A novel M2-like tumor associated macrophages-related gene signature for predicting the prognosis and immunotherapy efficacy in gastric cancer.

BACKGROUND: M2-like tumor-associated macrophages (M2-like TAMs) play key roles in tumor progression and the immune response. However, the clinical significance and prognostic value of M2-like TAMs-associated regulatory genes in gastric cancer (GC) have not been clarified. METHODS: Herein, we identified M2-like TAM-related genes by weighted gene coexpression network analysis of TCGA-STAD and GSE84437 cohort. Lasso-Cox regression analyses were then performed to screen for signature genes, and a novel signature was constructed to quantify the risk score for each patient. Tumor mutation burden (TMB), survival outcomes, immune cells, and immune function were analyzed in the risk groups to further reveal the immune status of GC patients. A gene-drug correlation analysis and sensitivity analysis of anticancer drugs were used to identify potential therapeutic agents. Finally, we verified the mRNA expression of signature genes in patient tissues by qRT-PCR, and analyzed the expression distribution of these genes by IHC. RESULTS: A 4-gene (SERPINE1, MATN3, CD36, and CNTN1) signature was developed and validated, and the risk score was shown to be an independent prognostic factor for GC patients. Further analyses revealed that GC patients in the high-risk group had a worse prognosis than those in the low-risk group, with significant differences in TMB, clinical features, enriched pathways, TIDE score, and tumor microenvironment features. Finally, we used qRT-PCR and IHC analysis to verify mRNA and protein level expression of signature genes. CONCLUSION: These findings highlight the importance of M2-like TAMs, provide a new perspective on individualized immunotherapy for GC patients.

Efficacy and safety of variceal embolization for primary prophylaxis in cirrhosis patients with challenges in standard treatments: preliminary results.

Objectives: Nonselective beta blockers (NSBBs) or endoscopic therapies are currently recommended by guidelines for preventing the first variceal bleed in patients with high-risk varices. However, there is a lack of detailed treatment strategies for patients who are intolerant to both NSBBs and endoscopic approaches. Our study aimed to assess the efficacy and safety of variceal embolization as a primary prophylaxis method in cirrhosis patients who are not suitable candidates for NSBBs or endoscopic treatments. Methods: The study included 43 cirrhotic patients with high-risk varices who were candidates for primary prophylaxis against variceal bleeding. These patients underwent variceal embolization at the Xijing Hospital between January 2020 and June 2022. The primary endpoint was the occurrence of bleeding from varices, and the secondary endpoints were the recurrence of varices and the emergence of complications. Results: The procedure of variceal embolization had a success rate of 93.0% (40 out of 43 patients). Over a 2-year follow-up period, the rate of variceal bleeding was 11.6% (5 out of 43 patients), the recurrence rate of varices was 14.0% (6 out of 43 patients), and the rate of severe complications was limited to 2.3% (1 out of 43 patients). Conclusion: Variceal embolization is a viable primary prophylactic intervention for cirrhotic patients who are at risk of variceal bleeding when standard treatments, such as NSBBs or endoscopic therapies, are difficult to perform.

Inhomogeneous Diffusion-Induced Network for Multiview Semi-Supervised Classification.

The challenges posed by heterogeneous data in practical applications have made multiview semi-supervised classification a focus of attention for researchers. While several graph-based approaches have been suggested for this task, they tend to use homogeneous feature propagation, leading to even diffusion of node information to their neighbors. However, this diffusion strategy results in nodes acquiring information of equal proportion from dissimilar samples. In this article, we propose a solution to address these issues by introducing a graph diffusion-induced network for multiview semi-supervised classification. By formulating a discretized partial differential equation on a manifold, we derive a nonlinear and inhomogeneous diffusion equation to govern information propagation on the graph. Then, we investigate the impact of various nonlinear activation functions on random switching edge directions and their suppressive effects on information diffusion between different nodes. In addition, the cross-view consistency under the semi-supervised scenarios is defined and guaranteed for better information fusion. The comprehensive experimental results demonstrate the superiority of the proposed method compared with state-of-the-art approaches. The effectiveness of the proposed approach in handling diverse and heterogeneous data showcases its potential for advancing multiview semi-supervised classification techniques.

