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Background/Aims: Utilization of low-volume preparation agents is crucial to improve patient willingness to undergo repeat colonoscopies. However, gastric safety data on preparation agents are limited. This study evaluated the acute gastropathy associated with bowel preparation agents. Methods: This retrospective study enrolled healthy subjects who underwent both esophagogastroduodenoscopy and colonoscopy screening. Baseline patient characteristics, bowel preparation success, acute gastropathy, and polyp and adenoma detection rates were evaluated for 1 L polyethylene glycol with ascorbic acid (1 L PEG/Asc) and oral sulfate tablet (OST) groups. Results: Comparison of the OST group (n=2,463) with the 1 L PEG/Asc group (n=2,060) revealed that the rates of successful cleansing and high-quality cleansing were similar between the two groups. Polyp and adenoma detection rates were significantly higher in the OST group than in the 1 L PEG/Asc group (p

Abstract N 6-adenosine methylation (m6A) is critical for controlling cancer cell growth and tumorigenesis. However, the function and detailed mechanism of how m6A methyltransferases modulate m6A levels on specific targets remain unknown. In the current study, we identified significantly elevated levels of RBM15, an m6A writer, in basal-like breast cancer (BC) patients compared to nonbasal-like BC patients and linked this increase to worse clinical outcomes. Gene expression profiling revealed correlations between RBM15 and serine and glycine metabolic genes, including PHGDH, PSAT1, PSPH, and SHMT2. RBM15 influences m6A levels and, specifically, the m6A levels of serine and glycine metabolic genes via direct binding to target RNA. The effects of RBM15 on cell growth were largely dependent on serine and glycine metabolism. Thus, RBM15 coordinates cancer cell growth through altered serine and glycine metabolism, suggesting that RBM15 is a new therapeutic target in BC.

Background/Aims The impact of coronavirus disease 2019 (COVID-19) on the management of colorectal cancer (CRC) may worse in elderly population, as almost all COVID-19 deaths occurred in the elderly patients. This study aimed to evaluate the impact of COVID-19 on CRC management in the elderly population. Methods The numbers of patients who underwent colonoscopy, who visited hospitals or operated for CRC in 2020 and 2021 (COVID-19 era) were compared with those in 2019, according to 3 age groups (≥70 years, 50–69 years, and ≤49 years), based on the nationwide, population-based database (2019–2021) in South Korea. Results The annual volumes of colonoscopy and hospital visits for CRC in 2020 were more significantly declined in the old age group than in the young age group (both P

Background/Aims Long-term immunosuppressive therapies used to treat inflammatory bowel disease (IBD) are associated with an increased risk of infections, many of which can be prevented by vaccination. We assessed physicians’ current approaches and clinical practices regarding vaccinations for IBD patients in different Asian countries/regions. Methods An internet-based survey was conducted among members of the Asian Organization for Crohn’s and Colitis from September 2020 to November 2020. The questionnaire consisted of 2 parts covering general opinion on the relevance of vaccinations and clinical practice of vaccination. Results Overall, 384 Asian medical doctors responded to the survey. The majority of respondents considered it very (57.6%) or sufficiently (39.6%) important to perform vaccinations as recommended by the guidelines. About half of the Asian physicians (52.6%) were usually or always performing vaccinations. The influenza vaccine was the most frequently recommended vaccine for IBD patients. Half of the respondents (51.3%) did not recommend hepatitis A vaccine, especially in China (61.6%) and Japan (93.6%). The diphtheria, tetanus, and pertussis vaccine were never (35.2%) or rarely (29.4%) recommended. Conclusions The findings of this survey indicated similarities among countries/regions in terms of the current approaches and practices regarding vaccination of IBD patients; however, there are some differences that might reflect each country’s domestic vaccination guidelines and health insurance particularly with certain vaccines in some countries/regions. Although Asian physicians largely recommend vaccination, more awareness among doctors and Asian consensus regarding differences in IBD vaccination among countries/regions may be required.

Abstract Esophageal granular cell tumors (GCTs), the second most common subepithelial tumors (SETs) of the esophagus, are potentially malignant with no definite management guidelines available. We retrospectively enrolled 35 patients with endoscopically resected esophageal GCTs between December 2008 and October 2021 and evaluated the clinical outcomes from the various methods performed. Several modified endoscopic mucosal resections (EMRs) were performed for treating esophageal GCTs. Clinical and endoscopic outcomes were evaluated. Mean age of patients was 55.8 ± 8.2, with majority being men (57.1%). Mean tumor size was 7.2 ± 2.6 mm, most (80.0%) were asymptomatic and present in the distal third of the esophagus (77.1%). Endoscopic characteristics predominantly included broad-based (85.7%) and whitish-to-yellowish color changes (97.1%). Endoscopic ultrasound (EUS) of 82.9% of the tumors revealed homogeneous hypoechoic SETs originating from the submucosa. The five endoscopic treatment methods used were: ligation-assisted (77.1%), conventional (8.7%), cap-assisted (5.7%), and underwater (5.7%) EMRs and ESD (2.9%). Mean procedure time was 6.6 ± 2.1 min, and no procedure-associated complications were noted. The en-bloc and complete histologic resection rates were 100% and 94.3%, respectively. No recurrences were noted during follow-up, and no significant differences in the clinical outcomes of the different methods of endoscopic resection were found. Based on tumor characteristics and therapeutic outcomes, modified EMR methods can be effective and safe. However, there were no significant differences in the clinical outcomes of the different methods of endoscopic resection.

