Efficacy, tolerability, and safety of oral sulfate tablet versus 2 L-polyethylene glycol/ascorbate for bowel preparation in older patients: prospective, multicenter, investigator single-blinded, randomized study.

BACKGROUND: We compared the efficacy, tolerability, and safety of oral sulfate tablets (OST, which contains simethicone) and 2 L-polyethylene glycol/ascorbate (2 L-PEG/Asc) with a split-dosing regimen in older individuals aged ≥ 70 years who underwent scheduled colonoscopy. METHODS: This prospective, randomized, investigator-blinded, multicenter study was conducted between June 2022 and October 2023. Participants aged ≥ 70 years were randomized at a ratio of 1:1 to the OST or 2 L-PEG/Asc groups. RESULTS: In total, 254 patients were evaluated using a modified full analysis set. Successful overall bowel preparation was excellent and similar between the OST and 2 L-PEG/Asc groups for the Boston Bowel Preparation Scale (BBPS) (96.5% vs. 96.6%) and Harefield Cleansing Scale (HCS) (96.5% vs. 97.4%). The overall high-quality preparation rate was higher in the OST group than in the 2 L-PEG/Asc group (BBPS: 55.7% vs. 28.4%, P < 0.001; HCS: 66.1% vs. 38.8%, P < 0.001). The overall adenoma detection rate (54.8% vs. 35.3, P = 0.003) was superior in the OST group compared to the 2 L-PEG/Asc group. Tolerability scores, including overall satisfaction, were generally higher in the OST group than in the 2 L-PEG/Asc group. The incidence of major solicited adverse events was comparable between the two groups (55.7% vs. 68.1, P = 0.051), and there were no clinically significant changes in the serum laboratory profiles on the day of or 7 days after colonoscopy. CONCLUSIONS: OST is an effective and safe low-volume agent for colonoscopy, with better tolerance than 2 L-PEG/Asc, in older individuals aged ≥ 70 years.

Single-Cell Network-Based Drug Repositioning for Discovery of Therapies against Anti-Tumour Necrosis Factor-Resistant Crohn's Disease.

Primary and secondary non-response affects approximately 50% of patients with Crohn's disease treated with anti-tumour necrosis factor (TNF) monoclonal antibodies. To date, very little single cell research exists regarding drug repurposing in Crohn's disease. We aimed to elucidate the cellular phenomena underlying resistance to anti-TNF therapy in patients with Crohn's disease and to identify potential drug candidates for these patients. Single-cell transcriptome analyses were performed using data (GSE134809) from the Gene Expression Omnibus and Library of Integrated Network-Based Cellular Signatures L1000 Project. Data aligned to the Genome Reference Consortium Human Build 38 reference genome using the Cell Ranger software were processed using the Seurat package. To capture significant functional terms, gene ontology functional enrichment analysis was performed on the marker genes. For biological analysis, 93,893 cells were retained (median 20,163 genes). Through marker genes, seven major cell lineages were identified: B-cells, T-cells, natural killer cells, monocytes, endothelial cells, epithelial cells, and tissue stem cells. In the anti-TNF-resistant samples, the top 10 differentially expressed genes were HLA-DQB-1, IGHG1, RPS23, RPL7A, ARID5B, LTB, STAT1, NAMPT, COTL1, ISG20, IGHA1, IGKC, and JCHAIN, which were robustly distributed in all cell lineages, mainly in B-cells. Through molecular function analyses, we found that the biological functions of both monocyte and T-cell groups mainly involved immune-mediated functions. According to multi-cluster drug repurposing prediction, vorinostat is the top drug candidate for patients with anti-TNF-refractory Crohn's disease. Differences in cell populations and immune-related activity within tissues may influence the responsiveness of Crohn's disease to anti-TNF agents. Vorinostat may serve as a promising novel therapy for anti-TNF-resistant Crohn's disease.

SUMOylation of the cardiac sodium channel NaV1.5 modifies inward current and cardiac excitability.

