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OBJECTIVE: There is an economic evaluation on the family-based Helicobacter pylori screen-and-treat strategy (FBHS) in China. This study aimed to compare the cost-effectiveness of the FBHS with the traditional H. pylori screen-and-treat strategy (TBHS). MATERIALS AND METHODS: A seven-state microsimulation model, including H. pylori infection and gastric cancer states, was constructed on the basis of the target family samples from 29 provinces in China. Taking a lifetime horizon from a healthcare system perspective, the long-term costs and health outcomes of the FBHS and TBHS screening strategies were simulated separately, and economic evaluations were performed. The model parameters were primarily derived from real-world data, published literature, and expert opinions. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost/quality-adjusted life-year (QALY) gained. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analysis were performed to assess the uncertainty of the results. RESULTS: The base-case analysis revealed that the average costs for FBHS and TBHS were 563.67 CNY and 574.08 CNY, respectively, with corresponding average QALYs of 14.83 and 14.79. The ICER for the comparison between the two strategies was -214.07, indicating that FBHS was an absolutely dominant strategy with better cost-effectiveness. The results of both one-way sensitivity analysis and probabilistic sensitivity analysis were robust. When taking into account the added benefit of the higher H. pylori eradication rate in FBHS, the average costs were further reduced, and the average QALYs were increased, solidifying its position as an unequivocally dominant strategy. CONCLUSION: The FBHS is an absolutely dominant and cost-effective strategy that enables an optimized allocation of screening resources. Decision-makers should prioritize FBHS when developing H. pylori prevention and control strategies.
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Análisis Costo-Beneficio , Infecciones por Helicobacter , Helicobacter pylori , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/economía , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , China , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/genética , Tamizaje Masivo/economía , Tamizaje Masivo/métodos , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Masculino , Femenino , Adulto , Simulación por Computador , Neoplasias Gástricas/microbiologíaRESUMEN
BACKGROUND: ChatGPT is a novel and online large-scale language model used as a source providing up-to-date and useful health-related knowledges to patients and clinicians. However, its performance on Helicobacter pylori infection-related questions remain unknown. This study aimed to evaluate the accuracy of ChatGPT's responses on H. pylori-related questions compared with that of gastroenterologists during the same period. METHODS: Twenty-five H. pylori-related questions from five domains: Indication, Diagnostics, Treatment, Gastric cancer and prevention, and Gut Microbiota were selected based on the Maastricht VI Consensus report. Each question was tested three times with ChatGPT3.5 and ChatGPT4. Two independent H. pylori experts assessed the responses from ChatGPT, with discrepancies resolved by a third reviewer. Simultaneously, a nationwide survey with the same questions was conducted among 1279 gastroenterologists and 154 medical students. The accuracy of responses from ChatGPT3.5 and ChatGPT4 was compared with that of gastroenterologists. RESULTS: Overall, both ChatGPT3.5 and ChatGPT4 demonstrated high accuracy, with median accuracy rates of 92% for each of the three responses, surpassing the accuracy of nationwide gastroenterologists (median: 80%) and equivalent to that of senior gastroenterologists. Compared with ChatGPT3.5, ChatGPT4 provided more concise responses with the same accuracy. ChatGPT3.5 performed well in the Indication, Treatment, and Gut Microbiota domains, whereas ChatGPT4 excelled in Diagnostics, Gastric cancer and prevention, and Gut Microbiota domains. CONCLUSION: ChatGPT exhibited high accuracy and reproducibility in addressing H. pylori-related questions except the decision for H. pylori treatment, performing at the level of senior gastroenterologists and could serve as an auxiliary information tool for assisting patients and clinicians.
