Feasibility and clinical value of linear endoscopic ultrasonography imaging in the lower gastrointestinal subepithelial lesions.

Linear endoscopic ultrasonography (EUS) has been extensively utilized as a novel diagnostic and therapeutic modality across various fields. However, there have been relatively few studies focusing on lower gastrointestinal lesions. The aim of our study was to investigate the feasibility, safety and clinical value of linear EUS in the lower gastrointestinal subepithelial lesions. This was a retrospective study involving patients with lower gastrointestinal subepithelial lesions diagnosed by linear EUS from August 2019 to April 2023 at the Second Affiliated Hospital of Anhui Medical University. The data, including basic clinical information, linear EUS features, technical success rate, complications, and follow-up, were retrospectively collected and analyzed. A total of 69 patients with lower gastrointestinal subepithelial lesions underwent examination by linear EUS. Excluding the rectum, the technical success rate of linear EUS was 90.6% (29/32). Apart from the 7 patients whose diagnosis remained unknown, 3 patients with no abnormal EUS findings, and 3 patients failed the procedure, 56 patients were included in the final diagnostic performance analysis. The most common locations of the lesions were the rectum (37/56, 66.1%) and sigmoid colon (7/56, 12.5%). Based on endoscopy findings and pathological results, the most prevalent types of subepithelial lesions in the lower gastrointestinal tract were neuroendocrine tumor (NET) (12/56, 20.3%), lipoma (8/56, 13.6%) and extraluminal compression (8/56, 13.6%). The majority of lesions ranged in diameter from 1 to 3 cm (χ2 = 18.750, p < 0.001). After undergoing linear EUS examination, 36 patients received EUS-FNA (3/36), biopsy (5/36), endoscopic resection (25/36), or surgical excision (3/36) respectively. The pathological results of 29 patients were entirely consistent with the diagnosis made using linear EUS, with an 80.6% (29/36) diagnostic accuracy rate. Follow-up indicated that the lesions remained unchanged within 6-36 months. All patients tolerated the procedure well without any complications. In conclusion, linear EUS demonstrates technical feasibility, safety, and a high diagnostic accuracy for subepithelial lesions in the lower gastrointestinal tract.

Healthy plant-based diet might be inversely associated with gastric precancerous lesions: new evidence from a case-control study based on dietary pattern and fecal metabolic profiling.

Preventing the progression of gastric precancerous lesions (GPLs) can reduce the morbidity and mortality of gastric cancer (GC). The preventive effect of a plant-based diet on cancers has been widely recognised. In this case-control study, 1,130 subjects were included using 1:1 propensity score matching for age and sex. Dietary habits, anthropometry and sample collection were conducted using standard and effective methods. Plant-based diet indices (PDIs) were calculated using a previously reported method. Faecal samples were analysed by untargeted metabolomics. Our study found that adherence to a healthy plant-based diet was inversely associated with the occurrence of GPLs. Metabolomic analysis identified six different metabolites correlated with GPLs, among which luteolin-related metabolites may be used as biomarkers of the association between PDIs and GPLs. In addition, the difference in N-acyl amides found in PDIs needs further verification. Our findings suggest that a healthy plant-based diet may have a protective effect against GPLs.

The effect of short-term training about depth predicting score on the diagnostic ability of invasion depth for differentiated early gastric Cancer among non-expert endoscopists.