Objective: To explore the influencing factors of Yang deficiency constitution in traditional Chinese medicine (TCM) from the perspective of mathematics with the use of calculation formulas, so as to protect patients from getting diseases caused by Yang deficiency constitution and provide suggestions for TCM disease prevention. Methods: Based on the classification and determination criteria of TCM constitution implemented by China Association of Chinese Medicine, data for 24 solar terms from May 5, 2020 (Start of Summer) to April 20, 2021 (Grain Rain) for the identification of Yang deficiency were collected by mobile constitution identification system. The grey correlation analysis method was used to determine the grey correlation degree of the factors influencing Yang deficiency constitution. In addition, a random forest model was constructed for the verification of the results from the grey correlation analysis, and for the evaluation of correlation degree between Yang deficiency constitution and its influencing factors. Results: A total of 16 259 sets of data were collected from healthy or sub-healthy individuals aged from 18 to 60 years living in the central and northeastern parts of Sichuan Province (China) for the identification of TCM constitutions. After screening and preprocessing, a total of 544 sets of data for the identification of Yang deficiency constitution, involving 18 aspects of factors influencing Yang deficiency constitution. The results of the grey correlation analysis showed that there were 12 influencing factors whose grey correlation degree with Yang deficiency constitution was greater than 0.6. The accuracy of these 12 influencing factors with the training set and validation set of the Yang deficiency constitution random forest model were 98.39% and 93.12%, respectively. Conclusion: In the sample data selected in this paper, grey correlation analysis is the appropriate technology to analyze the influencing factors of Yang deficiency constitution. It provides a new idea and a new methodological reference for the research and analysis of the influencing factors of TCM constitution.

Background/Aims Some sessile serrated lesions (SSLs) progress into dysplasia and colorectal cancer, however, the clinical and endoscopic characteristics of SSLs with dysplasia remain to be determined. In this study, we elucidated these characteristics in SSLs with dysplasia/carcinoma, compared with those of SSLs without dysplasia. Methods We retrospectively collected the clinical, endoscopic, and pathological data of 254 SSLs from 216 patients endoscopically resected between January 2009 and December 2020. Results All SSLs included 179 without dysplasia and 75 with dysplasia/carcinoma, including 55 with low-grade dysplasia, 10 with high-grade dysplasia, and 10 with submucosal cancer. In clinical characteristics, SSLs with dysplasia/carcinoma were significantly associated with advanced age, metabolic diseases, and high-risk adenomas. In endoscopic characteristics, SSLs with dysplasia/carcinoma were significantly associated with the distal colon, large size, polypoid morphology, surface-changes, no mucus cap, and narrow-band imaging international colorectal endoscopic classification (NICE) type 2/3. In the multivariate analysis, high-risk adenomas (odds ratio [OR], 2.98; p = 0.01), large size (OR, 1.18; p < 0.01), depression (OR, 11.74; p = 0.03), and NICE type 2/3 (OR, 14.97; p < 0.01) were significantly associated with SSLs with dysplasia/carcinoma. Conclusions SSLs had a higher risk of dysplasia in the distal colon than in the proximal colon. SSLs with large size, depression, and adenomatous surface-patterns, as well as those in patients with high-risk adenomas, increased the risk of dysplasia/carcinoma. This suggests that the clinical and endoscopic characteristics can aid in the diagnosis and management of SSLs with dysplasia/carcinoma.

Objective Poor medication adherence remains highly prevalent and adversely affects health outcomes. Patients frequently describe properties of the pills themselves, like size and shape, as barriers, but this has not been evaluated objectively. We sought to determine the extent to which oral medication properties thought to be influential translate into lower objectively-measured adherence.Design Retrospective cohort study.Setting US nationwide commercial claims database, 2016–2019.Participants Among patients initiating first-line hypertension, diabetes or hyperlipidaemia treatment based on clinical guidelines, we measured pill size, shape, colour and flavouring, number of pills/day and fixed-dose combination status as properties.Outcome measures Outcomes included discontinuation after the first fill (ie, never filling again over a minimum of 1-year follow-up) and long-term non-adherence (1-year proportion of days covered

Abstract The metabolites of gut microbiota show favorable therapeutic effects on nonalcoholic fatty liver disease (NAFLD), but the active metabolites and mechanisms against NAFLD have not been documented. The aim of the study was to investigate the active metabolites and mechanisms of gut microbiota against NAFLD by network pharmacology. We obtained a total of 208 metabolites from the gutMgene database and retrieved 1256 targets from similarity ensemble approach (SEA) and 947 targets from the SwissTargetPrediction (STP) database. In the SEA and STP databases, we identified 668 overlapping targets and obtained 237 targets for NAFLD. Thirty-eight targets were identified out of those 237 and 223 targets retrieved from the gutMgene database, and were considered the final NAFLD targets of metabolites from the microbiome. The results of molecular docking tests suggest that, of the 38 targets, mitogen-activated protein kinase 8-compound K and glycogen synthase kinase-3 beta-myricetin complexes might inhibit the Wnt signaling pathway. The microbiota-signaling pathways-targets-metabolites network analysis reveals that Firmicutes, Fusobacteria, the Toll-like receptor signaling pathway, mitogen-activated protein kinase 1, and phenylacetylglutamine are notable components of NAFLD and therefore to understanding its processes and possible therapeutic approaches. The key components and potential mechanisms of metabolites from gut microbiota against NAFLD were explored utilizing network pharmacology analyses. This study provides scientific evidence to support the therapeutic efficacy of metabolites for NAFLD and suggests holistic insights on which to base further research.

