The efficacy and safety of fexuprazan in treating erosive esophagitis: a phase III, randomized, double-blind, multicenter study.

BACKGROUND AND AIM: Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). This study aimed to explore the noninferior efficacy and safety of fexuprazan to esomeprazole in treating erosive esophagitis (EE). METHODS: This was a phase III, randomized, double-blind multicenter study. Patients with endoscopically confirmed EE were randomized to receive fexuprazan 40 mg or esomeprazole 40 mg once a daily for 4-8 weeks. The healing rates of EE, symptom response, GERD-health-related quality life (GERD-HRQL), and treatment-emergent adverse events (TEAEs) were compared between fexuprazan group and esomeprazole group. RESULTS: A total of 332 subjects were included in full analysis set (FAS) and 311 in per-protocol set (PPS). The healing rates of fexuprazan and esomeprazole groups at 8 weeks were 88.5% (146/165) and 89.0% (145/163), respectively, in FAS and 97.3% (145/149) and 97.9% (143/146), respectively, in PPS. Noninferiority of fexuprazan compared with esomeprazole according to EE healing rates at 8 weeks was demonstrated in both FAS and PPS analysis. No significant difference was found between groups in EE healing rates at 4 weeks, symptom responses, and changes of GERD-HRQL. The incidence of drug-related AEs was 19.4% (32/165) in fexuprazan arm and 19.6% (32/163) in esomeprazole arm. CONCLUSION: This study demonstrated noninferior efficacy of fexuprazan to esomeprazole in treating EE. The incidence of TEAEs was similar between fexuprazan and esomeprazole. Trial registration number NCT05813561.

Effects of exosomes derived from platelet-rich plasma on osteogenic differentiation of dental pulp stem cells.

Platelet-rich plasma (PRP) can cause osteogenic differentiation of dental pulp stem cells (DPSCs). However, the effect of exosomes derived from PRP (PRP-Exos) on osteogenic differentiation of DPSCs remains unclear. Herein, we evaluated the impact of PRP-Exos on osteogenic differentiation of DPSCs. PRP-Exos were isolated and identified by transmission electron microscopy (TEM) and western blotting (WB). Immunofluorescence staining was performed to evaluate endocytosis of PRP-Exos by DPSCs. Alkaline phosphatase staining, alizarin red staining, western blot and qRT-PCR were carried out to evaluate the DPSCs osteogenic differentiation. The sequencing microRNA (miRNA) was conducted to determine the microRNA profile of PRP-Exos treated and untreated DPSCs. The results showed that endocytosis of PRP-Exos stimulated DPSCs odontogenic differentiation by elevated expression of ALP, DMP-1, OCN, and RUNX2. ALP activity and calcified nodules formation of PRP-Exos treated DPSCs were considerably elevated relative to that of the control group. MicroRNA sequencing revealed that 112 microRNAs considerably varied in PRP-Exos treated DPSCs, of which 84 were elevated and 28 were reduced. Pathway analysis suggested that genes targeted by differentially expressed (DE) miRNAs were contributed to many signaling cascades, such as the Wnt cascade. 65 genes targeted by 30 DE miRNA were contributed to Wnt signaling. Thus, it can be infered that PRP-Exos could enhance osteogenic differentiation and alter the miRNA expression profile of DPSCs.

Development and evaluation of a program based on a generative pre-trained transformer model from a public natural language processing platform for efficiency enhancement in post-procedural quality control of esophageal endoscopic submucosal dissection.

