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Diverse cellular insults converge on activation of the heat shock factor 1 (HSF1), which regulates the proteotoxic stress response to maintain protein homoeostasis. HSF1 regulates numerous gene programmes beyond the proteotoxic stress response in a cell-type- and context-specific manner to promote malignancy. However, the role(s) of HSF1 in immune populations of the tumour microenvironment remain elusive. Here, we leverage an in vivo model of HSF1 activation and single-cell transcriptomic tumour profiling to show that augmented HSF1 activity in natural killer (NK) cells impairs cytotoxicity, cytokine production and subsequent anti-tumour immunity. Mechanistically, HSF1 directly binds and regulates the expression of key mediators of NK cell effector function. This work demonstrates that HSF1 regulates the immune response under the stress conditions of the tumour microenvironment. These findings have important implications for enhancing the efficacy of adoptive NK cell therapies and for designing combinatorial strategies including modulators of NK cell-mediated tumour killing.
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BACKGROUND: Risk of early-stage lung adenocarcinoma (LUAD) recurrence after surgical resection is significant, and post-recurrence median survival is approximately two years. Currently there are no commercially available biomarkers that predict recurrence. Here, we investigated whether microbial and host genomic signatures in the lung can predict recurrence. METHODS: In 91 early-stage (Stage IA/IB) LUAD-patients with extensive follow-up, we used 16s rRNA gene sequencing and host RNA-sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples. RESULTS: 23 out of 91 subjects had tumor recurrence over 5-year period. In tumor samples, LUAD recurrence was associated with enrichment with Dialister, Prevotella, while in unaffected lung, recurrence was associated with enrichment with Sphyngomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with LUAD recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial-host features in the unaffected lung samples associated with recurrence, enrichment with Stenotrophomonas geniculata and Chryseobacterium were positively correlated with upregulation of IL-2, IL-3, IL-17, EGFR, HIF-1 signaling pathways among the host transcriptome. In tumor samples, enrichment with Veillonellaceae Dialister, Ruminococcacea, Haemophilus Influenza, and Neisseria were positively correlated with upregulation of IL-1, IL-6, IL17, IFN, and Tryptophan metabolism pathways. CONCLUSIONS: Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC=0.83). IMPACT: This study suggests that LUAD recurrence is associated with distinct pathophysiological mechanisms of microbial-host interactions in the unaffected lung rather than those present in the resected tumor.
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Purpose: Visceral adiposity is a significant risk factor for severe COVID-19. However, the impact of the Chinese visceral adiposity index (CVAI) on the efficacy of SARS-CoV-2 vaccines remains poorly understood. This study aims to explore the impact of CVAI on the production of neutralizing antibodies (NAb) in inactivated SARS-CoV-2 vaccines and the potential mechanism, thereby optimizing vaccination guidance. Methods: In this cross-sectional study, 206 health workers (completed two SARS-CoV-2 vaccination on February 8th and March 10th, 2021, respectively) were recruited. All baseline anthropometric parameters of the participants were collected, and venous blood samples were obtained 6 weeks later to measure peripheral innate immune cells, inflammatory cytokines, and NAb titers against SARS-CoV-2. CVAI were calculated according to the formula and divided participants into two groups depending on CVAI median. Results: The median NAb titer among healthcare workers was 12.94 AU/mL, with an efficacy of 87.86% for the SARS-CoV-2 vaccine. NAb titers were lower in the CVAI dysfunction group than in the CVAI reference group (median: 11.40 AU/mL vs 15.57 AU/mL), the hsCRP levels (median: 0.50 mg/L vs 0.30 mg/L) and peripheral monocyte count (mean: 0.47 × 109/L vs 0.42 × 109/L) in the CVAI dysfunction group were higher than in the CVAI reference group. Additionally, CVAI showed positive correlations with hsCRP, monocytes, lymphocytes, and B-lymphocytes, and a negative correlation with NAb titers. Conclusion: CVAI may inhibit SARS-CoV-2 neutralizing antibody expression through inducing immune dysfunction and chronic inflammation. Thus, more attention should be paid to the vaccination for high CVAI population to improve the effectiveness of vaccination, which could provide more robust support for COVID-19 epidemic prevention and control.
