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Background: Osteonecrosis of the femoral head (ONFH) is acknowledged as a prevalent, challenging orthopedic condition for patients. Purpose: This study aimed to evaluate the efficacy of various interventions for non-traumatic ONFH and provide guidance for clinical decision-makers. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases from inception to February 2023 for relevant randomized controlled trials evaluating treatments for femoral head necrosis, without language restrictions. Quality evaluation was performed using the Cochrane risk-of-bias assessment tool, and analysis was performed using Stata 15.1. Results: Eleven randomized controlled trials were included in this study. The meta-analysis results revealed that CellTherapy [MD= -3.46, 95%CI= (-5.06, -1.85)], InjectableMed [MD= -3.68, 95%CI= (-6.11, -1.21)], ESWT [MD= -2.84, 95%CI= (-4.23, -1.45)], ESWT+InjectableMed [MD= -3.86, 95%CI= (-6.22, -1.53)] were significantly more effective in improving VAS pain score than CD+PTRI, as well as CD+BG+CellTherapy, and CD+BG. Furthermore, CD+BG+CellTherapy was better than CD+BG [MD= -0.97, 95%CI= (-1.71, -0.19)]. The SUCRA ranking for HHS score indicated that CellTherapy (77%) has the best effectiveness rate, followed by ESWT+InjectableMed (72.2%), ESWT (58.3%), InjectableMed (50%), CD+PTRI (31.4%), and CD+BG (11%). In terms of WOMAC and Lequesne scores, the meta-analysis showed no statistically significant differences between the experimental group CD+BG+CellTherapy and the control group CD+BG. Conclusion: CellTherapy and non-surgical ESWT combined with medication or CellTherapy have the best effect on ONFH. Surgical CD+BG combined with CellTherapy is more effective than CD+BG alone. ESWT+InjectableMed is recommended for short-term or acute onset patients, while ESWT is recommended for long-term patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024540122.
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Necrosis de la Cabeza Femoral , Osteonecrosis , Humanos , Tratamiento con Ondas de Choque Extracorpóreas/métodos , Necrosis de la Cabeza Femoral/terapia , Metaanálisis en Red , Osteonecrosis/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
The existing electronic waste (e-waste) and leaching solutions generated by industries accumulate significant amounts of gold (Au), even in excess of those in natural minerals. Therefore, the recycling of Au is extremely significant for the potential sustainability of chemical industry. By designing ionic covalent organic frameworks (COFs), here we synthesize a series of Ionic-COF-X (X=Cl-, Br-, AcO-, and SO42-) by anion regulation strategy. All these ionic COFs exhibit ultrahigh gold adsorption efficiency and excellent regeneration. Moreover, anion regulation could indeed affect the Au capture performance. In particular, when Cl- ions serve as counter ions, the Au capacity of Ionic-COF-Cl could reach 1270.8 mg g-1. Moreover, in the actual CPU leaching solution test, the selectivity of Ionic-COF-Cl towards Au3+ ion hits 39000 and 4600 times higher than that of Cu2+ and Ni2+ ions, respectively, suggesting that the Ionic-COF-Cl is a promising material for highly selective recovering gold from actual e-waste. DFT calculations further reveal that counter ions can regulate the adsorption affinity of ionic COF framework toward Au. In short, this work provides a useful anion regulation strategy to design ionic COFs as a promising platform for gold selective recovery from actual e-waste.
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BACKGROUND: In radiography procedures, radiographers' suboptimal positioning and exposure parameter settings may necessitate image retakes, subjecting patients to unnecessary ionizing radiation exposure. Reducing retakes is crucial to minimize patient X-ray exposure and conserve medical resources. OBJECTIVE: We propose a Digital Radiography (DR) Pre-imaging All-round Assistant (PIAA) that leverages Artificial Intelligence (AI) technology to enhance traditional DR. METHODS: PIAA consists of an RGB-Depth (RGB-D) multi-camera array, an embedded computing platform, and multiple software components. It features an Adaptive RGB-D Image Acquisition (ARDIA) module that automatically selects the appropriate RGB camera based on the distance between the cameras and patients. It includes a 2.5D Selective Skeletal Keypoints Estimation (2.5D-SSKE) module that fuses depth information with 2D keypoints to estimate the pose of target body parts. Thirdly, it also uses a Domain expertise (DE) embedded Full-body Exposure Parameter Estimation (DFEPE) module that combines 2.5D-SSKE and DE to accurately estimate parameters for full-body DR views. RESULTS: Optimizes DR workflow, significantly enhancing operational efficiency. The average time required for positioning patients and preparing exposure parameters was reduced from 73 seconds to 8 seconds. CONCLUSIONS: PIAA shows significant promise for extension to full-body examinations.
