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BACKGROUND: Patients with different stages of colorectal cancer (CRC) exhibit different abdominal computed tomography (CT) signs. Therefore, the influence of CT signs on CRC prognosis must be determined. AIM: To observe abdominal CT signs in patients with CRC and analyze the correlation between the CT signs and postoperative prognosis. METHODS: The clinical history and CT imaging results of 88 patients with CRC who underwent radical surgery at Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University were retrospectively analyzed. Univariate and multivariate Cox regression analyses were used to explore the independent risk factors for postoperative death in patients with CRC. The three-year survival rate was analyzed using the Kaplan-Meier curve, and the correlation between postoperative survival time and abdominal CT signs in patients with CRC was analyzed using Spearman correlation analysis. RESULTS: For patients with CRC, the three-year survival rate was 73.86%. The death group exhibited more severe characteristics than the survival group. A multivariate Cox regression model analysis showed that body mass index (BMI), degree of periintestinal infiltration, tumor size, and lymph node CT value were independent factors influencing postoperative death (P < 0.05 for all). Patients with characteristics typical to the death group had a low three-year survival rate (log-rank χ 2 = 66.487, 11.346, 12.500, and 27.672, respectively, P < 0.05 for all). The survival time of CRC patients was negatively correlated with BMI, degree of periintestinal infiltration, tumor size, lymph node CT value, mean tumor long-axis diameter, and mean tumor short-axis diameter (r = -0.559, 0.679, -0.430, -0.585, -0.425, and -0.385, respectively, P < 0.05 for all). BMI was positively correlated with the degree of periintestinal invasion, lymph node CT value, and mean tumor short-axis diameter (r = 0.303, 0.431, and 0.437, respectively, P < 0.05 for all). CONCLUSION: The degree of periintestinal infiltration, tumor size, and lymph node CT value are crucial for evaluating the prognosis of patients with CRC.
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Liver transplantation (LT) is an ideal therapeutic option for selected patients with hepatocellular carcinoma (HCC). The selection criteria of HCC for LT have evolved in recent decades. Downstaging therapy is a promising strategy for patients with tumor burden beyond transplant criteria to increase the chance of receiving LT and improve posttransplant survival. Downstaging therapy is also a selection tool that refines the conventional selection criteria based on tumor morphology. Recently, the success of systemic treatment, including immune checkpoint inhibitors, antiangiogenic tyrosine kinase inhibitors, and VEGF inhibitors, in advanced HCC has prompted the discussion regarding the role of systemic therapies for HCC downstaging before transplantation. In this review, we aimed to summarize the current advances in selection criteria and therapeutic options of downstaging therapy for HCC before LT.
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Osteoblast-mediated bone formation and osteoclast-mediated bone resorption are critical processes in bone metabolism. Annexin A, a calcium-phospholipid binding protein, regulates the proliferation and differentiation of bone cells, including bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts, and has gradually become a marker gene for the diagnosis of osteoporosis. As calcium channel proteins, the annexin A family members are closely associated with mechanical stress, which can target annexins A1, A5, and A6 to promote bone cell differentiation. Despite the significant clinical potential of annexin A family members in bone metabolism, few studies have reported on these mechanisms. Therefore, based on a review of relevant literature, this article elaborates on the specific functions and possible mechanisms of annexin A family members in bone metabolism to provide new ideas for their application in the prevention and treatment of bone diseases, such as osteoporosis.
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The objective of this study was to determine the pharmacokinetics of enrofloxacin and its metabolite, ciprofloxacin, in Nanyang cattle after a single intravenous (IV), and intramuscular (IM) administration of enrofloxacin at 2.5 mg/kg body weight (BW). Blood samples were collected at predetermined time points. Enrofloxacin and ciprofloxacin concentrations in plasma were simultaneously determined using a high-performance liquid chromatography (HPLC) assay method and subjected to a non-compartmental analysis. After IV administration, enrofloxacin had a mean (±SD) volume of distribution at steady state (VSS) of 1.394 ± 0.349 L/kg, a terminal half-life (t1/2λz) of 3.592 ± 1.205 h, and a total body clearance (Cl) of 0.675 ± 0.16 L/h/kg. After IM administration, enrofloxacin was absorbed relatively slowly but completely, with a mean absorption time (MAT) of 6.051 ± 1.107 h and a bioavailability of 99.225 ± 7.389%. Both compounds were detected simultaneously in most plasma samples following both routes of administration, indicating efficient biotransformation of enrofloxacin to ciprofloxacin. After IV injection, the peak concentration (Cmax) of ciprofloxacin was 0.315 ± 0.017 µg/mL, observed at 0.958 ± 0.102 h. Following IM injection, the corresponding values were 0.071 ± 0.006 µg/mL and 3 ± 1.095 h, respectively. Following IV and IM administration, the conversion ratio of enrofloxacin to ciprofloxacin was calculated as 59.2 ± 9.6% and 31.2 ± 7.7%, respectively. The present results demonstrated favorable pharmacokinetic profiles for enrofloxacin, characterized by complete absorption with relatively slow kinetics, extensive distribution, efficient biotransformation to ciprofloxacin, and prolonged elimination in Nanyang cattle.