Esophageal abscess caused by acute phlegmonous esophagitis is rare but life-threatening. Rapid abscess drainage is an important part of the treatment, and endoscope-assisted intra-luminal abscess drainage is frequently performed. Although endoscopic drainage is less invasive than surgery, it has the potential to cause esophageal stricture as a complication. We present a rare case of esophageal stricture as a complication of intra-luminal drainage and evaluate a method to minimize the incidence of esophageal stricture complications.

In England, all blood donations are screened in pools of 24 by nucleic acid test (NAT) for hepatitis E virus (HEV) RNA. During 2016–2020, this screening successfully identified and intercepted 1,727 RNA-positive donations. However, review of previous donations from infected platelet donors identified 9 donations in which HEV RNA detection was missed, of which 2 resulted in confirmed transmission: 1 infection resolved with ribavirin treatment, and 1 proceeded to fatal multiorgan failure within a month from infection. Residual risk calculations predict that over the 5-year study period, HEV RNA detection was missed by minipool NAT in 12–23 platelet and 177–354 whole-blood donations, but transmission risk remains undetermined. Although screening has been able to largely eliminate infectious HEV from the blood supply in England, missed detection of low levels of HEV RNA in donated blood can lead to a severe, even fulminant, infection in recipients and could be prevented by more sensitive screening.

Olmesartan, a recently introduced angiotensin II receptor blocker for hypertension, has been reported to cause drug-induced small bowel enteropathy. The diagnosis of olmesartan-associated enteropathy (OAE) needs clinical suspicion and the exclusion of coeliac disease, as it mimics coeliac sprue. Once diagnosed, it can be completely cured with the discontinuation of olmesartan. However, due to the extremely low incidence of OAE in Korea, clinical suspicion and diagnosis may be a challenge. The authors report the first case of OAE presenting with chronic diarrhea and acute kidney injury in Korea.

The early rectal cancer (ERC) has increased with the national cancer screening project for early detection of colorectal cancer. The gold standard treatment for low rectal cancer is low anterior resection (LAR) based on total mesorectal excision. However, radical resection results in a high mortality and complication rate, and the deterioration of quality of life due to LAR syndrome, genitourinary dysfunction, and possible permanent stoma. Local excision with chemoradiation therapy could be one of the alternative therapeutic strategies for the organ preservation and a cure of cancer. To decide the treatment strategies, it is important to establish sophisticated indications that can maximize the therapeutic effect. ERC has heterogeneous pathological features, including aggressive behavior and occult lymph node metastasis, with different responses to chemoradiotherapy. Therefore, radiologic, endoscopic and pathologic evaluation to predict the risk of lymph node metastasis and local recurrence has been evolving to determine the optimal treatment strategy in the patient-tailored medicine. Recently, the long-term outcomes of prospective randomized clinical trials provide new hope for organ preservation in patients with ERC. In this paper, we aim to review various risk factors related to local recurrence and discuss the optimal treatment strategy for ERC.

Abstract Sialic acid (SA) is present in glycoconjugates and important in cell–cell recognition, cell adhesion, and cell growth and as a receptor. Among the four mammalian sialidases, cytosolic NEU2 has a pivotal role in muscle and neuronal differentiation in vitro. However, its biological functions in vivo remain unclear due to its very low expression in humans. However, the presence of cytoplasmic glycoproteins, gangliosides, and lectins involved in cellular metabolism and glycan recognition has suggested the functional importance of cytosolic Neu2 sialidases. We generated a Neu2 knockout mouse model via CRISPR/Cas9-mediated genome engineering and analyzed the offspring littermates at different ages to investigate the in vivo function of cytosolic Neu2 sialidase. Surprisingly, knocking out the Neu2 gene in vivo abrogated overall lipid metabolism, impairing motor function and leading to diabetes. Consistent with these results, Neu2 knockout led to alterations in sialylated glycoproteins involved in lipid metabolism and muscle function, as shown by glycoproteomics analysis.

