Phytochemicals targeting ferroptosis in cardiovascular diseases: Recent advances and therapeutic perspectives.

Ferroptosis is a form of iron-dependent regulatory cell death that is related to the pathogenesis and progression of various cardiovascular diseases, such as arrhythmia, diabetic cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, and heart failure. This makes it a promising therapeutic target for cardiovascular diseases. It is interesting that a significant number of cardiovascular disease treatment drugs derived from phytochemicals have been shown to target ferroptosis, thus producing cardioprotective effects. This study offers a concise overview of the initiation and control mechanisms of ferroptosis. It discusses the core regulatory factors of ferroptosis as potential new therapeutic targets for various cardiovascular diseases, elucidating how ferroptosis influences the progression of cardiovascular diseases. In addition, this review systematically summarizes the regulatory effects of phytochemicals on ferroptosis, emphasizing their potential mechanisms and clinical applications in treating cardiovascular diseases. This study provides a reference for further elucidating the molecular mechanisms of phytochemicals in treating cardiovascular diseases. This may accelerate their application in the treatment of cardiovascular diseases and is worth further research in this field.

Magnoflorine alleviates dextran sulfate sodium-induced ulcerative colitis via inhibiting JAK2/STAT3 signaling pathway.

Magnoflorine (Mag), a natural alkaloid component originating from the Ranunculaceae Juss. Family, has a various of pharmacological activities. This study aimed to investigate the therapeutic effects and potential mechanism of Mag on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) based on comprehensive approaches. Therapeutic effects of Mag on 3% DSS-induced UC mice were analyzed. UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway of Mag on DSS-induced UC. Furthermore, the predicted mRNA and protein levels of JAK2/STAT3 signaling pathway in colon tissue were verified and assessed by qRT-PCR and Western Blotting, respectively. Therapeutic effects of Mag on UC mice were presented in down-regulation serum biochemical indices, alleviating histological damage of colon tissue. Serum untargeted metabolomics analysis showed that the potential mechanism of Mag on UC is mainly associated with the regulation of six biomarkers and 11 pathways, which may be responsible for the therapeutic efficacy of UC. The "component-metabolites-targets" interactive network indicated that Mag exerts its anti-UC effect by regulating PTGS1 and PTGS2, thereby regulating arachidonic acid. Moreover, the results of qRT-PCR showed that Mag could substantially decrease the relative mRNA expression level of Hub genes. In addition, it was found that Mag could inhibit the relative mRNA and protein expression of JAK2/STAT3 signaling pathway. The present results highlighted the role of Mag ameliorated colon injury in DSS-induced UC mice by inhibiting the JAK2/STAT3 signaling pathway. These results suggest that Mag may be an effective agent for the treatment of UC.

General practitioner residents' experiences and perceptions of outpatient training in primary care settings in China: a qualitative study.

OBJECTIVES: The implementation of outpatient training in primary care settings is an essential part of residency training for general practitioner (GP) residents. However, limited research exists on their experiences and perceptions of this training. This study aimed to explore the experiences and perceptions of GP residents regarding outpatient training in primary care settings in China and provide insights and recommendations to enhance training quality. DESIGN: A qualitative descriptive study employing in-depth interviews. SETTING: Two community healthcare centres (CHCs) that implement outpatient training programmes for GP residents in Zhejiang Province, China. PARTICIPANTS: In total, 20 GP residents affiliated with 14 CHCs and two hospitals across Zhejiang Province and Guizhou Province who had completed outpatient training in either CHC for over 1 month. RESULTS: Of the 20 participants in this study, 11 (55%) were women, and the mean age was 28 years. GP residents completed the process of consultation, physical examination and therapy independently; subsequently, the community preceptors provided feedback based on their clinical performance and modelled their clinical skills. The benefits perceived by GP residents included improved clinical skills and confidence in practice, and they learned approaches to maintaining good relationships with patients. They preferred dealing with complex cases, discussions with peers and the indirect supervision of community preceptors in the training session. Residents recommended that measures be taken to improve the training quality regarding patient selection and recruitment, clinical skills in the training session, and assessment of clinical performance. CONCLUSIONS: The outpatient training in primary care settings provides constructive opportunities for GP residents to improve their professional competencies. Although the current training sessions and the abilities of community preceptors largely satisfy the needs of GP residents, further research is needed to evaluate the effectiveness of training and explore approaches to improve its quality.