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To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.
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Environmental pollutant is considered to be one of the important factors affecting adolescent growth. However, the effects of volatile organic compounds (VOCs) exposure on adolescent growth have not been assessed. Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 was used to examine the associations between VOCs exposure and adolescent growth indicators through three statistical models. The mediating effect of bone mineral density (BMD) on these associations was examined. The potential pathways and key targets were identified by the network pharmacology analysis methods. This study included 746 adolescents. Three statistical methods consistently showed a negative correlation between VOCs exposure and adolescent growth indicators. Furthermore, BMD mediated the relationship between VOCs exposure and adolescent growth indicators, with mediated proportion ranging from 4.3 % to 53.4 %. Network pharmacology analysis found a significant enrichment in IL-17 signaling pathway. Moreover, the adverse effects of VOCs exposure on adolescent growth were observed to significantly attenuate in adolescents with high serum vitamin D levels. Our results suggested that VOCs exposure was an adverse factor affecting adolescent growth, with BMD playing a significant regulatory role, and IL-17 signaling pathway was the underlying mechanism. Vitamin D supplementation may be a viable strategy to prevent VOCs exposure from affecting adolescent growth.
Subject(s)
Bone Density , Volatile Organic Compounds , Volatile Organic Compounds/toxicity , Adolescent , Humans , Female , Male , Bone Density/drug effects , Environmental Exposure , Vitamin D/blood , Nutrition Surveys , Interleukin-17 , Adolescent Development/drug effects , Air Pollutants/toxicityABSTRACT
Achieving high energy density has always been the goal of lithium-ion batteries (LIBs). SiOx has emerged as a compelling candidate for use as a negative electrode material due to its remarkable capacity. However, the huge volume expansion and the unstable electrode interface during (de)lithiation, hinder its further development. Herein, we report a facile strategy for the synthesis of surface fluorinated SiOx (SiOx@vG-F), and investigate their influences on battery performance. Systematic experiments investigations indicate that the reaction between Li+ and fluorine groups promotes the in-situ formation of stable LiF-rich solid electrolyte interface (SEI) on the surface of SiOx@vG-F anode, which effectively suppresses the pulverization of microsized SiOx particles during the charge and discharge cycle. As a result, the SiOx@vG-F enabled a higher capacity retention of 86.4% over 200 cycles at 1.0 C in the SiOx@vG-F||LiNi0.8Co0.1Mn0.1O2 full cell. This approach will provide insights for the advancement of alternative electrode materials in diverse energy conversion and storage systems.
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OBJECTIVE: This study aimed to assess the use of two-dimensional (2D) ultrasound combined with high-definition flow (HD-flow) render mode and spatiotemporal image correlation (STIC) in diagnosing and classifying fetal persistent left superior vena cava (PLSVC). METHODS: Overall, 114 cases of fetal PLSVC were diagnosed using 2D ultrasound combined with STIC, and 114 normal fetuses of the same gestational week were selected. These cases were retrospectively analyzed to evaluate the effectiveness of the diagnostic approach. RESULTS: All 114 PLSVC cases were diagnosed using 2D ultrasound combined with STIC. Although the diagnostic coincidence rate of PLSVC in the HD-flow combined with STIC was similar to that in the 2D ultrasound combined with HD-flow (96.8 vs 96.2%), 2D ultrasound with STIC enabled dynamic visualization of the PLSVC, furthering prenatal diagnosis. These cases were classified as type I PLSVC: 80 cases of type Ia, 29 cases of type Ib, and 5 cases of type Ic. Seventy isolated PLSVC cases (61.4%) were noted, whereas 44 cases (35.6%) were associated with concomitant structural abnormalities. Intracardiac structural malformations accounted for the highest proportion (n = 53, 58.89%), followed by single umbilical artery and facial/bodily abnormalities (n = 10, 11.11%). CONCLUSION: Combining HD-flow and STIC complements 2D ultrasound in diagnosing and classifying fetal PLSVC, demonstrating significant clinical relevance.