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The simultaneous enhancement of lipophagy and mitochondrial biogenesis has emerged as a promising strategy for lipid lowering. The transcription factor EB (TFEB) exhibits a dual role, whereby it facilitates the degradation of lipid droplets (LDs) through the process of lipophagy while simultaneously stimulating mitochondrial biogenesis to support the utilization of lipophagy products. The purpose of this study was to explore the effect of astragaloside I (AS I) on hyperlipidemia and elucidate its underlying mechanism. AS I improved serum total cholesterol and triglyceride levels and reduced hepatic steatosis and lipid accumulation in db/db mice. AS I enhanced the fluorescence colocalization of LDs and autophagosomes and promoted the proteins and genes related to the autolysosome. Moreover, AS I increased the expression of mitochondrial biogenesis-related proteins and genes, indicating that AS I promoted lipophagy and mitochondrial biogenesis. Mechanistically, AS I inhibits the protein level of p-TFEB (ser211) expression and promotes TFEB nuclear translocation. The activation of TFEB by AS I was impeded upon the introduction of the mammalian target of rapamycin (mTOR) agonist MHY1485. The inhibition of p-mTOR by AS I and the activation of TFEB were no longer observed after administration of the Akt agonist SC-79, which indicated that AS I activated TFEB to promote lipophagy-dependent on the Akt/mTOR pathway and may be a potentially effective pharmaceutical and food additive for the treatment of hyperlipidemia.
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T cells expressing PD-1 in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD1-triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1- T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T cell activation-related pathways compared with PD-1- T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity towards autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1/CD28 fusion receptor combined with a CD19 chimeric antigen receptor (CAR) into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1/CD28-CD19-CAR PD-1+ T cells. None of these patients experienced severe side effects and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for cancer patients.
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The microscopic reaction pathway plays a crucial role in determining the electrochemical performance. However, artificially manipulating the reaction pathway still faces considerable challenges. In this study, we focus on the classical acidic water oxidation based on RuO2 catalysts, which currently face the issues of low activity and poor stability. As a proof-of-concept, we propose a strategy to create local structural symmetry but oxidation-state asymmetric Mn4-δ-O-Ru4+δ active sites by introducing Mn atoms into RuO2 host, thereby switching the reaction pathway from traditional adsorbate evolution mechanism to oxide path mechanism. Through advanced operando synchrotron spectroscopies and density functional theory calculations, we demonstrate the synergistic effect of dual-active metal sites in asymmetric Mn4-δ-O-Ru4+δ microstructure in optimizing the adsorption energy and rate-determining step barrier via an oxide path mechanism. This study highlights the importance of engineering reaction pathways and provides an alternative strategy for promoting acidic water oxidation.
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BACKGROUND: Ischemic stroke belongs to "apoplexy" and its pathogenesis is characterized by qi deficiency and blood stasis combining with phlegm-damp clouding orifices. Buqi-Huoxue-Tongnao decoction (BHTD) is a traditional Chinese medicine formula for qi deficiency, blood stasis and phlegm obstruction syndrome. However, its efficacy and potential mechanism on ischemic stroke are still unclear. This study aims to investigate the protective effect and potential mechanism of BHTD against ischemic stroke. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) surgery was carried out to establish an ischemic stroke model in rats. Subsequently, the rats were gavaged with different doses of BHTD (2.59, 5.175, 10.35 g/kg) for 14 days. The protective effects of BHTD on the brain and gut were evaluated by neurological function scores, cerebral infarction area, levels of brain injury markers (S-100B, NGB), indicators of gut permeability (FD-4) and bacterial translocation (DAO, LPS, D-lactate), and tight junction proteins (Occludin, Claudin-1, ZO-1) in brain and colon. 16S rRNA gene sequencing and metabolomic analysis were utilized to analyze the effects on gut microecology and screen for marker metabolites to explore potential mechanisms of BHTD protection against ischemic stroke. RESULTS: BHTD could effectively mitigate brain impairment, including reducing neurological damage, decreasing cerebral infarction and repairing the blood-brain barrier, and BHTD showed the best effect at the dose of 10.35 g/kg. Moreover, BHTD reversed gut injury induced by ischemic stroke, as evidenced by decreased intestinal permeability, reduced intestinal bacterial translocation, and enhanced intestinal barrier integrity. In addition, BHTD rescued gut microbiota dysbiosis by increasing the abundance of beneficial bacteria, including Turicibacter and Faecalibaculum. Transplantation of the gut microbiota remodeled by BHTD into ischemic stroke rats recapitulated the protective effects of BHTD. Especially, BHTD upregulated tryptophan metabolism, which promoted gut microbiota to produce more indole lactic acid (ILA). Notably, supplementation with ILA by gavage could alleviate stroke injury, which suggested that driving the production of ILA in the gut might be a novel treatment for ischemic stroke. CONCLUSION: BHTD could increase gut microbiota-derived indole lactic acid to attenuate ischemic stroke via the gut-brain axis. Our current finding provides evidence that traditional Chinese medicine can ameliorate central diseases through regulating the gut microbiology.