BACKGROUND: Decreased peak sodium current (INa) and increased late sodium current (INa,L), through the cardiac sodium channel NaV1.5 encoded by SCN5A, cause arrhythmias. Many NaV1.5 posttranslational modifications have been reported. A recent report concluded that acute hypoxia increases INa,L by increasing a small ubiquitin-like modifier (SUMOylation) at K442-NaV1.5. OBJECTIVE: The purpose of this study was to determine whether and by what mechanisms SUMOylation alters INa, INa,L, and cardiac electrophysiology. METHODS: SUMOylation of NaV1.5 was detected by immunoprecipitation and immunoblotting. INa was measured by patch clamp with/without SUMO1 overexpression in HEK293 cells expressing wild-type (WT) or K442R-NaV1.5 and in neonatal rat cardiac myocytes (NRCMs). SUMOylation effects were studied in vivo by electrocardiograms and ambulatory telemetry using Scn5a heterozygous knockout (SCN5A+/-) mice and the de-SUMOylating protein SENP2 (AAV9-SENP2), AAV9-SUMO1, or the SUMOylation inhibitor anacardic acid. NaV1.5 trafficking was detected by immunofluorescence. RESULTS: NaV1.5 was SUMOylated in HEK293 cells, NRCMs, and human heart tissue. HyperSUMOylation at NaV1.5-K442 increased INa in NRCMs and in HEK cells overexpressing WT but not K442R-Nav1.5. SUMOylation did not alter other channel properties including INa,L. AAV9-SENP2 or anacardic acid decreased INa, prolonged QRS duration, and produced heart block and arrhythmias in SCN5A+/- mice, whereas AAV9-SUMO1 increased INa and shortened QRS duration. SUMO1 overexpression enhanced membrane localization of NaV1.5. CONCLUSION: SUMOylation of K442-Nav1.5 increases peak INa without changing INa,L, at least in part by altering membrane abundance. Our findings do not support SUMOylation as a mechanism for changes in INa,L. Nav1.5 SUMOylation may modify arrhythmic risk in disease states and represents a potential target for pharmacologic manipulation.

Impact of the COVID-19 Pandemic on Esophagogastroduodenoscopy and Gastric Cancer Claims in South Korea: A Nationwide, Population-Based Study.

PURPOSE: There has been little information about the impact of coronavirus disease 2019 (COVID-19) pandemic on esophagogastroduodenoscopy (EGD) and gastric cancer claims. This study aimed to measure the impact of COVID-19 pandemic on EGD and gastric cancer claims in South Korea. MATERIALS AND METHODS: This nationwide, population-based study compared the claims data of EGD, gastric cancer, early gastric cancer (EGC), advanced gastric cancer (AGC) and gastric cancer operation in 2020 and 2021 (COVID-19 era) to those in 2019 (before COVID-19 pandemic). RESULTS: The annual claims of EGD, gastric cancer, EGC, and AGC were reduced by 6.3%, 5.0%, 4.7%, and 3.6% in 2020 and by 2.2%, 1.0%, 0.6%, and 1.9% in 2021, respectively, compared to 2019. The amount of annual claims of gastric cancer operation was reduced by 8.8% in 2020, but increased by 0.9% in 2021, compared to those in 2019. The monthly claims of EGD, gastric cancer, EGC, AGC, and gastric cancer operation were mainly reduced in the first epidemic wave of COVID-19, but decreased in the 2nd to 4th epidemic wave. Compared to 2019, the monthly claim of EGD, gastric cancer, EGC, AGC, and gastric cancer operation were reduced by 28.8%, 14.3%, 18.1%, 9.2%, and 5.8% in March 2020 and by 17.2%, 10.8%, 10.3%, 7.2%, and 35.4% in April 2020, respectively. CONCLUSION: Negative impact of the COVID-19 pandemic on EGD, gastric cancer, EGC, AGC, and gastric cancer operation was worst during the first surge of COVID-19, but decreased in the 2nd to 4th epidemic wave of the disease in 2020 and 2021.

Clinical and pathological characteristics of early-onset colorectal cancer in South Korea.