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BACKGROUND: Although the patient survival rate for many malignancies has been improved with immune checkpoint inhibitors (ICIs), some patients experience various immune-related adverse events (irAEs). IrAEs impact several organ systems, including the kidney. With anti-programmed cell death protein 1 (PD-1) therapy (pembrolizumab), kidney-related adverse events occur relatively rarely compared with other irAEs. However, the occurrence of AKI usually leads to anti-PD-1 therapy interruption or discontinuation. Therefore, there is an urgent need to clarify the mechanisms of renal irAEs (R-irAEs) to facilitate early management. This study aimed to analyse the characteristics of peripheral blood mononuclear cells (PBMCs) in R-irAEs. METHODS: PBMCs were collected from three patients who developed R-irAEs after anti-PD-1 therapy and three patients who did not. The PBMCs were subjected to scRNA-seq to identify cell clusters and differentially expressed genes (DEGs). Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses were performed to investigate the most active biological processes in immune cells. RESULTS: Fifteen cell clusters were identified across the two groups. FOS, RPS26, and JUN were the top three upregulated genes in CD4+ T cells. The DEGs in CD4+ T cells were enriched in Th17 differentiation, Th1 and Th2 cell differentiation, NF-kappa B, Nod-like receptor, TNF, IL-17, apoptosis, and NK cell-mediated cytotoxicity signaling pathways. RPS26, TRBV25-1, and JUN were the top three upregulated genes in CD8+ T cells. The DEGs in CD8+ T cells were enriched in Th17 cell differentiation, antigen processing and presentation, natural killer cell-mediated cytotoxicity, the intestinal immune network for IgA production, the T-cell receptor signalling pathway, Th1 and Th2 cell differentiation, the phagosome, and cell adhesion molecules. CONCLUSIONS: In conclusion, R-irAEs are associated with immune cell dysfunction. DEGs and their enriched pathways identified in CD4+ T cells and CD8+ T cells play important roles in the development of renal irAEs related to anti-PD-1 therapy. These findings offer fresh perspectives on the pathogenesis of renal damage caused by anti-PD-1 therapy.
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Leucocitos Mononucleares , Neoplasias Pulmonares , Análisis de la Célula Individual , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Neoplasias Pulmonares/genética , Femenino , Anciano , Receptor de Muerte Celular Programada 1 , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Análisis de Secuencia de ARN , Lesión Renal Aguda/inducido químicamenteRESUMEN
Background: Long non-coding RNAs (lncRNAs) are implicated in a variety of regulatory functions within tumors, yet their specific roles in glioma remain underexplored. Methods: We extracted glioma patient data from The Cancer Genome Atlas and UCSC Xena database for analysis using R, focusing on genomic characterization, biological enrichment, immune evaluation, and the development of a predictive model employing machine learning techniques. Additionally, we conducted cell culture and proliferation assays. Results: Our analysis revealed that the lncRNA SLC16A1-AS1 plays a pivotal role in glioma pathogenesis and prognosis. We observed that abnormal expression of SLC16A1-AS1 varied with tumor grade, IDH mutation status, and histological type, correlating with worse survival outcomes. Genomically, SLC16A1-AS1 was associated with Tumor Mutational Burden and other prognostic biomarkers. The expression of this lncRNA was also linked to the activation of critical biological pathways and appeared to modulate the immune microenvironment, enhancing the presence of immune cells and checkpoints, which may be predictive of immunotherapy outcomes. Our predictive model, constructed from genes associated with SLC16A1-AS1, accurately forecasted glioma prognosis, strongly correlating with survival and treatment responses. In vitro experiments further demonstrated that SLC16A1-AS1 significantly influences glioma cell proliferation, invasion, and migration, underscoring its role in tumor aggression and its potential as a therapeutic target. Conclusions: This study underscores the significant influence of SLC16A1-AS1 on glioma progression and prognosis, with its expression correlating with tumor traits and immune responses. The findings highlight the potential of targeting SLC16A1-AS1 in therapeutic strategies aimed at mitigating glioma aggressiveness.