BACKGROUND: Post-procedural quality control of endoscopic submucosal dissection (ESD) is emphasized in guidelines. However, this process can be tedious and time-consuming. Recently, a pre-training model called generative pre-trained transformer (GPT) on a public natural language processing platform has emerged and garnered significant attention, whose capabilities align well with the post-procedural quality control process and have the potential to streamline it. Therefore, we developed a simple program utilizing this platform and evaluated its performance. METHODS: Esophageal ESDs were retrospectively included. The manual quality control process was performed and act as reference standard. GPT's prompt was optimized through multiple iterations. A Python program was developed to automatically submit prompt with pathological report of each ESD procedure and collect quality control information provided by GPT. Its performance on quality control was evaluated with accuracy, precision, recall, and F-1 score. RESULTS: 165 cases were involved into the dataset, of which 5 were utilized as the prompt optimization dataset and 160 as the validation dataset. Definitive prompt was achieved through seven iterations. Time spent on the validation dataset by GPT was 13.47 ± 2.43 min. Accuracies of pathological diagnosis, invasion depth, horizontal margin, vertical margin, vascular invasion, and lymphatic invasion of the quality control program were (0.940, 0.952) (95% CI), (0.925, 0.945) (95% CI), 0.931, 1.0, and 1.0, respectively. Precisions were (0.965, 0.969) (95% CI), (0.934, 0.954) (95% CI), and 0.957 for pathological diagnosis, invasion depth, and horizontal margin, respectively. Recalls were (0.940, 0.952) (95% CI), (0.925, 0.945) (95% CI), and 0.931 for factors as mentioned, respectively. F1-score were (0.945, 0.957) (95% CI), (0.928, 0.948) (95% CI), and 0.941 for factors as mentioned, respectively. CONCLUSIONS: This quality control program was qualified of post-procedural quality control of esophageal ESDs. GPT can be easily applied to this quality control process and reduce workload of the endoscopists.

Sacral Nerve Stimulation Alleviates Intestinal Inflammation Through Regulating the Autophagy of Macrophages and Activating the Inflammasome Mediated by a Cholinergic Antiinflammatory Pathway in Colitis Rats.

BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic progressive intestinal inflammation. Sacral nerve stimulation (SNS) ameliorates colon inflammation caused by IBD. The aim of this study was to investigate the antiinflammatory benefits of SNS in colitis rats and explore the roles of the cholinergic antiinflammatory pathway, macrophage autophagy, and nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory bodies. MATERIALS AND METHODS: Rats were divided into four groups: healthy control, dextran sulfate sodium (DSS), DSS + sham-SNS, and DSS + SNS groups. An electrode was surgically placed in the right sacral nerve (S3) for stimulation. The disease activity index (DAI) score was recorded each day, and the degree of inflammatory injury was evaluated using hematoxylin and eosin staining. The alpha7 nicotinic acetylcholine receptor (α7nAChR) and autophagy- and NLRP3-related factors were assessed using immunofluorescence staining and Western blotting. RESULTS: The DSS group showed a higher DAI score, colon shortening, upregulated proinflammatory action, and colon damage, and the DSS + SNS group showed significantly improved symptoms. The number of α7nAChR+ cells and the expression level of autophagy decreased in the DSS group but increased in the DSS + SNS group. Conversely, the DSS group showed increased activation of NLRP3 inflammatory bodies, whereas the DSS + SNS group showed decreased activation of NLRP3 inflammatory bodies. CONCLUSION: In this study, SNS ameliorated colon inflammation by enhancing macrophage autophagy and inhibiting the activation of NLRP3 inflammatory bodies, which may be related to the opening of the cholinergic antiinflammatory pathway.

Dynamic effective connectivity among large-scale brain networks mediates risk of anxiety.

Anxiety is characterized by altered brain networks. Directional information flows among dynamic brain networks concerning neuropathogenesis of anxiety have not yet been investigated. The role of directional influences between networks in gene-environment effects on anxiety remains to be further elucidated. In a large community sample, this resting-state functional MRI study estimated dynamic effective connectivity among large-scale brain networks based on a sliding-window approach and Granger causality analysis, providing dynamic and directional information for signal transmission in networks. We first explored altered effective connectivity among networks related to anxiety in distinct connectivity states. Due to the potential gene-environment effects on brain and anxiety, we further performed mediation and moderated mediation analyses to investigate the role of altered effective connectivity networks in relationships between polygenic risk scores, childhood trauma, and anxiety. State and trait anxiety scores showed correlations with altered effective connectivity among extensive networks in distinct connectivity states (p < .05, uncorrected). Only in a more frequent and strongly connected state, there were significant correlations between altered effective connectivity networks and trait anxiety (PFDR <0.05). Furthermore, mediation and moderated mediation analyses showed that the effective connectivity networks played a mediating role in the effects of childhood trauma and polygenic risk on trait anxiety. State-dependent effective connectivity changes among brain networks were significantly related to trait anxiety, and mediated gene-environment effects on trait anxiety. Our work sheds novel light on the neurobiological mechanisms underlying anxiety, and provides new insights into early objective diagnosis and intervention evaluation.