Background: Early-onset colorectal cancer (EOCRC) may differ by race and ethnicity, and recently South Korea has witnessed a surge in cases. We aimed to evaluate the clinical and pathological features of patients with EOCRC, and to determine the predictors of overall survival. Methods: In this retrospective study, EOCRC was defined as CRC diagnosed in patients aged < 50 years, and late-onset CRC was defined as CRC diagnosed in those over 75 years of age. The clinical and pathological characteristics of patients with EOCRC were compared with late-onset CRC. We also used multivariable Cox proportional hazard models to find predictors of overall survival in patients with EOCRC. Results: The proportion of early-onset CRC was 9.1% of 518 patients with CRC, and the clinical and pathological characteristics were similar between early-onset (n = 47) and late-onset CRC (n = 134). However, EOCRC had a preponderance for distal tumor location (70.2% vs. 50.7%, P = 0.02) and T1-2 stage disease (23.4% vs. 11.2%, P = 0.04), compared with those of late-onset CRC. Using multivariable Cox proportional hazard models, only vascular invasion (hazard ratio = 8.75, 95% confidence interval 1.139‒67.197) was found to be a risk factor for overall survival (P = 0.04) for patients with CRC. Conclusion: EOCRC had preponderance for distal tumor location and early T-stage disease, compared with late-onset CRC. Considering the increasing incidence of EOCRC, more studies on clinical and pathological characteristics of EOCRC may be warranted.

Neutrophil to lymphocyte ratio can predict overall survival in patients with stage II to III colorectal cancer.

The neutrophil-to-lymphocyte ratio (NLR) is a prognostic inflammatory marker in colorectal cancer (CRC), however, little is known for its prognostic role in stage II to III CRC patients underwent curative resection. This study was aimed to investigate prognostic role of NLR in stage II to III CRC patients underwent surgery. Medical records of 1378 newly diagnosed CRC patients between June 2006 and March 2020 were reviewed. Data were collected by using electronic medical record software. Survival rate were analyzed using the Kaplan-Meier method. The cutoff values of NLR in stage II to III CRC patients were defined by maximally selected log-rank statistics. Multivariable cox proportional-hazard models were performed to find risk factors associated with overall survival (OS) in stage II to III CRC patients underwent surgery. Among 1378 CRC patients enrolled, 910 patients underwent surgery. In entire surgical cohort, age, body mass index (BMI), CEA, carbohydrate antigen 19-9 (CA 19-9), lymphatic invasion, NLR, and albumin-to-globulin ratio (AGR) were found to be risk factors associated with OS (all P < .05). In stage II to III CRC patients underwent curative resection (n = 623), age, BMI, lymphatic invasion, AGR, and NLR were found to be risk factors associated with OS (all P < .05). In the multivariable analysis, CA 19-9 and lymphatic invasion were independent risk factors for OS in entire surgical cohort. In the multivariable analysis for the stage II to III CRC patients, age, BMI, lymphatic invasion and NLR (Hazard ratio = 2.41, 95% confidential interval [CI]: 1.04-5.595, P = .041) were independent risk factors for OS. NLR can be used as a clinically simple and useful parameter for predicting OS in stage II to III CRC patients undergoing curative resection, however, its optimal cutoff value should be further evaluated.

Involvement of Ca2+ in Signaling Mechanisms Mediating Muscarinic Inhibition of M Currents in Sympathetic Neurons.

Acetylcholine can excite neurons by suppressing M-type (KCNQ) potassium channels. This effect is mediated by M1 muscarinic receptors coupled to the Gq protein. Although PIP2 depletion and PKC activation have been strongly suggested to contribute to muscarinic inhibition of M currents (IM), direct evidence is lacking. We investigated the mechanism involved in muscarinic inhibition of IM with Ca2+ measurement and electrophysiological studies in both neuronal (rat sympathetic neurons) and heterologous (HEK cells expressing KCNQ2/KCNQ3) preparations. We found that muscarinic inhibition of IM was not blocked either by PIP2 or by calphostin C, a PKC inhibitor. We then examined whether muscarinic inhibition of IM uses multiple signaling pathways by blocking both PIP2 depletion and PKC activation. This maneuver, however, did not block muscarinic inhibition of IM. Additionally, muscarinic inhibition of IM was not prevented either by sequestering of G-protein ßγ subunits from Gα-transducin or anti-Gßγ antibody or by preventing intracellular trafficking of channel proteins with blebbistatin, a class-II myosin inhibitor. Finally, we re-examined the role of Ca2+ signals in muscarinic inhibition of IM. Ca2+ measurements showed that muscarinic stimulation increased intracellular Ca2+ and was comparable to the Ca2+ mobilizing effect of bradykinin. Accordingly, 20-mM of BAPTA significantly suppressed muscarinic inhibition of IM. In contrast, muscarinic inhibition of IM was completely insensitive to 20-mM EGTA. Taken together, these data suggest a role of Ca2+ signaling in muscarinic modulation of IM. The differential effects of EGTA and BAPTA imply that Ca2+ microdomains or spatially local Ca2+ signals contribute to inhibition of IM.