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Infecciones por Helicobacter , Helicobacter pylori , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Humanos , Helicobacter pylori/efectos de los fármacos , Encuestas y Cuestionarios , Masculino , Femenino , Adulto , Persona de Mediana EdadRESUMEN
Helicobacter pylori (H. pylori) infection remains the leading cause of gastric adenocarcinoma, and its eradication primarily relies on the prolonged and intensive use of two antibiotics. However, antibiotic resistance has become a compelling health issue, leading to H. pylori eradication treatment failure worldwide. Additionally, the powerlessness of antibiotics against biofilms, as well as intracellular H. pylori and the long-term damage of antibiotics to the intestinal microbiota, have also created an urgent demand for antibiotic-free approaches. Herein, we describe an antibiotic-free, multifunctional copper-organic framework (HKUST-1) platform encased in a lipid layer comprising phosphatidic acid (PA), rhamnolipid (RHL), and cholesterol (CHOL), enveloped in chitosan (CS), and loaded in an ascorbyl palmitate (AP) hydrogel: AP@CS@Lip@HKUST-1. This platform targets inflammatory sites where H. pylori aggregates through electrostatic attraction. Then, hydrolysis by matrix metalloproteinases (MMPs) releases CS-encased nanoparticles, disrupting bacterial urease activity and membrane integrity. Additionally, RHL disperses biofilms, while PA promotes lysosomal acidification and activates host autophagy, enabling clearance of intracellular H. pylori. Furthermore, AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu2+ release while preserving the intestinal microbiota. Collectively, this platform presents an advanced therapeutic strategy for eradicating persistent H. pylori infection without inducing drug resistance.
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Chronic pancreatitis (CP) is marked by progressive fibrosis and the activation of pancreatic stellate cells (PSCs), accompanied by the destruction of pancreatic parenchyma, leading to the loss of acinar cells (ACs). Few research studies have explored the mechanism by which damaged ACs (DACs) contribute to PSCs activation and pancreatic fibrosis. Currently, there are no effective drugs for curing CP or limiting the progression of pancreatic fibrosis. In this research, co-culture with intact acinar cells (IACs) suppressed PSC activation, while co-culture with DACs did the opposite. Krüppel-like factor 4 (KLF4) was significantly upregulated in DACs and was established as the key molecule that switches ACs from PSCs-suppressor to PSCs-activator. We revealed the exosomes of IACs contributed to the anti-activated function of IACs-CS on PSCs. MiRNome profiling showed that let-7 family is significantly enriched in IAC-derived exosomes (>30% miRNome), which partially mediates IACs' suppressive impacts on PSCs. Furthermore, it has been observed that the enrichment of let-7 in exosomes was influenced by the expression level of KLF4. Mechanistic studies demonstrated that KLF4 in ACs upregulated Lin28A, thereby decreasing let-7 levels in AC-derived exosomes, and thus promoting PSCs activation. We utilized an adeno-associated virus specifically targeting KLF4 in ACs (shKLF4-pAAV) to suppress PSCs activation in CP, resulting in reduced pancreatic fibrosis. IAC-derived exosomes hold potential as potent weapons against PSCs activation via let-7s, while activated KLF4/Lin28A signaling in DACs diminished such functions. ShKLF4-pAAV holds promise as a novel therapeutic approach for CP.
