ABSTRACT
Objective: This investigation aimed to delineate the association between the advanced lung cancer inflammation index (ALI) and all-cause mortality (ACM) in individuals experiencing acute ischemic stroke (AIS). Methods: Drawing on information from the Medical Information Mart for Intensive Care (MIMIC)-IV database, release 2.2, covering the years 2012 to 2019, this research assessed the advanced lung cancer inflammation index (ALI) by factoring in body mass index (BMI), serum albumin levels (ALB), and the neutrophil-to-lymphocyte ratio (NLR). Patients with AIS were identified using codes from the International Classification of Diseases (ICD). To address potential confounding factors, a 1:1 propensity score matching (PSM) method was utilized. The investigation identified the pivotal ALI level impacting patient survival using maximally selected rank statistics. It then examined the effects on short- and long-term ACM through multivariate Cox proportional hazards regression models and Kaplan-Meier (K-M) survival analysis. Additionally, restricted cubic spline (RCS) methods were applied to delve into the linear or nonlinear nature of the relationship between ALI and ACM, with further insights gained from interaction and subgroup analyses. Results: The cohort comprised 838 AIS patients. Post-PSM, analysis involved 199 matched patient pairs. Adjusted Cox proportional hazard models indicated a significant association of low ALI (<10.38) with increased in-hospital ACM, both before (HR: 1.98; 95% CI: 1.36-2.88; p < 0.001) and after PSM (HR: 2.16; 95% CI: 1.32-3.52; p = 0.002). Associations of low ALI with elevated risk were consistent across ICU, 30 days, 90 days, and 1 year ACM pre- and post-PSM. Subsequent RCS analysis post-PSM underscored a negative nonlinear relationship between ALI and ACM over both short and long terms, without significant interaction effects across different subgroups for ACM. Conclusion: In this retrospective cohort study, by utilizing a nationally representative sample of United States patients with AIS, our analysis elucidates a negative correlation between the ALI and ACM in individuals with AIS, underscoring the utility of ALI as a novel, efficacious, and accessible inflammatory biomarker for prognosticating ACM. These results carry profound implications for public health policy and practice. A deeper comprehension of these associations can empower public health practitioners and researchers to devise more targeted interventions and policies, aimed specifically at catering to the distinct needs of the AIS patient population, thereby enhancing their health outcomes. The further research in other races/ethnicity is urgent, particularly before applying these findings in clinical practice.
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BACKGROUND: The Triglyceride Glucose-Body Mass Index (TyG-BMI) has been established as a robust indicator of insulin resistance (IR), reflecting metabolic health across various populations. In general, lower TyG-BMI values are often associated with better metabolic health outcomes and a reduced risk of adverse health events in non-critically ill populations. Previous studies have highlighted a significant negative association between TyG-BMI and all-cause mortality (ACM) among critically ill atrial fibrillation patients. Given the high prevalence and severe outcomes associated with stroke, understanding how TyG-BMI at the time of ICU admission correlates with ACM in critically ill stroke patients becomes imperative. This study aims to assess the correlation between TyG-BMI and ACM in this specific patient cohort, exploring how traditional associations between TyG-BMI and metabolic health may differ in the context of acute, life-threatening illness. METHODS: Patient data were retrieved by accessing the Medical Information Mart for Intensive Care IV (MIMIC-IV 2.2) database, categorizing patients into three groups on the basis of TyG-BMI tertiles. The study evaluated both primary and secondary outcomes: the primary outcomes included the 90-day, 180-day, and 1-year ACM, while secondary outcomes encompassed ICU, in-hospital, and 30-day ACM. Our study employed the Kaplan-Meier (K-M) curve method for outcome comparison across the groups while utilizing multivariate Cox proportional-hazards regression models and restricted cubic splines (RCS) to explore TyG-BMI association with these outcomes. Additionally, interaction and subgroup analyses were performed, focusing on different mortality time points. RESULTS: Among a cohort of 1707 individuals diagnosed with stroke, the average age was 68 years (interquartile range [IQR]: 58-78 years), with 946 (55.42%) of the participants being male. The analysis of K-M curves suggested that patients having a lower TyG-BMI level faced a heightened risk of long-term ACM, whereas the short-term ACM exhibited no statistically significant differences across the three TyG-BMI groups. Furthermore, Cox proportional-hazards regression analysis validated a statistically significant increased risk of long-term ACM among patients belonging to the lowest TyG-BMI tertile. Additionally, RCS analysis results demonstrated L-shaped correlations between the TyG-BMI index and both short- and long-term ACM. These findings underscore the TyG-BMI predictive value for long-term mortality in stroke patients, highlighting a nuanced relationship that varies over different time frames. The results revealed no interactions between TyG-BMI and the stratified variables, with the exception of age. CONCLUSION: In our study, lower TyG-BMI levels in critically ill stroke patients are significantly related to a higher risk of long-term ACM within the context of the United States. This finding suggests the potential of TyG-BMI as a marker for stratifying long-term risk in this patient population. However, it's crucial to note that this association was not observed for short-term ACM, indicating that the utility of TyG-BMI may be more pronounced in long-term outcome prediction. Additionally, our conclusion that TyG-BMI could serve as a reliable indicator for managing and stratifying stroke patients over the long term is preliminary. To confirm our findings and assess the universal applicability of TyG-BMI as a prognostic tool, it is crucial to conduct rigorously designed research across various populations.