Objective To investigate the correlation of the texture parameters of T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) with the efficacy of chemoradiotherapy in cervical squamous cell carcinoma. Methods Patients with squamous cell carcinoma of the cervix that underwent chemoradiotherapy from February 2015 to January 2016 in Peking Union Medical College Hospital were included retrospectively, and were divided into the disease-progressive group and the disease-stable group according to their prognosis. Texture analysis of baseline T2WI and DWI images before chemoradiotherapy was carried out with Texrad software, and the texture parameters of spatial scale filter (SSF) with radius values of 2, 4 and 6 were obtained. The differences of texture parameters between the two groups were compared, and the correlation between the texture parameters and the curative of chemoradiotherapy in patients with cervical squamous cell carcinoma was analyzed by multivariate Cox regression. Receiver operating characteristic (ROC) curve was used to analyze the performance of texture parameters in predicting disease progression after chemoradiotherapy in patients with cervical squamous cell carcinoma. Results A total of 121 patients with squamous cell carcinoma of the cervix that met the inclusion and exclusion criteria were enrolled in this study. There were 46 cases in the disease-progressive group and 75 cases in the disease-stable group. In T2WI sequential images, there were significant differences in the texture parameters of means (SSF2, SSF4, SSF6), skewness (SSF2, SSF4), and entropy (SSF4, SSF6) between disease-progressive group and disease-stable group (all P < 0.05). In DWI sequential images, there were significant differences in the texture parameters of means (SSF2, SSF4, SSF6), skewness (SSF4, SSF6), and kurtosis (SSF2, SSF4) between the two groups (all P < 0.05). Multivariate Cox regression analysis showed that the texture parameter of means (SSF2, SSF4, SSF6) of T2WI and the texture parameters of means (SSF2, SSF6), entropy (SSF2, SSF4, SSF6) and skewness (SSF4, SSF6) of DWI were correlated with the efficacy of chemoradiotherapy in patients with cervical squamous cell carcinoma (P < 0.05). The Results of ROC analysis showed that the texture parameter of means (T2WI-SSF2, T2WI-SSF4, T2WI-SSF6, DWI-SSF2, DWI-SSF6) and skewness (DWI-SSF6) could predict the progression of cervical squamous cell carcinoma after chemoradiotherapy in patients with cervical squamous cell carcinoma. The area under the curve (AUC) was 0.625-0.746. Among them, the mean of T2WI-SSF4 was the most effective (AUC: 0.746), followed by the mean of T2WI-SSF2 (AUC: 0.725) and the mean of T2WI-SSF6 (AUC: 0.703). Conclusions The texture parameters of baseline T2WI and DWI sequences were correlated with the curative effect of chemoradiotherapy in patients with cervical squamous cell carcinoma. The parameters of means and skewness can predict the progression of cervical squamous carcinoma after chemoradiotherapy, and the mean has a higher predictive power.

Emodin, an emerging mycotoxin, is known to be hepatotoxic, but its mechanism remains unclear. We hypothesized that emodin could induce endoplasmic reticulum (ER) stress through the inositol-requiring enzyme 1 alpha (IRE1α)–X-box-binding protein 1 (XBP1) pathway and apoptosis, which are closely correlated and contribute to hepatotoxicity. To test this hypothesis, a novel IRE1α inhibitor, STF-083010, was used. An MTT assay was used to evaluate metabolic activity, and quantitative PCR and western blotting were used to investigate the gene and protein expression of ER stress or apoptosis-related markers. Apoptosis was evaluated with flow cytometry. Results showed that emodin induced cytotoxicity in a dose-dependent manner in HepG2 cells and upregulated the expression of binding immunoglobulin protein (BiP), C/EBP homologous protein (CHOP), IRE1α, spliced XBP1, the B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax)/Bcl-2 ratio, and cleaved caspase-3. Cotreatment with emodin and STF-083010 led to the downregulation of BiP and upregulation of CHOP, the Bax/Bcl-2 ratio, and cleaved caspase-3 compared with single treatment with emodin. Furthermore, the apoptosis rate was increased in a dose-dependent manner with emodin treatment. Thus, emodin induced ER stress in HepG2 cells by activating the IRE1α–XBP1 axis and induced apoptosis, indicating that emodin can cause hepatotoxicity.

Abstract [68Ga]PSMA-11 is a prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for diagnostic PET imaging. Its application can be extended to targeted radionuclide therapy (TRT). In this study, we characterize the biodistribution and pharmacokinetics of [68Ga]PSMA-11 in PSMA-positive and negative (22Rv1 and PC3, respectively) tumor-bearing mice and subsequently estimated its internal radiation dosimetry via voxel-level dosimetry using a dedicated Monte Carlo simulation to evaluate the absorbed dose in the tumor directly. Consequently, this approach overcomes the drawbacks of the conventional organ-level (or phantom-based) method. The kidneys and urinary bladder both showed substantial accumulation of [68Ga]PSMA-11 without exhibiting a washout phase during the study. For the tumor, a peak concentration of 4.5 ± 0.7 %ID/g occurred 90 min after [68Ga]PSMA-11 injection. The voxel- and organ-level methods both determined that the highest absorbed dose occurred in the kidneys (0.209 ± 0.005 Gy/MBq and 0.492 ± 0.059 Gy/MBq, respectively). Using voxel-level dosimetry, the absorbed dose in the tumor was estimated as 0.024 ± 0.003 Gy/MBq. The biodistribution and pharmacokinetics of [68Ga]PSMA-11 in various organs of subcutaneous prostate cancer xenograft model mice were consistent with reported data for prostate cancer patients. Therefore, our data supports the use of voxel-level dosimetry in TRT to deliver personalized dosimetry considering patient-specific heterogeneous tissue compositions and activity distributions.