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Células Acinares , Exosomas , Fibrosis , Factor 4 Similar a Kruppel , MicroARNs , Células Estrelladas Pancreáticas , Pancreatitis Crónica , Factor 4 Similar a Kruppel/metabolismo , Animales , Células Estrelladas Pancreáticas/metabolismo , Células Estrelladas Pancreáticas/patología , Exosomas/metabolismo , Pancreatitis Crónica/metabolismo , Pancreatitis Crónica/genética , Pancreatitis Crónica/patología , MicroARNs/genética , Células Acinares/metabolismo , Células Acinares/patología , Dependovirus/genética , Ratones , Humanos , Factores de Transcripción de Tipo Kruppel/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Modelos Animales de Enfermedad , Vectores Genéticos/genética , Vectores Genéticos/administración & dosificación , Masculino , Técnicas de Cocultivo , Páncreas/metabolismo , Páncreas/patología , Terapia Genética/métodosRESUMEN
BACKGROUND: Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in pancreatic and biliary tract cancers. The aim of this study is to characterize the cfDNA fragmentomics in biliopancreatic cancers and develop an accurate method for cancer detection. METHODS: One hundred forty-seven patients with biliopancreatic cancers and 71 non-cancer volunteers were enrolled, including 55 patients with cholangiocarcinoma, 30 with gallbladder cancer, and 62 with pancreatic cancer. Low-coverage whole-genome sequencing (median coverage: 2.9 ×) was performed on plasma cfDNA. Three cfDNA fragmentomic features, including fragment size, end motif and nucleosome footprint, were subjected to construct a stacked machine learning model for cancer detection. Integration of carbohydrate antigen 19-9 (CA19-9) was explored to improve model performance. RESULTS: The stacked model presented robust performance for cancer detection (area under curve (AUC) of 0.978 in the training cohort, and AUC of 0.941 in the validation cohort), and remained consistent even when using extremely low-coverage sequencing depth of 0.5 × (AUC: 0.905). Besides, our method could also help differentiate biliopancreatic cancer subtypes. By integrating the stacked model and CA19-9 to generate the final detection model, a high accuracy in distinguishing biliopancreatic cancers from non-cancer samples with an AUC of 0.995 was achieved. CONCLUSIONS: Our model demonstrated ultrasensitivity of plasma cfDNA fragementomics in detecting biliopancreatic cancers, fulfilling the unmet accuracy of widely-used serum biomarker CA19-9, and provided an affordable way for accurate noninvasive biliopancreatic cancer screening in clinical practice.
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Neoplasias del Sistema Biliar , Ácidos Nucleicos Libres de Células , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/sangre , Neoplasias del Sistema Biliar/genética , Neoplasias del Sistema Biliar/diagnóstico , Neoplasias del Sistema Biliar/sangre , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/sangre , AdultoRESUMEN
BACKGROUND: Eradication of oral Helicobacter pylori (H. pylori) not only reduces the infection rate from the transmission route but also improves the success rate of intragastric eradication. MAXPOWER Biological Bacteriostatic Liquid, developed in our previous work, is a composite biological preparation with strong antibacterial ability and unique antibacterial mechanism. The present study evaluated the efficacy of the MAXPOWER biocontrol solution on H. pylori and its success rate in eradicating oral H. pylori in clinical patients. METHODS: Live-dead cell staining and hemolysis test were used to evaluate the cellular safety of MAXPOWER biocontrol solution; plate spreading, live-dead bacterial staining, and scanning electron microscopy methods were used to evaluate its antimicrobial effect against H. pylori. Transcriptomics was used to analyze the changes in H. pylori genes before and after treatment. After seven days of gavage treatment, H&E staining and mice feces were collected for 16SrDNA sequencing to evaluate the animals' safety. Oral H. pylori-positive patients were randomized to be given a placebo and MAXPOWER Bio-Bacteriostatic Liquid gargle for seven days to evaluate the effect on oral H. pylori eradication. RESULTS: In vitro tests demonstrated that this product has excellent biocompatibility and hemocompatibility and can effectively eradicate oral H. pylori. In vivo tests further showed that it has good biosafety and virtually no adverse effect on intestinal microflora. Transcriptomics analysis revealed that it kills H. pylori cells mainly by disrupting their cell membranes and metabolism. Additionally, the results of randomized controlled trials on humans disclosed that the oral H. pylori eradication rates achieved by MAXPOWER Biological Antibacterial Liquid were 71.4% and 78.9% according to the intention-to-treat and the per-protocol analysis, respectively. CONCLUSION: MAXPOWER Biological Antibacterial Liquid is both safe and efficacious in the eradication of oral H. pylori. TRIAL REGISTRATION: This study was retrospectively registered in the ClinicalTrials.gov Trial Registry on 21/09/2023 (NCT06045832).
