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Objective: To explore the associations between dietary zinc intake and cardiovascular diseases (CVDs), including congestive heart failure (CHF), coronary heart disease (CHD), angina, heart attack, and cerebrovascular accident (CVA), this study was performed. Setting: Data from the National Health and Nutrition Examination Survey (2005-2018) were used in this study. Dietary zinc intake was stratified into quartiles. Restricted cubic splines were constructed to assess nonlinear associations and identify cut-off values based on the type of nonlinearity. Binary logistic regressions were performed using the cut-offs. Results: Positive associations were detected between the second, third, and fourth quantiles of dietary zinc intake and decreased risks of overall CVDs (Q2: OR = 0.83, 95 % CI = 0.72-0.96; Q3: OR = 0.83, 95 % CI = 0.71-0.96; Q4: OR = 0.79, 95 % CI = 0.67-0.93). The second, third, and fourth quantiles were significantly associated with decreased risks of various CVDs (all P < 0.05), except for CHD and angina (all P > 0.05). Restricted cubic spline regression revealed significant nonlinear trends for associations of dietary zinc intake with the risk of developing CVDs and CHF (both P for nonlinear <0.05), whereas those for heart attack and CVA were marginally significant (P for nonlinear = 0.072, and 0.075, respectively). Conclusions: This study revealed that high dietary zinc intake is associated with reduced risks of developing CVDs, CHF, heart attack, and CVA, but not CHD or angina.
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BACKGROUND: Colon adenocarcinoma (COAD) is a prevalent malignant tumor globally, contributing significantly to cancer-related mortality. COAD guidelines label MSI (Microsatellite instability) and MSS (Microsatellite stability) subtypes as global classification criteria and treatment strategy selection criteria for COAD. Various combination therapies involving PD-L1 inhibitors and adjuvant therapy to enhance anti-tumor efficacy. METHODS: Datasets from single-cell RNA sequencing and bulk RNA sequencing in the TCGA and GEO databases were utilized to identify differentially expressed genes (DEGs). Furthermore, the correlation between ATP8B3 and PD-L1 was validated using siRNA, shRNA, and western blot analysis. Additionally, the association between ATP8B3 and immune checkpoint blockade (ICB) therapy was investigated through immune infiltration analysis and flow cytometry in both in vivo and in vitro assays. RESULTS: In the COAD patient group, ATP8B3 significantly contributed to the establishment of an immunosuppressive microenvironment. Inhibiting ATP8B3 led to a reduction in PD-L1 expression in colon cancer cell lines. Additionally, ATP8B3 expression levels could serve as a potential guide for PD-L1 treatment in MSI-H COAD patients, with higher ATP8B3 expression associated with increased sensitivity to PD-L1 therapy. However, due to the lack of immuno-killer cells in the microenvironment of MSS subtypes, elevated ATP8B3 expression couldn't increase the sensitivity of MSS COAD patients to PD-L1 inhibitors. CONCLUSION: Our research results support that Inhibiting ATP8B3 could enhance TIL (tumor-infiltrating lymphocyte) infiltration by reducing PD-L1 expression in MSI-H COAD, thereby serving as an effective strategy to improve PD-L1 blocker efficacy. The treatment strategy of combining ATP8B3 inhibitors and immunotherapy for MSI/MSS COAD patients will be the best choice.
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Osteoarthritis (OA) is a common chronic disease characterized by progressive cartilage degeneration and secondary synovial inflammation. Bergamottin (Ber) is an important natural derivative of the furanocoumarin compound, extracted from natural foods, such as the pulp of grapefruits and pomelos. Ber exhibits several characteristicsthat are beneficial to human health, such as anti-inflammation, antioxidant, and anti-cancer effects. However, the role of Ber in the treatment of OA has not been elucidated to date. Therefore, in the present study, in vitro experiments were conducted, which demonstrated that Ber reduces the secretion of inducible nitric oxide synthase (iNOS), nitric oxide (NO), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) under the stimulation of interleukin-1ß (IL-1ß). Ber also reversed the IL-1 ß-mediated aggrecan and type II collagen degradation within the extracellular matrix (ECM). In addition, in vivo experiments were conducted, in which Ber ameliorated the progression of OA in mice. It was revealed that Ber exerted its cellular effect by activating the Sirt1/NF-kB pathways. In conclusion, the present study demonstrated the therapeutic potential of Ber in the context of OA.