Preclinical evidence evaluation of Xiaoyao san in treating chronic unpredictable mild stress model of depression based on meta-analysis.

BACKGROUND: In view of the current challenges in the treatment of depression, in order to improve the efficacy and avoid adverse reactions, people pay attention to the treatment of traditional Chinese medicine. Xiaoyao san is a classic prescription commonly used in the treatment of depression, with the role of harmonizing liver and spleen, and shows great potential in the treatment of depression. PURPOSE: The purpose of this study is to comprehensively evaluate the efficacy and specific mechanism of Xiaoyao san in the treatment of chronic unpredictable mild stress (CUMS) model of depression through systematic evaluation and meta-analysis, so as to provide strong preclinical evidence for the clinical treatment of Xiaoyao san and provide a new strategy for the development of antidepressants. METHODS: The preclinical literature published before March 2023 was searched in Cochrane Library, PubMed, Web of Science, EMbase, CNKI, VMIS, Wan-Fang, and CBM and other database systems. Stata15 was used for overall effect analysis and subgroup analysis, and summarized the potential mechanism of action. RESULTS: A total of 25 studies were included, involving 569 animals. The average score of methodological quality was 7.48/10. Meta-analysis shows that Xiaoyao san can effectively improve food intake and body weight, restore sucrose consumption, reduce the immobility time in forced swimming, and increase the total exercise distance, grid crossing and upright times in the open field experiment. Its therapeutic effect is closely related to improving the abnormal activation of Hypothalamic-pituitary-adrenal axis and inhibiting the expression of glutamate. CONCLUSION: To sum up, in CUMS animal model, Xiaoyao san can significantly improve the symptoms of depression, restore the lost pleasure behavior and curiosity about the new environment, relieve tension and anxiety, and improve the occurrence of depression in many ways, which may be a new treatment strategy for CUMS model of depression.

Rab31 promotes metastasis and cisplatin resistance in stomach adenocarcinoma through Twist1-mediated EMT.

Stomach adenocarcinoma (STAD) is one of the leading causes of cancer-related death globally. Metastasis and drug resistance are two major causes of failures in current chemotherapy. Here, we found that the expression of Ras-related protein 31 (Rab31) is upregulated in human STAD tissues and high expression of Rab31 is closely associated with poor survival time. Furthermore, we revealed that Rab31 promotes cisplatin resistance and metastasis in human STAD cells. Reduced Rab31 expression induces tumor cell apoptosis and increases cisplatin sensitivity in STAD cells; Rab31 overexpression yielded the opposite result. Rab31 silencing prevented STAD cell migration, whereas the overexpression of Rab31 increased the metastatic potential. Further work showed that Rab31 mediates cisplatin resistance and metastasis via epithelial-mesenchymal transition (EMT) pathway. In addition, we found that both Rab31 overexpression and cisplatin treatment results in increased Twist1 expression. Depletion of Twist1 enhances sensitivity to cisplatin in STAD cells, which cannot be fully reversed by Rab31 overexpression. Rab31 could activate Twist1 by activating Stat3 and inhibiting Mucin 1 (MUC-1). The present study also demonstrates that Rab31 knockdown inhibited tumor growth in mice STAD models. These findings indicate that Rab31 is a novel and promising biomarker and potential therapeutic target for diagnosis, treatment and prognosis prediction in STAD patients. Our data not only identifies a novel Rab31/Stat3/MUC-1/Twist1/EMT pathway in STAD metastasis and drug resistance, but it also provides direction for the exploration of novel strategies to predict and treat STAD in the future.

Helicobacter pylori infection eradication for nonalcoholic fatty liver disease: a randomized controlled trial.

