulated in onac106-1D under salt stress. Interestingly, onac106-1D also exhibited a wide tiller angle phenotype throughout development, and the tiller angle-related gene LPA1 was down-regulated in onac106-1D. Using yeast one-hybrid assays, we found that ONAC106 binds to the promoter regions of SGR, NYC1, OsNAC5 and LPA1. Taking these results together, we propose that ONAC106 functions in leaf senescence, salt stress tolerance and plant architecture by modulating the expression of its target genes that function in each signaling pathway.

Mutation of SPOTTED LEAF3 (SPL3) impairs abscisic acid-responsive signalling and delays leaf senescence in rice.

Lesion mimic mutants commonly display spontaneous cell death in pre-senescent green leaves under normal conditions, without pathogen attack. Despite molecular and phenotypic characterization of several lesion mimic mutants, the mechanisms of the spontaneous formation of cell death lesions remain largely unknown. Here, the rice lesion mimic mutant spotted leaf3 (spl3) was examined. When grown under a light/dark cycle, the spl3 mutant appeared similar to wild-type at early developmental stages, but lesions gradually appeared in the mature leaves close to heading stage. By contrast, in spl3 mutants grown under continuous light, severe cell death lesions formed in developing leaves, even at the seedling stage. Histochemical analysis showed that hydrogen peroxide accumulated in the mutant, likely causing the cell death phenotype. By map-based cloning and complementation, it was shown that a 1-bp deletion in the first exon of Oryza sativa Mitogen-Activated Protein Kinase Kinase Kinase1 (OsMAPKKK1)/OsEDR1/OsACDR1 causes the spl3 mutant phenotype. The spl3 mutant was found to be insensitive to abscisic acid (ABA), showing normal root growth in ABA-containing media and delayed leaf yellowing during dark-induced and natural senescence. Expression of ABA signalling-associated genes was also less responsive to ABA treatment in the mutant. Furthermore, the spl3 mutant had lower transcript levels and activities of catalases, which scavenge hydrogen peroxide, probably due to impairment of ABA-responsive signalling. Finally, a possible molecular mechanism of lesion formation in the mature leaves of spl3 mutant is discussed.

A Retrospective study of anatomical differences in levator aponeurosis angle and length in East-Asian blepharoplasty.

This study aimed to analyze the anatomical differences in levator aponeurosis angle and length between both sides in double eyelidplasty in East Asians. The retrospective study included patients with mild blepharoptosis who underwent upper blepharoplasty with levator aponeurosis. In the study, 140 patients were enrolled, 126 females and 14 males, with an age range of 16-73 years. The mean levator aponeurosis angle was 19.2 ± 2.9° on the right and 17.0 ± 3.8° on the left, which was significantly different (95% CI, p < 0.001). The mean length was 24.1 mm on the right and 23.2 mm on the left, a difference that was also statistically significant (95% CI, p < 0.001). The relationship between the dominant eye and levator aponeurosis prominence was also investigated, although there was no apparent correlation. Within the limitations of the study, it seems that this is the first study of the anatomical differences of the levator aponeurosis between both sides, leading to a greater predictability of surgery to maximize postoperative symmetry.

Outcomes of Extracorporeal Membrane Oxygenation in COVID-19: A Single-Center Study.

Background: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory failure, which frequently necessitates invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO). However, the limited availability of ECMO resources poses challenges to patient selection and associated decision-making. Consequently, this retrospective single-center study was undertaken to evaluate the characteristics and clinical outcomes of patients with COVID-19 receiving ECMO. Methods: Between March 2020 and July 2022, 65 patients with COVID-19 were treated with ECMO and were subsequently reviewed. Patient demographics, laboratory data, and clinical outcomes were examined, and statistical analyses were performed to identify risk factors associated with mortality. Results: Of the patients studied, 15 (23.1%) survived and were discharged from the hospital, while 50 (76.9%) died during their hospitalization. The survival group had a significantly lower median age, at 52 years (interquartile range [IQR], 47.5-61.5 years), compared to 64 years (IQR, 60.0-68.0 years) among mortality group (p=0.016). However, no significant differences were observed in other underlying conditions or in factors related to intervention timing. Multivariable analysis revealed that the requirement of a change in ECMO mode (odds ratio [OR], 366.77; 95% confidence interval [CI], 1.92-69911.92; p=0.0275) and the initiation of continuous renal replacement therapy (CRRT) (OR, 139.15; 95% CI, 1.95-9,910.14; p=0.0233) were independent predictors of mortality. Conclusion: Changes in ECMO mode and the initiation of CRRT during management were associated with mortality in patients with COVID-19 who were supported by ECMO. Patients exhibiting these factors require careful monitoring due to the potential for adverse outcomes.