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OBJECTIVE: This study aims to assess the efficacy and safety of CT-guided percutaneous cryoablation in treating hepatocellular carcinoma (HCC) located explicitly in high-risk sites. MATERIALS AND METHODS: Data were collected retrospectively from 685 HCC patients undergoing percutaneous cryoablation at Tianjin Medical University Cancer Hospital between January 2018 and December 2021. Of these, 106 patients had lesions in high-risk sites, defined as a minimum distance of less than 10 mm from the heart/great vessels, diaphragm, gastrointestinal tract, and gallbladder, as determined by preoperative CT or MRI imaging. Technical success rate, complete ablation rate, and complications at 1, 12, and 24 months post-surgery were evaluated. A statistical analysis of the ablation effect difference between the high-risk site and non-high-risk site groups was conducted, utilizing propensity score matching (PSM) to mitigate patient selection bias. Univariate and multivariate logistic regression analyzes were performed to identify risk factors for the incidence of coronary heart disease. RESULTS: The study comprised 106 cases in the high-risk group and 218 cases in the non-high-risk group. After PSM analysis until December 2021, 95 matched pairs were included. Both groups demonstrated a 100% intraoperative technical success rate, and no major complications related to cryoablation were observed. Follow-up ranged from 24 to 38 months. The complete ablation rate was 82.1% and 71.7% in the high-risk group and 83.9% and 73.9% in the non-high-risk group at 12 and 24 months, respectively. There was no significant difference in complete ablation rates between the two groups before and after PSM (P > 0.05). Multivariate analysis identified the distance between the tumor edge and high-risk site ≤ 5 mm and preoperative transarterial chemoembolization (TACE) treatment as independent risk factors for cryoablation effect. CONCLUSION: CT-guided percutaneous cryoablation proves to be a safe and effective approach for HCC patients with high-risk sites, serving as an alternative to surgical treatment.
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Organisms are generally exposed to target contaminant with stable concentrations in traditional ecotoxicological studies. However, it is difficult to truly represent the dynamics and complexity of actual aquatic pollution for risk management. Contaminants may enter nearby aquatic systems in pulsed exposure, thus resulting in that aquatic organisms will be exposed to contaminants at fluctuating concentrations. Especially during the season of summer, due to the changes in displacement or periodic emissions of veterinary antibiotics in aquaculture, algal blooms occur frequently in surrounding waters, thus leading to eutrophication of the water. Florfenicol (FFC) is currently widely used as a veterinary antibiotic, but the aquatic ecological risks of FFC under concentration fluctuations are still unknown. Therefore, the acute exposure, chronic exposure and pulsed exposure effects of FFC on Microcystis aeruginosa were investigated to comprehensively evaluate the ecological risk of FFC and raise awareness of the pulsed exposure mode. Results indicated that the toxic effects of FFC on M. aeruginosa were dominated by exposure mode, exposure duration, exposure frequency, and exposure concentration. The maximum growth inhibition rate of the 10 µg/L FFC treatment amounted to 4.07% during chronic exposure of 18 days. However, the growth inhibition rate decreased from 55.1% to 19.31% when algae was exposure to 10 µg/L FFC during the first pulsed exposure (8 h). Therefore, when the concentration of FFC was equal under chronic and pulsed exposure, FFC exhibited greater toxicity on M. aeruginosa in short pulsed exposure than in continuous exposure. In addition, repetitive pulsed exposure strengthened the resistance of M. aeruginosa on FFC. The adaptive regulation of algae was related to the duration and frequency of exposure. Above results suggested that traditional toxicity assessments lacked consideration for fluctuating concentrations during pollutant emissions, thus underestimating the environmental risk of contaminant. This investigation aims to facilitate the standardization of pulsed exposure.