Previous studies have suggested that Helicobacter pylori (H. pylori) infection is associated with nonalcoholic fatty liver disease (NAFLD). The purpose of the present study was to investigate the effect of H. pylori eradication treatment on NAFLD patients. Two hundred NAFLD patients who tested positive for H. pylori infection were randomized into the H. pylori eradication treatment group or the control group. Metabolic and inflammatory parameters and FibroScan were measured in all subjects at baseline and 1 year after treatment. At 1 year after treatment, the decrease in metabolic indicators, such as fasting blood glucose, glycosylated haemoglobin, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, body mass index and controlled attenuation parameter values, were more obvious in the treatment group. Moreover, the inflammatory indicators white blood count and high-sensitivity C-reactive protein (hs-CRP) and the inflammatory factors interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) were also significantly decreased. H. pylori eradication can further reduce the metabolic indices of NAFLD and the degree of liver steatosis. H. pylori infection may participate in the occurrence and development of NAFLD through its influence on inflammatory factors. Thus, checking for the presence of H. pylori infection in patients at risk of NAFLD may be beneficial.

Machine learning: A non-invasive prediction method for gastric cancer based on a survey of lifestyle behaviors.

Gastric cancer remains an enormous threat to human health. It is extremely significant to make a clear diagnosis and timely treatment of gastrointestinal tumors. The traditional diagnosis method (endoscope, surgery, and pathological tissue extraction) of gastric cancer is usually invasive, expensive, and time-consuming. The machine learning method is fast and low-cost, which breaks through the limitations of the traditional methods as we can apply the machine learning method to diagnose gastric cancer. This work aims to construct a cheap, non-invasive, rapid, and high-precision gastric cancer diagnostic model using personal behavioral lifestyles and non-invasive characteristics. A retrospective study was implemented on 3,630 participants. The developed models (extreme gradient boosting, decision tree, random forest, and logistic regression) were evaluated by cross-validation and the generalization ability in our test set. We found that the model developed using fingerprints based on the extreme gradient boosting (XGBoost) algorithm produced better results compared with the other models. The overall accuracy of which test set was 85.7%, AUC was 89.6%, sensitivity 78.7%, specificity 76.9%, and positive predictive values 73.8%, verifying that the proposed model has significant medical value and good application prospects.

Hepatic epithelioid hemangioendothelioma after thirteen years' follow-up: A case report and review of literature.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (EHE) is a rare vascular endothelial cell tumor of the liver, consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix. Immunohistochemistry is usually positive for vascular markers, such as factor VIII-related antigen, CD31, and CD34. Hepatic EHE can have a varied clinical course; treatment includes liver transplantation, liver resection, chemotherapy, and radiation therapy. CASE SUMMARY: A 46-year-old woman with abdominal discomfort and elevated serum carcinoembryonic antigen was found to have multiple low-density lesions in the liver and lung on computed tomography (CT) evaluation. An ultrasound-guided fine needle aspiration biopsy revealed a fibrous stroma with dendritic cells, containing intracellular vacuoles. Immunohistochemical staining found that the tumor cells were positive for CD34, CD31, and factor VIII-related antigen. The patient received four courses of combined chemotherapy and was followed-up for 13 years, at which time the patient was in stable condition without disease progression and a confined neoplasm, as evidenced by CT scans. CONCLUSION: The histology and immunohistochemical characteristics of hepatic EHE are well described. Chemotherapy may be effective in patients with extrahepatic lesions.

Effect of Amniotic Membrane/Collagen-Based Scaffolds on the Chondrogenic Differentiation of Adipose-Derived Stem Cells and Cartilage Repair.