Oral microbial changes and oral disease management before and after the treatment of hematological malignancies: a narrative review.

OBJECTIVES: Patients with hematological malignancies have dynamic changes in oral microbial communities before and after treatment. This narrative review describes the changes in oral microbial composition and diversity, and discusses an oral microbe-oriented strategy for oral disease management. MATERIALS AND METHODS: A literature search was performed in PubMed/Medline, Web of Science, and Embase for articles published between 1980 and 2022. Any articles on the changes in oral microbial communities in patients with hematological malignancies and their effects on disease progression and prognosis were included. RESULTS: Oral sample detection and oral microbial sequencing analysis of patients with hematological malignancies showed a correlation between changes in oral microbial composition and diversity and disease progression and prognosis. The possible pathogenic mechanism of oral microbial disorders is the impairment of mucosal barrier function and microbial translocation. Probiotic strategies, antibiotic strategies, and professional oral care strategies targeting the oral microbiota can effectively reduce the risk of oral complications and the grade of severity in patients with hematological malignancies. CLINICAL RELEVANCE: This review provides dentists and hematologists with a comprehensive understanding of the host-microbe associated with hematologic malignancies and oral disease management advice.

Comparison of efficiency and safety between dual-clip and rubber band-assisted ESD and conventional ESD for colonic lateral spreading tumors (LSTs) with different levels of technical difficulty: a retrospective case-control study.

BACKGROUND: Dual-clip and rubber band-assisted endoscopic submucosal dissection (DCRB-ESD) is a useful technique in the management of lateral spreading tumors (LSTs) of the colon and is suggested by researchers compared with conventional ESD (C-ESD). The aim of this retrospective study is to further analyze the efficiency and safety of DCRB-ESD in a setting with varying technical difficulties. METHODS: Patients who underwent endoscopic treatment (DCRB-ESD or C-ESD) due to LSTs between Jan 1st, 2019 and Jan 1st, 2022, were retrospectively collected. Patients were classified into the following two groups: the DCRB-ESD group (n = 46) and the C-ESD group (n = 81). Baselines were compared and propensity score matching (PSM) was employed to manage the heterogeneity. The technical difficulty and outcomes of the two groups were evaluated based on a semiquantitative model (CS-CRESD) previously described. RESULTS: The baseline characteristics of the two groups were balanced except sex and LST classification before PSM and were corrected after PSM. The median ESD operation time of DCRB-ESD was shorter than that of C-ESD (32 vs 41 and 30 vs 44 before and after PSM respectively, P < 0.05). The operation durations of cases with different CS-CRESD scores were different (P < 0.05). In the subgroup with a score of 0, DCRB-ESD showed no advantage than C-ESD in terms of operation duration before and after PSM. In subgroups with a score of 1-3, DCRB-ESD was faster than C-ESD. In subgroups with a score of 4-5, the between-group operation duration was not significantly different due to the limited number of cases, although the median time of DCRB-ESD was shorter. The R0 resection rates, curative resection, complications, and additional surgery in both groups were not significantly different. No adverse events, such as a clip falling off or rubber band rupturing occurred during this study. CONCLUSION: DCRB-ESD was an efficient and safe procedure in the management of colonic LSTs. With DCRB-ESD, the operation duration of difficult cases can be shortened without sacrificing complication risk. However, not all cases would benefit from DCRB-ESD. For easy cases (CS-CRESD score = 0), DCRB-ESD may not be prior to C-ESD by experienced endoscopists. A pre-ESD technical difficulty evaluation was recommended to decide whether to perform DCRB-ESD or not.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Gastric Electrical Stimulation Increases the Proliferation of Interstitial Cells of Cajal and Alters the Enteric Nervous System in Diabetic Rats.