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in England. Substantial yearly increases of autochthonous infections were observed during 2003–2016 and again during 2017–2019. Previous studies associated acute HEV cases with consumption of processed pork products, we investigated risk factors for autochthonous HEV infections in the blood donor population in England. Study participants were 117 HEV RNA–positive blood donors and 564 HEV RNA–negative blood donors. No persons with positive results were vegetarian; 97.4% of persons with positive results reported eating pork products. Consuming bacon (OR 3.0, 95% CI 1.7–5.5; p

Objectives Antioxidants are common dietary compounds with multiple health benefits. This study aimed to identify the association between dietary antioxidant consumption and the incidence of type 2 diabetes (T2D) mellitus (defined using the Korean Diabetes Association criteria) in South Korean adults.Design Baseline and follow-up data from the Health Examinees (HEXA) study, a large-scale community-based genomic cohort study conducted in South KoreaSetting A South Korean community.Participants A total of 20 594 participants, aged 40–79 years, who participated in the baseline and follow-up surveys of the HEXA study were included. After an average of 5 years of follow-up, there were 332 men and 360 women with T2D.Results Participants with the highest total flavonoid consumption (Q5) had a lower risk of T2D (men: HR 0.63; 95% CI 0.42 to 0.93; p value for trend=0.0169; and women: HR 0.54; 95% CI 0.438 to 0.78; p value for trend=0.0001) than those with the lowest consumption (Q1). Dietary total antioxidant capacity was significantly inversely associated with the development of T2D mellitus in women participants alone (HR 0.58; 95% CI 0.40 to 0.83; p value for trend=0.0004). Stratified analyses according to age and body mass index (BMI) showed that dietary total flavonoid consumption and total antioxidant capacity had a negative association with the development of T2D in women aged >52 years and women with BMI >25 kg/m2.Conclusions Dietary flavonoid consumption and total antioxidant capacity were associated with a lower risk of T2D in South Korean adults, especially in women aged >52 years and overweight. The findings of this study may provide reference data for the modification of dietary guidelines for South Koreans.

Abstract Dual-functional quantum-dots light emitting diodes (QLEDs) have been fabricated using solution processable vanadium oxide (V2O5) hole injection layer to control the carrier transport behavior. The device shows selectable functionalities of photo-detecting and light-emitting behaviors according to the different operating voltage conditions. The device emitted a bright green light at the wavelength of 536 nm, and with the maximum luminance of 31,668 cd/m2 in a forward bias of 8.6 V. Meanwhile, the device could operate as a photodetector in a reverse bias condition. The device was perfectly turned off in a reverse bias, while an increase of photocurrent was observed during the illumination of 520 nm wavelength light on the device. The interfacial electronic structure of the device prepared with different concentration V2O5 solution was measured in detail using x-ray and ultraviolet photoelectron spectroscopy. Both the highest occupied molecular orbital and the gap state levels were moved closer to the Fermi level, according to increase the concentration of V2O5 solution. The change of gap state position enables to fabricate a dual-functional QLEDs. Therefore, the device could operate both as a photodetector and as a light-emitting diode with different applied bias. The result suggests that QLEDs can be used as a photosensor and as a light-emitting diode for the future display industry.

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 .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.

Background/Aims: Needle knife fistulotomy (NKF) is a technique to facilitate pancreatic and biliary duct access during ERCP. The double-guidewire technique (DGT) is also used in cases of difficult cannulation, but it can increase the incidence of post-ERCP-pancreatitis (PEP). This study examined the success and complication rates of NKF after unsuccessful standard cannulation or DGT in patients with pancreaticobiliary disease. Methods: The data of 209 patients who received NKF as a rescue procedure between January 2009 and December 2016 were reviewed retrospectively. The cannulation success and complication rates were assessed. Results: The overall cannulation success rate was 90.4%. The success rates of patients who received NKF after standard cannulation or DGT were similar (82.6% [142/172] and 73.0% [27/37], respectively, p=0.179). Furthermore, there was no significant difference in the incidence of procedure-related adverse events between the two groups (10.5% [18/172] and 16.2% [6/37], respectively, p=0.391). Endoscopic retrograde pancreatic drainage (ERPD) insertion decreased the incidence of PEP (0% [0/16] in ERPD and 14.6% [19/130] in non-ERPD, p=0.132) among patients who received PD cannulation. Conclusions: NKF is an effective and safe method that can be considered for rescue management after the initial failure of standard cannulation or DGT. NKF following standard cannulation can be preferred over NKF following DGT because of the higher success rate and the lower rate of pancreatitis, but the difference was not significant. PD stenting in patients at high risk of PEP can be considered to decrease pancreatitis.