Objectives: Repairing articular cartilage damage is challenging. Clinically, tissue engineering technology is used to induce stem cell differentiation and proliferation on biological scaffolds to repair defective joints. However, no ideal biological scaffolds have been identified. This study investigated the effects of amniotic membrane/collagen scaffolds on the differentiation of adipose-derived stem cells (ADSCs) and articular cartilage repair. Methods: Adipose tissue of New Zealand rabbits was excised, and ADSCs were isolated and induced for differentiation. An articular cartilage defect model was constructed to identify the effect of amniotic membrane/collagen scaffolds on cartilage repair. Cartilage formation was analyzed by imaging and toluene blue staining. Knee joint recovery in rabbits was examined using hematoxylin and eosin, toluidine, safranine, and immunohistochemistry at 12 weeks post-operation. Gene expression was examined using ELISA, RT-PCR, Western blotting, and immunofluorescence. Results: The adipose tissue was effectively differentiated into ADSCs, which further differentiated into chondrogenic, osteogenic, and lipogenic lineages after 3 weeks' culture in vitro. Compared with platelet-rich plasmon (PRP) scaffolds, the amniotic membrane scaffolds better promoted the growth and differentiation of ADSCs. Additionally, scaffolds containing the PRP and amniotic membrane efficiently enhanced the osteogenic differentiation of ADSCs. The levels of COL1A1, COL2A1, COL10A1, SOX9, and ACAN in ADSCs + amniotic membrane + PRP group were significantly higher than the other groups both in vitro and in vivo. The Wakitani scores of the ADSC + amniotic membrane + PRP group were lower than that in ADSC + PRP (4.4 ± 0.44**), ADSC + amniotic membrane (2.63 ± 0.38**), and control groups (6.733 ± 0.21) at week 12 post-operation. Osteogenesis in rabbits of the ADSC + amniotic membrane + PRP group was significantly upregulated when compared with other groups. Amniotic membranes significantly promoted the expression of cartilage regeneration-related factors (SOX6, SOX9, RUNX2, NKX3-2, MEF2C, and GATA4). The ADSC + PRP + amniotic membrane group exhibited the highest levels of TGF-ß, PDGF, and FGF while exhibiting the lowest level of IL-1ß, IL6, and TNF-α in articular cavity. Conclusion: Amniotic membrane/collagen combination-based scaffolds promoted the proliferation and cartilage differentiation of ADSCs, and may provide a new treatment paradigm for patients with cartilage injury.

Association of serum pepsinogen with degree of gastric mucosal atrophy in an asymptomatic population.

BACKGROUND: Atrophic gastritis is a precancerous lesion of the stomach. It has been reported that pepsinogen (PG) can reflect the morphology and function of the gastric mucosa, and it is therefore used as a marker for the early diagnosis of atrophic gastritis. AIM: To evaluate the diagnostic value of serum PG for degree of gastric mucosal atrophy in asymptomatic Chinese upon physical examination. METHODS: Medical data were collected from subjects who underwent transnasal gastroscopy between October 2016 and October 2018. For each study subject, serum PG levels and presence of Helicobacter pylori (H. pylori) infection were investigated. Pathology was evaluated using the Operative Link for Gastritis Assessment (OLGA) classification and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) systems. All statistical analyses were carried out using SPSS statistical software. RESULTS: A total of 2256 subjects were enrolled and 1922 cases were finally included in the study. Based on the OLGA grading system, the levels of PGI were slightly decreased, while those of PGII were slightly increased. The PGI/PGII ratio (PGR) was reduced with increasing atrophy. The association between PG and OLGA grading was higher compared with that between PG and the OLGIM grading system. Compared with the OLGA-0 group, a statistically significant difference was observed in the mean age of OLGA-I, III, and IV groups (P < 0.05). In the H. pylori-positive subjects, the PGR levels were notably lower in the OLGA-I, II, and III groups compared with the OLGA-0 group (P < 0.05). H. pylori-positive subjects exhibited significantly higher PGI and PGII serum levels and a significantly lower PGR compared with H. pylori-negative patients in different OLGA groups (P < 0.05). CONCLUSION: Serum PG levels may represent a non-invasive screening marker for gastric mucosal atrophy in asymptomatic subjects.

Metabolomic Study of Zuojin Pill in Relieving 1-Methyl-3-nitro-1-nitrosoguanidine-Induced Chronic Atrophic Gastritis.