BACKGROUND: Lack of interstitial cells of Cajal (ICC) and neuropathy were the most possible pathological mechanisms of diabetic gastroparesis. Gastric electrical stimulation (GES) is a promising way to treat gastroparesis. This study aimed to explore the impact of GES on ICC together with enteric neurons in diabetic rats and the possible mechanisms involved. MATERIALS AND METHODS: A total of 60 rats were randomized into six groups, including the normal control group, diabetic group (DM), diabetic with sham GES group (DM + SGES), and three groups of diabetic rats with GES (DM + GES1, DM + GES2, and DM + GES3). The proliferation of ICC and expressions of 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5, and glia cell line-derived neurotrophic factor (GDNF) in the antrum of the stomach were evaluated by immunofluorescence staining or Western blot. The levels of 5-HT in blood and tissue were determined by enzyme-linked immunosorbent assay. RESULTS: The proliferation of ICC was significantly reduced in the DM group, together with the DM + SGES group, but increased in the three DM + GES groups. The expression of 5-HT2B was decreased in the DM group and enhanced in the DM + GES groups. Similarly, the levels of 5-HT in the blood and distal stomach tissue were increased in the DM + GES groups. Both nNOS labeled neurons and CHAT-positive neurons were reduced in the myenteric plexus of the DM group, whereas these neurons were dramatically increased the in DM + GES groups. The expression of GDNF protein in the diabetic rats was down-regulated, whereas GES increased the expression of GDNF. CONCLUSIONS: GES improves the proliferation of ICC possibly related with the 5-HT/5-HT2B signal pathway and alters the enteric nervous system partly though the GDNF expression.

OTSC assisted EFTR for the treatment of GIST: 40 cases analysis.

BACKGROUND AND AIMS: To verify the safety and efficacy of over-the-scope clip (OTSC)-assisted endoscopic full-thickness resection (EFTR) for the excision of stromal tumors. MATERIAL AND METHODS: Forty patients with gastric stromal tumors treated in the Department of Gastroenterology, Binzhou Medical University Hospital from December 2015 to March 2017 were included in this study. The surgical procedures included marking the lesion boundaries, cutting open the top surface of the lesion, installing an OTS, sucking the lesion into the transparent cap of the anatomical clip which was then released, application of an endoloop for EFTR, and confirming the complete resection and pathological examination of the lesion. Statistical analysis of the tumor site and size, operation time, success rates, complications, pathological examination results, and follow-up status was performed. RESULTS: The average operation duration was 38.40 ± 24.9 min. Three cases had an incomplete resection, but the lesion was later found to have fallen off together with the OTSC. Therefore, the treatment success rate was 100%. Postoperative pathological examination revealed leiomyomas in four cases and stromal tumors in the remaining 36 cases. CONCLUSIONS: OTSC-assisted EFTR is safe and effective for resection of gastrointestinal stromal tumors, especially for those <20 mm in size.

Influence of Sedation on the Detection Rate of Early Cancer and Precancerous Lesions During Diagnostic Upper Gastrointestinal Endoscopies: A Multicenter Retrospective Study.