BACKGROUND: The depth-predicting score (DPS) was proposed based on conventional white-light imaging (C-WLI) endoscopic features of early gastric cancer (EGC) to determine the invasion depth of the neoplasm. However, the effect of DPS on training endoscopists remains unclear. Therefore, we aimed to investigate the effect of short-term DPS training on improving the diagnostic ability of EGC invasion depth and compare the training effect among non-expert endoscopists at different levels. METHODS: In the training session, the definitions and scoring rules of DPS were instructed, and classic C-WLI endoscopic example graphics were exhibited to the participants. Another C-WLI endoscopic images of 88 cases of histologically proven differentiated EGC were selected as an independent test dataset for evaluating the training effect. Each participant was tested, and the diagnostic accuracy rate of invasion depth was calculated differently one week before the training and after the completion of training. RESULTS: A total of 16 participants were enrolled and completed the training. Participants were divided into a trainee group and a junior endoscopist group according to the total number of C-WLI endoscopies performed. The total number of C-WLI endoscopies performed showed a significant difference between the trainee group and junior endoscopist group (350 vs. 2500, P = 0.001). No significant difference between the trainee group and junior endoscopist group was observed for pre-training accuracy. The overall diagnostic accuracy of invasion depth was improved significantly after completing DPS training compared with before (68.75 ± 5.71% vs. 61.58 ± 9.61%, P = 0.009). In the subgroup analysis, the post-training accuracy was higher than the pre-training accuracy, but significant improvement was observed only in the trainee group (61.65 ± 7.33% vs. 68.32 ± 5.71%, P = 0.034). In addition, no significant difference in post-training accuracy between the two groups was observed. CONCLUSION: Short-term DPS training can improve the diagnostic ability of the invasion depth of EGC and homogenize the diagnostic ability of non-expert endoscopists at different levels. The depth-predicting score was convenient and effective for endoscopist training.

Comparison of diagnostic accuracy between linear EUS and miniprobe EUS for submucosal invasion in suspected cases of early gastric cancer

Objective: this study assessed the accuracy of linear endoscopic ultrasound (EUS) to diagnose submucosal (SM)invasion and compared linear EUS with miniprobe EUS insuspected early gastric cancer (EGC) patients.Methods: patients diagnosed with biopsy-verified suspected EGC were analyzed retrospectively. All cases wereexamined by linear EUS or miniprobe EUS for preoperativediagnosis of invasion depth and underwent endoscopic orsurgical treatment for radical resection. The invasion depthevaluated by EUS and pathology were categorized as noinvasion of SM and invasion of SM or deeper. The diagnosis of EUS was compared with postoperative pathologyresults.Results: a total of 105 patients were included in the finalanalysis. The overall prediction accuracy of linear EUS(n = 57) for SM invasion in suspected EGC was higherthan that of miniprobe EUS (n = 48), although no statistically significant differences were noted (82.5 % vs 72.9 %,p = 0.344). The negative predictive value (NPV) of linear EUSwas significantly higher than that of miniprobe EUS (100 %vs 82.8 %, p = 0.037). The binary logistic regression analysis showed that tumor size (p = 0.036), the presence of ulceration (p < 0.001) and EUS type (p = 0.027) were independentrisk factors for the diagnosis of SM invasion by EUS. Thearea under the receiver operating curve (ROC) was 0.889and 0.719 for linear and miniprobe EUS, respectively.Conclusion: linear EUS diagnosed suspected EGC for SMinvasion with a higher accuracy than miniprobe EUS. Inaddition, large and ulcerative lesions may lead to overestimation. (AU)

Favorable effect of rivaroxaban against vascular dysfunction in diabetic mice by inhibiting NLRP3 inflammasome activation.

Cardiovascular disease (CVD) is the leading cause of death in various complications of type 2 diabetes mellitus (T2DM). Rivaroxaban (Xarelto; Bayer), an oral direct factor Xa (FXa) inhibitor, prevents the activation of the coagulation cascade in CVD. Considering its anticoagulant and anti-inflammatory effects, we assessed the hypothesis that rivaroxaban treatment may attenuate the vascular lesion and dysfunction in T2DM mice. C57BL/6, BKS-db/db, BKS-db/+, wild-type (WT), and NLRP3-/- mice were fed with standard chow or high-fat diet (HFD). Biochemical indexes, vascular lesions, and protein expression were evaluated using Western blot analysis, immunofluorescent staining, and RNA interference. Rivaroxaban presented favorable protection of vascular dysfunction in T2DM mice with significantly relieved vascular tension, intima-media thickness, and collagen deposition. Similar improvements in NLR family pyrin domain containing 3 (NLRP3) knockout groups and rivaroxaban pointed to the positive role of rivaroxaban against vascular dysfunction in diabetic mice by ameliorating NLRP3 inflammasome activation. Furthermore, the augmentation of inflammation and cell dysfunction in mice aortic endothelial cells (MAECs) and smooth muscle cells (MOVASs) induced by soluble FXa may be blocked by rivaroxaban via protease-activated receptors (PAR-1, PAR-2), mitogen-activated protein kinase (MAPK), and nuclear factor κ-B (NF-κB) pathway. The data indicate that the development of vascular dysfunction and inflammation in T2DM mice may be blocked by rivaroxaban in vivo and in vitro. Rivaroxaban treatment may also attenuate NLRP3 inflammasome activation via PARs, MAPK, and NF-κB pathway. This study provides mechanistic evidence of rivaroxaban therapies for vascular complications of T2DM.

