Oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles attenuates gastric and small intestinal mucosal ferroptosis caused by hypoxia through inhibiting HIF-1α- and HIF-2α-mediated lipid peroxidation.

The prevention and treatment of gastrointestinal mucosal injury caused by a plateau hypoxic environment is a clinical conundrum due to the unclear mechanism of this syndrome; however, oxidative stress and microbiota dysbiosis may be involved. The Robinia pseudoacacia L. flower, homologous to a functional food, exhibits various pharmacological effects, such as antioxidant, antibacterial, and hemostatic activities. An increasing number of studies have revealed that plant exosome-like nanoparticles (PELNs) can improve the intestinal microbiota and exert antioxidant effects. In this study, the oral administration of Robinia pseudoacacia L. flower exosome-like nanoparticles (RFELNs) significantly ameliorated hypoxia-induced gastric and small intestinal mucosal injury in mice by downregulating hypoxia-inducible factor-1α (HIF-1α) and HIF-2α expression and inhibiting hypoxia-mediated ferroptosis. In addition, oral RFELNs partially improved hypoxia-induced microbial and metabolic disorders of the stomach and small intestine. Notably, RFELNs displayed specific targeting to the gastrointestinal tract. In vitro experiments using gastric and small intestinal epithelial cell lines showed that cell death caused by elevated HIF-1α and HIF-2α under 1% O2 mainly occurred via ferroptosis. RFELNs obviously inhibited HIF-1α and HIF-2α expression and downregulated the expression of NOX4 and ALOX5, which drive reactive oxygen species production and lipid peroxidation, respectively, suppressing ferroptosis under hypoxia. In conclusion, our findings underscore the potential of oral RFELNs as novel, naturally derived agents targeting the gastrointestinal tract, providing a promising therapeutic approach for hypoxia-induced gastric and small intestinal mucosal ferroptosis.

Asia-Pacific Colorectal Screening Score Combined With Stool DNA Test Improves the Detection Rate for Colorectal Advanced Neoplasms.

BACKGROUND & AIMS: The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to stratify the risk of colorectal advanced neoplasm (AN). We aimed to evaluate the performance of the APCS score combined with a stool DNA test used for colorectal cancer screening. METHODS: A total of 2842 subjects who visited outpatient clinics or cancer screening centers were enrolled. Age, sex, smoking status, and family history were recorded and APCS scores were calculated in 2439 participants. A stool DNA test (SDC2 and SFRP2 tests) and fecal immunochemical test (FIT) were performed and colonoscopy was used as the gold standard among 2240 subjects who completed all study procedures. We used a threshold of 4.4 µg/g for the FIT, in addition to the manufacturer's recommended threshold of 20 µg/g to match the specificity of a stool DNA test. RESULTS: Based on the APCS score, 38.8% (946 of 2439) of the subjects were categorized as high risk, and they had a 1.8-fold increase in risk for AN (95% CI, 1.4-2.3) compared with low and moderate risk. The APCS combined with the stool DNA test detected 95.2% of invasive cancers (40 of 42) and 73.5% of ANs (253 of 344), while the colonoscopy workload was only 47.1% (1056 of 2240). The sensitivity for AN of APCS combined with stool DNA test was significantly higher than that of APCS combined with FIT (73.5% vs 62.8% with FIT cut-off value of 20 µg/g, and 73.5% vs 68.0% with FIT cut-off value of 4.4 µg/g; both P < .01). CONCLUSIONS: The APCS score combined with a stool DNA test significantly improved the detection of colorectal ANs, while limiting colonoscopy resource utilization (Chictr.org.cn, ChiCTR-DDD-17011169).

Endoscopic resection of gastric low-grade dysplasia with high risk factors is associated with decreased advanced neoplasia: a single-center retrospective cohort study.