Chasm between Public Perceptions and Epidemiological Data on Colorectal Cancer.

Background/Aims: Only a few studies have examined perceptions of the incidence and prognosis of colorectal cancer (CRC) in the general Korean population. The aim of this study was to determine public perceptions of the lifetime incidence rate and survival of CRC. Methods: All adults older than 50 years who visited the Kyung Hee University Hospital at Gangdong were invited to participate in this survey for 5 months in 2021. During the study period, eligible individuals participated in this survey through a link or quick response code on a poster posted in the hospital, which was linked to a web-based questionnaire. The questionnaire used for this survey included demographic and socioeconomic data, perceptions of CRC, and awareness of the CRC incidence and 5-year survival rate. Results: Among 203 respondents, 196 answers were analyzed after the exclusion of seven incomplete answers. In our survey, half of the respondents (49.5%) answered the expected lifetime incidence rate of CRC as 0% to 4.9%. Koreans perceived CRC as a more fatal disease than epidemiological data, as 70.9% of the respondents expected the 5-year survival rate of CRC to be less than 70% for the general population. However, Koreans perceived stage IV CRC as a less fatal disease than epidemiological data, because only 20.9% of the respondents expected the 5-year survival rate of stage IV CRC to be less than 10% for general population. Conclusions: Koreans recognized CRC as a more common and fatal disease than actual epidemiological data of CRC. Therefore, more efforts should be made to provide more correct information on CRC for better decision-making and communication.

Complementary and alternative medicine for functional dyspepsia: An Asian perspective.

A considerable number of Asian patients with functional dyspepsia (FD) are searching for complementary and alternative medicine (CAM) because they are unsatisfied with conventional medical treatment. However, no article has focused on CAM for FD from Asian perspective. In Asian countries, many traditional herbal formulas, including Banha-sasim-tang, Soyo-san, Sihosogan-san, Yukgunja-tang, and Pyeongwi-san, are used in patients with FD. In the few blinded and placebo-controlled studies conducted, the weak evidence regarding the effectiveness of herbal prescriptions in patients with FD did not allow any conclusions to be made. The clinical efficacy and safety of STW-5 were proven in several prospective randomized controlled trials and systematic reviews. Hence, it was recently approved as a therapeutic option for the treatment of FD. Peppermint and caraway, FDgard, black seed oil, and Jollab have been used in patients with FD, but there is limited evidence supporting their use. Reviews of acupuncture in patients with FD showed inconsistent results: a Cochrane review reported a negative result, while other meta-analyses reported positive results. Psychotherapy, including hypnotherapy, psychoanalytic psychotherapy, and cognitive behavioral therapy, may be used in patients with FD, although it is only supported by weak evidence. Therefore, well-planned, large-scale studies are necessary to evaluate the efficacy of CAM in treating FD, especially in Asian countries.

Metabolic rescue ameliorates mitochondrial encephalo-cardiomyopathy in murine and human iPSC models of Leigh syndrome.

BACKGROUND: Mice with deletion of complex I subunit Ndufs4 develop mitochondrial encephalomyopathy resembling Leigh syndrome (LS). The metabolic derangement and underlying mechanisms of cardio-encephalomyopathy in LS remains incompletely understood. METHODS: We performed echocardiography, electrophysiology, confocal microscopy, metabolic and molecular/morphometric analysis of the mice lacking Ndufs4. HEK293 cells, human iPS cells-derived cardiomyocytes and neurons were used to determine the mechanistic role of mitochondrial complex I deficiency. RESULTS: LS mice develop severe cardiac bradyarrhythmia and diastolic dysfunction. Human-induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) with Ndufs4 deletion recapitulate LS cardiomyopathy. Mechanistically, we demonstrate a direct link between complex I deficiency, decreased intracellular (nicotinamide adenine dinucleotide) NAD+ /NADH and bradyarrhythmia, mediated by hyperacetylation of the cardiac sodium channel NaV 1.5, particularly at K1479 site. Neuronal apoptosis in the cerebellar and midbrain regions in LS mice was associated with hyperacetylation of p53 and activation of microglia. Targeted metabolomics revealed increases in several amino acids and citric acid cycle intermediates, likely due to impairment of NAD+ -dependent dehydrogenases, and a substantial decrease in reduced Glutathione (GSH). Metabolic rescue by nicotinamide riboside (NR) supplementation increased intracellular NAD+ / NADH, restored metabolic derangement, reversed protein hyperacetylation through NAD+ -dependent Sirtuin deacetylase, and ameliorated cardiomyopathic phenotypes, concomitant with improvement of NaV 1.5 current and SERCA2a function measured by Ca2+ -transients. NR also attenuated neuronal apoptosis and microglial activation in the LS brain and human iPS-derived neurons with Ndufs4 deletion. CONCLUSIONS: Our study reveals direct mechanistic explanations of the observed cardiac bradyarrhythmia, diastolic dysfunction and neuronal apoptosis in mouse and human induced pluripotent stem cells (iPSC) models of LS.