INTRODUCTION: The influence of sedation on the endoscopic detection rate of upper gastrointestinal (UGI) early cancer (EC) and precancerous lesions, including high-grade intraepithelial neoplasia (HGIN) and low-grade intraepithelial neoplasia, has not been assessed. The aim of this research is to assess whether the use of sedation can help improve the detection rate of UGI EC and precancerous lesions. The second objective is to evaluate its potential influencing factors. METHODS: The study includes 432,202 patients from a multicenter database from January 2012 to July 2019. Information on endoscopic findings and histology biopsies was obtained from endoscopy quality-control system. Associations of sedation with the detection rate of EC and precancerous lesions were assessed. RESULTS: The sedation group has a higher detection rate of UGI EC and HGIN compared with the no-sedation group, whereas the detection rate of low-grade intraepithelial neoplasia was similar between the 2 groups. There were more cases examined by using staining, image enhancement, or magnifying techniques in the sedation group (P < 0.001). And, the mean observation time was also longer in the sedation group (P < 0.001). The type 0-IIb esophageal HGIN and EC cases were significantly increased in the sedation group. No significant difference was detected on lesion subtypes for gastric HGIN and EC according to the Paris classification. More gastric HGIN and EC were detected at gastric body in the sedation group (P = 0.001). DISCUSSION: Sedation may improve the endoscopic detection rate of EC and HGIN in the UGI tract probably through enhancing the use of accessary endoscopic techniques, prolonging observation time, and taking more biopsies in different locations (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/AJG/B926).

A tomato receptor-like cytoplasmic kinase, SlZRK1, acts as a negative regulator in wound-induced jasmonic acid accumulation and insect resistance.

Jasmonates accumulate rapidly and act as key regulators in response to mechanical wounding, but few studies have linked receptor-like cytoplasmic kinases (RLCKs) to wound-induced jasmonic acid (JA) signaling cascades. Here, we identified a novel wounding-induced RLCK-XII-2 subfamily member (SlZRK1) in tomato (Solanum lycopersicum) that was closely related to Arabidopsis HOPZ-ETI-DEFICIENT 1 (ZED1)-related kinases 1 based on phylogenetic analysis. SlZRK1 was targeted to the plasma membrane of tobacco mesophyll protoplasts as determined by transient co-expression with the plasma membrane marker mCherry-H+-ATPase. Catalytic residue sequence analysis and an in vitro kinase assay indicated that SlZRK1 may act as a pseudokinase. To further analyse the function of SlZRK1, we developed two stable knock-out mutants by CRISPR/Cas9. Loss of SlZRK1 significantly altered the expression of genes involved in JA biosynthesis, salicylic acid biosynthesis, and ethylene response. Furthermore, after mechanical wounding treatment, slzrk1 mutants increased transcription of early wound-inducible genes involved in JA biosynthesis and signaling. In addition, JA accumulation after wounding and plant resistance to herbivorous insects also were enhanced. Our findings expand plant regulatory networks in the wound-induced JA production by adding RLCKs as a new component in the wound signal transduction pathway.

5-FU inhibits migration and invasion of CRC cells through PI3K/AKT pathway regulated by MARCH1.

Colorectal cancer is a major health problem with a significant impact on the patients' quality of life. 5-Fluorouracil is the most common chemotherapy drug used for this type of cancer. While its molecular mechanism is the inhibition of DNA synthesis via the inhibition of thymine nucleotide synthetase, its complete anticancer mechanism is not clear. Membrane-associated RING-CH-1 (MARCH1) is an E3 ubiquitin ligase that plays an important role in antigen presentation. However, MARCH1 has not been studied in the context of colorectal cancer. In this study, we demonstrated that MARCH1 is highly expressed in colorectal cancer tissues and cell lines. Furthermore, migration and invasion of colorectal tumor cells were inhibited via transfection with small interfering RNAs to suppress the expression of MARCH1. The western blot analysis showed that MARCH1 regulates epithelial-mesenchymal transition and the PI3K/AKT pathway. Moreover, 5-fluorouracil inhibited the proliferation, migration, and invasion of tumor cells, via the targeting of MARCH1 and the consequent downregulation of the PI3K/AKT pathway, impacting the progression of epithelial-mesenchymal transition. In conclusion, our study shows that MARCH1 may play a role as an oncogene in colorectal cancer and may represent a new target molecule of 5-fluorouracil.