Purpose To identify the effects of superoxide dismutase (SOD)3 on diabetes mellitus (DM)-induced retinal changes in a diabetic rat model. Methods Diabetic models were established by a single intraperitoneal injection of streptozotocin (STZ) in Sprague-Dawley rats. After purification of the recombinant SOD3, intravitreal injection of SOD3 was performed at the time of STZ injection, and 1 and 2 weeks following STZ injection. Scotopic and photopic electroretinography (ERG) were recorded. Immunofluorescence staining with ɑ-smooth muscle actin (SMA), glial fibrillary acidic protein (GFAP), pigment epithelium-derived factor (PEDF), Flt1, recoverin, parvalbumin, extracellular superoxide dismutase (SOD3), 8-Hydroxy-2’deoxyguanosine (8-OHdG) and tumor necrosis factor-ɑ (TNF-ɑ) were evaluated. Results In the scotopic ERG, the diabetic group showed reduced a- and b-wave amplitudes compared with the control group. In the photopic ERG, b-wave amplitude showed significant (p < 0.0005) reduction at 8 weeks following DM induction. However, the trend of a- and b-wave reduction was not evident in the SOD3 treated group. GFAP, Flt1, 8-OHdG and TNF-ɑ immunoreactivity were increased, and ɑ-SMA, PEDF and SOD3 immunoreactivity were decreased in the diabetic retina. The immunoreactivity of these markers was partially recovered in the SOD3 treated group. Parvalbumin expression was not decreased in the SOD3 treated group. In the diabetic retinas, the immunoreactivity of recoverin was weakly detected in both of the inner nuclear layer and inner plexiform layer compared to the control group but not in the SOD3 treated group. Conclusions SOD3 treatment attenuated the loss of a/b-wave amplitudes in the diabetic rats, which was consistent with the immunohistochemical evaluation. We also suggest that in rod-dominant rodents, the use of blue on green photopic negative response (PhNR) is effective in measuring the inner retinal function in animal models of diabetic retinopathy. SOD3 treatment ameliorated the retinal Müller cell activation in diabetic rats and pericyte dysfunction. These results suggested that SOD3 exerted protective effects on the development of diabetic retinopathy.

BackgroundAbdominal ultrasonography (US) is the backbone of hepatocellular carcinoma (HCC) surveillance. Although previous studies have evaluated clinical factors related to surveillance failure, none have focused specifically on US blind spots.MethodsThis study included 1,289 patients who underwent 6 months intervals surveillance using US and serum alpha-fetoprotein (AFP) and were eventually diagnosed with single-nodular HCC. Patients were divided into US-detected group (n = 1,062) and US-missed group (HCC detected only by AFP ≥ 20ng/mL; n = 227). Blind spots consisted of four locations: hepatic dome, caudate lobe or around the inferior vena cava, ResultsA higher proportion of HCCs were located within blind spots in the US-missed group than in the US-detected group (64.3% vs. 44.6%, P < 0.001). HCC ≥ 2 cm detected in blind spots was higher than in non-blind areas (60.3% vs. 47.1%, P = 0.001). Blind spot HCCs were more treated with surgery, whereas those located in a non-blind area were more treated with local ablation. Patients with an HCC located within a blind spot in the US-detected group had better overall survival than the same in the US-missed group (P = 0.008).ConclusionsUsing the current surveillance test, blind spots affected the initially detected HCC tumor size, applicability of the treatment modality, and overall survival. Physicians should pay attention to US blind spots when performing US-based HCC surveillance.

Background Diet, environment, and genomic context have a significant impact on humans’ intestinal microbiota. Moreover, migration may be accompanied by changes in human eating habits and living environment, which could, in turn, affect the intestinal microbiota. Located in southwestern China, Tibet has an average altitude of 4,000 meters and is known as the world’s roof. Xianyang is situated in the plains of central China, with an average altitude of about 400 meters. Methods To understand the association between intestinal microbiota and population migration, we collected the fecal samples from 30 Tibetan women on the first day (as TI1st), six months (as TI2nd), and ten months (as TI3rd) following migration from Tibet to Xianyang. Fecal samples were collected from 29 individuals (belonging to the Han women) as a control. The dietary information of the Tibetan women and the Han women was gathered. We performed a 16S rRNA gene survey of the collected fecal samples using Illumina MiSeq sequencing. Results Following the migration, the alpha and beta diversity of Tibetan women’s intestinal microbiota appeared unaffected. Linear discriminant analysis effect size (LEfSe) analysis showed that Klebsiella, Blautia, and Veillonella are potential biomarkers at TI1st, while Proteobacteria and Enterobacteriaceae were common in TI3rd. Finally, functional prediction by phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) found no significant up-regulation or down-regulation gene pathway in the intestinal microbiota of Tibetan women after migration. The present study reveals that the higher stability in Tibetan women’s intestinal microbiota was less affected by the environment and diet, indicating that Tibetan women’s intestinal microbiota is relatively stable. The main limitations of the study were the small sample size and all volunteers were women.

Objective To observe the effect of infiltration resin combined with cold light whitening in the treatment of dental fluorosis. Methods According to the distance between teeth and the long axis of each tooth, 18 anterior teeth were divided equally and randomly between group A and B. Samples in group A underwent cold light whitening, while samples in group B were treated with infiltration resin combined with cold light whitening. The color was measured before and after the treatment. Then, 6 teeth (the first subgroup) were randomly selected from the 18 anterior teeth after measurement for scanning electron microscopy (SEM) to observe the surface microstructure of the teeth. Then, another 6 teeth (the second subgroup) were selected from the remaining 12 teeth for the measurement of the color level and ΔE after being dyed with tea. Results After treatment, the color level changed significantly in group A and B (P < 0.05), ΔE in group A and B was 13.75, 14.98. There was no significant difference in the color level change between group B and group A, there was a significant difference in the ΔE between the two groups (t = ⁃3.58, P < 0.05). SEM showed that the enamel surface was intact and that the enamel space was filled in group B. In group A, the enamel surface was reduced and uneven, and the characteristic badminton racquet shape of the enamel was not obvious. The color level was lower in both groups after staining, and these differences were significant (P < 0.05), ΔE in group A and B was 19.69, 18.95. There was no significant difference in the color level (t = 1.00, P > 0.05) and ΔE (t = 0.02, P > 0.05) between two groups. Conclusion Cold light whitening combined with infiltration resin is better for treating dental fluorosis than cold light whitening alone.