Gastrointestinal Bleeding in Extracorporeal Membrane Oxygenation Patients: A Comprehensive Analysis of Risk Factors and Clinical Outcomes.

Background: Extracorporeal membrane oxygenation (ECMO) is an intervention for severe heart and lung failure; however, it poses the risk of complications, including gastrointestinal bleeding (GIB). Comprehensive analyses of GIB in patients undergoing ECMO are limited, and its impact on clinical outcomes remains unclear. Methods: This retrospective study included 484 patients who received venovenous and venoarterial ECMO between January 2015 and December 2022. Data collected included patient characteristics, laboratory results, GIB details, and interventions. Statistical analyses were performed to identify risk factors and assess the outcomes. Results: GIB occurred in 44 of 484 patients (9.1%) who received ECMO. Multivariable analysis revealed that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.06; p=0.0130) and need to change the ECMO mode (OR, 3.74; 95% CI, 1.75-7.96; p=0.0006) were significant risk factors for GIB, whereas no association was found with antiplatelet or systemic anticoagulation therapies during ECMO management. Half of the patients with GIB (22/44, 50%) underwent intervention, with endoscopy as the primary modality (19/22, 86.4%). Patients who underwent ECMO and developed GIB had higher rates of mortality (40/44 [90.9%] vs. 262/440 [59.5%]) and ECMO weaning failure (38/44 [86.4%] vs. 208/440 [47.3%]). Conclusion: GIB in patients undergoing ECMO is associated with adverse outcomes, including increased risks of mortality and weaning failure. Even in seemingly uncomplicated cases, it is crucial to avoid underestimating the significance of GIB.

Prognostic Impact of Minimal Pelvic Fluid in Locally Advanced Pancreatic Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIMS: Minimal pelvic fluid (MPF) is occasionally encountered on computed tomography (CT) scans during the initial staging of newly diagnosed pancreatic cancer. However, its clinical relevance has scarcely been studied. This study intends to explore the incidence of minimal pelvic fluid and its relevance in terms of survival in locally advanced pancreatic cancer (LAPC) patients. MATERIALS AND METHODS: The medical records of patients with LAPC at 4 tertiary referral institutions were retrospectively reviewed from January 2005 to December 2015. Minimal pelvic fluid was defined as a fluid collection volume in the pelvic cavity of <100 mL as determined by abdominal CT. The association between the presence of MPF and patient survival was evaluated. RESULTS: A total of 59 patients (male:female, 33:26; median age, 68 years; range 46-82 years) with LAPC were enrolled. Of the 59 patients, 22.0% (n = 13) had MPF, and 78.0% (n = 46) had no pelvic fluid (NPF). Baseline clinical characteristics in the 2 groups, including extent of the tumor stage, extent of spread to the lymph nodes stage, and pattern of treatments, were not significantly different. However, median overall survival was significantly less in the MPF group [9.7 months, (95% CI, 5.9-13.5)] than in the NPF group as determined by the log-rank test [16.9 months, (95% CI, 9.3-24.5)] (P = .002), and univariate and multivariate analyses showed that the presence of MPF independently predicted a poor prognosis. CONCLUSION: The presence of MPF was found to be significantly associated with reduced survival and an independent poor prognostic biomarker in LAPC patients.

Effect of a Proton Pump Inhibitor on the Duodenum Microbiome of Gastric Ulcer Patients.