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Antibacterianos , Infecciones por Helicobacter , Helicobacter pylori , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/genética , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Antibacterianos/farmacología , Animales , Ratones , Masculino , Femenino , Persona de Mediana Edad , Adulto , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVES: Acute pancreatitis (AP) has a high incidence of hospitalizations, morbidity, and mortality worldwide. A growing number of studies on AP pathogenesis are based on cerulein-induced experimental model, which simulates human AP in vivo. It has been demonstrated that both pancreatic acinar cells and peritoneal macrophages are involved in pancreatic inflammation and damage. However, their connection has not been well understood. METHODS: A cerulein-induced AP model was established on the pancreatic acinar cell line AR42J. Rat macrophages were isolated from the peritoneal cavity. The effects of cerulein-induced pancreatic exosomes on the peritoneal macrophage and pancreas in vivo and in vitro were examined. The underlying molecular mechanism was investigated by exploring the regulatory role of downstream molecules. RESULTS: We found that exosomes derived from cerulein-treated AR42J cells induced rat peritoneal macrophage M1 polarization and pyroptosis. miR-24-3p was upregulated in cerulein-stimulated exosomes, whereas the miR-24-3p inhibitor counteracted the effect of pancreatic exosomes on peritoneal macrophage M1 polarization and pyroptosis. Furthermore, miR-24-3p inhibited March3 expression, whereas MARCH3 mediated NLRP3 ubiquitination in rat peritoneal macrophages, which, in turn, contributed to the apoptosis, reactive oxygen species production, and inflammation in AR42J cells. CONCLUSIONS: Exosomes derived from cerulein-stimulated pancreatic acinar cells mediate peritoneal macrophage M1 polarization and pyroptosis via an miR-24-3p/MARCH3/NLRP3 axis in AP.
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Células Acinares , Ceruletida , Exosomas , Macrófagos Peritoneales , MicroARNs , Proteína con Dominio Pirina 3 de la Familia NLR , Pancreatitis , Piroptosis , Animales , Exosomas/metabolismo , Exosomas/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Pancreatitis/metabolismo , Pancreatitis/genética , Pancreatitis/inducido químicamente , Pancreatitis/patología , MicroARNs/genética , MicroARNs/metabolismo , Piroptosis/genética , Células Acinares/metabolismo , Células Acinares/patología , Macrófagos Peritoneales/metabolismo , Ratas , Masculino , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Línea Celular , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Páncreas/metabolismo , Páncreas/patología , Transducción de Señal , Enfermedad AgudaRESUMEN
OBJECTIVE: Current study aims to investigate whether serum exosomal microRNAs (miRNAs) could be potential biomarkers in predicting APs with POF at early phase. BACKGROUND: Novel biomarkers are sorely needed for early prediction of persistent organ failure (POF) in acute pancreatitis (AP) patients. METHODS: In the discovery stage, exosomal miRNAs were profiled in sera from APs with or without POF (5 vs. 5) using microarrays. POF-associated miRNA signatures then were assessed in training cohort (n=227) and further validated in three independent cohorts (n=516), including one nested case-control cohort. RESULTS: A total of 743 APs were recruited in this large-scale biomarker identification study with a nested case-control study. Data from the discovery cohort demonstrated that 90 exosomal miRNAs were significantly dysregulated in APs with POF compared with controls. One miRNA classifier (Cmi) comprising 3 miRNAs (miR-4265, 1208, 3127-5p) was identified in the training cohort, and was further evaluated in two validation cohorts for their predictive value for POF. AUCs for Cmi ranged from 0.88 to 0.90, which was statistically superior to AUCs of APACHE-II and BISAP, and outperformed BUN and creatinine in POF prediction across all cohorts (P<.05). Higher levels of Cmi indicated increased need for ICU admission, prolonged hospitalization, and elevated mortality rate, thus poor prognosis. In the nested case-control study, Cmi could help identify prediagnostic POF in post-ERCP pancreatitis cases within "golden hours" after ERCP with high efficacy. CONCLUSIONS: Serum exosomal Cmi may be an early predictor for POF in AP, even within "golden hours" after AP onset. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02602808).