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Objectives: Parkinson disease (PD) is the third leading cause of mortality among middle-aged and older individuals in China. This study aimed to explore the trends and distribution features of PD mortality in China from 2013 to 2021 and make predictions for the next few decades. Methods: Relevant data were obtained from the Chinese Center for Disease Control and Prevention Disease Surveillance Point system. The joinpoint regression model was used to evaluate trends. The R software was used to predict future trends. Results: Age-standardized mortality rate (ASMR) of PD increased from 0.59 per 100,000 individuals to 1.22 per 100,000 individuals from 2013 to 2021, with an average annual percent change (AAPC) of 9.50 (95% CI: 8.24-10.78). The all-age ASMR of PD were higher in male individuals than in female individuals, and ASMR increased with age. The number of deaths and ASMR increased gradually from west to east and from rural to urban areas. Furthermore, ASMR is expected to increase to 2.66 per 100,000 individuals by 2040. Conclusions: The heightened focus on the ASMR of PD among male individuals, urban areas, eastern China, and individuals aged ≥85 years has become a key determinant in further decreasing mortality, thereby exhibiting novel challenges to effective strategies for disease prevention and control.
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Inhibition of leucine-rich repeat kinase 2 is a genetically supported mechanism for the treatment of Parkinson's disease. We previously disclosed the discovery of an indazole series lead that demonstrated both safety and translational risks. The safety risks were hypothesized to be of unknown origin, so structural diversity in subsequent chemical matter was prioritized. The translational risks were identified due to a low brain Kpu,u in nonhuman primate studies, which raised concern over the use of an established peripheral biomarker as a surrogate for central target engagement. Given these challenges, the team sought to leverage structure- and property-based drug design and expanded efflux transporter profiling to identify structurally distinct leads with enhanced CNS drug-likeness. Herein, we describe the discovery of a "reinvented" indazole series with improved physicochemical properties and efflux transporter profiles while maintaining excellent potency and off-target kinase selectivity, which resulted in advanced lead, compound 23.
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Heat stress (HS) brings great challenges to the poultry industry. Vitamin B6 (VB6) is an essential micro-nutrient for animals to maintain normal physiological functions and possesses antioxidant and anti-inflammatory properties. This study aimed to explore the effect of VB6 on alleviating HS-induced intestinal barrier impairment in broilers. A total of 250 broilers (609.76 ± 0.34 g) were randomly allocated to 5 groups with 5 replicate cages of 10 birds each. The broilers in thermoneutral (TN) group were raised in thermoneutral conditions (23 ± 1°C) and fed with a basal diet. The birds in other four groups were housed under cycle high temperature (34 ± 1°C for 8 h/d) from d 21 to 35 and fed with the basal diet (HS group) or basal diet supplemented with 6, 12, or 24 mg/kg VB6 (HB-6, HB-12, HB-24 groups). The results showed that HS reduced the growth performance, increased ileum inflammatory cytokines levels, and impaired the gut barrier function (P < 0.05). Compared to the HS group, final body weight, average daily gain, and average daily feed intake, and the feed conversion ratio were improved by VB6 supplementation. The diamine oxidase, interleukin (IL)-1ß, tumor necrosis factor-α, IL-18, IL-10, and interferon-γ levels were reduced by VB6 supplementation (P < 0.05). Moreover, VB6 supplementation linearly or quadratically enhanced villus height and villus height-to-crypt depth ratio of duodenum and jejunum, and decreased crypt depth of duodenum and ileum. The mRNA expression of Occlaudin, ZO1, Mucin2, Mucin4, E-cadhein, and ß-catenin were increased by VB6 treatment (P < 0.05). Furthermore, dietary VB6 altered the diversity and community of gut microbiota (P < 0.05). A total of 83 differential metabolites associated with the amelioration of VB6 were identified, which were primarily enriched in glycerophospholipid metabolism, caffeine metabolism, and glutathione metabolism pathway. Collectively, VB6 may improve the growth performance and intestinal barrier function of heat-stressed broilers by regulating the ileal microbiota and metabolic homeostasis.