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Antibacterianos , Acuicultura , Contaminantes Químicos del Agua , Antibacterianos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisis , Microcystis/crecimiento & desarrollo , Tianfenicol/análogos & derivados , Tianfenicol/toxicidad , Eutrofización , Monitoreo del Ambiente/métodosRESUMEN
Fucoxanthin, a carotenoid exclusively derived from algae, exerts its bioactivities with the modulation of the gut microbiota in mice. However, mechanisms through which fucoxanthin regulates the gut microbiota and its derived metabolites/metabolism in humans remain unclear. In this study, we investigated the effects of fucoxanthin on the gut microbiota and metabolism of non-obese individuals using an in vitro simulated digestion-fermentation cascade model. The results showed that about half of the fucoxanthin was not absorbed in the intestine, thus reaching the colon. The gut microbiota from fecal samples underwent significant changes after 48 or 72 hours in vitro fermentation. Specifically, fucoxanthin significantly enhanced the relative abundance of Bacteroidota and Parabacteroides, leading to improved functions of the gut microbiota in its development, glycan biosynthesis and metabolism as well as in improving the digestive system, endocrine system and immune system. The recovery of fucoxanthin during fermentation showed a decreasing trend with the slight bio-conversion of fucoxanthinol. Notably, fucoxanthin supplementation significantly altered metabolites, especially bile acids and indoles in the simulated human gut ecosystem. Correlation analysis indicated the involvement of the gut microbiota in the manipulation of these metabolites by fucoxanthin. Moreover, all these altered metabolites revealed the improvement in the capacity of fucoxanthin in manipulating gut metabolism, especially lipid metabolism. Overall, fucoxanthin determinedly reshaped the gut microbiota and metabolism, implying its potential health benefits in non-obese individuals.
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Heces , Fermentación , Microbioma Gastrointestinal , Xantófilas , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Xantófilas/metabolismo , Xantófilas/farmacología , Heces/microbiología , Masculino , Adulto , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genéticaRESUMEN
OBJECTIVE: To investigate the esophageal motility characteristics of gastroesophageal reflux disease (GERD) and their relationship with symptoms. PATIENTS AND METHODS: We examined 101 patients diagnosed with GERD by endoscopy and divided them into 3 groups as follows: nonerosive reflux disease (NERD), reflux esophagitis, and Barrett esophagus. Esophageal high-resolution manometry and the GERD Questionnaire were used to investigate the characteristics of esophageal dynamics and symptoms. In addition, the reflux symptom index was completed and the patients were divided into 7 groups according to symptoms. We then determined the correlation between dynamic esophageal characteristics and clinical symptoms. RESULTS: Upper (UES) and lower (LES) esophageal sphincter pressures and the 4-second integrated relaxation pressure in the RE group were lower than those in the NERD group. The 4-second integrated relaxation pressure in the Barrett esophagus group was also lower than that in the NERD group. In the analysis of extraesophageal symptoms, high-resolution manometry showed significant differences in UES pressures among all groups. Further subgroup analysis showed that compared with the group without extraesophageal symptoms, the UES pressure of the groups with pharyngeal foreign body sensation, throat clearing, and multiple extraesophageal symptoms was lower. CONCLUSIONS: As GERD severity increases, motor dysfunction of the LES and esophageal body gradually worsens, and the LES plays an important role in GERD development. Decreased UES pressure plays an important role in the occurrence of extraesophageal symptoms, which is more noticeable in patients with pharyngeal foreign body sensation and throat clearing.
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Reflujo Gastroesofágico , Manometría , Humanos , Reflujo Gastroesofágico/fisiopatología , Reflujo Gastroesofágico/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Esófago de Barrett/fisiopatología , Esofagitis Péptica/fisiopatología , Esofagitis Péptica/diagnóstico , Esfínter Esofágico Inferior/fisiopatología , Presión , Índice de Severidad de la EnfermedadRESUMEN
Brain-inspired computing, drawing inspiration from the fundamental structure and information-processing mechanisms of the human brain, has gained significant momentum in recent years. It has emerged as a research paradigm centered on brain-computer dual-driven and multi-network integration. One noteworthy instance of this paradigm is the hybrid neural network (HNN), which integrates computer-science-oriented artificial neural networks (ANNs) with neuroscience-oriented spiking neural networks (SNNs). HNNs exhibit distinct advantages in various intelligent tasks, including perception, cognition and learning. This paper presents a comprehensive review of HNNs with an emphasis on their origin, concepts, biological perspective, construction framework and supporting systems. Furthermore, insights and suggestions for potential research directions are provided aiming to propel the advancement of the HNN paradigm.
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BACKGROUND: The effectiveness of flipped classroom (FC) on puncture skills in medical education is still uncertain. This study aimed to assess the role of the FC model in puncture skills and investigate the acceptance and approval of FC among medical students and instructors. METHODS: A mixed research approach of quasi-experimental research design and descriptive qualitative research was conducted in September 2022 for one month, using an FC teaching method that combined instructional videos and group learning. The study participants were 71 fifth-year medical students from two classes at a Chinese medical school and four instructors. The medical students were randomly divided into two groups: the traditional classroom (TC) group (Group A) and the FC group (Group B). For teaching, Group B used FC, and Group A used PowerPoint-based TC. The effectiveness of the two teaching models was assessed with Objective Structured Clinical Examination (OSCE), and questionnaires were distributed to the medical students and instructors after the assessment. Two independent sample t-tests were used to analyse the differences in demographic data and the OSCE scores of the two groups of medical students. RESULTS: Group B scored higher in puncture skills than Group A, especially regarding abdominal puncture (p = 0.03), thoracentesis (p < 0.001), bone marrow puncture (p < 0.001) and average performance of puncture skills (p < 0.001). For lumbar puncture, no difference in skill scores was observed between groups A and B (p > 0.409). The medical students thought that the FC improved their self-learning ability and helped them acquire knowledge. Regarding the OSCE of their skills, most medical students thought that it was more innovative and objective than traditional examinations and that it was better for assessing their overall abilities. Both the FC and OSCE were supported by the medical students. The instructors were also satisfied with the students' performance in the FC and supported the teaching model, agreeing to continue using it. CONCLUSIONS: This study shows that FC teaching that combines instructional videos and group learning is a reliable and well-received teaching method for puncture skills, which supplements and expands existing teaching methods in the medical field.
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Aprendizaje , Estudiantes de Medicina , Humanos , Examen Físico , Punciones , Encuestas y Cuestionarios , Enseñanza , Aprendizaje Basado en Problemas/métodos , CurriculumRESUMEN
Formamidine lead triiodide (FAPbI3 ) perovskites have attracted increasing interest for photovoltaics attributed to the optimal bandgap, high thermal stability, and the record power conversion efficiency (PCE). However, the materials still face several key challenges, such as phase transition, lattice defects, and ion migration. Therefore, external ions (e.g., cesium ions (Cs+ )) are usually introduced to promote the crystallization and enhance the phase stability. Nevertheless, the doping of Cs+ into the A-site easily leads to lattice compressive strain and the formation of pinholes. Herein, trioctylphosphine oxide (TOPO) is introduced into the precursor to provide tensile strain outside the perovskite lattice through intermolecular forces. The special strain compensation strategy further improves the crystallization of perovskite and inhibits the ion migration. Moreover, the TOPO molecule significantly passivates grain boundaries and undercoordinated Pb2+ defects via the forming of PâOâPb bond. As a result, the target solar cell devices with the synergistic effect of Cs+ and TOPO additives have achieved a significantly improved PCE of 22.71% and a high open-circuit voltage of 1.16 V (voltage deficit of 0.36 V), with superior stability under light exposure, heat, or humidity conditions.
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Neurodegenerative diseases associated with aging are often accompanied by cognitive decline and gut microbiota disorder. But the impact of gut microbiota on these cognitive disturbances remains incompletely understood. Short chain fatty acids (SCFAs) are major metabolites produced by gut microbiota during the digestion of dietary fiber, serving as an energy source for gut epithelial cells and/or circulating to other organs, such as the liver and brain, through the bloodstream. SCFAs have been shown to cross the blood-brain barrier and played crucial roles in brain metabolism, with potential implications in mediating Alzheimer's disease (AD) and Parkinson's disease (PD). However, the underlying mechanisms that SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, the dietary sources which determine these SCFAs production was not thoroughly evaluated yet. This comprehensive review explores the production of SCFAs by gut microbiota, their transportation through the gut-brain axis, and the potential mechanisms by which they influence age-related neurodegenerative disorders. Also, the review discusses the importance of dietary fiber sources and the challenges associated with harnessing dietary-derived SCFAs as promoters of neurological health in elderly individuals. Overall, this study suggests that gut microbiota-derived SCFAs and/or dietary fibers hold promise as potential targets and strategies for addressing age-related neurodegenerative disorders.
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Medical image fusion aims to integrate complementary information from multimodal medical images and has been widely applied in the field of medicine, such as clinical diagnosis, pathology analysis, and healing examinations. For the fusion task, feature extraction is a crucial step. To obtain significant information embedded in medical images, many deep learning-based algorithms have been proposed recently and achieved good fusion results. However, most of them can hardly capture the independent and underlying features, which leads to unsatisfactory fusion results. To address these issues, a multibranch residual attention reconstruction network (MBRARN) is proposed for the medical image fusion task. The proposed network mainly consists of three parts: feature extraction, feature fusion, and feature reconstruction. Firstly, the input medical images are converted into three scales by image pyramid operation and then are input into three branches of the proposed network respectively. The purpose of this procedure is to capture the local detailed information and the global structural information. Then, convolutions with residual attention modules are designed, which can not only enhance the captured outstanding features, but also make the network converge fast and stably. Finally, feature fusion is performed with the designed fusion strategy. In this step, a new more effective fusion strategy is correspondently designed for MRI-SPECT based on the Euclidean norm, called feature distance ratio (FDR). The experimental results conducted on Harvard whole brain atlas dataset demonstrate that the proposed network can achieve better results in terms of both subjective and objective evaluation, compared with some state-of-the-art medical image fusion algorithms.
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Algoritmos , Encéfalo , Encéfalo/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Procesamiento de Imagen Asistido por ComputadorRESUMEN
Colorimetric analysis for mercury detection has great application potential in the prevention of health damage caused by mercury in the environment. Sensitivity, selectivity, and portability are core competencies of sensors, and concentrating these properties in a single sensor for efficient mercury detection remains a great challenge. Herein, a hollow structure CuS@CuSe@PVP (CCP) was prepared in which the enzyme-like activities could be activated by Hg2+ due to the antagonism between Hg and Se, inspiring the establishment of a colorimetric method for Hg2+ detection. As for Hg2+ detection performance, the linear range (LR) and limit of detection (LOD) were 1-900 and 0.81 nM in the POD-like activity system, respectively. Also, 5-550 nM of LR and 2.34 nM of LOD were achieved in the OD-like activity system. Further, a smartphone-mediated portable RGB nanosensor was fabricated, with a LOD down to 6.65 nM in the POD-like system and 7.97 nM in the OD-like system. Moreover, the excellent self-calibration and satisfactory recovery of 94.77%-106.16% were shown in the application of real water samples analysis. This study represented advanced progress toward emerging applications of nanozymes with multiple enzyme-like activities in heavy metal detection and will accelerate the development of efficient and portable heavy metal sensors.
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Colorimetría , Mercurio , Calibración , Límite de DetecciónRESUMEN
The effect of Zn/Ca ratio on the corrosion behavior of Mg-3Zn-0.2Ca-1.0MgO (3ZX) and Mg-1Zn-0.2Ca-1.0MgO (ZX) was investigated on the as-extruded specimens. Microstructure observations revealed that the low Zn/Ca ratio led to the grain growth from 1.6 µm in 3ZX to 8.1 µm in ZX. At the same time, the low Zn/Ca ratio changed the nature of second phase from the existence of Mg-Zn and Ca2Mg6Zn3 phases in 3ZX to the dominated Ca2Mg6Zn3 phase in ZX. The local galvanic corrosion caused by the excessive potential difference was alleviated obviously due to the missing of MgZn phase in ZX. Besides, the in vivo experiment also showed that ZX composite exhibited a good corrosion performance and the bone tissue around the implant grew well.
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Ginseng is widely regarded as a panacea in Oriental medicine mainly due to its immunomodulatory activity. We previously found that sulfur fumigation, a commonly used pesticidal and anti-bacterial processing practice, weakened the immunomodulatory activity of ginseng. However, if and how sulfur fumigation affects the polysaccharides in ginseng, the crucial components contributing to the immunomodulatory function, remain unknown. Here we report that polysaccharides extracted from sulfur-fumigated ginseng (SGP) presented different chemical properties with polysaccharides extracted with non-fumigated ginseng (NGP), particularly increased water extraction yield and decreased branching degree. SGP had weaker immunomodulatory activity than NGP in immunocompromised mice, as evidenced by less improved immunophenotypes involving body weight, immune organ indexes, white blood cells, lymphocyte cell populations and inflammation. The different immunomodulatory activities were accompanied by changes in the interaction between the polysaccharides and gut microbiota, in which SGP stimulated the growth of different bacteria but produced less SCFAs as compared to NGP. Fecal microbiota transplantation experiment suggested that gut microbiota played a central role in causing the weakened immunomodulatory activity in vivo. This study provides definite evidence that sulfur fumigation affects the chemistry and bioactivity of ginseng polysaccharides, thereby contributing to understanding how sulfur fumigation weakens the immunomodulatory activity of ginseng.
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Panax , Ratones , Animales , Panax/química , Fumigación , Azufre/química , Polisacáridos/farmacología , Extractos VegetalesRESUMEN
Introduction: Cold and exercise are two important stimuli affecting the secretion of osteokines and adipomyokines, which often occur simultaneously. However, few studies have investigated the changes in osteokines and adipomyokines induced by exercise during severe cold and their corresponding associations. Therefore, this study aimed to investigate the changes in sclerostin and meteorin-like (metrnl) protein before and after cold exercise (ice swimming [IS]) and observe their correlation. Methods: For this, 56 daily ice swimmers' data were included in this study. Serum sclerostin and metrnl were measured 30 min before IS and 30 min after. The fat mass, visceral fat area, fat-free mass, skeletal muscle mass, lumbar spine, and femoral neck bone mineral density of the ice swimmers were measured. Results: After IS, sclerostin exhibited significant decreases, whereas metrnl showed no significant change. In addition, the baseline level of sclerostin and the decrease in sclerostin were positively correlated with serum metrnl after adjusting for age, gender, and body composition indicators. Discussion: IS caused a significant decrease in sclerostin but did not affect metrnl. Furthermore, the associations between sclerostin and metrnl suggested a correlation between osteokines and adipomyokines; this encourages future exploration of the interconnection between bone, muscle, and fat, which will be beneficial for identifying potential common therapeutic targets for diseases such as osteoporosis, sarcopenia, and obesity.
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Dioscoreae Rhizoma (Chinese yam; derived from the rhizome of Dioscorea opposita Thunb.) (DR), commonly consumed as a food or supplement, is often sulfur-fumigated during post-harvest handling, but it remains largely unknown if and how sulfur fumigation impacts the chemistry of DR. In this study, we report the impact of sulfur fumigation on the chemical profile of DR and then the molecular and cellular mechanisms potentially involved in the chemical variations induced by sulfur fumigation. The results show that sulfur fumigation significantly and specifically changed the small metabolites (molecular weight lower than 1000 Da) and polysaccharides of DR at both qualitative and quantitative levels. Multifaceted molecular and cellular mechanisms involving chemical transformations (e.g., acidic hydrolysis, sulfonation, and esterification) and histological damage were found to be responsible for the chemical variations in sulfur-fumigated DR (S-DR). The research outcomes provide a chemical basis for further comprehensive and in-depth safety and functional evaluations of sulfur-fumigated DR.
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PURPOSE: The Asia-Pacific Colorectal Screening (APCS) score and its derivatives have been used to predict advanced colorectal neoplasia (ACN). However, it remains unknown whether they apply to the current Chinese population in general clinical practice. Therefore, we aimed to update the APCS score system by applying data from two independent asymptomatic populations to predict the risk of ACN in China. METHODS: We developed an adjusted APCS (A-APCS) score by using the data of asymptomatic Chinese patients undergoing colonoscopies from January 2014 to December 2018. Furthermore, we validated this system in another cohort of 812 patients who underwent screening colonoscopy between January and December 2021. The discriminative calibration ability of the A-APCS and APCS scores was comparatively evaluated. RESULTS: Univariate and multivariate logistic regression were applied to assess the risk factors for ACN, and an adjusted scoring system of 0 to 6.5 points was schemed according to the results. Utilizing the developed score, 20.2%, 41.2%, and 38.6% of patients in the validation cohort were classified as average, moderate, and high risk, respectively. The corresponding ACN incidence rates were 1.2%, 6.0%, and 11.1%, respectively. In addition, the A-APCS score (c-statistics: 0.68 for the derivation and 0.80 for the validation cohort) showed better discriminative power than using predictors of APCS alone. CONCLUSIONS: The A-APCS score may be simple and useful in clinical applications for predicting ACN risk in China.
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Neoplasias Colorrectales , Pueblos del Este de Asia , Humanos , China/epidemiología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/patología , Pueblos del Este de Asia/estadística & datos numéricos , Enfermedades Asintomáticas/epidemiología , Medición de Riesgo , Indicadores de SaludRESUMEN
BACKGROUND: PDAC is a highly malignant and immune-suppressive tumor, posing great challenges to therapy. METHODS: In this study, we utilized multi-center RNA sequencing and non-negative matrix factorization clustering (NMF) to identify a group of metabolism-related genes that could effectively predict the immune status and survival (both disease-free survival and overall survival) of pancreatic ductal adenocarcinoma (PDAC) patients. Subsequently, through the integration of single cell sequencing and our center's prospective and retrospective cohort studies, we identified ABHD17C, which possesses metabolic and immune-related characteristics, as a potential biomarker for predicting the prognosis and response to anti-PD1 therapy in PDAC. We then demonstrated how ABHD17C participates in the regulation of the immune microenvironment through in vitro glycolytic function experiments and in vivo animal experiments. RESULTS: Through screening for pancreatic cancer metabolic markers and immune status, we identified a critical molecule that inhibits pancreatic cancer survival and prognosis. Further flow cytometry analysis confirmed that ABHD17C is involved in the inhibition of the formation of the immune environment in PDAC. Our research found that ABHD17C participates in the metabolic process of tumor cells in in vitro and in vivo experiments, reshaping the immunosuppressive microenvironment by downregulating the pH value. Furthermore, through LDHA inhibition experiments, we demonstrated that ABHD17C significantly enhances glycolysis and inhibits the formation of the immune suppressive environment. In in vivo experiments, we also validated that ABHD17C overexpression significantly mediates resistance to anti-PD1 therapy and promotes the progression of pancreatic cancer. CONCLUSION: Therefore, ABHD17C may be a novel and effective biomarker for predicting the metabolic status and immune condition of PDAC patients, and provide a potential predictive strategy for anti-PD1 therapy in PDAC.
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Background: Molecular targeted therapy combined with immunotherapy significantly improves the prognosis of patients with advanced liver cancer. Additionally, hepatic arterial infusion chemotherapy (HAIC) can improve the prognosis of patients with advanced liver cancer. This real-world study aimed to evaluate the clinical efficacy and safety of HAIC combined with molecular targeted therapy and immunotherapy in the treatment of primary unresectable hepatocellular carcinoma (uHCC). Methods: A total of 135 patients with uHCC were enrolled in this study. Progression-free survival (PFS) was the primary endpoint. The efficacy of the combination therapy was assessed based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) guidelines. Overall survival (OS), adverse events (AEs) and surgical conversion rate were the secondary endpoints. Univariate and multivariate Cox regression analyses were performed to examine independent prognostic factors. For sensitivity analysis, inverse probability weighting (IPW) was used to balance the influence of the tested confounding factors between groups to verify the robustness of conversion surgery for survival benefits. The E-values were estimated to assess robustness to unmeasured confounders. Results: The median number of therapies was three. Approximately 60% of the patients had portal vein tumour thrombosis (PVTT). The most common targeted drugs were lenvatinib and bevacizumab, whereas the most common immunotherapy drug was sintilimab. The overall objective response rate (ORR) was 54.1%, and the disease control rate (DCR) was 94.6%. A total of 97 (72%) patients experienced AEs of grades 3-4. Fatigue, pain and fever were the most common symptoms of grade 3-4 AEs. The median PFS was 28 months and 7 months in the successful and unsuccessful conversion groups, respectively. The median OS was 30 months and 15 months in the successful and unsuccessful conversion groups, respectively. Successful conversion surgery, sex, hapatic vein invasion, BCLC stage, baseline tumour size, AFP levels and maximum therapeutic response were independent prognostic factors for PFS. Successful conversion surgery, number of interventions, hapatic vein invasion and total bilirubin levels were independent prognostic factors for OS. After IPTW, no standardised differences exceeding 0.1 were found. IPW-adjusted Kaplan-Meier curves showed that successful conversion surgery was an independent prognostic factor for both PFS and OS. The E-values of successful conversion surgery were 7.57 and 6.53 for OS and PFS, respectively, which indicated a relatively robust impact of successful conversion surgery on the prognosis of patients. Conclusion: Patients with primary uHCC undergoing HAIC combined with immunotherapy and molecular targeted therapy have a higher tumour regression rate and the side effects are manageable. Patients undergoing surgery after combination therapy have survival benefits.