Subject(s)
Biomarkers , Blood Glucose , Body Mass Index , Critical Illness , Databases, Factual , Intensive Care Units , Stroke , Triglycerides , Humans , Male , Aged , Female , Blood Glucose/metabolism , Time Factors , Middle Aged , Risk Assessment , Triglycerides/blood , Risk Factors , Biomarkers/blood , Stroke/mortality , Stroke/blood , Stroke/diagnosis , Prognosis , Critical Illness/mortality , Retrospective Studies , Aged, 80 and over , Insulin Resistance , United States/epidemiologyABSTRACT
BACKGROUND: Hemorrhagic stroke (HS), including non-traumatic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), constitutes a substantial proportion of cerebrovascular incidents, accounting for around 30% of stroke cases. The triglyceride-glucose index (TyG-i) represents a precise insulin resistance (IR) indicator, a crucial metabolic disturbance. Existing literature has demonstrated an association between TyG-i and all-cause mortality (ACM) among individuals suffering from ischemic stroke (IS). Yet, the TyG-i prognostic implications for severe HS patients necessitating intensive care unit (ICU) admission are not clearly understood. Considering the notably elevated mortality and morbidity associated with HS relative to IS, investigating this association is warranted. Our primary aim was to investigate TyG-i and ACM association among critically ill HS patients within an ICU context. METHODS: Herein, patients with severe HS were identified by accessing the Medical Information Mart for Intensive Care-IV (MIMIC-IV, version 2.2) database, using the International Classification of Diseases (ICD)-9/10 as diagnostic guidelines. Subsequently, we stratified the subjects into quartiles, relying on their TyG-i scores. Moreover, we measured mortality at ICU, in-hospital, 30 days, 90 days, and 1 year as the outcomes. Cox proportional hazards regression analysis and restricted cubic splines (RCS) were deployed for elucidating the relation between the TyG-i and ACM while utilizing the Kaplan-Meier (K-M) method to estimate survival curves. The findings' robustness was assessed by conducting subgroup analysis and interaction tests employing likelihood ratio tests. RESULTS: The analysis included 1475 patients, with a male predominance of 54.4%. Observed mortality rates in the ICU, hospital, 30 days, 90 days, and 1 year were 7.3%, 10.9%, 13.8%, 19.7%, and 27.3%, respectively. Multivariate Cox regression analysis results manifested that heightened TyG-i was significantly related to ACM at 30 days (adjusted hazard ratio [aHR]: 1.32; 95% confidence interval [CI]: 1.05-1.67; P = 0.020), 90 days (aHR: 1.27; 95% CI: 1.04-1.55; P = 0.019), and 1 year (aHR: 1.22; 95% CI: 1.03-1.44; P = 0.023). The results of RCS analysis demonstrated a progressive elevation in ACM risk with rising TyG-i levels. Interaction tests found no significant effect modification in this relationship. CONCLUSION: In summary, TyG-i exhibits a significant correlation with ACM among patients enduring critical illness due to HS. This correlation underscores the probable utility of TyG-i as a prognostic tool for stratifying HS patients according to their risk of mortality. Applying TyG-i in clinical settings could enhance therapeutic decision-making and the management of disease trajectories. Additionally, this investigation augments existing research on the linkage between the TyG-i and IS, elucidating the TyG-i's role in predicting mortality across diverse stroke categories.
Subject(s)
Hemorrhagic Stroke , Ischemic Stroke , Stroke , Humans , Male , Female , Critical Illness , Retrospective Studies , Stroke/diagnosis , Glucose , Triglycerides , Blood Glucose , Risk Factors , BiomarkersABSTRACT
INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory diseases in China and impose significant burdens on the healthcare system. Moreover, the co-occurrence of COPD and OSA exacerbates clinical outcomes significantly. However, comprehensive epidemiological investigations in China remain scarce, and the defining characteristics of the population affected by COPD and OSA, alongside their intrinsic relationship, remain ambiguous. METHODS AND ANALYSIS: We present a protocol for a prospective, multicentre, observational cohort study based on a digital health management platform across three different healthcare tiers in five sites among Chinese patients with COPD. The study aims to establish predicative models to identify OSA among patients with COPD and to predict the prognosis of overlap syndrome (OS) and acute exacerbations of COPD through the Internet of Things (IoT). Moreover, it aims to evaluate the feasibility, effectiveness and cost-effectiveness of IoT in managing chronic diseases within clinical settings. Participants will undergo baseline assessment, physical examination and nocturnal oxygen saturation measuring. Specific questionnaires screening for OSA will also be administered. Diagnostic lung function tests and polysomnography will be performed to confirm COPD and OSA, respectively. All patients will undergo scheduled follow-ups for 12 months to record the changes in symptoms, lung functions and quality of life. Primary outcomes include the prevalence and characteristics of OS, while secondary outcomes encompass OS prognosis and the feasibility of the management model in clinical contexts. A total of 682 patients with COPD will be recruited over 12-24 months. ETHICS AND DISSEMINATION: The study has been approved by Peking University Third Hospital, and all study participants will provide written informed consent. Study results will be published in an appropriate journal and presented at national and international conferences, as well as relevant social media and various stakeholder engagement activities. TRIAL REGISTRATION NUMBER: NCT04833725.