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Infectious diseases have caused enormous disasters in human society, and asymptomatic carriers are an important challenge in our epidemic prevention and control process. Nucleic acid testing has played an important role in rapid testing for asymptomatic individuals. How to carry out nucleic acid testing in a scientific manner is a practical problem encountered in normal production and life. Based on the real COVID-19 epidemic data from Shanghai, we established a susceptible-exposed-infected-asymptomatic-recovered-death (SEIARD) dynamic model. The least squares method was used to fit the data and estimate the unknown parameters ß and E(0) in the model, and MATLAB software was employed to simulate the development of the epidemic. The data fitting results indicated that the SEIARD model can better describe the early development patterns of the epidemic (R2 = 0.98; MAPE = 2.54%). We calculated the basic reproduction number of the Shanghai epidemic as R0 = 2.86. As the frequency of nucleic acid testing increased, the basic reproduction number R0 continued to decrease. When there is one latent carrier and one asymptomatic carrier in the nucleic acid testing team, the number of queues is directly proportional to the number of infected individuals, the nucleic acid testing team increases by 50 people, and the number of new asymptomatic cases increases by approximately 4 people. If both susceptible individuals (S) and asymptomatic patients (A) are not wearing masks, the infection rate reaches approximately 7%; after wearing masks, the final infection rate is less than 1% at 1.5 m between two people. The queue spacing is inversely proportional to the number of infected individuals. With a distance of d = 1 m, a nucleic acid testing team of 100 people added 8% of the infected individuals; when d = 1.5 m, fewer than 2% of the newly infected individuals. The results confirmed that controlling the queue size for nucleic acid testing, strictly wearing masks, and maintaining a queue spacing of more than 1.5 m are safe and effective nucleic acid testing strategies. Our findings are also applicable to the prevention of other newly emerging infectious diseases.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , China/epidemiología , Prueba de Ácido Nucleico para COVID-19/métodos , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/genética , Epidemias/prevención & control , Número Básico de ReproducciónRESUMEN
Renal fibrosis (RF) is a common endpoint of various chronic kidney diseases, leading to functional impairment and ultimately progressing to end-stage renal failure. Glycolytic reprogramming plays a critical role in the pathogenesis of fibrosis, which maybe a potential therapeutic target for treating renal fibrosis. Here, we revealed the novel role of ZEB1 in renal fibrosis, and whether targeting ZEB1 is the underlying mechanism for the anti-fibrotic effects of ethyl caffeate (EC) to regulate the glycolytic process. Treatment of EC attenuated the renal fibrosis and inhibited ZEB1 expression in vivo and in vitro, reducing the upregulated expression of glycolytic enzymes (HK2, PKM2, PFKP) and key metabolites (lactic acid, pyruvate). ZEB1 overexpression promoted the renal fibrosis and glycolysis, whereas knockout of ZEB1 apparently attenuated renal fibrosis in vivo and in vitro. EC interacted with ZEB1 to modulate the glycolytic enzymes for suppressing the elevated glycolytic reprogramming during renal fibrosis. In summary, our study reveals that ZEB1 plays an important role in regulating glycolytic reprogramming during the renal tubular epithelial cell fibrosis, suggesting inhibition of ZEB1 may be a potential strategy for treating renal fibrosis. Additionally, EC is a potential new drug candidate for the treatment of renal fibrosis and CKD.
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OBJECTIVE: Accurate and rapid identification of causative pathogens is essential to guide the clinical management of lower respiratory tract infections (LRTIs). Here we conducted a single-centre prospective study in 284 patients suspected of lower respiratory tract infections to evaluate the utility of a nucleic acid test based on highly multiplexed polymerase chain reaction (PCR) and CRISPR-Cas12a. METHODS: We determined the analytical and diagnostic performance of the CRISPR assay using a combination of reference standards, including conventional microbiological tests (CMTs), metagenomic Next-Generation Sequencing (mNGS), and clinical adjudication by a panel of experts on infectious diseases and microbiology. RESULTS: The CRISPR assay showed a higher detection rate (63.0%) than conventional microbiological tests (38.4%) and was lower than metagenomic Next-Generation Sequencing (72.9%). In detecting polymicrobial infections, the positivity rate of the CRISPR assay (19.4%) was higher than conventional microbiological tests (3.5%) and lower than metagenomic Next-Generation Sequencing (28.9%). The overall diagnostic sensitivity of the CRISPR assay (67.8%) was higher than conventional microbiological tests (41.8%), and lower than metagenomic Next-Generation Sequencing (93.2%). CONCLUSIONS: Considering the low cost, ease of operation, short turnaround time, and broad range of pathogens detected in a single test, the CRISPR assay has the potential to be implemented as a screening tool for the aetiological diagnosis of lower respiratory tract infections patients, especially in cases where atypical bacteria or coinfections are suspected.