Malignant melanoma is one of the most common malignant diseases of the gastrointestinal tract. It has been reported that the malignant melanoma metastasizes not only to the small intestine due to the abundant blood supply, but also to the stomach, colon, and esophagus. Gastrointestinal metastasis is usually suspected depending on the clinical symptoms, as well as based on radiological or endoscopic findings. Imunohistochemical stains, such as Melan-A/Melanoma antigen recognized by T cell-1 or human melanoma black-45, are useful for confirming the diagnosis of malignant melanoma. A 44-year-old male received an operation due to a malignant melanoma at the left thumb two years ago. On the national health screening endoscopy, a submucosal tumor with hyperemic change on the top was found. The final diagnosis was a metastatic malignant melanoma in the stomach, pancreas, and pelvic bone. We recommend that endoscopists should consider the potential malignancy of subepithelial tumor with mucosa change, despite the tumor size being less than 1 cm.

Background/Aims: This study evaluated the value of abdominal computed tomography (CT) in preoperative N staging of early gastric cancers (EGCs) within standard and expanded indications of endoscopic resection (ER) and investigated the factors affecting accuracy. Methods: Between March 2009 and March 2016, a total of 268 patients with EGC within the standard and expanded indications of ER underwent preoperative abdominal CT and surgical gastrectomy with lymph node (LN) dissection. Preoperative N staging of CT was compared with the pathologic result. Results: The accuracy of N staging for EGCs within the standard and expanded indications was 86.1% (235/268). There was no LN metastasis in patients with cN1 in CT staging. LN metastasis was found in 7 patients with EGCs that met the expanded ER indication and cN0 in CT staging. According to the univariate analysis, ulcers, including scars, were associated with the false positive of lymph node metastasis in abdominal CT (odds ratio 3.56; 95% confidence interval 1.56-8.15). Conclusions: The present study suggests that the value of abdominal CT is limited for nodal staging of EGCs that meet the ER indication.

Background/Aims: Benign esophageal stricture after esophagectomy is not an infrequent complication. Anastomotic esophageal stricture requires frequent multiple dilations. We aimed to evaluate the clinical outcomes of dilation therapies using an endoscopic balloon or bougie dilator and analyzed the risk factors associated with refractory stricture. Methods: Between January 2009 and May 2016, the medical records of 21 patients treated with endoscopic balloon dilation or bougie dilation for esophageal anastomotic strictures were retrospectively reviewed. Results: During the study periods, a total of 21 patients were diagnosed with esophageal anastomotic stricture and included for analysis (17 male; mean age, 68.2±7.2 years at the first procedure). The mean stricture length was 6.4±8.1 mm. The refractory stricture was found in 28.6% of patients, and successful relief of dysphagia was achieved in 71.4% of patients. The major complication associated with dilations was absent. Factors associated with refractory stricture were stricture length (> 10 mm, p

BACKGROUND AND AIM:Endoscopic submucosal dissection (ESD) has been accepted as the treatment of choice for early gastric cancer (EGC) without lymph node metastasis. However, additional surgical gastrectomy should be considered after non-curative endoscopic resection. We aimed to evaluate the predictive factors associated with non-curative endoscopic resection. METHODS:Between November 2008 and June 2015, a retrospective study was conducted in a single, tertiary, referral hospital. A total of 596 EGC lesions resected by ESD were analyzed. Non-curative endoscopic resection was defined as the occurrence of lesions associated with piecemeal resection, positive resection margins, lymphovascular invasion, or lesions that did not meet the expanded indications for ESD. RESULTS:The rate of non-curative endoscopic resection was 16.1%. The mean follow-up period was 35.3 ± 25.0 months. Associated predictive factors for non-curative endoscopic resection were female sex (OR, 2.470; p = 0.004), lesion size ≥ 20 mm (OR 3.714; p < 0.001), longer procedure time (OR 2.449, p = 0.002), ulceration (OR 3.538, p = 0.002), nodularity (OR 2.967, p

Background High mobility group box 1 (HMGB1) is a well-known damage-related alarmin that participates in cellular inflammatory responses. However, the mechanisms leading to HMGB1 release in inflammatory conditions and the therapeutic agents that could prevent it remain poorly understood. This study attempted to examine whether the Curcumin longa herb, which is known to have anti-inflammatory property, can modulate cellular inflammatory responses by regulating HMGB1 release. Methods The murine macrophage RAW264.7 cells were treated with lipopolysaccharide (LPS) and/or a C. longa extract-loaded nanoemulsion (CLEN). The levels of released HMGB1, nitric oxide (NO) production, inducible NO synthase (iNOS) expression, and phosphorylation of mitogen-activated protein kinases were analyzed in RAW264.7 macrophages. The effects of CLEN on survival of endotoxemic model mice, circulating HMGB1 levels, and tissue iNOS expression were also evaluated. Results We have shown that a nanoemulsion loaded with an extract from the C. longa rhizome regulates cellular inflammatory responses and LPS-induced systemic inflammation by suppressing the release of HMGB1 by macrophages. First, treatment of RAW264.7 macrophages with the nanoemulsion significantly attenuated their LPS-induced release of HMGB1: this effect was mediated by inhibiting c-Jun N-terminal kinase activation, which in turn suppressed the NO production and iNOS expression of the cells. The nanoemulsion did not affect LPS-induced p38 or extracellular signal-regulated kinase activation. Second, intraperitoneal administration of the nanoemulsion improved the survival rate of LPS-injected endotoxemic mice. This associated with marked reductions in circulating HMGB1 levels and tissue iNOS expression. Discussion The present study shows for the first time the mechanism by which C. longa ameliorates sepsis, namely, by suppressing NO signaling and thereby inhibiting the release of the proinflammatory cytokine HMGB1. These observations suggest that identification of agents, including those in the herb C. longa, that can inhibit HMGB1 production and/or activity may aid the treatment of endotoxemia.