Subject(s)
Internet of Things , Pulmonary Disease, Chronic Obstructive , Sleep Apnea, Obstructive , Humans , Prospective Studies , Quality of Life , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/epidemiology , Delivery of Health Care , Cohort Studies , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/complications , Observational Studies as Topic , Multicenter Studies as TopicABSTRACT
Targeted reprogramming of cancer-associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs toward deactivated state still remains immense challenge. To tackle this challenge, herein, one perylene N, N'-bis(2-((dimethylammonium)ethylene)-2-(methoxylethyl))-1, 6, 7, 12-tetrachloroperylene-3, 4, 9, 10-tetracarboxylic diimide (PDIC-OC) is prepared, which can trigger endogenous reactive oxygen species (ROS) burst to result in cytoskeletal dysfunction and cell apoptosis so that suppress transforming growth factor ß (TGF-ß) production. As a result, PDIC-OC can reprogram the activated CAFs and relieve immunosuppressive tumor microenvironment by efficient polarization of M2-typed macrophages into M1-typed ones, downregulation of alpha-smooth muscle actin (α-SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realizes outstanding antitumor performance on B16F10 tumor-xenografted and lung-metastatic mouse model even at low concentration of 1 mg kg-1 body weight. This work thus presents a novel strategy that cytoskeleton dysfunction and cell apoptosis cooperatively suppress the secretion of TGF-ß to reprogram CAFs and meanwhile clarifies intrinsic mechanism for perylene-triggered chemo-immunotherapy against hypoxic tumors.
Subject(s)
Cancer-Associated Fibroblasts , Cytoskeleton , Immunotherapy , Perylene , Animals , Perylene/analogs & derivatives , Perylene/pharmacology , Perylene/chemistry , Mice , Cytoskeleton/metabolism , Cytoskeleton/drug effects , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/drug effects , Cancer-Associated Fibroblasts/pathology , Immunotherapy/methods , Cell Line, Tumor , Tumor Microenvironment/drug effects , Transforming Growth Factor beta/metabolism , Apoptosis/drug effects , Humans , Reactive Oxygen Species/metabolism , Mice, Inbred C57BLABSTRACT
Activation of stimulator of interferon genes (STING) by cyclic dinucleotides (CDNs) has been considered as a powerful immunotherapy strategy. While promising, the clinical translation of CDNs is still overwhelmed by its limited biostability and the resulting systemic immunotoxicity. Being differentiating from current application of exogenous CDNs to address these challenges, we herein developed one perylene STING agonist PDIC-NS, which not only promotes the production of endogenous CDNs but also inhibits its hydrolysis. More significantly, PDIC-NS can well reach lung-selective enrichment, and thus mitigates the systemic immunotoxicity upon intravenous administration. As a result, PDIC-NS had realized remarkable in vivo antitumor activity, and backward verified on STING knock out mice. Overall, this study states that PDIC-NS can function as three-in-one small-molecule STING agonist characterized by promoting the content and biostability of endogenous CDNs as well as possessing good tissue specificity, and hence presents an innovative strategy and platform for tumor chemo-immunotherapy.
Subject(s)
Neoplasms , Perylene , Animals , Mice , Nucleotides, Cyclic , Immunotherapy/methods , Membrane Proteins/genetics , Neoplasms/drug therapyABSTRACT
Background: Stroke represents a prominent global health issue, exhibiting the third highest incidence of disability and a significant burden on both healthcare and the economy. Stress hyperglycemia, an acute reaction of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, leading to adverse outcomes and mortality. Several previous studies have indicated that stress hyperglycemia, as evaluated by the stress hyperglycemia ratio (SHR), significantly increases the risk of adverse outcomes and mortality in stroke patients. However, there is a lack of further investigation into the influence of dynamic changes in stress hyperglycemia on the clinical outcomes of acute ischemic stroke (AIS) patients. Consequently, we performed a meticulous analysis, considering dose-response relationships from existing studies, to ascertain the correlation between dynamic changes in stress hyperglycemia and the susceptibility to adverse outcomes in patients with AIS. Methods: This investigation was prospectively registered in PROSPERO and adhered to the PRISMA guidelines. A comprehensive search was performed across English and Chinese databases. A two-sided random-effects model was employed to consolidate the odds ratios (ORs) of the highest vs. lowest categories of SHR. Restricted cubic spline (RCS) models were employed to estimate potential non-linear trends between SHR and the risk of adverse outcomes in AIS patients. Egger's test was utilized to assess publication bias. Heterogeneity was evaluated using Cochran's Q-test. The Newcastle-Ottawa Scale (NOS) tool was employed to evaluate the risk of bias of the included studies. Results: The final analysis incorporated a total of thirteen studies, which were published between 2019 and 2023, encompassing a participant cohort of 184,179 individuals. The SHR exhibited a significant association with