Gastrointestinal and non-gastrointestinal complication rates associated with diagnostic esophagogastroduodenoscopy under sedation.

ABSTRACT: Esophagogastroduodenoscopy (EGD) under sedation may result in gastrointestinal (GI) and non-GI complications. However, no previous studies have reported 30-day GI and non-GI complications after diagnostic EGD under sedation.We conducted a retrospective, observational study of 30-day GI and non-GI complication rates after outpatient diagnostic EGD under sedation in subjects ≥18 years between January 2012 and December 2017 based on a common data model database. Thirty-day complication rates were compared with EGD under sedation or not, type of sedation drugs (midazolam only vs midazolam/propofol) and age groups (18-64 year vs ≥65 year) for GI (bleeding and perforation) and non-GI complications (pneumonia, acute myocardial infarction, congestive heart failure and cerebral stroke).In total, 39,910 were performed with sedation (midazolam only, n = 16,033 and midazolam/propofol, n = 23,864) and 22,894 were performed without sedation. Elderly patients significantly favored EGD without sedation (P < .01). GI and non-GI complication rates were similar between EGD under sedation and without sedation (all P > .1) except for acute myocardial infarction rate, which was significantly higher in EGD without sedation than EGD under sedation (1.7/10,000 vs 0.3/10,000 persons, P = .043). All GI and non-GI complications were also similar between the midazolam/propofol and midazolam only groups as well as between young and old patients (all P > .1).Outpatient diagnostic EGD under sedation has an excellent safety profile. In addition, it can be safely performed with midazolam only or midazolam/propofol and in young and old patients.

Uncovering Novel Pre-Treatment Molecular Biomarkers for Anti-TNF Therapeutic Response in Patients with Crohn's Disease.

Neutralising monoclonal antibodies for tumour necrosis factor (TNF) has been widely used to treat Crohn's disease (CD) in clinical practice. However, differential individual response necessitates a therapeutic response assessment of anti-TNF agents in CD patients for optimizing therapeutic strategy. We aimed to predict anti-TNF therapy response in CD patients using transcriptome analyses. Transcriptome analyses were performed using data from the Gene Expression Omnibus, GeneCards, and Human Protein Atlas databases. The significantly mitigated biological functions associated with anti-TNF therapy resistance in CD patients encompassed immune pathways, including Interleukin-17 (IL-17) signaling, cytokine-cytokine receptor interaction, and rheumatoid arthritis. The scores of immune cell markers, including neutrophils, monocytes, and macrophages/monocytes were also significantly decreased in non-responders compared with that measured in anti-TNF therapy responders. The KAT2B gene, associated with IL-17 cytokine mediated neutrophil mobilization and activation, was significantly under-expressed in both tissue and peripheral blood mononuclear cells (PBMCs) in anti-TNF therapy-resistant CD patients. The reduced expression of several pro-inflammatory cytokines due to down-regulated IL-17 signaling, is suggestive of the primary non-response to anti-TNF agents in CD patients. Furthermore, the PBMC KAT2B gene signature may be a promising pre-treatment prognostic biomarker for anti-TNF drug response in CD patients.

Artificial intelligence-based measurement outperforms current methods for colorectal polyp size measurement.