Preliminary clinical analysis and pathway study of S100A8 as a biomarker for the diagnosis of acute deep vein thrombosis.

Herein, we aimed to identify blood biomarkers that compensate for the poor specificity of D-dimer in the diagnosis of deep vein thrombosis (DVT). S100A8 was identified by conducting protein microarray analysis of blood samples from patients with and without DVT. We used ELISA to detect S100A8, VCAM-1, and ICAM-1 expression levels in human blood and evaluated their correlations. Additionally, we employed human recombinant protein S100A8 to induce human umbilical vein endothelial cells and examined the role of the TLR4/MAPK/VCAM-1 and ICAM-1 signaling axes in the pathogenic mechanism of S100A8. Simultaneously, we constructed a rat model of thrombosis induced by inferior vena cava stenosis and detected levels of S100A8, VCAM-1, and ICAM-1 in the blood of DVT rats using ELISA. The associations of thrombus tissue, neutrophils, and CD68-positive cells with S100A8 and p38MAPK, TLR4, and VCAM-1 expression levels in vein walls were explored. The results revealed that blood S100A8 was significantly upregulated during the acute phase of DVT and activated p38MAPK expression by combining with TLR4 to enhance the expression and secretion of VCAM-1 and ICAM-1, thereby affecting the occurrence and development of DVT. Therefore, S100A8 could be a potential biomarker for early diagnosis and screening of DVT.

The intake of solid fat and cheese may be associated with a reduced risk of Helicobacter pylori infection status: a cross-sectional study based on NHANES 1999-2000.

BACKGROUND: Diet plays an important role in Helicobacter pylori (HP) infection, and our objective was to investigate potential connections between dietary patterns, specific food groups, and HP infection status in U.S. adults. METHODS: The data for this study was obtained from the NHANES (National Health and Nutrition Survey) database for the year 1999-2000. This cross-sectional study involved the selection of adults aged 20 years and older who had undergone dietary surveys and HP testing. Factor analysis was employed to identify dietary patterns, and logistic regression models were utilized to assess the association between these dietary patterns and specific food groups with HP infection status. RESULT: Based on the inclusion and exclusion criteria, our final analysis included 2,952 individuals. The median age of participants was 51.0 years, and 48.7% were male. In the study population, the overall prevalence of HP infection was 44.9%. Factor analysis revealed three distinct dietary patterns: High-fat and high-sugar pattern (including solid fats, refined grains, cheese, and added sugars); Vegetarian pattern (comprising fruits, juices, and whole grains); Healthy pattern (encompassing vegetables, nuts and seeds, and oils). Adjusted results showed that the high-fat and high-sugar pattern (OR = 0.689, 95% CI: 0.688-0.690), vegetarian pattern (OR = 0.802, 95% CI: 0.801-0.803), and healthy pattern (OR = 0.717, 95% CI: 0.716-0.718) were all linked to a lower likelihood of HP infection. Further analysis of the high-fat and high-sugar pattern revealed that solid fats (OR = 0.717, 95% CI: 0.716-0.718) and cheese (OR = 0.863, 95% CI: 0.862-0.864) were protective factors against HP infection, while refined grains (OR = 1.045, 95% CI: 1.044-1.046) and added sugars (OR = 1.014, 95% CI: 1.013-1.015) were identified as risk factors for HP infection. CONCLUSION: Both the Vegetarian pattern and the Healthy pattern are associated with a reduced risk of HP infection. Interestingly, the High-fat and High-sugar pattern, which is initially considered a risk factor for HP infection when the score is low, becomes a protective factor as the intake increases. Within this pattern, animal foods like solid fats and cheese play a protective role, while the consumption of refined grains and added sugars increases the likelihood of HP infection.

Clinical features and prognostic factors of duodenal neuroendocrine tumours: A comparative study of ampullary and nonampullary regions.