BACKGROUND: The natural course of gastric low-grade dysplasia (LGD) remains unclear, and there are inconsistent management recommendations among guidelines and consensus. OBJECTIVE: This study aimed to investigate the incidence of advanced neoplasia in patients with gastric LGD and identify the related risk factors. METHODS: Cases of biopsy demonstrated LGD (BD-LGD) at our center from 2010 to 2021 were reviewed retrospectively. Risk factors related to histological progression were identified, and outcomes of patients based on risk stratification were evaluated. RESULTS: Ninety-seven (23.0%) of 421 included BD-LGD lesions were diagnosed as advanced neoplasia. Among 409 superficial BD-LGD lesions, lesion in the upper third of the stomach, H. pylori infection, larger size, and narrow band imaging (NBI)-positive findings were independent risk factors of progression. NBI-positive lesions and NBI-negative lesions with or without other risk factors had 44.7%, 1.7%, and 0.0% risk of advanced neoplasia, respectively. Invisible lesions, visible lesions (VLs) without a clear margin, and VLs with a clear margin and size ≤ 10 mm, or > 10 mm had 4.8%, 7.9%, 16.7%, and 55.7% risk of advanced neoplasia, respectively. In addition, endoscopic resection decreased the risk of cancer (P < 0.001) and advanced neoplasia (P < 0.001) in patients with NBI-positive lesions, but not in NBI-negative patients. Similar results were found in patients with VLs with clear margin and size > 10 mm. Moreover, NBI-positive lesions had higher sensitivity and lower specificity for predicting advanced neoplasia than VLs with a clear margin and size > 10 mm determined by white-light endoscopy (97.6% vs. 62.7%, P < 0.001; and 63.0% vs. 85.6%, P < 0.001, respectively). CONCLUSION: Progression of superficial BD-LGD is associated with NBI-positive lesions, as well as with VLs with a clear margin (size > 10 mm) if NBI is unavailable, and selective resection of those lesions offers benefits for patients by decreasing the risk of advanced neoplasia.

Aspiration and coagulation to reduce risk of delayed bleeding after gastric endoscopic submucosal dissection (with video).

OBJECTIVES: The purpose of this study was to evaluate the feasibility of a simple method named aspiration and coagulation (AC) for reducing the risk of postoperative bleeding after gastric endoscopic submucosal dissection (ESD). METHODS: Data were retrospectively reviewed and collected from the medical records and endoscopic and pathologic reports about consecutive patients who underwent ESD for early gastric cancer or precancerous lesions or gastric submucosal lesions from January 2016 to December 2021 at the Seventh Medical Center of Chinese PLA General Hospital. Enrolled patients who underwent the AC method during ESD were included in the AC group, and the others were included in the control group. Propensity score (PS) matching (1:1 match) was used to compensate for the differences that might affect post-ESD bleeding. Massive hemorrhage and overall delayed bleeding events after gastric ESD were compared between the two groups. RESULTS: Propensity score matching analysis created 242 matched pairs in the study. Characteristics of the subjects such as age and use of antithrombotic drugs were all similar between the two groups after PS matching. The rate of massive hemorrhage and overall delayed bleeding was both significantly lower in the AC group than in the control (0.4% vs. 3.3% for massive hemorrhage, P = 0.037, and 1.2% vs. 5.0% for overall delayed bleeding, P = 0.032), predominantly in mucosal lesions (0.6% vs. 4.4% for massive hemorrhage, P = 0.032, and 1.2% vs. 5.6% for overall delayed bleeding, P = 0.031). CONCLUSIONS: Our study demonstrated that the AC method effectively decreased delayed bleeding events after ESD.

A Comparison of Incomplete Resection Rate of Large and Small Colorectal Polyps by Cold Snare Polypectomy.