Comparison of amide proton transfer imaging and magnetization transfer imaging in revealing glioma grades and proliferative activities: a histogram analysis.

PURPOSE: Comprehensive understanding glioma metabolic characters is of great help for patient management. We aimed to compare amide proton transfer imaging (APTw) and magnetization transfer imaging (MT) in predicting glioma malignancy and reflecting tumor proliferation. METHODS: Thirty low-grade gliomas (LGGs) and 39 high-grade gliomas (HGGs) were prospectively included, of which 58 samples Ki-67 levels were quantified. Anatomical MRI, APTw, and MT were scanned, and magnetization transfer ratio (MTR) and asymmetric magnetic transfer ratio at 3.5 ppm (MTRasym(3.5ppm)) were calculated. ROIs were semi-automatically drawn with ImageJ, from which histogram features, including 5th, 25th, 50th, mean, 70th, 90th, and 95th percentiles were extracted. The independent t test was used to test differences in LGGs and HGGs, and correlations between histogram features and tumor grades, Ki-67 were revealed by Spearman's rank or Pearson's correlation analysis. RESULTS: The maximum correlation coefficient (R) values of APTw were 0.526 (p < 0.001) with tumor grades and 0.397 (p < 0.001) with Ki-67 at 90th percentiles, while only 5th and 25th percentiles of MT significantly correlated with tumor grades. Moreover, APTw features were significantly different in LGGs and HGGs, except 5th percentile. The most significantly different feature was 95th percentile, providing the excellent AUC of 0.808. However, the best feature in MTR was 5th percentiles with AUC of 0.703. Combing 5th and 95th of APTw achieved highest AUC Of 0.837. CONCLUSIONS: Both APTw and MT provide quantitative information for tumor metabolite imaging. However, APTw supplys more specific information in reflecting glioma biological behaviors than MT, and well differentiates glioma malignancy.

Changes of white matter integrity and structural network connectivity in nondemented cerebral small-vessel disease.

BACKGROUND: Previous studies have found widespread impairment of white matter (WM) integrity and disruption of structural network connectivity in cerebral small-vessel disease, but have not evaluated these changes jointly in nondemented patients. PURPOSE: To jointly investigate the microstructural impairment of WM and the related alterations of structural network topology in nondemented cerebral small-vessel disease (CSVD-ND). STUDY TYPE: Prospective. POPULATION: Thirty-seven CSVD-ND patients and 34 elderly controls, who were age-, sex-, and education-matched. FIELD STRENGTH/SEQUENCE: 3.0T/diffusion tensor imaging (DTI). ASSESSMENT: Clinical characteristics, lacunar infarct, and white matter hyperintensity (WMH) was assessed. A multiatlas likelihood fusion (MALF) algorithm was used for DTI-based brain segmentation and network node defining. Then the alterations of WM integrity and structural network topology were investigated jointly. STATISTICAL TESTS: Student's t-test, chi-square test, Mann-Whitney U-test, linear regression, Pearson correlation, and multiple comparison correction. RESULTS: Decreased fractional anisotropy and increased trace values were observed in predefined structures (P < 0.05, familywise error rate-corrected), including major commissural fibers, projection fibers, and some association fibers. Topologically, both groups showed small-worldness. CSVD-ND patients showed reduced global and local efficiency (P < 0.001). Despite widespread impairment of WM integrity, CSVD-ND patients only showed reduced nodal efficiency in the right superior occipital gyrus and the right lingual gyrus (P < 0.05, familywise error rate-corrected). The nodal local efficiency of the right precuneus was associated with the processing speed after adjusting the effect of lacunar infarct and WMH (r = -0.499, P = 0.038). DATA CONCLUSION: WM integrity was widely impaired in nondemented CSVD patients but structural network connectivity was relatively preserved. DTI may potentially provide information for the pathophysiology of CSVD in the nondemented phase. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1162-1169.

Delayed bowel obstruction after seat belt injury: a case report.