the risk of various adverse outcomes. Specifically, a higher SHR was correlated with a 2.64-fold increased risk of 3-month poor functional outcomes (OR: 2.64, 95% CI 2.05-3.41, I2 = 52.3%, P < 0.001), a 3.11-fold increased risk of 3-month mortality (OR: 3.11, 95% CI 2.10-4.59, I2 = 38.6%, P < 0.001), a 2.80-fold increased risk of 1-year mortality (OR: 2.80, 95% CI 1.81-4.31, I2 = 88%, P < 0.001), a 3.90-fold increased risk of intracerebral hemorrhage (ICH) and 4.57-fold increased risk of symptomatic ICH (sICH) (ICH-OR: 3.90, 95% CI 1.52-10.02, I2 = 84.3%, P = 0.005; sICH-OR: 4.57, 95% CI 2.05-10.10, I2 = 47.3%, P < 0.001), a 1.73-fold increased risk of neurological deficits (OR: 1.73, 95 CI 1.44-2.08, I2 = 0%, P < 0.001), and a 2.84-fold increased risk of stroke recurrence (OR: 2.84, 95 CI 1.48-5.45, I2 = 50.3%, P = 0.002). It is noteworthy that, except for hemorrhagic transformation (HT) and stroke recurrence, the remaining adverse outcomes exhibited a "J-shaped" non-linear dose-response relationship. Conclusion: In summary, our findings collectively suggest that increased exposure to elevated SHR is robustly linked to a heightened risk of adverse outcomes and mortality in individuals with AIS, exhibiting a non-linear dose-response relationship. These results underscore the significance of SHR as a predictive factor for stroke prognosis. Therefore, further investigations are warranted to explore the role of SHR in relation to adverse outcomes in stroke patients from diverse ethnic populations. Furthermore, there is a need to explore the potential benefits of stress hyperglycemia control in alleviating the physical health burdens associated with AIS. Maintaining a lower SHR level may potentially reduce the risk of adverse stroke outcomes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023424852.
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BACKGROUND: Stroke, which is the main element of cerebrovascular disease (CVD), has become the foremost reason for death and disability on a global scale. The systemic inflammation response index (SIRI), a newly developed and comprehensive indicator, has demonstrated promise in forecasting clinical results for diverse ailments. Nevertheless, the uncertainty surrounding the assessment and prediction of clinical outcomes for stroke patients by SIRI persists, and the conflicting findings from the limited studies conducted on this matter further complicate the situation. Consequently, we performed a thorough systematic review and meta-analysis to explore the correlation between SIRI and the clinical results in individuals suffering from stroke. METHODS: This research was registered in PROSPERO and carried out following the PRISMA guidelines. A thorough investigation was carried out on PubMed, Embase, the Cochrane Library, Web of Science, and Scopus databases. Furthermore, we conducted a manual search in Chinese databases, such as China national Knowledge Infrastructure (CNKI), WanFang, VIP, and China Biology Medicine (CBM). We assessed the potential for bias in the studies included by utilizing the Newcastle-Ottawa Scale (NOS) tool. Adverse clinical outcomes were the main focus of the study, with secondary endpoints including mortality, the predictive value of SIRI, SIRI values across various endpoints, and clinical parameters associated with subarachnoid hemorrhage (SAH) in relation to low and high SIRI group. RESULTS: Following rigorous evaluation, a grand total of 22 investigations, encompassing a populace of 12,737 individuals, were considered suitable for incorporation in the final analysis. The findings from our meta-analysis indicate a strong and consistent correlation between elevated SIRI levels and adverse functional outcomes, irrespective of the method used to evaluate unfavorable outcomes. Furthermore, increased SIRI values have a strong correlation with mortality rates in both the short and long term. Besides, SIRI is a useful indicator of the severity of SAH. SIRI demonstrates strong predictive ability in identifying unfavorable outcomes and stroke-related pneumonia (SAP), as higher SIRI values are typically linked to negative endpoints. Nevertheless, the meta-analysis indicated that there was no significant increase in the risk of early neurological deterioration (END) and acute hydrocephalus (AHC) in high SIRI group when comparing to low SIRI. CONCLUSION: This study could potentially pave the way for groundbreaking insights into the relationship between SIRI and stroke patient outcomes, as it appears to be the first meta-analysis to explore this association. Given the critical role of the inflammatory response in stroke recovery, closely monitoring patients with high SIRI levels could represent a promising strategy for mitigating brain damage post-stroke. Thus, further investigation into SIRI and its impact on clinical outcomes is essential. While our initial findings offer valuable insights into this area, continued research is necessary to fully elucidate the potential of SIRI, ideally through dynamic monitoring and large-scale, multi-center studies. Ultimately, this research has the potential to inform clinical decision-making and improve patient outcomes following stroke. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/ ; Identifier CRD42023405221.