The classic prescription Zuojin Pill (ZJP) shows a good therapeutic effect on chronic atrophic gastritis (CAG); it is of great significance to clarify its specific mechanism. Therefore, we explore the mechanism of ZJP on MNNG-induced CAG by integrating approaches. First of all, through the pathological changes of gastric tissue and the expression level of PGI and PGI/II in serum, the expression of inflammation-related factors was determined by RT-PCR to determine the efficacy. Then, UPLC-Q-TOF/MS was used for plasma and urine metabolomic analysis to screen the specific potential biomarkers and metabolic pathway of ZJP in ameliorating CAG and to explore its possible mechanism. ZJP significantly ameliorate the pathological injury of gastric tissue, increase levels of PGI and PGI/II, and reduce the expression level of proinflammatory factors. Through metabolomic analysis, 9 potential metabolic differences were identified and 6 related metabolic pathways were enriched. These findings indicate for the first time the potential mechanism of ZJP in improving CAG induced by MNNG and are of great significance to the clinical development and application of ZJP-related drugs.

Glycosylated Hemoglobin as an Age-Specific Predictor and Risk Marker of Colorectal Adenomas in Non-Diabetic Adults.

Background: Diabetes is a risk factor for colorectal neoplasms. The association between the level of glycosylated hemoglobin (HbA1c) and the risk of colorectal adenomas (CRAs) in non-diabetic adults needs to be investigated. Methods: A cross-sectional study was performed on non-diabetic adults with normal HbA1c level who underwent colonoscopy between January 2010 and December 2016 during health check-ups in our hospital in China. The association between HbA1c level and CRAs was assessed by multiple logistic regression models stratified by age group (<40, ≥40 and <50, and ≥50 years old). The age group-specified thresholds for HbA1c on elevated risk of CRAs were estimated using the piecewise logistic regression. Results: Among the 2,764 subjects, 445 (16.1%) had CRA. The prevalence of CRA varied across the three age groups. A higher HbA1c level was found to be significantly associated with increased CRA risk in the 40-50 years group (odds ratio [OR]=1.70, 95% confidence interval [CI] 1.04-2.78, p=0.035) after adjusting for other related factors, while this association was borderline significant among the 50 years and older group (OR=1.57, 95% CI 0.97-2.54, p=0.067). Based on the piecewise logistic regression analysis results, the thresholds for HbA1c on elevated risk of CRA were 5.44% for the 40-50 years group and 4.81% for the 50 years and older group, respectively. Conclusions: Higher levels of HbA1c, even within the normal range, were associated with elevated CRA risk among non-diabetic adults. The threshold effects of HbA1c on the risk of CRA varied across different age groups, and early screening colonoscopy might be needed for individuals in their 40s and with HbA1c levels ≥5.44%.

Clinical Efficacy and Safety of Shashen Maidong Decoction in the Treatment of Pediatric Mycoplasma Pneumonia: A Systematic Review and Meta-Analysis.

Objective: This study was intended to provide data to support the effect of Shashen Maidong Decoction in improving mycoplasma pneumonia in pediatric patients through systematic evaluation. Methods: PubMed, the Web of Science, EMbase, CNKI, CQVIP, Wan-Fang, and CBM databases were comprehensively searched from established in June 2021. Randomized controlled trials of TRQI were selected by screening the literature and extracting information. The Cochrane RCT Evaluation Manual was used to evaluate the methodological quality of all included studies, and Meta-analysis was performed using Stata 14.0 and Review Manager 5.4 software. Results: A total of 1,127 patients from 12 clinical studies met the inclusion criteria. Meta-analysis results showed that the treatment group of Shashen Maidong Decoction was able to significantly increase the overall efficiency level and significantly reduce the incidence of adverse reactions, time for disappearance of cough, time for relief of cough, time for defervescence, time for disappearance of lung rales, time for return to normal of chest X-ray, T lymphocyte subpopulation (CD3+) and tumor necrosis factor-α (TNF-α) and other index levels (p < 0.05). Conclusion: Shashen Maidong Decoction has a significant improvement in the levels of relevant indexes in pediatric mycoplasma pneumonia, which provides a basis for the safety and efficacy of pediatric mycoplasma pneumonia. However, due to the small sample size included in the study, the study quality was not high, and more randomized controlled trials of high quality are required for further validation.