BACKGROUND & AIMS: There are limited data regarding the safety and efficacy of cold snare polypectomy (CSP) for large colorectal polyps. We evaluated factors affecting the clinical outcomes of CSP for polyps between 5 and 15 mm in size. METHODS: This was a prospective single-center observational study involving 1000 patients undergoing colonoscopy. Polyps (5-15 mm) were removed using CSP, and biopsies were taken from the resection margin. The primary outcome was the incomplete resection rate (IRR), and was determined by the presence of residual neoplasia on biopsy. Correlations between IRR and polyp size, morphology, histology, and resection time were assessed by generalized estimating equation model. RESULTS: A total of 440 neoplastic polyps were removed from 261 patients. The overall IRR was 2.27%, 1.98% for small (5-9 mm) vs 3.45% for large (10-15 mm) polyps (P = .411). In univariate analysis, the IRR was more likely to be related to sessile serrated lesions (odds ratio [OR], 6.93; 95% confidence interval [CI], 1.88-25.45; P = .004), piecemeal resection (OR, 11.83; 95% CI, 1.20-116.49; P = .034), and prolonged resection time >60 seconds (OR, 7.56; 95% CI, 1.75-32.69; P = .007). In multivariable regression analysis, sessile serrated lesions (OR, 6.45; 95% CI, 1.48-28.03; P = .013) and resection time (OR, 7.39; 95% CI, 1.48-36.96; P = .015, respectively) were independent risk factors for IRR. Immediate bleeding was more frequent with resection of large polyps (6.90% vs 1.42%; P = .003). No recurrence was seen on follow-up colonoscopy in 37 cases with large polyps. CONCLUSIONS: CSP is safe and effective for removal of colorectal polyps up to 15 mm in size, with a low IRR. (ClinicalTrials.gov; Number: NCT03647176).

Immunomodulatory effects of fentanyl and morphine on DSS- and TNBS-induced colitis.

BACKGROUND: Opioid prescription for inflammatory bowel disease (IBD)-related pain is on the rise. However, the use of strong opioids can result in severe complications, and even death, in IBD patients. This study aimed to define the role of fentanyl and morphine, two representative strong opioids, in the pathogenesis of dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzenesulfonic acid solution (TNBS)-induced colitis. METHOD: DSS and TNBS models were induced in C57BL/6J and Balb/c mice, respectively. Disease activity index (DAI), histopathology, enzyme-linked immunosorbent assay (ELISA), multiplex ELISA, and flow cytometry were performed to evaluate the effects of fentanyl and morphine. RESULT: Fentanyl exacerbated DSS- and TNBS-induced colitis, while morphine exhibited no significant immunomodulatory effect. Fentanyl and morphine had no obvious effects on the serum levels of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), and prostaglandin E2 (PGE-2) in DSS and TNBS models. Fentanyl elevated the proportions of Th1 cells, µ-opioid receptor (MOR) + Th1 cells, and MOR + macrophages in the colonic mucosa of DSS-treated mice, and enhanced the proportions of Th1 cells, macrophages, MOR + Th1 cells, and MOR + macrophages in the colonic mucosa of TNBS-treated mice. We found that fentanyl upregulated the levels of inflammatory cytokines/chemokines in MOR + macrophages of the colonic lamina propria mononuclear cells (LPMCs) from DSS-treated mice, whereas it had no effect on the expression of most inflammatory cytokines/chemokines in MOR + macrophages in the colonic LPMCs from TNBS-treated mice. CONCLUSION: Our findings suggest that fentanyl exacerbates murine colitis via Th1 cell- and macrophage-mediated mechanisms, while morphine exhibits no significant immunomodulatory effect.

Tumor suppressor ATP4B serve as a promising biomarker for worsening of gastric atrophy and poor differentiation.

BACKGROUND: Hydrogen/potassium ATPase ß (ATP4B) is a proton pump acting an essential role in gastric acid secretion. This study aimed to investigate the diagnostic performance of ATP4B and its biological role in tumor progression in gastric cancer. METHODS: The correlations between ATP4B expression level and clinicopathologic parameters, as well as the relevance of ATP4B expression with overall survival were assessed. The functional roles of ATP4B in gastric cancer were verified by gain- and loss-of-function cell models and tumor xenograft models. The possible downstream effects of ATP4B were analyzed by iTRAQ-based quantitative proteomics analysis. RESULTS: A dramatic decrease in ATP4B was associated with malignant transformation in gastric mucosa lesions and correlated with poor differentiation. Restoration of ATP4B expression in gastric cancer cells significantly suppressed cell proliferation, cell viability, migration, invasion, tumorigenicity and induced apoptosis, whereas ATP4B silencing exerted the opposite effects. Mechanistically, we found a quality control on mitochondrial metabolism and functions in ATP4B-overexpression GC cells. CONCLUSIONS: Our data suggest that decreasing ATP4B is an indicator for gastric mucosa malignant transformation and GC aggressive phenotype and it plays an inhibitory role in gastric cancer as a tumor suppressor via regulating mitochondrial metabolism and apoptosis pathway.