The gut microbiota are regarded as a functional organ that plays a substantial role in human health and disease. Proton pump inhibitors (PPIs) are widely used in medicine but can induce changes in the overall gut microbiome and cause disease-associated dysbiosis. The microbiome of the duodenum has not been sufficiently studied, and the effects of PPIs on the duodenal microbiome are poorly understood. In this study, we investigated the effect of PPI administration on duodenum microbiota in patients with a gastric ulcer. A total of 12 gastric ulcer patients were included, and PPI (Ilaprazole, Noltec®, 10 mg) was prescribed in all patients for 4 weeks. A total of 17 samples from the second portion of the duodenum were analyzed. Microbiome compositions were assessed by sequencing the V3-V4 region of the 16s rRNA gene (Miseq). Changes in microbiota compositions after 4 weeks of PPI treatment were analyzed. a-Diversity was higher after PPI treatment (p = 0.02, at Chao1 index), and ß-diversity was significantly different after treatment (p = 0.007). Welch's t-test was used to investigate changes in phyla, genus, and species level, and the abundance of Akkermansia muciniphila, belonging to the phylum Verrucomicrobia, and Porphyromonas endodontalis, belonging to the phylum Bacteroidetes, was significantly increased after treatment (p = 0.044 and 0.05). PPI administration appears to induce duodenal microbiome dysbiosis while healing gastric ulcers. Further large-scale studies on the effects of PPIs on the duodenal microbiome are required.

Outcomes of Urgent Interhospital Transportation for Extracorporeal Membrane Oxygenation Patients.

Background: Extracorporeal membrane oxygenation (ECMO) can be used in patients with refractory cardiogenic shock or respiratory failure. In South Korea, the need for transporting ECMO patients is increasing. Nonetheless, information on urgent transportation and its outcomes is scant. Methods: In this retrospective review of 5 years of experience in ECMO transportation at a single center, the clinical outcomes of transported patients were compared with those of in-hospital patients. The effects of transportation and the relationship between insertion-departure time and survival were also analyzed. Results: There were 323 cases of in-hospital ECMO (in-hospital group) and 29 cases transferred to Hallym University Sacred Heart Hospital without adverse events (mobile group). The median transportation time was 95 minutes (interquartile range [IQR], 36.5-119.5 minutes), whereas the median transportation distance was 115 km (IQR, 15-115 km). Transportation itself was not an independent risk factor for 28-day mortality (odds ratio [OR], 0.818; IQR, 0.381-1.755; p=0.605), long-term mortality (OR, 1.099; IQR, 0.680-1.777; p=0.700), and failure of ECMO weaning (OR, 1.003; IQR, 0.467-2.152; p=0.995) or survival to discharge (OR, 0.732; IQR, 0.337-1.586; p=0.429). After adjustment for covariates, no significant difference in the ECMO insertion-departure time was found between the survival and mortality groups (p=0.435). Conclusion: The outcomes of urgent transportation, with active involvement of the ECMO center before ECMO insertion and adherence to the transport protocol, were comparable to those of in-hospital ECMO patients.

Endoscopic Ultrasound-Guided Pancreatic Interstitial Laser Ablation Using a Cylindrical Laser Diffuser: A Long-Term Follow-Up Study.

BACKGROUND AND AIMS: Local ablative treatment is another option for improving outcomes and has been evaluated for locally advanced pancreatic cancer. We previously suggested endoscopic ultrasound (EUS)-guided interstitial laser ablation using a cylindrical laser diffuser (CILA) might be a feasible therapeutic option based on experiments performed on pancreatic cancer cell lines and porcine model with a short follow-up (3 days). The aim of this study was to investigate the safety of EUS-CILA performed using optimal settings in porcine pancreas with a long-term follow-up (2 weeks). METHODS: EUS-CILA (laser energy of 450 J; 5 W for 90 s) was applied to normal pancreatic tissue in porcine (n = 5) under EUS guidance. Animals were observed clinically for 2 weeks after EUS-CILA to evaluate complications. Computed tomography and laboratory tests were carried out to evaluate safety. Two weeks after EUS-CILA, all pigs were sacrificed, and histopathological safety and efficacy evaluations were conducted. RESULTS: EUS-CILA was technically successful in all five cases. No major complications occurred during the follow-up period. Body weight of porcine did not change during the study period without any significant change in feed intake. Animals remained in excellent condition throughout the experimental period, and laboratory tests and computed tomography (CT) scans provided no evidence of a major complication. Histopathological evaluation showed complete ablation in the ablated area with clear delineation of surrounding normal pancreatic tissue. Mean ablated volume was 55.5 mm2 × 29.0 mm and mean ablated areas in the pancreatic sections of the five pigs were not significantly different (p = 0.368). CONCLUSIONS: In conclusion, our experimental study suggests that EUS-CILA is safe and has the potential to be an effective local treatment modality. No major morbidity or mortality occurred during the study period. Further evaluations are warranted before clinical application.