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Soybean (Glycine max (L.) Merr) is one of the most important crops worldwide, but its yield is vulnerable to abiotic stresses. In Arabidopsis, the AlkB homologue (ALKBH) family genes plays a crucial role in plant development and stress response. However, the identification and functions of its homologous genes in soybean remain obscured. Here, we identified a total of 22 ALKBH genes in soybean and classified them into seven subfamilies according to phylogenetic analysis. Gene duplication events among the family members and gene structure, conserved domains, and motifs of all candidate genes were analyzed. By comparing the changes in the m6A levels on mRNA from hair roots between soybean seedlings harboring the empty vector and those harboring the GmALKBH10B protein, we demonstrated that all four GmALKBH10B proteins are bona fide m6A RNA demethylases in vivo. Subcellular localization and expression patterns of the GmALKBH10B revealed that they might be functionally redundant. Furthermore, an analysis of cis-elements coupled with gene expression data demonstrated that GmALKBH10B subfamily genes, including GmALKBH10B1, GmALKBH10B2, GmALKBH10B3, and GmALKBH10B4, are likely involved in the cis-elements' response to various environmental stimuli. In summary, our study is the first to report the genome-wide identification of GmALKBH family genes in soybean and to determine the function of GmALKBH10B proteins as m6A RNA demethylases, providing insights into GmALKBH10B genes in response to abiotic stresses.
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BACKGROUND: In magnetic resonance imaging (MRI), maintaining a highly uniform main magnetic field (B0) is essential for producing detailed images of human anatomy. Passive shimming (PS) is a technique used to enhance B0 uniformity by strategically arranging shimming iron pieces inside the magnet bore. Traditionally, PS optimization has been implemented using linear programming (LP), posing challenges in balancing field quality with the quantity of iron used for shimming. PURPOSE: In this work, we aimed to improve the efficacy of passive shimming that has the advantages of balancing field quality, iron usage, and harmonics in an optimal manner and leads to a smoother field profile. METHODS: This study introduces a hybrid algorithm that combines particle swarm optimization with sequential quadratic programming (PSO-SQP) to enhance shimming performance. Additionally, a regularization method is employed to reduce the iron pieces' weight effectively. RESULTS: The simulation study demonstrated that the magnetic field was improved from 462 to 3.6 ppm, utilizing merely 1.2 kg of iron in a 40 cm diameter spherical volume (DSV) of a 7T MRI magnet. Compared to traditional optimization techniques, this method notably enhanced magnetic field uniformity by 96.7% and reduced the iron weight requirement by 81.8%. CONCLUSION: The results indicated that the proposed method is expected to be effective for passive shimming.