Paeoniflorin Protects against ANIT-Induced Cholestatic Liver Injury in Rats via the Activation of SIRT1-FXR Signaling Pathway.

Paeoniflorin (PF), a water-soluble monoterpene glycoside, is initially isolated from the dried roots of Paeonia lactiflora Pall., which has effects on ameliorating cholestasis in our previous study. However, comprehensive approaches for understanding the protective effects and mechanisms underlying cholestatic liver injury from the regulating of bile acid metabolism have not been sufficiently elucidated. This study was aimed to explore the effectiveness as well as potential mechanism of PF on alpha-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury. Rats with cholestasis induced by ANIT was used to evaluate the protective effects and mechanism of PF by regulating SIRT1/FXR and NF-κB/NLRP3 signaling pathway. Rats were intragastrically administrated with ANIT to establish cholestatic liver injury model. Serum levels of ALT, AST, TBA, TBIL, ALP, γ-GT and ALB in rats were detected. The histopathology of the liver of rats was analyzed in vivo. The relative mRNA expression and protein expression levels of IL-18, IL-1ß, TNF-α, HO-1, Nrf2, TLR4, NLRP3, Caspase-1, ASC, NF-κB, FXR, and SIRT1 in liver of rats were investigated. The results showed that the serum indexes and the liver histopathology were significantly improved by PF. The overexpression of IL-18, IL-1ß, TNF-α, NLRP3, ASC, and Caspase-1 in liver was markedly reduced by PF. Furthermore, PF dramatically increased the mRNA and protein expressions of SIRT1, FXR, HO-1, and Nrf2, but decreased NF-κB p65 and TLR4 levels in liver of rats. Taken together, the protective effects of PF on cholestatic liver injury were possibly related to the activation of the SIRT1/FXR and inhibition of NF-κB/NLRP3 inflammasome signaling pathway. These findings might provide a potential protection for cholestatic liver injury.

Diagnostic Value of Serum Pepsinogen Levels for Screening Gastric Cancer and Atrophic Gastritis in Asymptomatic Individuals: A Cross-Sectional Study.

BACKGROUND: Pepsinogens (PGs) can be used for gastric cancer (GC) screening, but the cutoff levels vary among studies, and PG levels are influenced by numerous factors. The aim of this article is to examine the diagnostic value of PG levels and Helicobacter pylori (Hp) status for GC and atrophic gastritis screening in asymptomatic individuals undergoing health checkup in China. PATIENTS AND METHODS: This was a multicenter cross-sectional study of subjects who underwent health checkup from 10/2016 to 10/2018 at nine International Healthcare Centers in China. All participants underwent gastroscopy and pathological examination, serum PG, 13C-urea breath test, and/or Hp serological current infection marker rapid test, all on the same day. PG-related parameters were analyzed in different Hp subgroups and regions. RESULTS: The patients were grouped as non-atrophic (NAG, n = 1,590), mild to moderate atrophic (MAG, n = 273), severe atrophic (SAG, n = 49), and GC (n = 10). The serum PG levels in these groups decreased with increasing pathological severity. In the same pathological groups, PGI and PGII levels were higher in the Hp-positive subgroup, while PGR (PGI/PGII ratio) was lower (P < 0.05). The best cutoff values for atrophy diagnosis were PGI ≤73.1 ng/ml and PGR ≤9.8, for severe atrophy were PGI ≤63.9 ng/ml and PGR ≤9.09, and for GC was PGR ≤4.7 (all P < 0.05 and area under the curve >0.7). The cutoff points varied with Hp status and China regions. CONCLUSION: Serum PG levels might be used for the screening of gastric atrophic gastritis lesions. The results suggest that different cutoff values should possibly be used in different Hp status groups and geographical regions, but it will have to be validated in future studies. Future studies should also examine the value of PG levels for GC detection.