Safe and effective hybrid endoscopic submucosal dissection with ALL IN ONE snare in porcine gastric model (with video).

This study aimed to evaluate the safety and efficiency of hybrid endoscopic submucosal dissection (H-ESD) using a newly developed ALL IN ONE (AIO) snare. This was a matched control study in a porcine model. Five paired simulated stomach lesions 2-2.5 cm in size were removed by H-ESD using an AIO snare or conventional ESD (C-ESD) using an endoscopic knife. The outcomes of the two procedures were compared, including en-bloc resection rates, procedure times, intraprocedural bleeding volumes, muscular injuries, perforations, thicknesses of the submucosal layer in resected specimens, and stomach defects. All simulated lesions were resected en-bloc. Specimens resected by H-ESD and C-ESD were similar in size (7.68 ± 2.92 vs. 8.42 ± 2.42 cm2; P = 0.676). H-ESD required a significantly shorter procedure time (13.39 ± 3.78 vs. 25.99 ± 4.52 min; P = 0.031) and submucosal dissection time (3.99 ± 1.73 vs. 13.1 ± 4.58 min; P = 0.003) versus C-ESD; H-ESD also yielded a faster dissection speed (241.37 ± 156.84 vs. 68.56 ± 28.53 mm2/min; P = 0.042) and caused fewer intraprocedural bleeding events (0.40 ± 0.55 vs. 3.40 ± 1.95 times/per lesion; P = 0.016) than C-ESD. The thicknesses of the submucosal layer of the resected specimen (1190.98 ± 134.07 vs. 1055.90 ± 151.76 µm; P = 0.174) and the residual submucosal layer of the stomach defect (1607.94 ± 1026.74 vs. 985.98 ± 445.58 µm; P = 0.249) were similar with both procedures. The AIO snare is a safe and effective device for H-ESD and improves the treatment outcomes of gastric lesions by shortening the procedure time.

A syrup containing L-arabinose and D-xylose appears superior to PEG-4000 as a bowel cleansing agent.

Adequate bowel cleansing is crucial for endoscopic diagnosis and treatment, and the recovery of gut microbiota after intestinal cleansing is also important. A hypertonic syrup predominantly comprising L-arabinose and D-xylose (20% xylo-oligosaccharides) can be extracted from the hemicellulose of corn husks and cobs. L-Arabinose and xylo-oligosaccharides have been reported to relieve constipation and improve the gut microbial environment. This study evaluated the bowel cleansing effect of the aforementioned syrup and its influence on the organism and intestinal microbiota after cleansing in comparison with polyethylene glycol-4000 (PEG-4000) in mice. Bowel cleansing was performed using syrup or PEG-4000 in C57BL/6J mice, and the effect of intestinal preparation and its influence on serum electrolytes and gut microbiota after bowel cleansing were evaluated. The volume of intestinal residual feces in the syrup group was significantly lower than that in the PEG-4000 group. Additionally, syrup disturbed serum electrolytes more mildly than PEG-4000. Alpha diversity in the gut microbiota was significantly higher in the syrup group than in the PEG-4000 group on the first day after bowel cleansing. However, no difference in beta diversity was observed between the two groups. Syrup increased the abundance of Bifidobacteria and Christensenella and decreased the abundance of Akkermansia in comparison with PEG-4000 on the first day after bowel cleansing. Thus, this syrup has potential clinical use as a bowel cleansing agent given the above effects, its benefits and safety, and better taste and acceptability.

Standard-definition White-light, High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. METHODS: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. RESULTS: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). CONCLUSION: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.

Serum metabolomics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau has unique characteristics.