BACKGROUND: Delayed bowel obstruction due to seat belt injury is extremely rare. The delayed onset of nonspecific symptoms makes a timely diagnosis difficult. A deep understanding of the characteristics of this condition is helpful for early diagnosis and treatment. CASE PRESENTATION: A 39-year-old male was transferred to our hospital from another hospital complaints of progressive abdominal distension and severe weakness. In the previous hospital, he was diagnosed with "adult megacolon" and was recommended for surgical treatment. In our hospital, he was diagnosed with delayed bowel obstruction due to seat belt injury and underwent surgical intervention. Following laparoscopic adhesiolysis and resection of the narrow small intestine, his symptoms improved rapidly, and he was discharged. CONCLUSION: Delayed bowel obstruction due to seat belt injury may present clinical symptoms any time after the injury. Imaging examination, ileus tube and small colonoscopy may provide us with valuable cues for the diagnosis and treatment of delayed bowel obstruction, and laparoscopy may be an alternative approach in surgical intervention.

Identification of novel alternative splicing isoform biomarkers and their association with overall survival in colorectal cancer.

BACKGROUND: Alternative splicing (AS) is an important mechanism of regulating eukaryotic gene expression. Understanding the most common AS events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC. METHODS: Publicly available RNA-seq data of 28 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify AS events using PSI and DEXSeq methods. RESULT: The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified AS events in 9 genes in CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6). Except for CHEK1, all other 8 splicing events were confirmed by TCGA data with 382 CRC tumors and 51 normal controls. The combination of three splicing events was used to build a logistic regression model that can predict sample type (CRC or normal) with near perfect performance (AUC = 1). Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The AS features of the 9 genes are highly consistent with previous reports and/or relevant to cancer biology. CONCLUSIONS: The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.

Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study.

OBJECTIVE: To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. DESIGN: This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. RESULTS: The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). CONCLUSIONS: The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

Endoscopic resection of giant gastrointestinal stromal tumor at the esophagogastric junction: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) at the esophagogastric junction are rare and its treatment is complicated and challenging. Endoscopic resection has advantages with less complications compared to open and laparoscopic surgery. CASE PRESENTATION: We report a 33-year-old male patient who was admitted to our department complaining of abdominal fullness for 20 days. A huge submucosal tumor at the esophagogastric junction was found by upper gastrointestinal endoscopy. We successfully resected the lesion through endoscopic submucosal excavation without complications, which was pathologically confirmed to be a GIST. The patient was discharged 5 days after operation and has been doing well, and there was no recurrence 8 months after the operation. CONCLUSION: ESE is possibly an effective and minimally invasive method of giant esophagogastric junction stromal tumor.

Extracellular vesicles isolated from curcumin-medium weakened RKO cell proliferation and migration.

Background: Curcumin (Cur) is a natural phytochemical that is expected to become an indispensable drug for the treatment of colorectal cancer. A comprehensive understanding of the anti-tumor mechanism of Cur will provide a better reference for its clinical application. This study aimed to examine the effects of extracellular vesicles (EVs) isolated from Cur-medium on RKO colorectal cancer cell proliferation, apoptosis, and migration. Methods: RKO cells were cultured in various concentrations of Cur-medium, and the EVs were isolated from the Cur-medium. The EVs were identified by transmission electron microscopy and western blotting. The effects of the EVs on RKO cell proliferation, apoptosis, and migration were analyzed, as was the expression of proliferating cell nuclear antigen (PCNA), Bax, vimentin, and E-cadherin. The expression of nuclear factor κB (NF-κB) p65 in the EVs was also detected. Results: Our results showed that the EVs isolated from the Cur-medium weakened RKO cell proliferation and migration but had no effect on cell apoptosis. Cur suppressed the expression of NF-κB p65 in the EVs. Overall, this study revealed that Cur exerts anti-tumor effects by suppressing NF-κB p65 in EVs to weaken RKO cell proliferation and migration. Conclusions: In conclusion, the packaging of Cur into EVs is expected to become an indispensable treatment of colorectal cancer in the future.