High NAFLD fibrosis score in non-alcoholic fatty liver disease as a predictor of carotid plaque development: a retrospective cohort study based on regular health check-up data in China.

PURPOSES: There is increasing concern regarding cardiovascular risk in non-alcoholic fatty liver disease (NAFLD) patients with liver fibrosis. This study aims: (1) to assess the association between NAFLD and liver fibrosis status and the development of carotid plaque (CP), and (2) to identify CP risk factors among general population with different baseline NAFLD and liver fibrosis status. METHODS: This retrospective cohort study included 14,288 adult participants who went for regular health check-ups between 2014 and 2019, in one hospital in Zhejiang, China. NAFLD was diagnosed by abdominal ultrasound and the NAFLD fibrosis score (NFS) was calculated to reflect the extent of liver fibrosis. Cox proportional hazards analyses were applied to assess the risk of CP development across groups with different baseline NAFLD and NFS status. RESULTS: NAFLD participants with high NFS had higher risk of CP compared to non-NAFLD participants (adjusted hazard ratio 1.68, 95% confidence interval [CI] 1.43-1.96, p < .001). Progression from NAFLD free and NAFLD with low NFS to NAFLD with high NFS are associated with 1.56-fold (95% CI 1.21-2.01, p = .001) and 1.43-fold (95% CI 1.11-1.84, p = .006) increased risk of CP, respectively. Risk factors associated with CP vary based on baseline NAFLD and NFS status. Among NAFLD participants with high NFS, hypertension is the only significant risk factor after adjustment for other potential influencing factors. CONCLUSIONS: NAFLD and liver fibrosis status can be an independent predictor for CP development regardless of metabolic abnormalities. Hypertension is a major risk factor for CP development among NAFLD patients with high NFS.KEY MESSAGESNon-alcoholic fatty liver disease (NAFLD) and liver fibrosis status can be an independent predictor for development of carotid plaque.Progression from NAFLD free and NAFLD with low NAFLD fibrosis score (NFS) to NAFLD with high NFS are associated with increased risk of carotid plaque.Risk factors associated with carotid plaque vary based on baseline NAFLD and NFS status, and hypertension plays the most important role among patients with NAFLD and high NFS.

Therapeutic effect of berberine on chronic atrophic gastritis based on plasma and urine metabolisms.

The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on chronic atrophic gastritis (CAG) and its potential mechanism. The effects of BBR on gastric histopathology, serum biochemical indexes and inflammatory factors in CAG rats were assessed. Moreover, plasma and urine metabolomics based on ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometer (UHPLC-Q-TOF/MS) were used to identify potential metabolic markers and possible pathways of BBR in the treatment of CAG. The results showed that BBR could significantly improve the pathological characteristics of gastric tissue, alleviate the serum biochemical indexes and reduce the mRNA expression of nuclear factor-κB, tumor necrosis factor-α, Cyclooxygenase-2, monocyte chemoattractant protein-1, Interleukin-17A and I interferon-γ. The results of metabolomic analysis show that the therapeutic effect of BBR on CAG may be related to the regulation of 15 metabolic markers and 12 metabolic pathways, which may be the potential mechanism for the treatment of CAG. This study provides new insights for elucidating the mechanism of BBR improving CAG.

Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N'-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis.