A rare case of duodenal spindle cell lipoma with gastrointestinal bleeding.

The manuscript reports a rare case of duodenal spindle cell lipoma (SCL), which is a rarely reported benign lipomatous neoplasm of the gastrointestinal tract. It is less commonly observed within the duodenum. Our patient presented with gastrointestinal bleeding, which is a rare symptom of lipomas. This report describes the appearance of the neoplasm on endoscopy as well as endoscopic ultrasonography. The ulcer on the surface of the neoplasm is another rare feature. The correct diagnosis of SCL was based on its microscopic features and immunohistochemical findings. We believe that our study makes a significant contribution to the literature because this information will be of practical use to clinicians for the management of similar conditions and encourage other researchers to validate our findings.

Comparison of diagnostic accuracy between linear EUS and miniprobe EUS for submucosal invasion in suspected cases of early gastric cancer.

OBJECTIVE: This study assessed the accuracy of linear endoscopic ultrasound (EUS) to diagnose submucosal (SM) invasion and compared linear EUS with mini-probe EUS in suspected early gastric cancer (EGC) patients. METHODS: Patients diagnosed with biopsy-verified suspected EGC were analyzed retrospectively. All cases were examined by linear EUS or miniprobe EUS for preoperative diagnosis of invasion depth and underwent endoscopic or surgical treatment for radical resection. The invasion depth evaluated by EUS and pathology were categorized as no invasion of SM and invasion of SM or deeper. The diagnosis of EUS was compared with postoperative pathology results. RESULTS: A total of 105 patients were included in the final analysis. The overall prediction accuracy of linear EUS (n = 57) for SM invasion in suspected EGC was higher than that of mini-probe EUS (n = 48), although no statistically significant differences were noted (82.5% vs 72.9%, p = 0.344). The negative predictive value (NPV) of linear EUS was significantly higher than that of mini-probe EUS (100% vs 82.8%, p = 0.037). The binary logistic regression analysis showed that tumor size (p = 0.036), the presence of ulceration (p < 0.001) and EUS type (p = 0.027) were independent risk factors for the diagnosis of SM invasion by EUS. The area under the receiver operating curve (ROC) was 0.889 and 0.719 for linear and mini-probe EUS, respectively. CONCLUSION: Linear EUS diagnosed suspected EGC for SM invasion with a higher accuracy than mini-probe EUS. In addition, large and ulcerative lesions may lead to overestimation.

Phospho-Smad3L promotes progression of hepatocellular carcinoma through decreasing miR-140-5p level and stimulating epithelial-mesenchymal transition.

BACKGROUND: The transforming growth factor ß (TGF-ß) activates JNK, phosphorylates Smad3 to linker-phosphorylated Smad3 (pSmad3L), resulting in liver tumorigenesis. However, the effect of pSmad3L on hepatocellular carcinoma (HCC) prognosis is obscure. AIM: To detect the effect of pSmad3L on HCC prognosis and investigate the mechanism. METHODS: The expressions of pSmad3L, E-cadherin, vimentin and MicroRNA-140-5p (miR-140-5p) were detected by using immunohistochemistry, immunofluorescence and in situ hybridization. Next, the relationships of pSmad3L and HCC patients' prognoses, pSmad3L and EMT markers, pSmad3L and miR-140-5p were analyzed using Spearman's rank correlation test. JNK/pSmad3L specific inhibitor SP600125 or Smad3 mutant plasmid was used to suppress JNK/pSmad3L pathway, and QPCR assay was performed to investigate the effect of pSmad3L on miR-140-5p level. The proliferation and invasion of hepatoma cells were observed using colony formation assay and transwell assay. RESULTS: We demonstrated that patient with high level of pSmad3L predicted poor prognosis. Next, we verified that pSmad3L promoted EMT of hepatoma cells in vivo and in vitro. In order to investigate the mechanism, we verified a negative correlation between pSmad3L and miR-140-5p, which was an EMT inhibitor, in the liver tissues of HCC patient and diethylnitrosamine (DEN)-induced rat HCC model. We further used SP600125 or pSmad3L mutant plasmid to decrease pSmad3L level of hepatoma cells, and inhibition of pSmad3L increased miR-140-5p level and suppressed EMT of hepatoma cells. CONCLUSIONS: JNK/pSmad3L pathway induces EMT by inhibiting miR-140-5p in HCC progression.

Impaired pain empathic abilities among patients with functional dyspepsia.

INTRODUCTION: Brain structure or functioning abnormality in regions such as insula and anterior cingulate cortex (ACC) is associated with functional dyspepsia (FD) and pain empathy, but the relationship between FD and pain empathy remains unclear. The aim of this study was to compare the pain empathic abilities of FD patients and healthy controls (HCs) and investigate the association of pain empathy with clinical characteristics and quality of life of FD patients. METHODS: Pain empathic abilities was measured in 30 FD patients and 30 HCs using a validated pain empathy paradigm. Demographic characteristics, Helicobacter pylori status, duration, dyspeptic symptom score and Nepean Dyspepsia Life Quality Index (NDLQI) were obtained from all patients. RESULTS: FD patients scored higher than HCs when rating painful pictures, but the accuracy for painful pictures was significantly lower than HCs. Pearson correlation analysis showed significant negative correlation between NDLQI and pain rating scores for painful pictures. When sex, age, educational level, the number of complaints, duration, H. pylori infection and NDLQI were included in multiple linear regression analysis, NDLQI was independently associated with pain ratings. CONCLUSIONS: FD patients showed abnormally enhanced pain empathic abilities, which may be associated with the severity of symptoms and quality of life.

Impaired decision-making under risk in patients with functional dyspepsia.

INTRODUCTION: The cognitive processing in patients with functional dyspepsia (FD) has not been well established. Decision-making is an important component of cognitive function. Most brain regions involved in decision-making are abnormal in FD patients. This study aimed to investigate the decision-making under ambiguity and risk in FD patients. METHODS: We recruited 40 FD patients meeting Rome III criteria and 40 healthy controls (HCs) matched for age, sex, marital status, and education level. The Hamilton Anxiety Scale (HAMA) and the 17-item Hamilton Depression Scale (HAMD-17) were used to evaluate their anxiety and depression emotions. The Iowa Gambling Task (IGT) and Game of Dice Task (GDT) were used to evaluate decision-making under ambiguity and risk, respectively. Helicobacter pylori status, disease duration, dyspeptic symptom score, and the Nepean Dyspepsia Life Quality Index (NDLQI) were obtained from all patients. RESULTS: In IGT, FD patients had a lower total net score, chose more adverse choices, and showed a slower response to change their behavior than HCs. However, there was no significant difference in the net score of the first 2 blocks between the two groups. In GDT, FD patients had a lower total net score, higher risk score, and lower use of negative feedback than HCs. In addition, FD patients showed better GDT performance than those without early satiation. CONCLUSIONS: FD patients showed impaired decision-making under risk. The deficiency might be related to dyspeptic symptoms of FD patients.

Natural products, extracts and formulations comprehensive therapy for the improvement of motor function in alcoholic liver disease.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide that afflicts human health. With the in-depth study of the disease, its pathogenesis has gradually become clear. Although great breakthroughs have been made in the research of ALD, the research and development of drugs related to ALD has lagged behind seriously. However, natural products have always inspired the development of drugs. Meanwhile, there is evidence that some natural products can also play a certain role in the treatment of ALD. Thus, we reviewed the natural products, extracts and formulations with potential anti-ALD activities by consulting the relevant data in the databases of PubMed, Web of Science and CNKI databases, in order to elucidate the regulated mechanism of these natural products. Sum up, the insights provided in present review will be needed for further exploration of botanical drugs in the development of ALD therapy.

Mitogen-activated protein kinase inhibitors reduce the nuclear accumulation of phosphorylated Smads by inhibiting Imp 7 or Imp 8 in HepG2 cells.

The transforming growth factor (TGF)-ß/Smad signaling pathway is involved in hepatocellular carcinoma development. Smad2 and Smad3 are phosphorylated following TGF-ß1 stimulation and subsequently oligomerize with Smad4 to form the Smad2/3/4 complex, which translocates into the nucleus and regulates target genes, including plasminogen activator inhibitor type 1 (PAI1). Importin (Imp)7 and Imp8 are responsible for transporting phosphorylated (p)Smad2/3 and Smad4 into the nucleus. In our previous study, it was demonstrated that mitogen-activated protein kinase (MAPK) inhibitors, including inhibitors of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 could inhibit the transcription of PAI1, but ERK inhibitor had no significant effect on the phosphorylation of Smad2/3, and the formation of Smad2/3/4 complexes, which was different from the effect of JNK or p38 inhibitor. We hypothesized that MAPK inhibitors, particularly ERK inhibitor, reduced the transport of Smads into the nucleus by affecting Imp7 and Imp8. To confirm this hypothesis, HepG2 cells were incubated with different MAPK inhibitors for 5 h and subsequently stimulated with TGF-ß1 for 1 h. Next, the intracellular locations of Smads (pSmad2C, pSmad2L, pSmad3C, pSmad3L and Smad4) and Imp7/8 were detected using immunofluorescence staining assays, and the expression of Imp7/8 was investigated using immunoblotting. It was revealed that JNK or p38 inhibitor decreased the phosphorylation of Smad2C, Smad2L and Smad3L, and affected their nuclear accumulation. Although only inhibiting the phosphorylation of Smad2C, ERK inhibitor affected the nuclear accumulation of pSmad2C, pSmad2L, pSmad3C and pSmad3L. The three MAPK inhibitors attenuated the nuclear distribution of Smad4, and the expression and nuclear accumulation of Imp7. ERK and JNK inhibitors attenuated the expression and nuclear accumulation of Imp8. Thus, the results of the present study suggest that MAPK inhibitors, particularly ERK inhibitor, modulate the nuclear accumulation of Smads via the inhibition of Imp 7/8.

Compound Astragalus and Salvia miltiorrhiza extracts suppress hepatocarcinogenesis by modulating transforming growth factor-ß/Smad signaling.

BACKGROUND AND AIM: Previous studies showed Compound Astragalus and Salvia miltiorrhiza extract (CASE), extract from Astragalus membranaceus and Salvia miltiorhiza, significantly suppresses hepatocellular carcinoma (HCC) in rats induced by diethylinitrosamine (DEN), and in vitro experiments further demonstrated that CASE's anti-HepG2 cell invasion is associated with transforming growth factor-ß (TGF-ß). We hypothesized that CASE's suppression of HCC is modulated by TGF-ß/Smad signaling, and we conducted this in vivo study to test this hypothesis. METHODS: Rats were divided into the normal control, the DEN group, and three CASE (60, 120, and 240 mg/kg) treatment groups. The expression of phosphorylation(p) Smad both at C-terminal and linker region, plasminogen activator inhibitor 1, and Smad4 and Smad7 of liver tissues were measured and compared across the five groups. RESULTS: The positive staining of pSmad2L and pSmad3L increased both in hepatoma nodule areas and adjacent relatively normal liver tissues in rats treated with DEN, while the positive staining of pSmad2C and pSmad3C increased only in relatively normal liver tissues adjacent to hepatoma tissues. The elevated expression of pSmad2C, pSmad2L, pSmad3L, Smad4, and plasminogen activator inhibitor 1 proteins were suppressed by CASE in a dose-dependent manner. CASE treatment also significantly reduced the intranuclear amounts of pSmad2L and pSmad3L, and upregulated the elevation of pSmad3C positive cells and protein expression in a dose-dependent manner. CONCLUSION: The results suggest that CASE significantly suppresses HCC progression by mediating TGF-ß/Smad signaling, especially by modulating Smad3 phosphorylation both at the C-terminal and linker region.

Effects of CYP2C19 genetic polymorphism on the pharmacokinetics and pharmacodynamics of omeprazole in Chinese people.

BACKGROUND: To investigate whether the pharmacodynamics and pharmacokinetics of omeprazole (OPZ) are dependent of the CYP2C19 genotype status in Chinese people. METHODS: Eighteen healthy subjects were voluntary to participate in the study, whose CYP2C19 genotype status were determined by polymerase chain reaction-restriction fragment length polymorphism method. There were six homozygous extensive metabolizers, six heterozygous extensive metabolizers and six poor metabolizers (PMs). All subjects were Helicobacter pylori-negative, determined by serology method and (13)C-urea breath test. After d1 and d8 orally received OPZ 20 mg once daily in the morning, intragastric pH values were monitored for 24 h by Digitrapper pH. Meanwhile, blood samples were collected at various time-points until 24 h after administration. The serum concentrations of OPZ were measured by liquid chromatography. RESULTS: After single or repeated doses, the PMs showed a significantly higher mean area under the serum concentration-time curves (AUC) values than that observed in the homozygous extensive metabolizers or the heterozygous extensive metabolizers, with a relative ratio of 1.0 : 1.1 : 4.2 and 1.0 : 1.3 : 3.3 (homozygous extensive metabolizers:heterozygous extensive metabolizers:poor metabolizers), respectively. After a single dose of OPZ, significant differences in intragastric pH median, pH > 3 holding time and pH > 4 holding time were observed among the three groups. After repeated doses, the PMs showed a significantly higher intragastric pH values than that observed in the homozygous extensive metabolizers or the heterozygous extensive metabolizers. CONCLUSION: The pharmacodynamic effects of OPZ and its pharmacokinetics depend on the CYP2C19 genotype status in Chinese people.

Pharmacodynamic and kinetic effect of rabeprazole on serum gastrin level in relation to CYP2C19 polymorphism in Chinese Hans.

AIM: To observe the pharmacokinetics and pharmaco-dynamics of rabeprazole and compare serum gastrin concentrations in different CYP2C19 genotype groups. METHODS: The CYP2C19 genotype status of Chinese Han healthy volunteers was determined by polymerase chain reaction-restriction fragment length polymorphism method. Twenty H pylori-negative healthy subjects voluntary participated in the study. They were divided into the following three groups: homozygous extensive metabolizers (homEM), heterozygous extensive metabolizers (hetEM) and poor metabolizers (PM). After they orally received rabeprazole 20 mg once daily in the morning of d 1 and d 8, blood samples were collected at various time-points until 24 h after administration and intragastric pH values were monitored for 24 h by Digitrapper pH. Serum gastrin concentrations were measured by radioimmunoassay. Serum concentrations of rabeprazole were measured by high performance liquid chromatography. RESULTS: The mean AUC values for rabeprazole after a single and repeated doses were significantly different between the homEM and PM groups, but not between the homEM and hetEM, or the hetEM and PM groups. No significant differences in intragastric pH medians were observed among the three different genotype groups after a single dose or repeated doses. The ratio of pH medians between d 1 and d 8 ranged from 84% to 108%. The mean gastrin AUC values were also different among the three genotype groups, with a relative ratio of 1.0, 1.2 and 1.5 after a single dose and 1.0, 1.5 and 1.6 after repeated doses in the homEM, hetEM and PM groups, respectively. The gastrin AUC values among the three different genotype groups showed no significant difference either after a single dose or repeated doses. The subject who had lower intragastric acidity showed higher serum gastrin levels and concentrations of rabeprazole. CONCLUSION: In Chinese Han healthy people, the pharmacokinetics of rabeprazole are dependent on the CYP2C19 genotype status, but acid-inhibitory efficacy of rabeprazole and the gastrin level are not influenced significantly.