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INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.
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Accurate spatial distribution of carbon dioxide (CO2) emissions is essential information needed to peaking emissions and achieving carbon neutral in China. The aim of this study was to map CO2 emissions with high spatial resolution at provincial scale and then explore the scale effect on mapping results. As an example, the spatiotemporal pattern and factors influencing CO2 emissions were examined in Guizhou Province in Western China. With the proposed method, a reasonable spatial distribution of CO2 emissions with high spatial resolution was obtained, which had relatively accurate information on spatial details. The optimal resolution of CO2 emissions at the provincial scale under high spatial resolution was approximately 90 m and 1260 m. More detailed grid data can better reflect the spatial variability of CO2 emissions. Emissions of CO2 were spatially heterogeneous in Guizhou, with high emissions in centers of big cities that gradually spread and decreased from city centers. From 2009 to 2019, the spatial distribution of CO2 emissions developed from agglomeration to dispersion. Areas of high carbon emissions decreased, those of medium carbon emissions increased, and many areas changed from no emissions to carbon emissions. Industrial land had the highest emissions, followed by commercial and transportation lands. Over 10 years, changes occurred in the relation between interregional economic level of Guizhou and CO2 emissions, with the relation changing from linear into an inverted U-shaped relation. The effect of industrial structure on CO2 emissions decreased, and the linear increase between CO2 emissions and the urban scale became more evident. The results of this study will contribute to accurate monitoring and management of carbon emissions in Guizhou, as well as provide support to formulate policies related to controls on carbon emissions in different regions.
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Topotactic reduction is critical to a wealth of phase transitions of current interest, including synthesis of the superconducting nickelate Nd0.8Sr0.2NiO2, reduced from the initial Nd0.8Sr0.2NiO3/SrTiO3 heterostructure. Due to the highly sensitive and often damaging nature of the topotactic reduction, however, only a handful of research groups have been able to reproduce the superconductivity results. A series of in situ synchrotron-based investigations reveal that this is due to the necessary formation of an initial, ultrathin layer at the Nd0.8Sr0.2NiO3 surface that helps to mediate the introduction of hydrogen into the film such that apical oxygens are first removed from the Nd0.8Sr0.2NiO3 / SrTiO3 (001) interface and delivered into the reducing environment. This allows the square-planar / perovskite interface to stabilize and propagate from the bottom to the top of the film without the formation of interphase defects. Importantly, neither geometric rotations in the square planar structure nor significant incorporation of hydrogen within the films is detected, obviating its need for superconductivity. These findings unveil the structural basis underlying the transformation pathway and provide important guidance on achieving the superconducting phase in reduced nickelate systems.
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Exploiting a photocatalyst with high stability and excellent activity for Cr(VI) reduction under mild conditions is crucial yet challenging. Herein, the rigid aromatic multicarboxylate ligand with chromophore anthracene was selected to coordinate with multivalent metal ion manganese and to obtain a stable two-dimensional (2D) Mn-based metal-organic framework (MOF), LCUH-120, which can efficiently and quickly convert Cr(VI) into Cr(III) under light without the need for any additional photosensitizer. The efficient photosensitive anthracene group serves as a photosensitizer center and multivalent Mn(II) ion as a photocatalyst center in LCUH-120, and the conversion of Cr(VI) to Cr(III) can be realized completely in just 40 min. Specifically, the rate constant (k) and reduction rate of the Cr(VI) photocatalytic reaction can be high up to 0.134 min-1 and 2.50 mgCr(VI) g-1cata min-1 in an acidic environment (pH = 2), respectively. Compared to our previously reported three-dimensional (3D) Sm-MOF, LCUH-120 exhibits a significantly higher catalytic reaction rate, which might be ascribed to the fact that the photocatalyst center Mn node can improve the rate of electron transfer and promote the separation of holes and photogenerated electrons. In an acidic environment, the reaction mechanism can be verified through various contrast experiments and theoretical simulations.