BACKGROUND: Duodenal neuroendocrine tumours (DNETs) are rare neoplasms. However, the incidence of DNETs has been increasing in recent years, especially as an incidental finding during endoscopic studies. Regrettably, there is no consensus regarding the ideal treatment of DNETs. Even there are few studies on the clinical features and survival analysis of DNETs. AIM: To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours. METHODS: The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected. Neuroendocrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group; neuroendocrine tumours in any part of the duodenum outside the ampullary area were divided into the nonampullary region group. Using a retrospective study, the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed. RESULTS: Twenty-nine DNET patients were screened. The male to female ratio was 1:1.9, and females comprised the majority. The ampullary region group accounted for 24.1% (7/29), while the nonampullary region group accounted for 75.9% (22/29). When diagnosed, the clinical symptoms of the ampullary region group were mainly abdominal pain (85.7%), while those of the nonampullary region groups were mainly abdominal distension (59.1%). There were differences in the composition of staging of tumours between the two groups (Fisher's exact probability method, P = 0.001), with nonampullary stage II tumours (68.2%) being the main stage (P < 0.05). After the diagnosis of DNETs, the survival rate of the ampullary region group was 14.3% (1/7), which was lower than that of 72.7% (16/22) in the nonampullary region group (Fisher's exact probability method, P = 0.011). The survival time of the ampullary region group was shorter than that of the nonampullary region group (P < 0.000). The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months. Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients (HR = 0.029, 95%CI 0.004-0.199, P < 0.000; HR = 12.609, 95%CI: 2.889-55.037, P = 0.001). Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter < 2 cm was longer than that of patients with a tumour diameter ≥ 2 cm (t = 7.243, P = 0.048). As of follow-up, 6 patients who died of nonampullary DNETs had a tumour diameter that was ≥ 2 cm, and 3 patients in stage IV had liver metastasis. Patients with a tumour diameter < 2 cm underwent surgical treatment, and all survived after surgery. CONCLUSION: Surgical treatment is a protective factor for prolonging the survival of DNET patients. Compared to DNETs in the ampullary region, patients in the nonampullary region group had a longer survival period. The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

Pro-Inflammatory Diet as a Risk Factor for Stomach Cancer: Findings from a Multicenter Study in Central and Western China.

Purpose: We conducted a multicenter cross-sectional study in central and western China to explore the association between inflammatory diet and stomach cancer odds. Patients and Methods: Participants from five hospitals in the central and western regions were collected. All participants completed the questionnaire we provided before the gastroscopy examination, which includes inquiries about risk factors for stomach cancer and food frequency. All participants underwent gastroscopy, and a mucosal biopsy was confirmed pathologically. Pathological findings were classified as chronic gastritis group, precancerous lesions group and stomach cancer group. Dietary Inflammatory Index (DII) scores were calculated based on the frequency of food occurrences in the questionnaire, and finally SPSS was used to calculate the correlation between variables. Results: A total of 1162 patients were included in this study, including 668 cases of chronic gastritis, 411 cases of precancerous lesions, and 83 cases of cancer. A single factor analysis was conducted to examine the risk factors of stomach cancer, revealing a significant association between a pro-inflammatory diet and the stomach cancer odds (p value < 0.05). The results of binary classification analysis further confirmed that a pro-inflammatory diet is a risk factor for stomach cancer 【odds ratio (OR) =7.400)】. Moreover, correlation analysis demonstrated a positive correlation between the severity of gastric mucosal diseases and an inflammatory diet (including anti-inflammatory and pro-inflammatory diets) (rs=0.274, p-value < 0.001). Conclusion: Pro-Inflammatory diet is a risk factor for stomach cancer, and may accelerate the progression of stomach mucosal disease.

Construction and Validation of a Gastric Cancer Diagnostic Model based on Blood Groups and Tumor Markers.