Subject(s)
Inflammation , Stroke , Humans , Prognosis , Stroke/diagnosisABSTRACT
Background: Non-traumatic subarachnoid hemorrhage (SAH), primarily due to the rupture of intracranial aneurysms, contributes significantly to the global stroke population. A novel biomarker, pan-immune-inflammation value (PIV) or called the aggregate index of systemic inflammation (AISI), linked to progression-free survival and overall survival in non-small-cell lung cancer and mortality in Coronavirus Disease 2019 (COVID-19) patients, has surfaced recently. Its role in non-traumatic SAH patients, however, remains under-researched. This study aims to determine the relationship between PIV and all-cause mortality in non-traumatic SAH patients. Methods: A retrospective analysis was conducted using data from the Medical Information Mart for Intensive Care (MIMIC-IV) database to examine the association between PIV and all-cause mortality in critically ill patients with non-traumatic SAH. PIV measurements were collected at Intensive Care Unit (ICU) admission, and several mortality measures were examined. To control for potential confounding effects, a 1:1 propensity score matching (PSM) method was applied. The optimal PIV cutoff value was identified as 1362.45 using X-tile software that is often used to calculate the optimal cut-off values in survival analysis and continuous data of medical or epidemiological research. The relationship between PIV and short- and long-term all-cause mortality was analyzed using a multivariate Cox proportional hazard regression model and Kaplan-Meier (K-M) survival curve analysis. Interaction and subgroup analyses were also carried out. Results: The study included 774 non-traumatic SAH patients. After PSM, 241 pairs of score-matched patients were generated. The Cox proportional hazard model, adjusted for potential confounders, found a high PIV (≥ 1362.45) independently associated with 90-day all-cause mortality both pre- (hazard ratio [HR]: 1.67; 95% confidence intervals (CI): 1.05-2.65; P = 0.030) and post-PSM (HR: 1.58; 95% CI: 1.14-2.67; P = 0.042). K-M survival curves revealed lower 90-day survival rates in patients with PIV ≥ 1362.45 before (31.1% vs. 16.1%%, P < 0.001) and after PSM (68.9% vs. 80.9%, P < 0.001). Similarly, elevated PIV were associated with increased risk of ICU (pre-PSM: HR: 2.10; 95% CI: 1.12-3.95; P = 0.02; post-PSM: HR: 2.33; 95% CI: 1.11-4.91; P = 0.016), in-hospital (pre-PSM: HR: 1.91; 95% CI: 1.12-3.26; P = 0.018; post-PSM: 2.06; 95% CI: 1.10-3.84; P = 0.034), 30-day (pre-PSM: HR: 1.69; 95% CI: 1.01-2.82; P = 0.045; post-PSM: 1.66; 95% CI: 1.11-2.97; P = 0.047), and 1-year (pre-PSM: HR: 1.58; 95% CI: 1.04-2.40; P = 0.032; post-PSM: 1.56; 95% CI: 1.10-2.53; P = 0.044) all-cause mortality. The K-M survival curves confirmed lower survival rates in patients with higher PIV both pre- and post PSM for ICU (pre-PSM: 18.3% vs. 8.4%, P < 0.001; post-PSM:81.7 vs. 91.3%, P < 0.001), in-hospital (pre-PSM: 25.3% vs. 12.8%, P < 0.001; post-PSM: 75.1 vs. 88.0%, P < 0.001), 30-day (pre-PSM: 24.9% vs. 11.4%, P < 0.001; post-PSM:74.7 vs. 86.3%, P < 0.001), and 1-year (pre-PSM: 36.9% vs. 20.8%, P < 0.001; P = 0.02; post-PSM: 63.1 vs. 75.1%, P < 0.001) all-cause mortality. Stratified analyses indicated that the relationship between PIV and all-cause mortality varied across different subgroups. Conclusion: In critically ill patients suffering from non-traumatic SAH, an elevated PIV upon admission correlated with a rise in all-cause mortality at various stages, including ICU, in-hospital, the 30-day, 90-day, and 1-year mortality, solidifying its position as an independent mortality risk determinant. This study represents an attempt to bridge the current knowledge gap and to provide a more nuanced understanding of the role of inflammation-based biomarkers in non-traumatic SAH. Nevertheless, to endorse the predictive value of PIV for prognosticating outcomes in non-traumatic SAH patients, additional prospective case-control studies are deemed necessary.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Subarachnoid Hemorrhage , Humans , Retrospective Studies , Critical Illness , InflammationABSTRACT
Idiopathic pulmonary fibrosis is a chronic and highly lethal lung disease that largely results from oxidative stress; however, effective antioxidant therapy by targeting oxidative stress pathogenesis is still lacking. The big challenge is to develop an ideal antioxidant material with superior antifibrotic effects. Herein, we report that V4C3 nanosheets (NSs) can serve as a potential antioxidant for treatment of pulmonary fibrosis by scavenging reactive oxygen and nitrogen species. Interestingly, subtle autoxidation can adjust the valence composition of V4C3 NSs and significantly improve their antioxidant behavior. Valence engineering triggers multiple antioxidant mechanisms including electron transfer, H atom transfer, and enzyme-like catalysis, thus endowing V4C3 NSs with broad-spectrum, high-efficiency, and persistent antioxidant capacity. Benefiting from antioxidant properties and good biocompatibility, V4C3 NSs can significantly prevent myofibroblast proliferation and extracellular matrix abnormality, thus alleviating the progression of bleomycin-induced pulmonary fibrosis in vivo by scavenging ROS, anti-inflammation, and rebuilding antioxidant defenses. This study not only provides an important strategy for designing excellent antioxidant nanomaterials, but also proposes a proof-of-concept demonstration for the treatment of pulmonary fibrosis and other oxidative stress-related diseases.