Semantic Segmentation of Pancreatic Cancer in Endoscopic Ultrasound Images Using Deep Learning Approach.

Endoscopic ultrasonography (EUS) plays an important role in diagnosing pancreatic cancer. Surgical therapy is critical to pancreatic cancer survival and can be planned properly, with the characteristics of the target cancer determined. The physical characteristics of the pancreatic cancer, such as size, location, and shape, can be determined by semantic segmentation of EUS images. This study proposes a deep learning approach for the segmentation of pancreatic cancer in EUS images. EUS images were acquired from 150 patients diagnosed with pancreatic cancer. A network with deep attention features (DAF-Net) is proposed for pancreatic cancer segmentation using EUS images. The performance of the deep learning models (U-Net, Attention U-Net, and DAF-Net) was evaluated by 5-fold cross-validation. For the evaluation metrics, the Dice similarity coefficient (DSC), intersection over union (IoU), receiver operating characteristic (ROC) curve, and area under the curve (AUC) were chosen. Statistical analysis was performed for different stages and locations of the cancer. DAF-Net demonstrated superior segmentation performance for the DSC, IoU, AUC, sensitivity, specificity, and precision with scores of 82.8%, 72.3%, 92.7%, 89.0%, 98.1%, and 85.1%, respectively. The proposed deep learning approach can provide accurate segmentation of pancreatic cancer in EUS images and can effectively assist in the planning of surgical therapies.

Anti-Diabetic Effects of Allium hookeri Extracts Prepared by Different Methods in Type 2 C57BL/J-db/db Mice.

This study was conducted to evaluate whether Allium hookeri can control diabetic symptoms. Aqueous extract (AE1: 100 mg/kg BW, AE2: 200 mg/kg BW) and ethanol extract (EE1: 100 mg/kg BW, EE2: 200 mg/kg BW) of A. hookeri were orally administrated to diabetic mice (C57BL/J-db/db) for 8 weeks. The negative (NC) and the positive (PC) control groups were treated with 0.9% saline and metformin (150 mg/kg BW), respectively. Glucose and lipid profile (triglyceride, total cholesterol (TC), LDL-C, and HDL-C) as biochemical parameters, toxicological factors such as liver/kidney functional parameters (ALT, AST, BUN, and Cr), and NK cell activity in blood were measured. Oral glucose tolerance test (OGTT) and histopathological examination were also conducted. Compared with the NC group, AE and EE decreased blood glucose, HbA1c, area under the curve (AUC) during OGTT, and leptin levels while increasing adiponectin levels. Serum lipid profiles and toxicological factors levels were reduced by the A. hookeri extract. Interestingly, HDL-C, glomerular mesangial expansion score in the kidney, and NK cell activity were effectively controlled in EE groups. Based on the results, EE is considered to be more effective in reducing high blood glucose, lipid profile, and related factor levels than AE, and is comparable to metformin in some biomarkers. It can be presumed that EE can more effectively control the major anomalies in the diabetic model than AE, and it may be used to prevent diabetic symptoms without toxicity in the Type 2 diabetic model.

High-intensity focused ultrasound treatment of abnormal vaginal bleeding secondary to uterine myoma.

We describe the use of high-intensity focused ultrasound for acute vaginal bleeding secondary to uterine myoma in 2 young female patients. Both patients had episodes of abnormal vaginal bleeding with severe dysmenorrhea that was not efficiently controlled by medical treatment. After high-intensity focused ultrasound ablation, both vaginal bleeding control and symptom relief were achieved without postinterventional complications. The patients remained free of symptoms during 2 months of follow-up and regained normal menstruation after high-intensity focused ultrasound therapy. High-intensity focused ultrasound treatment is one of the least invasive options for dysfunctional vaginal bleeding and may be an effective and safe alternative to other procedures in women of reproductive age with abnormal vaginal bleeding secondary to uterine myoma.