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Objective. Ulceration of the small intestine, which has a high incidence, includes Crohn's disease (CD), intestinal tuberculosis (ITB), primary small intestinal lymphoma (PSIL), cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), and non-specific ulcer (NSU). However, the ulceration morphology can easily be misdiagnosed through enteroscopy.Approach. In this study, DRCA-DenseNet169, which is based on DenseNet169, with residual dilated blocks and a channel attention block, is proposed to identify CD, ITB, PSIL, CMUSE, and NSU intelligently. In addition, a novel loss function that incorporates dynamic weights is designed to enhance the precision of imbalanced datasets with limited samples. DRCA-Densenet169 was evaluated using 10883 enteroscopy images, including 5375 ulcer images and 5508 normal images, which were obtained from the Shanghai Changhai Hospital.Main results. DRCA-Densenet169 achieved an overall accuracy of 85.27% ± 0.32%, a weighted-precision of 83.99% ± 2.47%, a weighted-recall of 84.36% ± 0.88% and a weighted-F1-score of 84.07% ± 2.14%.Significance. The results demonstrate that DRCA-Densenet169 has high recognition accuracy and strong robustness in identifying different types of ulcers when obtaining immediate and preliminary diagnoses.
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Intestino Delgado , Úlcera , Humanos , Úlcera/diagnóstico por imagen , China , Intestino Delgado/diagnóstico por imagen , Diagnóstico DiferencialRESUMEN
BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).
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Angiodisplasia , Hemorragia Gastrointestinal , Fármacos Hematológicos , Enfermedades Intestinales , Intestino Delgado , Talidomida , Humanos , Angiodisplasia/complicaciones , Angiodisplasia/tratamiento farmacológico , China , Método Doble Ciego , Hemorragia Gastrointestinal/tratamiento farmacológico , Hemorragia Gastrointestinal/etiología , Talidomida/administración & dosificación , Talidomida/efectos adversos , Talidomida/uso terapéutico , Resultado del Tratamiento , Enfermedades Intestinales/complicaciones , Enfermedades Intestinales/tratamiento farmacológico , Recurrencia , Intestino Delgado/irrigación sanguínea , Administración Oral , Fármacos Hematológicos/administración & dosificación , Fármacos Hematológicos/efectos adversos , Fármacos Hematológicos/uso terapéuticoRESUMEN
Purpose: Cuproptosis is a newly discovered type of cell death. Little is known about the roles that cuproptosis related genes (CRGs) play in colorectal cancer (CRC). The aim of this study is to evaluate the prognostic value of CRGs and their relationship with tumor immune microenvironment. Methods: TCGA-COAD dataset was used as the training cohort. Pearson correlation was employed to identify CRGs and paired tumor-normal samples were used to identify those CRGs with differential expression pattern. A risk score signature was constructed using LASSO regression and multivariate Cox stepwise regression methods. Two GEO datasets were used as validation cohorts for confirming predictive power and clinical significance of this model. Expression patterns of seven CRGs were evaluated in COAD tissues. In vitro experiments were conducted to validate the expression of the CRGs during cuproptosis. Results: A total of 771 differentially expressed CRGs were identified in the training cohort. A predictive model termed riskScore was constructed consisting of 7 CRGs and two clinical parameters (age and stage). Survival analysis suggested that patients with higher riskScore showed shorter OS than those with lower (P<0.0001). ROC analysis revealed that AUC values of cases in the training cohort for 1-, 2-, and 3-year survival were 0.82, 0.80, 0.86 respectively, indicating its good predictive efficacy. Correlations with clinical features showed that higher riskScore was significantly associated with advanced TNM stages, which were further confirmed in two validation cohorts. Single sample gene set enrichment analysis (ssGSEA) showed that high-risk group presented with an immune-cold phenotype. Consistently, ESTIMATE algorithm analysis showed lower immune scores in riskScore-high group. Expressions of key molecules in riskScore model are strongly associated with TME infiltrating cells and immune checkpoint molecules. Patients with a lower riskScore exhibited a higher complete remission rate in CRCs. Finally, seven CRGs involved in riskScore were significantly altered between cancerous and paracancerous normal tissues. Elesclomol, a potent copper ionophore, significantly altered expressions of seven CRGs in CRCs, indicating their relationship with cuproptosis. Conclusions: The cuproptosis-related gene signature could serve as a potential prognostic predictor for colorectal cancer patients and may offer novel insights into clinical cancer therapeutics.