Subject(s)
Pulmonary Fibrosis , Humans , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Antioxidants/pharmacology , Antioxidants/therapeutic use , Lung/metabolism , Vanadium , Oxidative Stress , Organic Chemicals , Reactive Oxygen Species/pharmacologyABSTRACT
Purpose: To systematically review the different types of irrigation fluid and the different temperatures of irrigation fluid on postoperative recurrence rates in the evacuation of chronic subdural hematoma (CSDH). Methods: We conducted a comprehensive search of electronic databases, including PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure (CNKI), WanFang, the Chinese VIP Information (VIP), and China Biology Medicine (CBM), and reference lists of relevant studies to identify all eligible studies. Two reviewers independently screened the titles and abstracts for inclusion, and the full-text articles were assessed for eligibility based on predetermined inclusion and exclusion criteria. Data were extracted using a standardized form, and the quality of the studies was assessed using a risk of bias tool. Meta-analyses were performed using a fixed-or random-effects model, and heterogeneity was assessed using the I2 statistic. The primary endpoint was the postoperative recurrence rate. Results: After stringent screening, a total of 11 studies were identified, including six English publications, four Chinese publications, and one Japanese publication, involving a population of 29,846 patients. Our meta-analysis provides evidence that artificial cerebrospinal fluid (ACF) could decrease the post-operative recurrence rate by 47% after the evacuation of CSDH when compared to normal saline (NS) [(odds ratio) OR 0.53, 95% confidence intervals (CI): 0.31-0.90, p = 0.02, I2 = 67%]. Besides, the irrigation fluid at body temperature could decrease the postoperative recurrence rate of CSDH by 64% when compared to room temperature (OR = 0.36, 95% CI = 0.22-0.59, p < 0.0001, I2 = 0%). Conclusion: Our analysis revealed significant difference in the choice of irrigation fluid for CSDH surgery. Notably, we found that irrigation with fluid at body temperature demonstrated superiority over irrigation with fluid at room temperature, resulting in fewer instances of recurrence. This straightforward technique is both safe and widely available, providing an opportunity to optimize outcomes for patients with CSDH. Our findings suggest that the use of body-temperature NS or ACF of room temperature during operation should be considered a standard of procedure in CSDH surgery. Nevertheless, whether the different temperature of ACF could be considered a standard of procedure in CSDH surgery still need high-quality RCTs to further identify. Systematic review registration: https://www.crd.york.ac.uk/prospero/; Identifier CRD42023424344.
ABSTRACT
Introduction: Stroke is a major global health concern and is ranked as the second leading cause of death worldwide, with the third highest incidence of disability. Intracerebral hemorrhage (ICH) is a devastating form of stroke that is responsible for a significant proportion of stroke-related morbidity and mortality worldwide. Hematoma expansion (HE), which occurs in up to one-third of ICH patients, is a strong predictor of poor prognosis and can be potentially preventable if high-risk patients are identified early. In this review, we provide a comprehensive summary of previous research in this area and highlight the potential use of imaging markers for future research studies. Recent advances: Imaging markers have been developed in recent years to aid in the early detection of HE and guide clinical decision-making. These markers have been found to be effective in predicting HE in ICH patients and include specific manifestations on Computed Tomography (CT) and CT Angiography (CTA), such as the spot sign, leakage sign, spot-tail sign, island sign, satellite sign, iodine sign, blend sign, swirl sign, black hole sign, and hypodensities. The use of imaging markers holds great promise for improving the management and outcomes of ICH patients. Conclusion: The management of ICH presents a significant challenge, and identifying high-risk patients for HE is crucial to improving outcomes. The use of imaging markers for HE prediction can aid in the rapid identification of such patients and may serve as potential targets for anti-HE therapies in the acute phase of ICH. Therefore, further research is needed to establish the reliability and validity of these markers in identifying high-risk patients and guiding appropriate treatment decisions.
ABSTRACT
Reactive oxygen species (ROS) can act as cytotoxic radicals to directly kill tumor cells and concurrently trigger immunogenic cell death (ICD) to efficiently achieve tumor therapy. Thus motivated, we herein present one perylene monoamide-based ROS supergenerator (PMIC-NC) that not only induces hypoxia-enhanced Type-I ROS burst aided by proton transients but also triggers Type-I/II ROS production by electron or energy transfer under near-infrared (NIR) light irradiation and also elicits a strong ICD effect. More interesting, the mitochondria- and lung-specific distribution of PMIC-NC also boosts the tumor therapeutic efficiency. As a result, PMIC-NC was employed for NIR-triggered photodynamic therapy, hypoxia-enhanced chemotherapy and also displayed robust immunogenicity for systemic tumor eradication. This work thus contributes one proof-of-concept demonstration of perylene as an integrated therapeutic platform for efficient immunogenic photochemotherapy against hypoxic tumors.