Doenjang, a Korean fermented soybean paste, is vulnerable to contamination by mycotoxins because it is directly exposed to environmental microbiota during fermentation. A method that simultaneously determines 20 mycotoxins in doenjang, including aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEN), and fumonisins (FBs) with an immunoaffinity column cleanup was optimized and validated in doenjang using LC-MS/MS. The method showed good performance in the analysis of 20 mycotoxins in doenjang with good linearity (R2 > 0.999), intra- and inter-day precision (

Cystin is a novel cilia-associated protein that is disrupted in the cpk mouse, a well-characterized mouse model of autosomal recessive polycystic kidney disease (ARPKD). Interestingly, overexpression of the Myc gene is evident in animal models of ARPKD and is thought to contribute to the renal cystic phenotype. Using a yeast two-hybrid approach, the growth suppressor protein necdin, known to modulate Myc expression, was found as an interacting partner of cystin. Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, we developed a luciferase reporter assay and observed that necdin strongly activated the Myc P1 promoter, and cystin did so more modestly. Interestingly, the necdin effect was significantly abrogated when cystin was co-transfected. Chromatin immunoprecipitation and electrophoretic mobility shift assays revealed a physical interaction with both necdin and cystin and the Myc P1 promoter, as well as between these proteins. The data suggest that these proteins likely function in a regulatory complex. Thus, we speculate that Myc overexpression in the cpk kidney results from the dysregulation of the cystin-necdin regulatory complex and c-Myc, in turn, contributes to cystogenesis in the cpk mouse.

BackgroundLater Pleistocene human evolution in East Asia remains poorly understood owing to a scarcity of well described, reliably classified and accurately dated fossils. Southwest China has been identified from genetic research as a hotspot of human diversity, containing ancient mtDNA and Y-DNA lineages, and has yielded a number of human remains thought to derive from Pleistocene deposits. We have prepared, reconstructed, described and dated a new partial skull from a consolidated sediment block collected in 1979 from the site of Longlin Cave (Guangxi Province). We also undertook new excavations at Maludong (Yunnan Province) to clarify the stratigraphy and dating of a large sample of mostly undescribed human remains from the site.Methodology/principal findingsWe undertook a detailed comparison of cranial, including a virtual endocast for the Maludong calotte, mandibular and dental remains from these two localities. Both samples probably derive from the same population, exhibiting an unusual mixture of modern human traits, characters probably plesiomorphic for later Homo, and some unusual features. We dated charcoal with AMS radiocarbon dating and speleothem with the Uranium-series technique and the results show both samples to be from the Pleistocene-Holocene transition: ∼14.3-11.5 ka.Conclusions/significanceOur analysis suggests two plausible explanations for the morphology sampled at Longlin Cave and Maludong. First, it may represent a late-surviving archaic population, perhaps paralleling the situation seen in North Africa as indicated by remains from Dar-es-Soltane and Temara, and maybe also in southern China at Zhirendong. Alternatively, East Asia may have been colonised during multiple waves during the Pleistocene, with the Longlin-Maludong morphology possibly reflecting deep population substructure in Africa prior to modern humans dispersing into Eurasia.

Abstract Background and aim The sensitivity and specificity of biomarkers and scoring systems used for predicting fatality of severe sepsis patients remain unsatisfactory. This study aimed to determine the prognostic value of circulating plasma DNA levels in severe septic patients presenting at the Emergency Department (ED). Methods Sixty-seven consecutive patients with severe sepsis and 33 controls were evaluated. Plasma DNA levels were estimated by real-time quantitative polymerase chain reaction assay using primers for the human β-hemoglobin and ND2 gene. The patients’ clinical and laboratory data on admission were analyzed. Results The median plasma nuclear and mitochondria DNA levels for severe septic patients on admission were significantly higher than those of the controls. The mean plasma nuclear DNA level on admission correlated with lactate concentration (γ = 0.36, p = 0.003) and plasma mitochondrial DNA on admission (γ = 0.708, p 0.001). Significant prognostic factors for fatality included mechanical ventilation within the first 24 hours (p = 0.013), mean sequential organ failure assessment (SOFA) score on admission (p = 0.04), serum lactate (p < 0.001), and both plasma nuclear and mitochondrial DNA on admission (p < 0.001). Plasma mitochondrial DNA was an independent predictor of fatality by stepwise logistic regression such that an increase by one ng/mL in level would increase fatality rate by 0.7%. Conclusion Plasma DNA has potential use for predicting outcome in septic patients arriving at the emergency room. Plasma mitochondrial DNA level on admission is a more powerful predictor than lactate concentration or SOFA scores on admission.