Few studies have provided data on the metabolomics characteristics of metabolic diseases such as hyperuricemia and hyperbilirubinemia in the Tibetan plateau. In the current study, we sought to investigate the serum metabolomics characteristics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau, with the aim to provide a basis for further research on their pathogenesis, prevention, and treatment. The study participants were born in low-altitude areas below 1000 m and had no prior experience living in a high-altitude area before entering Golmud, Tibet (average elevation: 3000 m) and Yushu, Qinghai (average elevation: 4200 m). Thirty-four participants with hyperbilirubinemia (18 in Golmud and 16 in Yushu), 24 participants with hyperuricemia, and 22 healthy controls were enrolled. The serum samples of subjects were separated and then sent to a local tertiary hospital for biochemical examination. Serum widely targeted technology, based on the ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) platform, was used to detect serum metabolites and differential metabolites. Compared to the healthy controls, hyperbilirubinemia patients from Golmud showed 19 differential metabolites, hyperbilirubinemia patients from Yushu showed 12 differential metabolites, and hyperuricemia patients from Yushu showed 23 differential metabolites. Compared to the hyperbilirubinemia patients from Golmud that is at a low altitude, the Yushu groups had 33 different metabolites. Differential metabolites are primarily classified into amino acids and their derivatives, nucleotides and their derivatives, organic acids and their derivatives, and lipids/fatty acids. These are related to metabolic pathways such as caffeine metabolism, arachidonic acid metabolism, and tyrosine metabolism. Hyperbilirubinemia and hyperuricemia in the Tibetan plateau have unique serum metabolomics characteristics. Glycine derivatives and arachidonic acid and its derivatives were associated with plateau hyperbilirubinemia, and vanillic acid and pentadecafluorooctanoic acid were associated with plateau hyperuricemia.

A novel detection technology for early gastric cancer based on Raman spectroscopy.

Despite universal endoscopic screening, early detection of gastric cancer is challenging, led researchers to seek for a novel approach in detecting. Raman spectroscopy measurements as a fingerprint of biochemical structure, enable accurate prediction of gastric lesions non-destructively. This study aimed to evaluate the diagnostic power of Raman spectroscopy in early gastric cancer (EGC), and reveal dynamic biomolecular changes in vitro from normal to EGC. To clarify the biochemical alterations in Correa's cascade, Raman spectra of human normal gastric mucosa, intestinal metaplasia, dysplasia, and adenocarcinoma were compared at tissue and cellular levels based on a self-developed data processing program. For effectively identify EGC, Raman spectroscopy was used combined with multiple machine learning methods, including partial least-squares discriminant analysis (PLS-DA), support vector machine (SVM), and convolutional neural network (CNN) with leave-one-out (LOO) cross validation. A total of 450 Raman spectra were investigated in this study. The upregulation of νsym(O-P-O) backbone (p < 0.001) was identified as a favorable factor for the diagnosis of EGC, the area under the ROC curve (AUC) was up to 0.918. In addition, higher levels of lactic acid (p < 0.001), lipids (p < 0.001), phenylalanine (p = 0.002), and carotenoids (p < 0.001) were detected in EGC. Multivariate machine learning methods for diagnosis of EGC based on Raman spectroscopy, the sensitivity, specificity, accuracy, and AUC were 91.0%, 100%, 94.8%, and 95.8% for SVM, and 84.8%, 92.0%, 88.8%, and 95.5% for CNN, respectively. Raman spectroscopy can be used as a powerful tool for detecting EGC while elucidating biomolecular dynamics in tumorigenesis. (Chictr.org.cn, ChiCTR2200060720.).

Career Development and Occupational Disease in Chinese Nurses: A Cross-Sectional Study.

BACKGROUND: A high tendency of intention to leave has been noted for nurses in China. The nursing profession is currently unstable. METHODS: A sample of 51406 nurses from 311 hospitals in China who completed the self-administered questionnaire online was recruited via the China Nursing Association by email and phone using a simple random sampling method. The recruitment occurred between July 2016 and July 2017. RESULTS: The majority of the nurses had working experience ≤20 years and had to work on night shifts. A high percentage of nurses (71.8%) had insomnia, followed by 37.0% who developed varicose veins and 40.9% who experienced musculoskeletal-related disorders. The proportions of the nurses who developed gastrointestinal and urinary system diseases were 56.0% and 18.2%, respectively. Nearly half of the nurses did not have a clear goal for their future career development and intended to leave. Nurses with long working hours each week were positively associated with the development of occupational diseases. The prevalence of occupational diseases was independently associated with career development. CONCLUSIONS: A high prevalence of occupational diseases was noted among nurses in China. The data indicated that 50% of the nurses were vague regarding their career planning. The data suggest that managers need to pay more attention and to prevent this problem. Appropriate interventions should also be provided.