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Acute pancreatitis (AP) had been one of the main reasons for hospitalization worldwide. However, the mechanisms related to AP remained to be unclear. This study identified 37 miRNAs and 189 mRNAs were differentially expressed in pancreatitis and normal samples. Bioinformatics analysis showed DEGs were significantly related to PI3K-Akt signaling, FoxO signaling, Oocyte meiosis, Focal adhesion, and Protein digestion and absorption. By constructing a signaling-DEGs regulation network, we found COL12A1, DPP4, COL5A1, COL5A2, and SLC1A5 were related to regulating Protein digestion and absorption, THBS2, BCL2, NGPT1, EREG, COL1A1 were related to regulating PI3K signaling, CCNB1, CDKN2B, IRS2, PLK2 were related to modulating FOXO signaling. Next, we constructed 1 miRNA-mRNA regulation network in AP, consisting of 34 miRNAs and 96 mRNAs. The protein-protein interaction networks and the miRNA-targets networks analysis show that hsa-miR-199a-5p, hsa-miR-150, hsa-miR-194, COL6A3 and CNN1 acted as hub regulators in AOf note, through comprehensive expression analysis, we found several miRNAs and mRNAs were significantly related to modulating autophagy signaling in AP, including hsa-miR-181c, hsa-miR-181d, hsa-miR-181b, hsa-miR-379 and hsa-miR-199a-5Overall, this study screening differently expressed miRNAs in AP and revealed miRNA- autophagy regulation may serve as a potential prognosis and Therapeutic marker for AP.
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MicroARNs , Pancreatitis , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Enfermedad Aguda , Pancreatitis/genética , MicroARNs/genética , MicroARNs/metabolismo , Transducción de Señal/genética , Redes Reguladoras de Genes , Antígenos de Histocompatibilidad Menor , Sistema de Transporte de Aminoácidos ASC/genética , Sistema de Transporte de Aminoácidos ASC/metabolismoRESUMEN
Flexible energy storage device is one of the most critical components as power source for wearable electronics. The emergence of MXenes, a growing family of 2D nanomaterials, has demonstrated a brand-new possibility for flexible energy storage. However, the fabrication of MXene films with satisfactory mechanical, electrical, and electrochemical reliabilities remains challenging due to the weak interlayer interactions and self-restacking of MXene sheets. Sequential bridging of polydopamine/polyethyleneimine-functionalized (PDA/PEI)-coated MXene sheets to induce synergistically covalent and hydrogen binding connections of MXene-based films is demonstrated here. By interrupting self-hydrogen bonding and π-π stacking interactions, the introduction of long-chain PEI can not only inhibit the massive aggregation of PDA, but also improve the continuity of the interconnection network of PDA/PEI between MXene layers. Hence, the as-prepared MXene/PDA/PEI composite film displays high mechanical strength (≈366 MPa) which achieves 12-fold improvement compared with pure MXene film, as well as superior energy storage capability (≈454 F g-1 at 5 mV s-1 ) and rate performance of ≈48% at 10 000 mV s-1 . This modulation of inserted polymer between MXene layers can provide an avenue for assembling high performance MXene films, and can even be extended to the fabrication of other 2D platelets for varied applications.