OBJECTIVES: An accurate polyp size estimation during colonoscopy is crucial to determine the surveillance interval and predict the risk of malignant progression. However, there is a high degree of subjectivity in estimating polyp size among endoscopists in clinical practice. We aimed to assess the efficacy of a novel method that uses artificial intelligence (AI) to measure the size of colon polyps and compare it with current approaches. METHODS: Using the W-Net model for vessel segmentation and based on retinal image datasets (DRIVE, STARE, CHASE-DB, and HRF) and colonoscopy images, we developed the bifurcation-to-bifurcation (BtoB) distance measuring method and applied it to endoscopic images. Measurements were compared with those obtained by eight endoscopists (four expert and four trainees). Diagnostic ability and reliability were evaluated using Lin's concordance correlation coefficients (CCCs) and Bland-Altman analyses. RESULTS: For both experts and trainees, visually estimated sizes of the same polyp were significantly inconsistent depending on the camera view used (P < 0.001). Bland-Altman analyses showed that there was a trend toward underestimation of the sizes of the polyps in both groups, especially for polyps larger than 10 mm. The new technique was highly accurate and reliable in measuring the size of colon polyp (CCC, 0.961; confidence interval 0.926-0.979), clearly outperforming the visual estimation and open biopsy forceps methods. CONCLUSION: The new AI measurement method improved the accuracy and reliability of polyp size measurements in colonoscopy images. Incorporating AI might be particularly important to improve the efficiency of trainees at estimating polyp size during colonoscopy.

What Are the Different Phenotypes of Inflammatory Bowel Disease in Asia?

The burden of inflammatory bowel disease (IBD) in Asia has been increasing over the past decades. Although patients with IBD show heterogenous phenotypes depending on the individual characteristics, no significant differences have been established in the IBD phenotypes of Western and Asian populations. However, despite the much lower incidence of IBD in Asia than in Western countries, the incidence has been rapidly increasing in Asia while remaining stable in Western countries. The incidence of ulcerative colitis (UC) showed an earlier and a more marked increase than the incidence of Crohn disease (CD), but the UC-to-CD ratio has recently decreased because of a relative increase in the incidence of CD in Asia. While CD shows a significant male predominance, UC only shows a slight male predominance. A recent study reported that the incidence of IBD in Asia showed a bimodal age distribution with increasing IBD prevalence, similar to the findings of Western studies. CD in Asian patients, especially those in East Asia, is characterized by ileocolonic involvement and perianal fistula. The frequency of extraintestinal manifestations, including primary sclerosing cholangitis, appears to be lower in Asia, but this finding should be interpreted with caution due to the transient and nonspecific nature of these manifestations. Although familial aggregation is lower in East Asia, it may also be explained by the low prevalence of IBD in Asia. Thus, more studies should focus on the differences in phenotypes in Asian IBD patients versus Western patients.

The microRNA-204-5p inhibits APJ signalling and confers resistance to cardiac hypertrophy and dysfunction.

BACKGROUND: MicroRNAs regulate cardiac hypertrophy development, which precedes and predicts the risk of heart failure. microRNA-204-5p (miR-204) is well expressed in cardiomyocytes, but its role in developing cardiac hypertrophy and cardiac dysfunction (CH/CD) remains poorly understood. METHODS: We performed RNA-sequencing, echocardiographic, and molecular/morphometric analysis of the heart of mice lacking or overexpressing miR-204 five weeks after trans-aortic constriction (TAC). The neonatal rat cardiomyocytes, H9C2, and HEK293 cells were used to determine the mechanistic role of miR-204. RESULTS: The stretch induces miR-204 expression, and miR-204 inhibits the stretch-induced hypertrophic response of H9C2 cells. The mice lacking miR-204 displayed a higher susceptibility to CH/CD during pressure overload, which was reversed by the adeno-associated virus serotype-9-mediated cardioselective miR-204 overexpression. Bioinformatic analysis of the cardiac transcriptomics of miR-204 knockout mice following pressure overload suggested deregulation of apelin-receptor (APJ) signalling. We found that the stretch-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation and hypertrophy-related genes expression depend on the APJ, and both of these effects are subject to miR-204 levels. The dynamin inhibitor dynasore inhibited both stretch-induced APJ endocytosis and ERK1/2 activation. In contrast, the miR-204-induced APJ endocytosis was neither inhibited by dynamin inhibitors (dynasore and dyngo) nor associated with ERK1/2 activation. We find that the miR-204 increases the expression of ras-associated binding proteins (e.g., Rab5a, Rab7) that regulate cellular endocytosis. CONCLUSIONS: Our results show that miR-204 regulates trafficking of APJ and confers resistance to pressure overload-induced CH/CD, and boosting miR-204 can inhibit the development of CH/CD.