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Food contamination has long plagued agriculture, posing significant health risks to consumers. The use of volatile gases for food safety detection has proven highly effective, with composite gas sensors that leverage the two-dimensional material MXene exhibiting notable advancements in detecting various target gases. This paper reviews the progress of MXene-based composite gas sensors in the detection of food safety-related gases. The review begins by examining MXene material synthesis methods and then presents an overview of techniques aimed at enhancing MXene-based sensor detection capabilities. Recently, advancements in MXene composite gas sensors tailored for food safety gases have been highlighted. Finally, challenges encountered in gas-sensing applications of MXene-based composites are outlined, alongside predictions for their future development, aiming to offer insights for the application and advancement of intelligent gas sensors for target gases in food safety.
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Contaminación de Alimentos , Inocuidad de los Alimentos , Gases , Gases/análisis , Contaminación de Alimentos/análisisRESUMEN
A three-dimensional magnetic probe system has been designed and implemented at the Space Plasma Environment Research Facility (SPERF). This system has been developed to measure the magnetic field with high spatial and temporal resolution, enabling studies of fundamental processes in space physics, such as magnetic reconnection at the Earth's magnetopause, on the basis of SPERF. The system utilizes inductive components as sensors, arranged in an array and soldered onto a printed circuit board (PCB), achieving a spatial resolution of 2.5 mm. The system's electrical parameters have been measured, and its amplitude-frequency response characteristics have been simulated. The system has demonstrated good performance with response capabilities below 50 kHz. The experimental setup and results are discussed, highlighting the system's effectiveness in accurately measuring weak magnetic signals and its suitability for magnetic reconnection experiments.
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BACKGROUND AND PURPOSE: Garlic is used as an important medicinal food for treatment of many diseases, however, the association between garlic consumption and dyslipidemia have yielded inconsistent results. So we carried this meta-analysis to explore the blood lipid-lowering effects of garlic. METHODS: Databases such as PubMed, Scopus, Web of science, Embase, Cochrane Library were systematically searched until June 2024. Heterogeneity among studies was examined using Q and I2 statistics. Also subgroup analysis were conducted to explore the potential heterogeneity. Combined weighted mean differences (WMD) with their 95% confidence interval (CI) were calculated using a random-effects model. The GRADE approach was used to evaluate the overall certainty of the evidence in the meta-analyses. RESULTS: A total of 21 RCTs studies involved association between garlic consumption and blood lipids level of dyslipidemia patients were included in the meta-analysis. The pooled results showed that garlic consumption significantly reduced total cholesterol (TC)(WMD = -0.64mmol/L, 95%CI = -0.75 --0.54, P < 0.001), triglyceride (TG)(WMD = -0.17mmol/L, 95%CI = -0.26 --0.09, P < 0.001), low-density lipoprotein(LDL-C)(WMD = -0.44mmol/L, 95%CI = -0.57 --0.31, P < 0.001) while slightly increased high-density lipoprotein (HDL-C)(WMD = 0.04mmol/L, 95%CI = -0.00 - 0.08, P < 0.001). And subgroup analyses showed that TC, TG and LDL-C significantly decreased in patients aged > 50 years compared to those aged ≤ 50 years. And garlic oil greatly reduced TC and LDL-C compared with garlic power. Finally, sensitivity analysis and publication bias showed that the results were reliable. CONCLUSIONS: Evidence from this meta-analysis suggested that garlic consumption could be effective in reducing the risk of dyslipidemia and preventing CVDs. Particularly the older people were more susceptible to the protective effects of garlic.
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Dislipidemias , Ajo , Ensayos Clínicos Controlados Aleatorios como Asunto , Dislipidemias/prevención & control , Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Humanos , Triglicéridos/sangre , Persona de Mediana Edad , Femenino , Masculino , LDL-Colesterol/sangre , Adulto , Lípidos/sangreRESUMEN
Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile.