Single-cell transcriptome sequencing-based analysis: probing the mechanisms of glycoprotein NMB regulation of epithelial cells involved in silicosis.

Chronic exposure to silica can lead to silicosis, one of the most serious occupational lung diseases worldwide, for which there is a lack of effective therapeutic drugs and tools. Epithelial mesenchymal transition plays an important role in several diseases; however, data on the specific mechanisms in silicosis models are scarce. We elucidated the pathogenesis of pulmonary fibrosis via single-cell transcriptome sequencing and constructed an experimental silicosis mouse model to explore the specific molecular mechanisms affecting epithelial mesenchymal transition at the single-cell level. Notably, as silicosis progressed, glycoprotein non-metastatic melanoma protein B (GPNMB) exerted a sustained amplification effect on alveolar type II epithelial cells, inducing epithelial-to-mesenchymal transition by accelerating cell proliferation and migration and increasing mesenchymal markers, ultimately leading to persistent pulmonary pathological changes. GPNMB participates in the epithelial-mesenchymal transition in distant lung epithelial cells by releasing extracellular vesicles to accelerate silicosis. These vesicles are involved in abnormal changes in the composition of the extracellular matrix and collagen structure. Our results suggest that GPNMB is a potential target for fibrosis prevention.

Inulin activates FXR-FGF15 signaling and further increases bile acids excretion in non-alcoholic fatty liver disease mice.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder defined as the presence of intrahepatic lipid deposition and steatosis as well as chronic inflammation without excessive alcohol consumption. Our previous studies found that inulin could dramatically improve lipid metabolism disorders in NAFLD murine models. In recent years, mounting evidence has approved that there are disproportionately increased bile acids (BAs) in patients with NAFLD while the hepatic bile acids signaling is suppressed. Meanwhile the primary function of bile acids is to promote the excretion of cholesterol and therefore keep the cholesterol metabolism balance. Hence, we investigate whether inulin exerts beneficial effects on lipid metabolism disorders by modulating bile acids signaling in our present study. And we found that inulin treatment significantly reversed the abnormal accumulation of bile acids in high-fat-induced NAFLD mice. Furthermore, our data confirmed that inulin supplementation attenuates NAFLD via restoring the activity of FXR accompanied by increasing hepatic bile acids de novo synthesis and further enhancing bile acids excretion in mice.

Diagnosis and treatment of Helicobacter pylori infection by physicians in China: A nationwide cross-sectional study.

BACKGROUND: To investigate the current state of knowledge and practice of Helicobacter pylori (H. pylori) infection management in China. MATERIALS AND METHODS: This nationwide, multicenter, cross-sectional questionnaire survey was conducted between March and April 2021 with respect to the diagnosis and treatment of H. pylori infection in 31 provinces, encompassing over 1000 hospitals in mainland China. General physician information, diagnostic and detection status, eradication treatment, reexamination and follow-up after treatment, and basic knowledge of physicians were collected and compared with the Fifth Chinese National Consensus Report on Management of H. pylori infection and the 2016 Maastricht V/Florence guidelines. The subgroup analysis was also performed. RESULTS: Of the 6873 questionnaire respondents, 48.8% were males, and 51.2% were females. Approximately, 26.5% of respondents indicated that their hospitals had dedicated clinics for managing H. pylori infection. Moreover, 88.0% of respondents prescribed a bismuth-containing quadruple regimen as the initial eradication treatment, and 92.7% deemed the gastric acid suppression critical. Furthermore, 91.0% of respondents routinely recommended a reexamination 1-2 months after eradication therapy, and 95.1% advised patients to stop PPI treatment at least 2 weeks before reexamination. The detail of following (the choice of target population/methods; the choice/availability of drugs/regimens, indications for eradication, factors influencing eradication efficacy/improvement methods and factors influencing adherence, management options/factors influencing relapse; the timing and methods, awareness of reinfection rates/prevention measures, and the approach to continuing education, awareness of guidelines, and acceptance of current core concepts of management) was also described. Subgroup analysis further revealed that significant differences were existed in being gastroenterologist or not, different education level, professional title, years of working, and provincial administrative regions. CONCLUSIONS: Chinese physicians' skills and knowledge about the diagnosis and treatment of H. pylori infection could be improved. More works on education are needed in future.

Upregulation of TIGIT and PD-1 in Colorectal Cancer with Mismatch-repair Deficiency.

Background: The role of T cell Ig and ITIM domain (TIGIT) and programmed cell death-1 (PD-1) in colorectal cancer (CRC) with mismatch repair deficiency is unknown.Methods: This was a study of 60 CRC patients with mismatch repair deficiency and 30 healthy controls between June 2015 and October 2015.Results: The expression of Foxp3, PD-1, and TIGIT was higher in cancer tissues compared with adjacent mucosa (all P < .05). Patients with advanced TNM stage had a significantly higher expression of TIGIT (P = .025) and PD-1 (P = .020) than patients with early-stage CRC. The disease-free survival (DFS) of patients with high TIGIT (HR = 3.96, 95%CI: 1.34-11.69, P = .013) or PD-1 (HR = 214.8, 95%CI: 49.88-925.2, P < .001) expression were better. The overall survival (OS) of the patients with CRC and high expression of PD-1 was worse than those with low expression (HR = 4.01, 95%CI:1.26-12.69, P = .019).Conclusion: TIGIT and PD-1 are upregulated in CRC with mismatch repair deficiency and associated with TNM stage and DFS.

Use of aspirin in the prevention of colorectal cancer through TIGIT-CD155 pathway.

Colorectal cancer (CRC) is one of the most widespread malignant cancers, with a high incidence and mortality all over the world. Aspirin (ASA) otherwise known as acetylsalicylic acid, is a non-steroidal anti-inflammatory drug that has shown promising results in the prevention of chronic diseases, including several cancers. In previous studies, aspirin has been shown to reduce the incidence of CRC. Immune checkpoint blockade of T cell Ig and ITIM domain receptor (TIGIT) alone or combined with other immune checkpoint blockades moleculars has gained impressive results in the treatment of the melanoma and glioblastoma. Here, we found that TIGIT and Poliovirus receptor (PVR, CD155) are expressed in tumour cells; the TIGIT and CD155 protein expression in cancer tissue has been found to be significantly higher than that in the precancerous tissue. T cell Ig and ITIM domain receptor and CD226 were expressed in the lymphocytes near the tumour tissue and the adjacent tissues. Aspirin has been found to inhibit cancer cell viability and promote CRC cell apoptosis.Similarly, aspirin has also been found to increase pro-apoptotic protein Bax's expression. We found that the expression of TIGIT decreased with an increase in the concentration of aspirin and that the suppression of TIGIT can affect the effect of aspirin on cell proliferation. In this paper, we found that aspirin attenuates cancer cell proliferation and induces CRC cells apoptosis by down-regulating the expression of TIGIT, which provides new evidence for the application of aspirin in cancer treatment.

Aplastic anemia associated with Crohn's disease: a tertiary center retrospective study.

Aplastic anemia (AA) has been reported to be associated with inflammatory bowel disease (IBD), but mostly with ulcerative colitis (UC). Little is known about the associations between AA and Crohn's disease (CD). We aim to determine the portraits of patients with AA-CD. Among a total of 657 patients with CD registered in Xijing Hospital of Digestive Diseases IBD center from January 2008 to October 2018, the patients diagnosed with concurrent AA were reviewed. Clinical presentation, medical history, endoscopic features, response to treatment, and prognosis in this set of patients were collected. Six male patients confirmed as CD associated with AA were identified. The incidence rate was 0.91% for CD associated with AA in our series. Average age at diagnosis of CD and AA was 41.5 and 39.2 years old, respectively. Abdominal pain and hyperpyrexia were the most common symptoms. Endoscopic findings showed discontinued severe inflammation, and all these patients presented with deformed ileocecal valve. Conventional pharmacotherapy failed to achieve a favorable effect. Four of six patients died from CD progression and its complications. None of these patients received bone marrow transplantation treatment because of poverty. Concurrence of AA and CD is a relatively rare condition. Immunologic impairment may play an important pathogenic role and deserves further attention. Males are more susceptible to this condition. Patients with AA-CD are prone to a severe clinical course and poor prognosis. Conventional therapy achieves no potent effect, and allogeneic stem cell transplantation may be a potentially efficient therapy.

Inulin Ameliorates Alcoholic Liver Disease via Suppressing LPS-TLR4-Mψ Axis and Modulating Gut Microbiota in Mice.

BACKGROUND: Alcoholic liver disease (ALD) represents a chronic liver disorder caused by alcohol abuse. Numerous studies have demonstrated that gut microbiota dysbiosis plays a critical role in ALD pathogenesis. Application of prebiotic, probiotic, and dietary supplementation to the modulation of gut microbiota contributes to a novel approach to the management of ALD. Inulin, a natural prebiotic found in plants, can restore gut dysbiosis in ALD. However, the exact mechanism of dietary inulin in ALD remains largely unknown. METHODS: Sixty female C57BL/6J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON); alcohol-fed (AF) group (AF/CON); PF with inulin (INU) group (PF/INU); and AF with INU group (AF/INU). All mice were fed with isocaloric modified Lieber-DeCarli liquid diets with or without alcohol. RESULTS: After 6 weeks of feeding, mice were euthanized and associated indications were investigated. The results showed that chronic ethanol (EtOH) intake led to the loss of body weights, abnormal levels of transaminases, and inflammatory indicators (lipopolysaccharide [LPS], interleukin [IL]-6, IL-10, tumor necrosis factor-α, IL-17A), while inulin administration ameliorated these effects. To further understand the underlying mechanism, we investigated macrophages (Mψs) and gut microbiota in diverse groups. The number of Mψs was reduced after dietary inulin treatment in chronic EtOH exposure. Hepatic Toll-like receptor 4 (TLR4+ ) Mψs in AF/INU group were lower than AF/CON group. 16S rRNA sequencing and analysis of gut microbiota indicated the reduction of Allobaculum, Lactobacillus, and Lactococcus, as well as the increase of Parasutterella in AF group compared with PF control. Increased Allobaculum, Lactobacillus, and Lactococcus but reduced Parasutterella in AF/INU group were confirmed that dietary inulin rectified gut dysbiosis to attenuate ALD. CONCLUSIONS: Dietary inulin ameliorates ALD via suppressing LPS-TLR4-Mψ axis and modulating gut microbiota in mice, thus potentially provides theoretical foundation for inulin intervention in the prevention and treatment of ALD.

Pyridothiadiazine derivatives as aldose reductase inhibitors having antioxidant activity.

A series of aldose reductase (ALR2) inhibitors based on pyridothiadiazine were prepared and evaluated for their activities in ALR2 inhibition, DPPH scavenging, and MDA inhibition. Comparison studies were carried out between analogs having either hydroxyl or methoxy groups substituted on the N2-benzyl side chains of the compounds. Most of the hydroxy-substituted compounds were found to be more potent compared to their methoxy-substituted analogs with respect to DPPH inhibition (>93%) and MDA inhibition (>73%). However, ALR2 inhibitory activity was found to be affected by the electron-withdrawing substituent at the C7 position in addition to the effect of the N2-substituted benzyl group. These results provide an array of multifunctional ALR2 inhibitors possessing capacities both for ALR2 inhibition and as antioxidants.

Phenolic 4-hydroxy and 3,5-dihydroxy derivatives of 3-phenoxyquinoxalin-2(1H)-one as potent aldose reductase inhibitors with antioxidant activity.

A group of novel quinoxalinone derivatives (4a-h) were prepared and investigated for their inhibitory activity against ALR2 and antioxidant activity. Most of them were found to be potent aldose reductase inhibitors with IC50 values ranging from 0.019 to 0.982 µM. The most active compound 2-(3-(4-hydroxyphenoxy)-6-fluoro-2-oxoquinoxalin-1(2H)-yl)acetic acid (4c) also had an excellent selectivity. In addition, a number of compounds showed strong antioxidant activity and the phenolic 3,5-dihydroxyl compound 4f with 7-chloro in the quinoxalinone core was most active in scavenging the DPPH radical and suppressing lipid peroxidation.

Cooperative production of monophenolic chemicals and carbon adsorption materials from cascade pyrolysis of acid hydrolysis lignin.

A novel cascade pyrolysis upgrading process for acid hydrolysis lignin (AHL), consisting of pyrolysis, catalytic upgrading of pyrolysis vapors, and pyrolysis char, was developed to improve the yield of value-added products (monophenolic chemicals and carbon materials). Pyrolysis of AHL at 450 °C and subsequent catalytic upgrading of pyrolysis vapors over Ni/H-ZSM-5 boosted the concentration of monophenolic chemicals in pyrolysis liquids by 58%. The carbon material prepared from pyrolysis char using KOH as activating agent exhibited a large specific surface area of 2902.5 m2/g and a large total pore volume of 1.45 cm3/g, thus affording good adsorption capacity for methylene blue (824.87 mg/g) and iodine (2333.17 mg/g). Moreover, the cascade pyrolysis upgrading of AHL achieved a yield of 68.52% desired products, which was much higher than the reported results (single production of monophenols and pyrolysis char). In summary, this work provides a potential reference for efficient utilization of lignin in large-scale applications.

Butyrate alleviates alcoholic liver disease-associated inflammation through macrophage regulation and polarization via the HDAC1/miR-155 axis.

BACKGROUND: We recently found that butyrate could ameliorate inflammation of alcoholic liver disease (ALD) in mice. However, the exact mechanism remains incompletely comprehended. Here, we examined the role of butyrate on ALD-associated inflammation through macrophage (Mψ) regulation and polarization using in vivo and in vitro experiments. METHODS: For in vivo experiments, C57BL/6J mice were fed modified Lieber-DeCarli liquid diets supplemented with or without ethanol and sodium butyrate (NaB). After 6 weeks of treatment, mice were euthanized and associated indicators were analyzed. For in vitro experiments, lipopolysaccharide (LPS)-induced inflammatory murine RAW264.7 cells were treated with NaB or miR-155 inhibitor/mimic to verify the anti-inflammatory effect and underlying mechanism. RESULTS: The administration of NaB alleviated pathological damage and associated inflammation, including LPS, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß levels in ALD mice. NaB intervention restored the imbalance of macrophage polarization by inhibiting inducible nitric oxide synthase (iNOS) and elevating arginase-1 (Arg-1). Moreover, NaB reduced histone deacetylase-1 (HDAC1), nuclear factor kappa-B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and miR-155 expression in ALD mice, but also increased peroxisome proliferator-activated receptor-γ (PPAR-γ). Thus, MiR-155 was identified as a strong regulator of ALD. To further penetrate the role of miR-155, LPS-stimulated RAW264.7 cells co-cultured with NaB were treated with the specific inhibitor or mimic. Intriguingly, miR-155 was capable of negatively regulated inflammation with NaB intervention by targeting SOCS1, SHIP1, and IRAK-M genes. CONCLUSION: Butyrate suppresses the inflammation in mice with ALD by regulating macrophage polarization via the HDAC1/miR-155 axis, which may potentially contribute to the novel therapeutic treatment for the disease.

Association of survival with adjuvant chemotherapy in patients with stage IB gastric cancer: a multicentre, observational, cohort study.

Background: Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. Methods: We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. Findings: Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52-1.00; DFS: HR, 0.91; 95% CI, 0.64-1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08-0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17-0.62; P < 0.001 for multiplicative interaction), or positive lymph nodes (HR, 0.17; 95% CI, 0.07-0.38; P < 0.001 for multiplicative interaction). The survival prediction models mainly based on variables associated with chemotherapy benefits in the subgroup analysis demonstrated good calibration and discrimination, with relatively high C-indexes. The C-indexes for OS were 0.74 for patients treated with adjuvant chemotherapy and 0.70 for patients treated with postoperative observation. Two nomograms were built from the models that can calculate individualized estimates of expected net survival gain attributable to adjuvant chemotherapy. Interpretation: In this cohort study, pathologic stage IB alone was not associated with survival benefits from adjuvant chemotherapy compared with postoperative observation in patients with early-stage GC. High-risk clinicopathologic features should be considered simultaneously when evaluating patients with stage IB GC for adjuvant chemotherapy. Funding: National Natural Science Foundation of China; the National Key R&D Program of China.

Detection of minimal hepatic encephalopathy in patients with cirrhosis based on the Stroop-CN model (NCRCID-CHESS 2106): a prospective multicenter study.

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Fractionation of poplar wood with different acid hydrotropes: Lignin dissolution behavior and mechanism evaluation.

Acid hydrotropes was considered a green medium for efficient wood fractionation at mild conditions. This study reported a comparative study on the dissolution of lignin in different acid hydrotropes, including p-toluenesulfonic acid (p-TsOH), 4-hydroxybenzenesulfonic acid (4-HSA), 5-sulfosalicylic acid (5-SSA), and maleic acid (MA). Under identical treatment conditions (80 °C, 60 min, and 70 % acid concentration), the removal of wood lignin varied significantly among four acid hydrotropes, 4-HSA exhibited the highest removal rate at 88.0 %, followed by p-TsOH at 81.2 %, 5-SSA at 51.1 %, and MA at 26.2 %. The molecular mechanism of the lignin dissolution was analyzed by quantum chemistry (QC) calculation and molecular dynamics (MD) simulation. The higher absorb free energy (E(absorb)) of the 4-HSA and veratrylglycerol-ß-guaiacyl ether (VG) complex (E(absorb) = 17.97 kcal/mol), and the p-TsOH and VG complex (E(absorb) = 17.16 kcal/mol) contributed to a higher efficiency of lignin dissolution. Under the same level of lignin removal (~ 60 %), the four acid hydrotropes showed variations in the ß-O-4 content of the extracted lignin: 4-HSA (3.1 %) < 5-SSA (10.4 %) < p-TsOH (15.9 %) < MA (63.7 %). The acidity and critical aggregation concentrations of acid hydrotropes were found to influence the content of ß-O-4 bonds in the extracted lignin.

Targeting the mitochondrial calcium uniporter inhibits cancer progression and alleviates cisplatin resistance in esophageal squamous cell carcinoma.

Cisplatin is the standard chemotherapeutic drug used for the treatment of esophageal squamous cell carcinoma (ESCC). Acquired cisplatin resistance is the primary obstacle to prolonging patient survival time. Here, the therapeutic effects of mitochondrial calcium uniporter (MCU) inhibition on tumor growth and cisplatin resistance in ESCC were assessed. MCU was stably overexpressed or knocked down in three ESCC cell lines and three cisplatin­resistant ESCC cell lines. Then, proliferation, migration, and mitochondrial membrane potential (MMP) were measured by colony formation, wound healing, Transwell, and JC­1 staining assays. MCU, MICU2, MICU1, and PD­L1 levels were detected through western blotting and immunofluorescence. ESCC and cisplatin­resistant ESCC xenograft mouse models were established. After MCU knockdown, tumor volume was measured. The expression levels of proliferation markers (CyclinD1 and Ki­67), MICU1/2, PD­L1, epithelial-mesenchymal transition (EMT) markers (vimentin, ß­catenin, and E­cadherin), and the angiogenesis marker CD34 were detected through western blotting, immunohistochemistry, or immunofluorescence. The results showed that MCU overexpression significantly promoted proliferation, migration, and MMP in ESCC cells and cisplatin­resistant ESCC cells. However, proliferation, migration, and MMP were suppressed following MCU knockdown. In ESCC cells, MCU overexpression markedly increased MICU2, MICU1, and PD­L1 levels, and the opposite results were observed when MCU was stably knocked down. Similarly, MCU inhibition decreased MICU2, MICU1, and PD­L1 expression in cisplatin­resistant ESCC cells. Moreover, MCU knockdown substantially decreased tumor growth, EMT, and angiogenesis in ESCC and cisplatin­resistant ESCC xenograft mice. Collectively, targeting MCU may inhibit cancer progression and alleviate cisplatin resistance in ESCC.

Endoscopic Ruler for varix size measurement: A multicenter pilot study.

BACKGROUND: We invented Endoscopic Ruler, a new endoscopic device to measure the size of varices in patients with cirrhosis and portal hypertension. AIM: To assess the feasibility and safety of Endoscopic Ruler, and evaluate the agreement on identifying large oesophageal varices (OV) between Endoscopic Ruler and the endoscopists, as well as the interobserver agreement on diagnosing large OV using Endoscopic Ruler. METHODS: We prospectively and consecutively enrolled patients with cirrhosis from 11 hospitals, all of whom got esophagogastroduodenoscopy (EGD) with Endoscopic Ruler. The primary study outcome was a successful measurement of the size of varices using Endoscopic Ruler. The secondary outcomes included adverse events, operation time, the agreement of identifying large OV between the objective measurement of Endoscopic Ruler and the empirical reading of endoscopists, together with the interobserver agreement on diagnosing large OV by Endoscopic Ruler. RESULTS: From November 2020 to April 2022, a total of 120 eligible patients with cirrhosis were recruited and all of them underwent EGD examinations with Endoscopic Ruler successfully without any adverse event. The median operation time of Endoscopic Ruler was 3.00 min [interquartile range (IQR): 3.00 min]. The kappa value between Endoscopic Ruler and the endoscopists while detecting large OV was 0.52, demonstrating a moderate agreement. The kappa value for diagnosing large OV using Endoscopic Ruler among the six independent observers was 0.77, demonstrating a substantial agreement. CONCLUSION: The data demonstrates that Endoscopic Ruler is feasible and safe for measuring the size of varices in patients with cirrhosis and portal hypertension. Endoscopic Ruler is potential to promote the clinical practice of the two-grade classification system of OV.

Progression of Gastrointestinal Injury During Antiplatelet Therapy After Percutaneous Coronary Intervention: A Secondary Analysis of the OPT-PEACE Randomized Clinical Trial.

Importance: Gastrointestinal injury progression induced by antiplatelet therapy in patients after percutaneous coronary intervention (PCI) has not been well studied. Objective: To assess the association of aspirin, clopidogrel, and their combination with gastrointestinal injury progression among patients without high bleeding risk after PCI. Design, Setting, and Participants: This secondary analysis assessed data from the Optimal Antiplatelet Therapy for Prevention of Gastrointestinal Injury Evaluated by ANKON Magnetically Controlled Capsule Endoscopy (OPT-PEACE) double-masked, placebo-controlled, multicenter randomized clinical trial. The OPT-PEACE trial was conducted at 28 centers in China, and recruitment took place from July 13, 2017, to July 13, 2019. The trial included patients with stable coronary artery disease or acute coronary syndromes without ST-segment elevation after PCI. Statistical analysis was conducted from September 13, 2022, to January 23, 2023. Interventions: Patients underwent magnetically controlled capsule endoscopy (MCE) at baseline and after 6 months of dual antiplatelet therapy (DAPT) with aspirin (100 mg/d) plus clopidogrel (75 mg/d). Those with no evidence of gastrointestinal ulcers or bleeding (ie, the intention-to-treat [ITT] cohort) were randomized (1:1:1) to aspirin (100 mg/d) plus matching placebo (aspirin alone), clopidogrel (75 mg/d) plus matching placebo (clopidogrel alone), or DAPT for an additional 6 months. A third MCE was performed 12 months after PCI. Main Outcomes and Measures: The primary outcome was the rate of gastric injury progression as assessed with the results of the 3 MCEs (at baseline, 6 months, and 12 months) in the modified intention-to-treat (mITT) population. The key secondary outcome was the rate of small-intestinal injury progression. Gastric or small-intestinal injury progression was defined as a quantitative increase in erosions or ulcers between the second and third MCEs (at 6 and 12 months, respectively). Results: This study included the 394 patients in the mITT cohort. Their mean (SD) age was 56.9 (8.7) years, and most were men (296 [75.1%]). A total of 132 patients were randomized to aspirin alone, 132 to clopidogrel alone, and 130 to DAPT. Gastric injury progression occurred in 49 aspirin users (37.1%), 64 clopidogrel users (48.5%), and 69 DAPT users (53.1%) (P = .02), reflecting a lower rate of gastric injury progression among aspirin users vs DAPT users (risk ratio [RR], 0.70 [95% CI, 0.49-0.99]; P = .009). No significant difference was observed between clopidogrel alone and DAPT (48.5% vs 53.1%; P = .46) or between aspirin alone and clopidogrel alone (37.1% vs 48.5%; P = .06). A total of 51 aspirin users (38.6%), 65 clopidogrel users (49.2%), and 71 DAPT users (54.6%) (P = .03) developed progressive small-intestinal injury, reflecting a lower rate of small-intestinal injury among aspirin users vs DAPT users (RR, 0.71 [95% CI, 0.50-0.99]; P = .01). No difference was observed between patients treated with clopidogrel vs DAPT (49.2% vs 54.6%; P = .38) or with aspirin vs clopidogrel (38.6% vs 49.2%; P = .08). Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, ongoing use of aspirin, clopidogrel, or their combination between 6 and 12 months after PCI was associated with progressive gastric and small-intestinal injury in a substantial proportion of patients, more so with DAPT than with monotherapy. Clopidogrel was at least as likely as aspirin to induce gastrointestinal injury progression. Future research is warranted to determine what impact the findings from MCEs would have on decision-making of antiplatelet therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03198741.

Serum autofluorescence, a potential serum marker for the diagnosis of liver fibrosis in rats.

Fluctuations in serum autofluorescence (AF) intensity have recently been widely used as markers of certain diseases such as cancer. To determine the diagnostic value of serum AF intensity for liver fibrosis in rats, we induced liver fibrosis by subcutaneous injection of carbon tetrachloride into rats. The rat serum AF intensities were detected at the excitation wavelength of 337 nm and the emission wavelength of 512 nm. The degree of liver fibrosis was evaluated by Van Gieson's staining. The relationship between serum AF intensity and the degree of liver fibrosis was analyzed by Spearman and Pearson Correlation. The diagnostic sensitivity and specificity of the serum AF was determined by analyzing the receiver operating characteristic (ROC) curves. Our results show that the serum AF intensity in the rat liver fibrosis model increased when compared with control rats eight weeks and twelve weeks post induction of liver fibrosis. However, there was no significant difference in serum AF intensity between fibrotic and control rats at four week post induction. Furthermore, serum AF intensity correlated positively with the severity of the degree of hepatic fibrosis. ROC analysis further suggested that serum AF intensity is a valid marker for staging fibrosis. Therefore, it may potentially be developed as a novel diagnostic tool for hepatic fibrosis.

Electrocardiographic, cardiac enzymes, and magnesium in patients with severe acute pancreatitis.

Severe acute pancreatitis (SAP) can lead to multiple-organ dysfunction syndrome (MODS). Electrocardiographic (ECG), cardiac enzyme, and serum magnesium abnormalities occur after SAP. Electrocardiographic and cardiac enzyme abnormalities are described as variables in SAP patients, which contribute to the effects of MODS. Hypomagnesium is also closely associated with ECG abnormalities; therefore, hypomagnesium was also considered to be a variable in this study. A consecutive series of 54 patients admitted within 72 hours after SAP occurred was studied. A standard 12-lead ECG, cardiac enzyme, and serum magnesium measurement were routinely performed at admission. Linear correlation was used to analyze the relationship between hypomagnesemia and sinus tachycardia. The nonparametic binomial test was used to analyze dichotomized dependent variables (premature beat, atrial fibrillation, ST-segment depression, abnormal T wave, and long QT interval). Hypomagnesemia was present in 15 patients (28%), who subsequently had sinus tachycardia. There was a significant negative relationship (-1 < r <0) between hypomagnesemia and sinus tachycardia (p < .05). There were 14 (17%) premature beat, 7 (8%) atrial fibrillation, 21 (25%) ST-segment depression, 18 (21%) abnormal T wave, and 17 (31%) long QT-interval events in 54 SAP patients. Hypomagnesemia is a reason for ECG abnormalities. Electrocardiographic and cardiac enzyme abnormalities are considered to be transitory variables that are present in patients with SAP.

Explore and Analyze the Composition and Characteristics of Intestinal Microbiota between Gastric Cancer Patients and Healthy People.

Gastric cancer is one of the most common malignant tumors in the world. As the intestine is downstream of the digestive tract, the occurrence of gastric cancer may have a certain significant impact on it. Therefore, it is particularly important to find out the intestinal bacteria closely related to gastric cancer, to identify the specific flora related to gastric cancer, and to maintain the stability of the core structure of intestinal microecology in patients with gastric cancer. Based on this, the fecal samples of gastric cancer patients and healthy people were collected, and the diversity and composition of intestinal flora in patients with gastric cancer were analyzed by 16S rRNA sequencing technology. We found that there was no significant difference in the diversity and abundance of intestinal flora between gastric cancer patients and healthy people. The relative abundance of Faecalibacterium, Bifidobacterium, and Subdoligranulum in the intestinal tract of patients with gastric cancer was significantly lower than that in healthy people, while the relative abundance of Enterococcus, Streptococcus, and Bacteroides was increased. This study found that there were six kinds of intestinal microflora closely related to the occurrence of gastric cancer, which provided a theoretical basis for further exploring the pathogenesis of gastric cancer.