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In this editorial we comment on the article published in a recent issue of the World Journal of Gastrointestinal Oncology. Characterized by high mortality rates and geographical variations in its incidence, esophageal cancer poses a major global health challenge. This editorial article synthesizes insights from the review of esophageal cancer conducted by Qu et al, which highlights the importance of tailored screening and treatment strategies. Key themes include the effect of regional disparities on screening protocols, advancements in early detection methodologies, and therapeutic management disparities between different regions. By embracing personalized approaches grounded in regional nuances and technological innovation, the article advocates for comprehensive and collaborative efforts to improve patient outcomes in esophageal cancer care.
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Fast photoinduced charge separation (CS) and long-lived charge-separated state (CSS) in small-molecules facilitate light-energy conversion, while simultaneous attainment of both remains challenging. Here we accomplish this through aggregation based on fullerene-indacenodithiophene dyads. Transient absorption spectroscopy reveals that, compared to solution, the CS time in aggregates is accelerated from 41.5 ps to 0.4 ps, and the CSS lifetime is prolonged from 311.4 ps to 40 µs, indicating that aggregation concomitantly promotes fast CS and long-lived CSS. Fast CS arises from the hot charge-transfer states dissociation, opening up additional resonant channels to free carriers (FCs); subsequently, charge recombination into intramolecular triplet CSS becomes favorable mediated by spin-uncorrelated FCs. Different from fullerene/indacenodithiophene blends, the unique CS mechanism in dyad aggregates reduces the long-lived CSS dependence on molecular order, resulting in a CSS lifetime 200 times longer than blends. This endows the dyad aggregates to exhibit both photoelectronic switch properties and superior photocatalytic capabilities.
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In this editorial, we discuss an article titled, "Significant risk factors for intensive care unit-acquired weakness: A processing strategy based on repeated machine learning," published in a recent issue of the World Journal of Clinical Cases. Intensive care unit-acquired weakness (ICU-AW) is a debilitating condition that affects critically ill patients, with significant implications for patient outcomes and their quality of life. This study explored the use of artificial intelligence and machine learning techniques to predict ICU-AW occurrence and identify key risk factors. Data from a cohort of 1063 adult intensive care unit (ICU) patients were analyzed, with a particular emphasis on variables such as duration of ICU stay, duration of mechanical ventilation, doses of sedatives and vasopressors, and underlying comorbidities. A multilayer perceptron neural network model was developed, which exhibited a remarkable impressive prediction accuracy of 86.2% on the training set and 85.5% on the test set. The study highlights the importance of early prediction and intervention in mitigating ICU-AW risk and improving patient outcomes.
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Background: Myocardial bridging (MB) is a congenital coronary anomaly and an important cause of chest pain. The long-term effects of MB on cardiovascular events remain elusive. Methods: We used the National Health Insurance Research Database of Taiwan to conduct an analysis. All patients who had undergone coronary angiography were considered for inclusion. The primary endpoint was a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death. Results: We identified 10,749 patients from 2008 to 2018 and matched them with an equal number of controls by propensity-score matching. The mean follow-up period was 5.78 years. In patients without coronary artery disease, MB increased the risk of the composite endpoint (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.44-1.72, p < 0.001), which was driven by increased risks of nonfatal myocardial infarction and cardiovascular death. In patients with significant coronary artery disease, MB did not increase the risk of major adverse cardiovascular events. MB was identical to insignificant coronary artery disease from the viewpoint of clinical outcomes. Conclusions: The presence of MB significantly increases cardiovascular risks in patients with normal coronary vessels. Atherosclerotic coronary artery disease mitigates the effect of MB on cardiovascular outcomes. MB can be considered an insignificant coronary artery disease equivalent.
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Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a ß-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.
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Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.
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BACKGROUND: Congenital sideroblastic anemia (CSA) is a rare and heterogeneous group of genetic disorders. Conventional treatment include pyridoxine (vitamin B6) and allogeneic hematopoietic stem cell transplantation (allo-HSCT), and can alleviate anemia in the majority of cases. Nevertheless, some CSA cases remain unresponsive to pyridoxine or are unable to undergo allo-HSCT. Novel management approaches is necessary to be developed. To explore the response of luspatercept in treating congenital sideroblastic anemia. CASE SUMMARY: We share our experience in luspatercept in a 4-year-old male patient with CSA. Luspatercept was administered subcutaneously at doses of 1.0 mg/kg/dose to 1.25 mg/kg/dose every 3 wk, three consecutive doses, evaluating the hematological response. Luspatercept leading to a significant improvement in the patient's anemia. The median hemoglobin during the overall treatment with three doses of luspatercept was 90 (75-101) g/L, the median absolute reticulocyte count was 0.0593 (0.0277-0.1030) × 1012/L, the median serum ferritin was 304.3 (234.4-399) ng/mL, and the median lifespan of mature red blood cells was 80 (57-92) days. Notably, no adverse reactions, such as headaches, dizziness, vomiting, joint pain, or back pain, were observed during the treatment period. CONCLUSION: We believe that luspatercept might emerge as a viable therapeutic option for the maintenance treatment of CSA or as a bridging treatment option before hematopoietic stem cell transplantation.
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Background: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM. Methods: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO. Results: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings. Conclusion: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.
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In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology. Acute liver failure (ALF) is a critical condition characterized by rapid hepatocellular injury and organ dysfunction, and it often necessitates liver transplant to ensure patient survival. Recent research has elucidated the involvement of distinct cell death pathways, namely ferroptosis and pyroptosis, in the pathogenesis of ALF. Ferroptosis is driven by iron-dependent lipid peroxidation, whereas pyroptosis is an inflammatory form of cell death; both pathways contribute to hepatocyte death and exacerbate tissue damage. This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF, highlighting the role of key regulators such as silent information regulator sirtuin 1. Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways. Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition.
Subject(s)
Ferroptosis , Liver Failure, Acute , Pyroptosis , Animals , Humans , Hepatocytes/metabolism , Iron/metabolism , Lipid Peroxidation , Liver/metabolism , Liver/pathology , Liver Failure, Acute/metabolism , Liver Failure, Acute/therapy , Liver Transplantation , Signal Transduction , Sirtuin 1/metabolismABSTRACT
CONTEXT: As living standards have improved and lifestyles have undergone changes, metabolic diseases associated with obesity have become increasingly prevalent. It is well established that sesamin (Ses) (PubChem CID: 72307), the primary lignans in sesame seeds and sesame oil, possess antioxidant and anti-inflammatory effects. OBJECTIVE: In this study, a systematic review and meta-analysis of the effects of Ses on animal models of obesity-related diseases was performed to assess their impact on relevant disease parameters. Importantly, this study sought to provide insights for the design of future human clinical studies utilizing Ses as a nutritional supplement or drug. DATA SOURCES: This study conducted a comprehensive search in PubMed, Web of Science, Embase, Scopus, and the Cochrane Library, identifying English language articles published from inception to April 2023. DATA EXTRACTION: The search incorporated keywords such as "sesamin," "obesity," "non-alcoholic fatty liver disease," "type 2 diabetes mellitus," and "metabolic syndrome." The meta-analysis included 17 articles on non-alcoholic fatty liver disease, type 2 diabetes, and metabolic syndrome. DATA ANALYSIS: Overall, the pooled results demonstrated that Ses significantly reduced levels of total serum cholesterol (P = .010), total serum triglycerides (P = .003), alanine transaminase (P = .003), and blood glucose (P < .001), and increased high-density lipoprotein cholesterol levels (P = .012) in animal models of nonalcoholic fatty liver disease. In the type 2 diabetes model, Ses mitigated drug-induced weight loss (P < .001), high-fat-diet-induced weight gain (P < .001), and blood glucose levels (P = .001). In the metabolic syndrome model, Ses was associated with a significant reduction in body weight (P < .001), total serum cholesterol (P < .001), total serum triglycerides (P < .001), blood glucose (P < .001), and alanine transaminase levels (P = .039). CONCLUSION: The meta-analysis results of this study suggest that Ses supplementation yields favorable effects in animal models of obesity-related diseases, including hypolipidemic, insulin-lowering, and hypoglycemic abilities, as well as organ protection from oxidative stress and reduced inflammation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. CRD42023438502.
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Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them remains unclear. This study aimed to investigate the causal relationship between the development of iridocyclitis and the genetic liability of glucocorticoid medication use on the risk of senile cataracts occurrence by performing Two-sample Mendelian randomization (MR) analyses. Instrumental variables (IVs) significantly associated with exposure factors (P < 5 × 10-8) were identified using published genome-wide association data from the FinnGen database and UK Biobank. Reliability analyses were conducted using five approaches, including inverse-variance weighted (IVW), MR-Egger regression, simple median, weighted median, and weighted mode. A sensitivity analysis using the leave-one-out method was also performed. Genetic susceptibility to glucocorticoid use was associated with an increased risk of developing senile cataracts (OR, 1.10; 95% CI, 1.02-1.17; P < 0.05). Moreover, iridocyclitis was significantly associated with a higher risk of developing senile cataracts (OR, 1.03; 95% CI, 1.01-1.05; P < 0.05). Nonetheless, some heterogeneity in the IVs was observed, but the MR results remained consistent after penalizing for outliers. The estimates were consistent in multivariate analyses by adjusting for body mass index (BMI) and diabetes mellitus type 2 (T2DM). This study provides new insights into the prevention and management of senile cataracts by highlighting the increased risk associated with iridocyclitis and the use of glucocorticoids.