Subject(s)
Nanoparticles , Neoplasms , Perylene , Photochemotherapy , Humans , Reactive Oxygen Species/metabolism , Perylene/pharmacology , Perylene/therapeutic use , Infrared Rays , Neoplasms/drug therapy , Neoplasms/metabolism , Hypoxia/drug therapy , Cell Line, Tumor , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Nanoparticles/therapeutic use , Oxygen/therapeutic useABSTRACT
Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions which can cause acute liver failure or even death in severe cases. With the incidence rate increasing over the years, DILI has became a frequent clinical liver disease and a global public health problem. As a biomarker of DILI, the detection of peroxynitrite (ONOO-) has became a powerful tool for the early diagnosis of liver injury. Here, we synthesized five mitochondria-targetable probes, 1-5, for detecting endogenous ONOO-. Through dye-screening, probe 5 was stood out by its excellent performance. In the presence of ONOO-, the fluorescence signal of probe 5 reduced 40-fold in 19 s with a low detection limit (9.36 nM). At the same time, the transformation can be observed with the naked eye under sunlight or UV lamp without being affected by the other reactive species. Even better, with low toxicity and high biocompatibility, probe 5 could successfully detect endogenous ONOO- in the mitochondrion of cells. Finally, probe 5 could specifically target the liver, and can be employed for monitoring the therapeutic effect of hepatoprotective medicine after drug-induced hepatotoxicity in vivo. In brief, probe 5 has the practical application capability for diagnosing the severity of the liver injury and researching the therapeutic effect of antidote in complex bio-systems.
Subject(s)
Chemical and Drug Induced Liver Injury , Peroxynitrous Acid , Humans , Fluorescent Dyes/pharmacology , FluorescenceABSTRACT
Perylene derivatives can be stimulated by the hypoxic tumor microenvironment to generate radical anion that is proposed to arouse electron exchange with oxidizing substance, and in turn, realize reactive oxygen species (ROS) burst. Here, three perylene therapeutic agents, PDI-NI, PDIB-NI, and PDIC-NI, are developed and it is found that the minimum lowest unoccupied molecular orbital (LUMO) energy level makes PDIC-NI most easily accept electrons from the oxidative respiratory chain to form lots of anions, and the resultant maximum ROS generation, establishing an unambiguous mechanism for the formation of perylene radical anions in the cell, presents solid evidence for LUMO energy level determining endogenous ROS burst. Stirringly, PDIC-NI-induced ROS generation arouses enhanced mitochondrial oxidative stress and concurrently activates immunogenic cell death (ICD), which not only efficiently kills lung tumor cells but also reprograms immunosuppressive tumor microenvironment, including the cytokine secretion, dendritic cell maturation, as well as cytotoxic T lymphocytes activation, to inhibit the growth of xenografted and metastasis tumor, presenting a proof-of-concept demonstration of perylene that acts as an integrated therapeutic agent to well realize hypoxia-activated chemotherapy with ICD-induced immunotherapy on lung cancer.
Subject(s)
Neoplasms , Perylene , Humans , Reactive Oxygen Species/metabolism , Electron Transport , Perylene/pharmacology , Perylene/therapeutic use , Electrons , Neoplasms/therapy , Hypoxia , Immunotherapy , Tumor MicroenvironmentABSTRACT
Both obstructive sleep apnea(OSA) and obesity can cause myocardial remodeling and cardiac insufficiency via corresponding pathophysiological pathways. Therefore, it is speculated that the superposition of OSA and obesity may cause more severe impairment of cardiac function. The objective of our study was to evaluate the early changes of left ventricular systolic function in obese patients with OSA with three-dimensional speckle tracking echocardiography(3D-STE). This study was conducted with 33 obese OSA, 46 non-obese OSA, and 20 healthy subjects. Demographic, biochemical, and Polysomnography(PSG) data were collected, and their relation with the left ventricular strain was measured and analyzed with 3D-STE. The left ventricular strain was significantly worse in the OSA group compared to the control group(P < 0.05). The global longitudinal strain(GLS) was significantly worse obese group compared to non-obese OSA group (P < 0.05). The GLS value positively correlated with body mass index(BMI)(r = 0.406, P < 0.001), apnea-hypopnea index(AHI)(r = 0.610, P < 0.001)and homeostasis model assessment of insulin resistance(HOME-IR)(r = 0.431, P < 0.001) in patients with OSA, as well as high sensitivity C-reactive protein(hs-CRP)(r = 0.394, P < 0.001). Multiple linear regression analysis showed BMI and AHI were predictors of GLS. In OSA patients, the myocardial strain was impaired before the damages in left ventricular ejection fraction, suggesting that the left ventricular systolic function is damaged early. The coexistence of obesity and OSA can lead to severe impairment of cardiac function through mechanisms such as hypoxia and insulin resistance.
Subject(s)
Insulin Resistance , Sleep Apnea, Obstructive , Ventricular Dysfunction, Left , Humans , Ventricular Function, Left , Stroke Volume/physiology , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/complications , Predictive Value of Tests , Echocardiography/methods , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Obesity/complications , Obesity/diagnosisABSTRACT
A carbon derivative with Fe-Cu bimetallic organic framework (Fe-Cu-MOF@C) was prepared by microwave synthesis and pyrolysis. Using potassium persulfate (PS) as oxidant and 2,4-dichlorophenol (2,4-DCP) as target pollutant, the optimal preparation conditions of Fe-Cu-MOF@C were studied. The factors affecting the synthesis of Fe-Cu-MOF include microwave power, microwave time, microwave temperature, the molar ratio of metal ions to organic ligands, the molar ratio of iron and copper, etc. In addition, the influence of pyrolysis temperature on the performance of Fe-Cu-MOF@C cannot be ignored. The results show that Fe-Cu-MOF@C has the best catalytic performance when the microwave time is 30 min, the microwave power is 600 W, the microwave temperature is 150 °C, the molar ratio of (Fe2+ + Cu2+)/H2BDC is 10:3, the molar ratio of Fe2+/Cu2+ is 10:1, and the pyrolysis temperature is 700 °C. After 90 min of reaction, 2,4-DCP was completely removed. Repeatable experiments show that Fe-Cu-MOF@C has good stability and its service life can be restored by heat treatment. In this study, a heterogeneous catalyst with strong catalytic capacity, high stability and easy recovery was prepared by a simple and efficient process, which is conducive to the development of advanced oxidation technology and the progress of water environmental protection.
Subject(s)
Microwaves , Pyrolysis , Catalysis , Carbon , CopperABSTRACT
Objective: Stress hyperglycemia (SH) is common in patients with acute diseases, such as stroke and myocardial infarction. Stress hyperglycemia ratio (SHR) is calculated by glucose/glycated hemoglobin and has been widely used for evaluating SH. But whether SHR is associated with clinical outcomes in stroke patients remains unclear so far. Although many studies have shown that higher SHR means poor outcomes, there is still no absolute evidence that SHR plays a critical role in stroke patients. Hence, we performed a systematic review and meta-analysis aiming to investigate the association between SHR and clinical outcomes in stroke patients. Methods: We performed a comprehensive literature search of the PubMed, Embase, Cochrane Library databases, Clinicaltrials.gov, and WHO-ICTRP. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we performed our study. The Newcastle-Ottawa Scale (NOS) tool was used to examine the potential bias of included studies. The endpoints including poor outcome, mortality, neurological deficit, hemorrhagic transformation (HT), and infectious complications were statistically analyzed. Results: Sixteen retrospective studies met the eligibility criteria, and a number of 183,588 patients were included. Our meta-analysis demonstrated a significant increase in the incidence of poor outcome, according to assessment by the modified Rankin Scale (mRS) ≥ 3 points [odds ratio (OR) 2.53, 95% confidence interval (CI) 1.99-3.22, P < 0.00001, I 2 = 68%], mortality (OR 1.96, 95% CI 1.58-2.44, P < 0.00001, I 2 = 61%), neurological deficit (OR 1.99, 95% CI 1.47-2.70, P < 0.00001, I 2 = 75%), hemorrhagic transformation (HT) (OR 3.70, 95% CI 2.69-5.08, P < 0.00001, I 2 = 0%), and infectious complications [(Pneumonia) OR 2.06, 95% CI 1.57-2.72, P < 0.00001, I 2 = 24%; (Urinary tract infection) OR 2.53, 95% CI 1.45-4.42, P = 0.001, I 2 = 57%] in stroke patients with higher SHR. However, no significant influence was observed for recanalization rate (OR 0.86, 95% CI 0.54-1.38, P = 0.53, I 2 = 0%). Conclusion: With or without diabetes, no matter whether undergoing intravenous thrombolysis or mechanical thrombectomy, higher SHR significantly increased the occurrence of poor outcomes, mortality, neurological deficit, HT, and infectious complications. The recanalization rate was not statistically significant between the two groups. More attention must be paid in clinical practice to SH. Future investigation should focus on the diagnostic value of SHR and the early control of hyperglycemia. Meanwhile, whether SHR could become a novel and promising target for early intervention is worthy of attention in further research. Besides, the influence of the dynamic change of glucose-to-HbA1c ratio, namely SHR, on intracerebral hemorrhage outcomes requires further investigation in future research. Although no randomized double-blind studies have been conducted, the available massive sample studies reflect the actual situation in the clinic and assist clinical decision makers. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022345587.
Subject(s)
Air Pollutants , Pulmonary Disease, Chronic Obstructive , Sleep Apnea, Obstructive , Humans , Polysomnography , SleepABSTRACT
BACKGROUND: Air pollution may be a contributing risk factor for obstructive sleep apnea (OSA). However, the health effects of co-exposure to multiple air pollutants on OSA patients remain unclear. OBJECTIVES: To assess the joint effect of multi-pollutant on sleep disordered breathing (SDB) parameters in patients with or without OSA and identify the dominant pollutants. METHODS: A total of 2524 outpatients from April 2020 to May 2021 were recruited in this cross-sectional study. Ambient air pollutant data were obtained from the nearest central monitoring stations to participants' residential address. SDB parameters were measured by the ApneaLink devices, including apnea-hypopnea index (AHI), hypopnea index (HI), oxygen desaturation index (ODI), average oxygen saturation (SpO2), percentage sleep time with <90% saturation (T90), and desaturation. Bayesian kernel machine regression (BKMR) was applied to evaluate the effects of multiple pollutants. RESULTS: Significant associations were observed between air pollutants and SDB parameters (including increases in AHI, HI, ODI, and desaturation) among patients with OSA. Co-exposure to air pollutants was positively correlated with AHI, HI, and ODI. PM10 and O3 dominated the effects of pollutant mixtures on OSA, with the highest posterior inclusion probability (PIP) values of 0.592 and 0.640, respectively. Stratified analysis showed that, compared to male patients with OSA, stronger effects on the SDB parameters were observed in female patients. Stronger associations were also found in the warm season than those in the cold season. CONCLUSION: Co-exposure to air pollutants was associated with SDB parameters among patients with OSA, PM10 and O3 might play the dominant roles.