BACKGROUNDS: Dehydroevodiamine (DHE) is a quinazoline alkaloid isolated from a Chinese herbal medicine, named Euodiae Fructus (Wu-Zhu-Yu in Chinese). This study aimed to investigate the therapeutic effects and potential mechanism of DHE on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced chronic atrophic gastritis (CAG) based on integrated approaches. METHODS: Therapeutic effects of DHE on serum biochemical indices and histopathology of gastric tissue in MNNG-induced CAG rats were analyzed. MNNG-induced GES-1 human gastric epithelial cell injury model was established. Cell viability and proliferation was quantified by a cell counting kit-8 assay. Cell morphology and mitochondrial membrane potential (MMP) were detected by a high content screening (HCS) assay. Cell migration and invasion were detected by a Transwell chamber. Moreover, UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway affecting the protective effects of DHE on MNNG-induced cell migration and invasion of GES-1. Furthermore, in view of the key role of angiogenesis in the transformation of inflammation and cancer, this study explored relative mRNA and protein expression levels of HIF-1α-mediated VEGF pathway in vivo and in vitro by RT-PCR and Western Blotting, respectively. RESULTS: The results showed that the therapeutic effects of DHE on CAG rats were presented in down-regulation serum biochemical indices and alleviating histological damage of gastric tissue. Besides, DHE has an effect on increasing cell proliferation of GES-1 cells, ameliorating MNNG-induced gastric epithelial cell damage and mitochondrial dysfunction. In addition, DHE could inhibit MNNG induced migration and invasion of GES-1 cells. Cell metabolomics analyses showed that the protective effect of DHE on GES-1 cells is mainly associated with the regulation of inflammation metabolites and energy metabolism related pathways. It was found that DHE has a regulating effect on tumor angiogenesis and can inhibit the relative gene and protein expression of HIF-1α-mediated VEGF signaling pathway. CONCLUSIONS: The present work highlighted the role of DHE ameliorated gastric injury in MNNG-induced CAG rats in vivo and GES-1 cell migration in vitro by inhibiting HIF-1α/VEGF angiogenesis pathway. These results suggest that DHE may be the effective components of Euodiae Fructus, which provides a new agent for the treatment of CAG.

Serum pepsinogen levels in different regions of China and its influencing factors: a multicenter cross-sectional study.

BACKGROUND: The aim of this study is to investigate the difference of serum pepsinogen (PG) baseline levels in different regions of China and its influencing factors. METHODS: From October 2016 to October 2018, asymptomatic health checkup people who underwent nasal endoscopy in nine health management centers in different regions of China were collected. Lifestyle questionnaires were conducted, and serum PG and gastroscopy were performed. The differences in PG levels in baseline population (OLGA-0 grade) were studied according to geographical subregions of China. SPSS software was used for statistical analysis. RESULTS: 1922 patients were included in the final analysis. Compared with the non-atrophy (OLGA-0) group, PGR levels in atrophy group (OLGA-I to IV) were significantly decreased with the atrophy degree (p < 0.05). A total of 1590 baseline people (OLGA-0) were included in the study, including 254 from South China, 574 from East China, 210 from Southwest China, 332 from Northeast China, and 220 from Central/Northern China. There were significant differences in baseline PGI levels among the five regions (p < 0.05). The PGII levels were also different among the five regions, except for Central/Northern versus Southern China. PGR (PGI/PGII ratio) levels in Southern China were higher than other four regions. Further studies were conducted on the related factors that might affect the baseline PG level, which was affected by nationality, dietary habits, smoking, Helicobacter pylori infection and other related factors. CONCLUSION: Influenced by many factors, the baseline PG levels are different in different regions of China. In the follow-up studies of PG cut-off value, different PG cut-off value based on region may be more effective in the screening of gastric cancer and precancerous lesions in China.

Berberine Attenuates Chronic Atrophic Gastritis Induced by MNNG and Its Potential Mechanism.

The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-ß1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1 morphology and proliferation were detected by high content screening (HCS) assay. The rat model of CAG was established by MNNG, and the therapeutic effect of BBR on stomach histopathology and serum supernatant were analyzed in vivo. In addition, the possible mechanism of BBR was further discussed, and the expression of related genes and proteins in TGF-ß1/PI3K signal pathway was detected. The results showed that BBR could significantly improve the survival rate and morphological changes of GES-1, improve the gastric tissue injury of CAG rats, and reduce the expression of G-17 and inflammatory factors IL-8, TNF-α, IL-6 and IL-1ß. In addition, BBR down-regulated the expression of TGF-ß1 axis-related signals such as TGF-ß1, PI3K, p-Akt/Akt, p-mTOR/mTOR and P70S6K, and promoted the expression of PTEN, LC3-II and Beclin-1. In Conclusion, BBR can improve CAG which may be closely related to TGF-ß1/PI3K signal pathway.