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Helicobacter pylori (H. pylori) is an infectious pathogen and the leading cause of gastrointestinal diseases, including gastric adenocarcinoma. Currently, bismuth quadruple therapy is the recommended first-line treatment, and it is reported to be highly effective, with >90% eradication rates on a consistent basis. However, the overuse of antibiotics causes H. pylori to become increasingly resistant to antibiotics, making its eradication unlikely in the foreseeable future. Besides, the effect of antibiotic treatments on the gut microbiota also needs to be considered. Therefore, effective, selective, antibiotic-free antibacterial strategies are urgently required. Due to their unique physiochemical properties, such as the release of metal ions, the generation of reactive oxygen species, and photothermal/photodynamic effects, metal-based nanoparticles have attracted a great deal of interest. In this article, we review recent advances in the design, antimicrobial mechanisms and applications of metal-based nanoparticles for the eradication of H. pylori. Additionally, we discuss current challenges in this field and future perspectives that may be used in anti-H. pylori strategies.
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Infecciones por Helicobacter , Helicobacter pylori , Nanopartículas , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Inhibidores de la Bomba de Protones/farmacología , Inhibidores de la Bomba de Protones/uso terapéutico , Quimioterapia Combinada , Antibacterianos/farmacología , Bismuto/farmacologíaRESUMEN
Background and Objectives: The Hot AXIOS system, which features a cautery-enhanced lumen-apposing metal stent, facilitates EUS-guided transmural drainage of pancreatic fluid collection (PFC). We aimed to evaluate the safety and efficacy of stents in a multicenter Chinese cohort. Patients and Methods: Thirty patients from nine centers with a single pancreatic pseudocyst (PP) or walled-off necrosis (WON) who underwent EUS-guided transgastric or transduodenal drainage with the novel stent were prospectively enrolled. Results: We included 15 (50%) patients with PPs and 15 (50%) with WONs. The mean diameter of the PFCs was 11.06 ± 3.56 cm. Stent placement was technically successful in all patients (100%), whereas clinical success was achieved in 93.3% of patients (28/30). Clinical success was defined as the alleviation of clinical symptoms combined with at least a 50% reduction in PFC diameter within 60 days after surgery. 73.3% (22/30) of AXIOS stents were removed after reaching clinical success in the 1st month of follow-up. A total of 14 (46.7%) PFC-associated infections occurred (4 pre- and 10 postoperation), which recovered within 1 week after treatment. Other complications included three (10%) partially or fully blocked stents and two (6.7%) stent migrations. Regarding the fully opened stent without blocking, complete remission of PFCs within 1 month was independently predicted by a previous pancreatitis attack > 6 months prior (adjusted odds ratio: 11.143; 95% confidence interval: 1.108-112.012; P = 0.041). Conclusion: EUS-guided drainage of PFCs using the Hot AXIOS system is safe and efficient. Regarding completely patent stents, a previous pancreatitis attack > 6 months prior predicts a greater chance of achieving 100% remission of PFCs within 1 month of AXIOS treatment.
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The optimal number of examined lymph nodes (ELNs) for gastric signet ring cell carcinoma recommended by National Comprehensive Cancer Network guidelines remains unclear. This study aimed to determine the optimal number of ELNs and investigate its prognostic significance. In this study, we included 1723 patients diagnosed with gastric signet ring cell carcinoma in the Surveillance, Epidemiology, and End Results database. X-tile software was used to calculate the cutoff value of ELNs, and the optimal number of ELNs was found to be 32 for adequate nodal staging. In addition, we performed propensity score matching (PSM) analysis to compare the 1-, 3-, and 5-year survival rates; 1-, 3-, and 5-year survival rates for total examined lymph nodes (ELNs < 32 vs. ELNs ≥ 32) were 71.7% vs. 80.1% (p = 0.008), 41.8% vs. 51.2% (p = 0.009), and 27% vs. 30.2% (p = 0.032), respectively. Furthermore, a predictive model based on 32 ELNs was developed and displayed as a nomogram. The model showed good predictive ability performance, and machine learning validated the importance of the optimal number of ELNs in predicting prognosis.