Objective: The aim of this study is to explore the value of combined detection of ABO blood group and tumor markers in the diagnosis of gastric cancer. Methods: A total of 3650 gastric cancer patients treated in our center from January 2015 to December 2019, and 5822 controls were recruited, and divided into training set and validation set according to 7:3. The diagnostic and predictive model of gastric cancer was constructed by binary logistic regression method in the training set. The diagnostic value of the prediction model for gastric cancer was evaluated by calculating the prediction probability P value and drawing the Receiver operating characteristic (ROC) curve, and was verified in the validation set. Results: The Area under the curve (AUC) of the diagnosis and prediction model in the training set was 0.936 (95%CI: 0.926-0.941), the sensitivity was 81.66%, and the specificity was 98.61%. In the validation set, the AUC was 0.941 (95%CI: 0.932-0.950), the sensitivity was 82.33%, and the specificity was 99.02%. Furthermore, the diagnostic model obtained in this study had a high diagnostic value for early gastric cancer patients in the healthy population (AUC of training set, validation set and total population were 0.906, 0.920 and 0.908, respectively). Conclusions: We constructed a diagnostic model for gastric cancer including blood group and tumor markers, which has high reference value for the diagnosis of gastric cancer patients, and the model can better distinguish early gastric cancer from healthy people.

Efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for Helicobacter pylori initial treatment: A randomized controlled trial.

BACKGROUND: With the development of traditional Chinese medicine research, berberine has shown good efficacy and safety in the eradication of Helicobacter pylori (H. pylori). The present study aimed to evaluate the efficacy and safety of triple therapy containing berberine, amoxicillin, and vonoprazan for the initial treatment of H. pylori. METHODS: This study was a single-center, open-label, parallel, randomized controlled clinical trial. Patients with H. pylori infection were randomly (1:1:1) assigned to receive berberine triple therapy (berberine 500 mg, amoxicillin 1000 mg, vonoprazan 20 mg, A group), vonoprazan quadruple therapy (vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, B group), or rabeprazole quadruple therapy (rabeprazole 10 mg, amoxicillin 1000 mg, clarithromycin 500 mg, colloidal bismuth tartrate 220 mg, C group). The drugs were taken twice daily for 14 days. The main outcome was the H. pylori eradication rate. The secondary outcomes were symptom improvement rate, patient compliance, and incidence of adverse events. Furthermore, factors affecting the eradication rate of H. pylori were further analyzed. RESULTS: A total of 300 H. pylori-infected patients were included in this study, and 263 patients completed the study. An intention-to-treat (ITT) analysis showed that the eradication rates of H. pylori in berberine triple therapy, vonoprazan quadruple therapy, and rabeprazole quadruple therapy were 70.0% (70/100), 77.0% (77/100), and 69.0% (69/100), respectively. The per-protocol (PP) analysis showed that the eradication rates of H. pylori in these three groups were 81.4% (70/86), 86.5% (77/89), and 78.4% (69/88), respectively. Both ITT analysis and PP analysis showed that the H. pylori eradication rate did not significantly differ among the three groups (P >0.05). In addition, the symptom improvement rate, overall adverse reaction rate, and patient compliance were similar among the three groups (P >0.05). CONCLUSIONS: The efficacy of berberine triple therapy for H. pylori initial treatment was comparable to that of vonoprazan quadruple therapy and rabeprazole quadruple therapy, and it was well tolerated. It could be used as one choice of H. pylori initial treatment.

Association between Gut Microbiota and Digestive System Cancers: A Bidirectional Two-Sample Mendelian Randomization Study.

Accumulating evidence indicates that gut microbiota closely correlates with the tumorigenesis of digestive system cancers (DSCs). However, whether the causality between gut microbiota and DSCs exists is unknown. Genome-wide association study (GWAS) summary statistics for gut microbiota and DSCs and the bidirectional two-sample Mendelian randomization (MR) analysis were utilized to assess the causality between gut microbiota and DSCs. Sensitivity analyses were performed to evaluate the robustness of our results. We found that the genus Eggerthella (OR = 0.464, 95%CI: 0.27 to 0.796, p = 0.005) was negatively associated with the risk of gastric cancer. The genetically predicted genus Lachnospiraceae FCS020 group (OR = 0.607, 95%CI: 0.439 to 0.84, p = 0.003) correlated with a lower risk of colorectal cancer, and genus Turicibacter (OR = 0.271, 95%CI: 0.109 to 0.676, p = 0.005) was a protective factor for liver cancer. In the reverse MR, DSCs regulated the relative abundance of specific strains of gut microbiota. We comprehensively screened the association between gut microbiota and DSCs using a bidirectional two-sample MR analysis and identified the causality between several microbial taxa and DSCs. Our discoveries are beneficial for the development of novel microbial markers and microbiota-modifying therapeutics for DSC patients.