1 L- versus 2 L-polyethylene glycol with ascorbic acid for bowel preparation in elderly patients: a randomized multicenter study.

BACKGROUND: 1 L-polyethylene glycol (PEG)/ascorbic acid (Asc) was developed to reduce the required oral preparation volume through increasing osmotic load through containing a greater quantity of ascorbate components. We aimed to compare the efficacy, tolerability, and safety of a split-dosing regimen of 1 L-PEG/Asc versus 2 L-PEG/Asc in elderly patients undergoing scheduled colonoscopy. METHODS: This was a prospective, non-inferiority, randomized, investigator-blinded multicenter study conducted in Korea between July 2019 and December 2020. Patients aged between 65 and 85 years were randomized at a ratio of 1:1 to either the 1 L-PEG/Asc or 2 L-PEG/Asc group. The efficacy of the bowel preparation was evaluated using the Harefield Cleansing Scale (HCS) and the Boston Bowel Preparation Scale (BBPS). RESULTS: A total of 202 patients were analyzed. Successful overall bowel preparation was similar between the 1 L-PEG/Asc and 2 L-PEG/Asc groups based on HCS (95.1% vs. 93.1%, P = 0.528) and BBPS (93.1% vs. 90.0%, P = 0.422). The perfect overall bowel preparation rate in the 1 L-PEG/Asc group was higher than that in the 2 L-PEG/Asc group (HCS, 40.2% vs. 25.0%, P = 0.021; BBPS, 80.4% vs. 68.0%, P = 0.044). There were more high-quality bowel preparations for the right colon in the 1 L-PEG/Asc group (HCS, 46.1% vs. 30.0%, P = 0.019; BBPS, 83.3% vs. 70.0%, P = 0.025). The adenoma detection rate (47.1% vs. 49.0%, P = 0.782), rate of adverse events (25.5% vs. 23.0%, P = 0.680), shifts in laboratory results, and tolerability were comparable between the groups. CONCLUSION: 1 L-PEG/Asc was as effective, safe, and tolerable as 2 L-PEG/Asc in elderly patients with comorbidities.

Pretreatment with Ranitidine Bismuth Citrate May Improve Success Rates of Helicobacter pylori Eradication: A Prospective, Randomized, Controlled and Open-Label Study.

Effective Helicobacter pylori (H. pylori) eradication is a major public health concern; however, eradication failure rates with the standard triple therapy remain high. We aimed to investigate the effectiveness and tolerability of ranitidine bismuth citrate (RBC) pretreatment before standard triple therapy for H. pylori eradication. A prospective, randomized, controlled, and open-label clinical trial was conducted from June to December 2019. H. pylori eradication rate, safety, and tolerability were compared between the standard treatment group (esomeprazole, amoxicillin, and clarithromycin for 7 days) and RBC pretreatment group (RBC for 2 weeks before standard triple therapy). This trial ended earlier than estimated owing to the N-nitrosodimethylamine concerns with ranitidine. Success rates of H. pylori eradication were 80.9% and 67.3% in the RBC pretreatment (n = 47) and standard treatment (n = 52) (p = 0.126) groups, respectively. Our trial was discontinued earlier than planned; however, a statistical significance would be achieved by expansion of our data (p = 0.031) if patient enrollment numbers reached those initially planned. Adverse event rates were comparable between groups (25.5% in the pretreatment group vs. 28.8% in the standard treatment group), without serious event. Tolerability was excellent in both groups, recorded as 97.9% and 100% in the pretreatment and standard treatment groups, respectively. Compared with the standard triple regimen, RBC pretreatment for 2 weeks may achieve higher H. pylori eradication rates, with excellent safety and tolerability. However, this study necessitates further validation as it was discontinued early owing to the N-nitrosodimethylamine issues of ranitidine.

PTEN downregulation induces apoptosis and cell cycle arrest in uterine cervical cancer cells.