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BACKGROUND AND AIMS: Current practice on Helicobacter pylori infection mostly focuses on individual-based care in the community, but family-based H. pylori management has recently been suggested as a better strategy for infection control. However, the family-based H. pylori infection status, risk factors and transmission pattern remain to be elucidated. METHODS: From September 2021 to December 2021, 10 735 families (31 098 individuals) were enrolled from 29 of 31 provinces in mainland China to examine family-based H. pylori infection, related factors and transmission pattern. All family members were required to answer questionnaires and test for H. pylori infection. RESULTS: Among all participants, the average individual-based H. pylori infection rate was 40.66%, with 43.45% for adults and 20.55% for children and adolescents. Family-based infection rates ranged from 50.27% to 85.06% among the 29 provinces, with an average rate of 71.21%. In 28.87% (3099/10 735) of enrolled families, there were no infections; the remaining 71.13% (7636/10 735) of families had 1-7 infected members, and in 19.70% (1504/7636), all members were infected. Among 7961 enrolled couples, 33.21% had no infection, but in 22.99%, both were infected. Childhood infection was significantly associated with parental infection. Independent risk factors for household infection were infected family members (eg, five infected members: OR 2.72, 95% CI 1.86 to 4.00), living in highly infected areas (eg, northwest China: OR 1.83, 95% CI 1.57 to 2.13), and large families in a household (eg, family of three: OR 1.97, 95% CI 1.76 to 2.21). However, family members with higher education and income levels (OR 0.85, 95% CI 0.79 to 0.91), using serving spoons or chopsticks, more generations in a household (eg, three generations: OR 0.79, 95% CI 0.68 to 0.92), and who were younger (OR 0.57, 95% CI 0.46 to 0.70) had lower infection rates (p<0.05). CONCLUSION: Familial H. pylori infection rate is high in general household in China. Exposure to infected family members is likely the major source of its spread. These results provide supporting evidence for the strategic changes from H. pylori individual-based treatment to family-based management, and the notion has important clinical and public health implications for infection control and related disease prevention.
Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Niño , Adulto , Adolescente , Humanos , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/prevención & control , Familia , Factores de Riesgo , China/epidemiología , Estudios Epidemiológicos , PrevalenciaRESUMEN
Background: Health education about Helicobacter pylori (H. pylori) is one of the most effective methods to prevent H. pylori infection and standardize H. pylori eradication treatment. Short videos enable people to absorb and remember information more easily and are an important source of health education. This study aimed to assess the information quality of H. pylori-related videos on Chinese short video-sharing platforms. Methods: A total of 242 H. pylori-related videos from three Chinese short video-sharing platforms with the most users, TikTok, Bilibili, and Kwai, were retrieved. The Global Quality Score (GQS) and the modified DISCERN tool were used to assess the quality and content of videos, respectively. Additionally, comparative analyzes of videos based on different sources and common H. pylori issues were also conducted. Results: The median GQS score and DISCERN score was 2 for H. pylori-related videos analyzed in this study. Non-gastroenterologists posted the most H. pylori-related videos (136/242, 56.2%). Videos from gastroenterologists (51/242, 21.0%) had the highest GQS and DISCERN scores, with a median of 3. Few videos had content on family-based H. pylori infection control and management (5.8%), whether all H. pylori-positive patients need to undergo eradication treatment (27.7%), and the adverse effects of H. pylori eradication therapy (16.1%). Conclusion: Generally, the content and quality of the information in H. pylori-related videos were unsatisfactory, and the quality of the video correlated with the source of the video. Videos from gastroenterologists provided more correct guidance with higher-quality information on the prevention and treatment of H. pylori infection.
Asunto(s)
Educación en Salud , Infecciones por Helicobacter , Helicobacter pylori , Medios de Comunicación Sociales , Humanos , Pueblo Asiatico , Estudios Transversales , Educación en Salud/normas , Fuentes de Información , Información de Salud al Consumidor/normas , Infecciones por Helicobacter/prevención & control , Infecciones por Helicobacter/terapia , China , Grabación en Video , GastroenterologíaRESUMEN
BACKGROUND: The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori ) infection status and CYP2C19 polymorphism on anaprazole. METHODS: In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. RESULTS: The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). CONCLUSIONS: The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers. REGISTRATION: ClinicalTrials.gov, NCT04215653.