Network pharmacology prediction and molecular docking-based strategy to discover the potential pharmacological mechanism of action of Wang Bu Liu Xing (Semen vaccariae) for colorectal cancer.

Background: Colorectal cancer (CRC) is the leading cause of cancer-related death worldwide. Wang Bu Liu Xing [Semen vaccariae (SV)] is a traditional Chinese medicine (TCM) ingredient with anti-angiogenic and anti-tumor effects. However, little research has been done on the ingredients found in SV or the putative process by which SV fights CRC, and this paper aims to reveal the components of SV that are effective in treating CRC. Methods: The open database and online platform were used in this study, Symptom Mapping (SymMap) and Traditional Chinese Medicine Systems Pharmacology (TCMSP) for SV ingredient and targets, Gene Expression Omnibus (GEO) for differentially expressed genes (DEGs) of CRC, Database for Annotation Visualization and Integrated Discovery (DAVID) for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, STRING-Cytoscape for protein-protein interaction (PPI), AutoDockTools for Molecular docking and others. were conducted to determine how SV affects CRC and what are the most important components, potential targets, and signaling pathways. Results: The findings of the network pharmacology study indicated that swerchirin and CDK2 potential target gene for SV was connected to anti-CRC actions. SV may inhibit CRC by interacting with crucial targets like BCL2L1, CDK2, and SERPINE1. Additionally, KEGG analysis revealed that the p53 signaling pathway may be a driver of the anti-CRC impact of SV. Molecular docking showed that swerchirin can bind with its target protein in a good bond by intermolecular force. Conclusions: In this study, the pharmacological effects of SV were examined, along with its potential therapeutic impact on CRC. These effects of SV appear to be mediated via a variety of substances, targets, and pathways. SV exerts pharmacological effects in CRC, p53 signaling pathway is great value. The main molecular docking is CDK2 and swerchirin. Moreover, our research offers a promising method for characterizing therapeutic pathways and identifying molecules in TCM.

Bifunctional catalytic degradation of diclofenac over Cu-Pd co-modified sponge iron-based trimetal: Parameter optimization.

Currently, the pharmaceutical and personal care products (PPCPs) have posed great challenge to advanced oxidation techniques (AOTs). In this study, we decorated sponge iron (s-Fe0) with Cu and Pd (s-Fe0-Cu-Pd) and further optimized the synthesis parameters with a response surface method (RSM) to rapidly degrade diclofenac sodium (DCF). Under the RSM-optimized conditions of Fe: Cu: Pd = 100: 4.23: 0.10, initial solution pH of 5.13, and input dosage of 38.8 g/L, 99% removal of DCF could be obtained after 60 min of reaction. Moreover, the morphological structure of trimetal was characterized with high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), X-ray diffraction (XRD), X-ray photoelectron spectra (XPS). Electron spin resonance (ESR) signals have also been applied to capture reactive hydrogen atoms (H*), superoxygen anions, hydroxyl radicals, and single state oxygen (1O2). Furthermore, the variations of DCF and its selective degradation products over a series of s-Fe0-based bi(tri)metals have been compared. Additionally, the degradation mechanism of DCF has also been explored. To our best knowledge, this is the first report revealing the selective dechlorination of DCF with low toxicity over Pd-Cu co-doped s-Fe0 trimetal.

Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus.