The tumor suppressors PTEN and p53 are often downregulated in various human cancer types, which has been associated with a poor prognosis. Recent evidence implies that PTEN downregulation may induce growth arrest of kidney cells and cancer cells. In the present study, the role of PTEN in the proliferation and survival of cervical cancer cells was investigated. It was found that PTEN silencing promoted apoptosis and cell-cycle arrest, accompanied by a significant decrease in the proportion of cells in the S1 phase of the cell cycle. Moreover, PTEN silencing in cervical cancer cells increased levels of p53, p27, p21, phospho-ERK and cleaved caspase-3, and decreased levels of cyclin A2 and cyclin D1. Furthermore, PTEN knockdown significantly impacted the viability of cervical cancer cells. P53 silencing did not affect the ability of PTEN knockdown to induce apoptosis in cervical cancer cells. Taken together, the present study results imply that PTEN silencing induces apoptosis and decreases proliferation in cervical cancer cells; hence, PTEN inhibition may represent a promising strategy for the treatment of cervical cancer.

Acupuncture as an Add-On Treatment for Functional Dyspepsia: A Systematic Review and Meta-Analysis.

Background: We aimed to critically evaluate the effectiveness and safety of acupuncture as an add-on therapy to conventional Western medication (WM) and assess the quality of evidence (QoE) of these findings. Methods: A total of 12 English, Korean, and Chinese databases were searched on December 18, 2020. Randomized controlled trials (RCTs) assessing the effectiveness of acupuncture as an add-on therapy to conventional WM for functional dyspepsia (FD) were included. The primary outcome was the symptom score of FD. The risk of bias of the included studies and QoE were evaluated using the Cochrane Collaboration's risk of bias tool and Grading of Recommendations, Assessment, Development, and Evaluation method, respectively. Results: A total of 22 RCTs were included. The total and individual FD symptom scores were significantly improved in the acupuncture combined with WM groups compared with the WM alone groups, except for in one study. The Nepean dyspepsia index score and total effective rate mostly improved significantly in the acupuncture group, regardless of the WM used and acupuncture type. FD-related biomarkers, such as ghrelin and gastrin levels, showed mixed results. The acupuncture group showed a significantly lower recurrence rate after 3-6 months of follow-up than the WM alone group. There were no differences in the incidence of adverse events between the two groups. The included studies generally had low methodological quality. The QoE for the main findings was generally very low to moderate. Conclusion: Limited evidence suggests that acupuncture has the potential to improve FD treatment in combination with conventional WM. Furthermore, the methodological quality of the included studies and QoE of the main findings were generally low. Therefore, RCTs with a rigorous methodology, including sham acupuncture and multiethnic subjects, should be performed. Systematic Review Registration: OSF registries [https://osf.io/mxren], PROSPERO [CRD42021226608].

Seasonal variations in the diagnosis of the top 10 cancers in Korea: A nationwide population-based study using a common data model.

BACKGROUND AND AIM: A better understanding of seasonal variations in cancer diagnosis may be the first step toward optimal resource distribution in the National Cancer Screening Program (NCSP). This study aimed to identify seasonal variations in the diagnosis of the top 10 major cancers in Korea. METHODS: We conducted a retrospective, observational cohort study in participants aged ≥ 20 years between 2012 and 2016 from the Health Insurance Review and Assessment-National Patient Sample database, previously converted to a common data model. We assessed the overall seasonal variations in the 10 major cancers. RESULTS: We analyzed the following top 10 cancers: stomach (n = 3435), colorectal (n = 5368), liver (n = 7605), pancreatic (n = 2946), gallbladder (n = 899), lung (n = 1598), prostate (n = 2897), thyroid (n = 1966), breast (n = 1313), and kidney (n = 668) cancers. All cancers showed similar seasonal variations in diagnosis, with a significant winter peak. A winter peak in diagnosis was observed for NCSP-covered cancers, such as stomach, colon, liver, and breast cancers, as well as other cancers not covered by the NCSP. The winter peak for cancer diagnosis was the highest for breast cancer (74.4%) followed by thyroid (51.0%) and stomach cancers, whereas it was the lowest for pancreatic cancer followed by prostate and colorectal cancers. CONCLUSIONS: Significant seasonal variations were found in the diagnosis of the top 10 major cancers, with a winter peak, which may be explained by the participants' behavior pattern with respect to the NCSP. Our findings suggest that trading off of NCSP healthcare resources between winter and other seasons may be beneficial.