Association between HBs Ag quantification and the risk of hepatocellular carcinoma in patients treated with tenofovir disoproxil fumarate or entecavir.

ABSTRACT: This study evaluated the clinical implications of hepatitis B surface antigen quantification (qHBs Ag) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) and identified the association between qHBs Ag and the risk of hepatocellular carcinoma (HCC) in these patients.Between January 2007 and December 2018, the qHBs Ag and clinical data of 183 CHB patients who initially received ETV (n = 45, 24.6%) or TDF (n = 138, 75.4%) were analyzed.The mean follow-up period of the 183 CHB patients was 45.3 months, of which 59 (32.2%) patients showed a reduction in qHBs Ag by >50% after 1 year of antiviral treatment (ETV or TDF). The HCC development (P = .179) or qHBs Ag reduction (P = .524) were similar in the ETV and TDF groups. Patients with a ≥50% decrease in qHBs Ag had a significantly lower incidence of HCC or decompensated cirrhosis complications (P = .005). Multivariate analysis showed that a >50% reduction of qHBs Ag (hazard ratio 0.085, P = .018) and the presence of cirrhosis (hazard ratio 3.32, P = .016) were independent factors predicting the development of HCC.Patients whose qHBs Ag value decreased >50% at 1 year after antiviral treatment for CHB showed a significant decrease in HCC or decompensated cirrhosis events. A reduction in qHBs Ag could be used as a predictive factor of HCC development or critical complications in CHB patients treated with TDF or ETV.

Deep Learning-Based Differentiation between Mucinous Cystic Neoplasm and Serous Cystic Neoplasm in the Pancreas Using Endoscopic Ultrasonography.

Mucinous cystic neoplasms (MCN) and serous cystic neoplasms (SCN) account for a large portion of solitary pancreatic cystic neoplasms (PCN). In this study we implemented a convolutional neural network (CNN) model using ResNet50 to differentiate between MCN and SCN. The training data were collected retrospectively from 59 MCN and 49 SCN patients from two different hospitals. Data augmentation was used to enhance the size and quality of training datasets. Fine-tuning training approaches were utilized by adopting the pre-trained model from transfer learning while training selected layers. Testing of the network was conducted by varying the endoscopic ultrasonography (EUS) image sizes and positions to evaluate the network performance for differentiation. The proposed network model achieved up to 82.75% accuracy and a 0.88 (95% CI: 0.817-0.930) area under curve (AUC) score. The performance of the implemented deep learning networks in decision-making using only EUS images is comparable to that of traditional manual decision-making using EUS images along with supporting clinical information. Gradient-weighted class activation mapping (Grad-CAM) confirmed that the network model learned the features from the cyst region accurately. This study proves the feasibility of diagnosing MCN and SCN using a deep learning network model. Further improvement using more datasets is needed.

Crlz1 activates transcription by mobilizing cytoplasmic CBFbeta into the nucleus.

Transcriptional function of a novel Crlz1 protein was examined by using the CBF site-containing IgJ enhancer, because it was originally cloned due to its ability to bind CBFbeta, a subunit of CBF heterodimer, of which Runx is the other subunit. In a cotransfection experiment, Crlz1 was shown to increase the IgJ enhancer activity due to its CBF sites, as verified by both the absence of Crlz1 effect on the CBF-site mutated IgJ enhancer and the presence of transcriptional synergy between Crlz1 and CBFbeta. Most significantly, the cytoplasmic CBFbeta was shown to be mobilized into the nucleus when it was coexpressed with the nuclear Crlz1. This mobilized nuclear CBFbeta could then heterodimerize with the nuclear Runx to bind to its target DNA site with a high affinity. Furthermore, in our coimmunoprecipitation and chromatin immunoprecipitation experiments, Crlz1 was found to be bound to the resulting CBF heterodimer in a form of ternary complex and to remain in that ternary complex even when CBF bound to its target DNA site such as IgJ enhancer.

Effect of itopride hydrochloride on the ileal and colonic motility in guinea pig in vitro.

PURPOSE: Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. MATERIALS AND METHODS: The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10 cm with 2-cm intervals. RESULTS: In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6) M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9) M). Dopamine (10(-8) M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6) M). Dopamine (10(-8) M) delayed colonic transit time that was also recovered after infusion of itopride. CONCLUSION: Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.