Islet ß-cell dysfunction is a basic pathophysiological characteristic of type 2 diabetes mellitus (T2DM). Appropriate assessment of islet ß-cell function is beneficial to better management of T2DM. Protecting islet ß-cell function is vital to delay the progress of type 2 diabetes mellitus. Therefore, the Pancreatic Islet ß-cell Expert Panel of the Chinese Diabetes Society and Endocrinology Society of Jiangsu Medical Association organized experts to draft the "Clinical expert consensus on the assessment and protection of pancreatic islet ß-cell function in type 2 diabetes mellitus." This consensus suggests that ß-cell function can be clinically assessed using blood glucose-based methods or methods that combine blood glucose and endogenous insulin or C-peptide levels. Some measures, including weight loss and early and sustained euglycemia control, could effectively protect islet ß-cell function, and some newly developed drugs, such as Sodium-glucose cotransporter-2 inhibitor and Glucagon-like peptide-1 receptor agonists, could improve islet ß-cell function, independent of glycemic control.

Thyroid Hormone Receptor-ß Agonists in NAFLD Therapy: Possibilities and Challenges.

Nonalcoholic fatty liver disease (NAFLD) is a progressive metabolic liver disease with an unknown pathogenesis and no FDA-approved drug treatment to date. Hypothyroidism has been identified as a risk factor for NAFLD as thyroxine is required for regulating metabolism in adults. Thyroxine has been shown to reduce fat in the livers of murine models with experimentally induced NAFLD. The use of synthetic thyroxine has been shown to increase lipid metabolism leading to weight loss; however, thyroxine has also been shown to cause many side effects, especially in the heart. Overcoming these cardiac side effects involves designing agonists specific to one of the 2 gene subtypes for the thyroid hormone (TH) receptor (TR), TRß. While the other TH receptor subtype, TRα, is mainly expressed in the heart and is responsible for thyroxine's cardiac function, TRß is mainly expressed in the liver and is involved in liver function. Using TRß-specific agonists to treat NAFLD can prevent cardiac and other adverse side effects. Several TRß-specific agonists have shown positive therapeutic effects in NAFLD animal models and have entered clinical trials. We seek to provide a comprehensive updated reference of TRß-specific agonists in this review and explore the future therapeutic potential of TRß-specific activation in the treatment of NAFLD.

Increased Prevalence of Thyroid Nodules Across Nearly 10 Years in Shanghai, China.

OBJECTIVE: This study aimed to determine whether the prevalence of thyroid nodules (TNs) increased due to modern lifestyles or other factors, despite the advances in screening and diagnostic tools. METHODS: This study included 3474 pairs of participants, who were matched by gender and age (±3 years) from two cross-sectional sampling surveys: (1) the program on the iodine nutritional status and related health status of residents in Shanghai in 2009; (2) the thyroid disease screening program for adults in Shanghai between 2017 and 2018. The prevalence of TNs and thyroid diseases in 2009 and 2017-2018 were compared, and the potential risk factors of TNs were detected. RESULTS: The prevalence of TNs in 2009 was 28.9%: 22.5% in males and 34.5% in females. In 2017, this increased to 43.8%: 37.9% in males and 49.1% in females. The prevalence of TNs significantly increased from 2009 to 2017 (odds ratio, 1.486; 95% confidence interval, 1.238-1.786). In addition, female gender, thyroid disease history, and age were the main risk factors for TNs after adjusting for confounders in the logistic regression across the time period. CONCLUSION: The prevalence of TNs significantly increased across nearly 10 years in Shanghai.

Chinese integrated guideline on the management of gastric precancerous conditions and lesions.

The standardized diagnosis and management of gastric precancerous conditions and lesions are important to prevent gastric cancer. This guideline, created by 5 traditional Chinese medicine and Western medicine associations, based on the current morbidity and diagnosis and treatment of gastric precancerous conditions and lesions, provides specific key points and strategies for diagnosis and treatment in the following five aspects: definition and epidemiology, diagnosis and stage, surveillance, treatment and efficacy evaluation. It is hoped that these aspects, assessed by integrating Western medicine and traditional Chinese medicine and involving multidisciplinary participation, will play a guiding role in clinical diagnosis and treatment and achieve effective secondary prevention of gastric cancer.