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ETHNOPHARMACOLOGICAL RELEVANCE: Caryopteris trichosphaera W. W. Sm., a traditional ethnic medicine, was recorded in the Compendium of Materia Medica for treating wound infection by pathogenic infection. However, its antibacterial potential and bioactive compositions against drug-resistant bacteria need to be validated. AIM OF THE STUDY: To investigate the chemical constituents of C. trichosphaera and explore its anti-MRSA component in vitro and in vivo, together with the antibacterial mechanism. MATERIALS AND METHODS: Bioactive constituents investigation was carried out by phytochemical method and antibacterial screening. The antibacterial mechanism was predicted by network pharmacology, which was further validated by time-kill analysis, membrane function tests, multigenerational resistance induction assay and biofilm test, and metabolomics analysis in vitro. In addition, MRSA-induced epidermal infection in mice was selected to evaluate its pharmacological effect in vivo. RESULTS: Six antibacterial diterpenoids against MRSA and VRE with MIC values 4-32 µg/mL from C. trichosphaera were reported for the first time, in which the major compound cativic acid (1) disrupted MRSA cell membranes by modulating permeability, depolarization, and fluidity while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels. It also displayed remarkable anti-biofilm activity without inducing bacterial resistance or cytotoxicity. Moreover, cativic acid affected MRSA biosynthesis of cofactors, amino acid biosynthesis, nucleotide metabolism by metabolomics analysis. Furthermore, cativic acid accelerated wound healing in MRSA-infected mouse skin wounds, even better than vancomycin. CONCLUSIONS: The results supported the traditional use of C. trichosphaera, and presented unreported anti-MRSA agent, cativic acid, as a plant-derived bactericide in vitro and in vivo for the first time.
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Cell-free DNA (cfDNA) analysis has shown potential in detecting early-stage lung cancer based on non-genetic features. To distinguish patients with lung cancer from healthy individuals, peripheral blood were collected from 926 lung cancer patients and 611 healthy individuals followed by cfDNA extraction. Low-pass whole genome sequencing and targeted methylation sequencing were conducted and various features of cfDNA were evaluated. With our customized algorithm using the most optimal features, the ensemble stacked model was constructed, called ESim-seq (Early Screening tech with Integrated Model). In the independent validation cohort, the ESim-seq model achieved an area under the curve (AUC) of 0.948 (95 % CI: 0.915-0.981), with a sensitivity of 79.3 % (95 % CI: 71.5-87.0 %) across all stages at a specificity of 96.0 % (95 % CI: 90.6-100.0 %). Specifically, the sensitivity of the ESim-seq model was 76.5 % (95 % CI: 67.3-85.8 %) in stage I patients, 100 % (95 % CI: 100.0-100.0 %) in stage II patients, 100 % (95 % CI: 100.0-100.0 %) in stage III patients and 87.5 % (95 % CI: 64.6%-100.0 %) in stage IV patients in the independent validation cohort. Besides, we constructed LCSC model (Lung Cancer Subtype multiple Classification), which was able to accurately distinguish patients with small cell lung cancer from those with non-small cell lung cancer, achieving an AUC of 0.961 (95 % CI: 0.949-0.957). The present study has established a framework for assessing cfDNA features and demonstrated the benefits of integrating multiple features for early detection of lung cancer.
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Introduction: Adiponectin is a factor secreted by adipocytes and has been shown to play an important role in many physiological and pathological processes. Previous studies have shown that adiponectin levels are closely related to the occurrence and prognosis of ischemic stroke, but the results of different studies are conflicting. Therefore, this study aimed to update the data in this area to explore the relationship between adiponectin levels and the occurrence and prognosis of ischemic stroke. Results: After searching 762 records, 14 studies were finally included, including 10 studies on the incidence of ischemic stroke and 4 studies on the prognosis of patients with ischemic stroke. The results of Meta-analysis showed that the correlation between the level of adiponectin and the occurrence and prognosis of ischemic stroke was not significant. The risk of ischemic stroke was not significantly changed in the population with high adiponectin levels (pooled RR=1.00, 95% CI=0.86-1.16, P=1.00). Similarly, there was no significant difference in all-cause mortality among those with high adiponectin levels compared with ischemic stroke patients with low adiponectin levels (pooled RR 0.61, 95% CI 0.47-0.80). However, significant heterogeneity was found during the meta-analysis, P<0.0001; I2=72% and P<0.0001; I2=88%, respectively. Subgroup analysis showed that factors such as study design, follow-up time and publication time could partly explain this heterogeneity. Conclusions: In conclusion, adiponectin level is not significantly correlated with the occurrence and prognosis of ischemic stroke, suggesting that adiponectin level may not be used as a potential biomarker for ischemic stroke risk assessment and patient prognosis prediction.
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PURPOSE: Infections caused by Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) plus Escherichia coli (E2SKAPE), in particular multidrug-resistant (MDR) E2SKAPE infections, occur frequently and pose a life-threatening to liver transplant (LT) recipients. To prevent E2SKAPE infections and improve the prognosis of LT recipients, the identification of risk factors for E2SKAPE infections and mortality is necessary. METHODS: E2SKAPE pathogens were isolated and identified from clinical samples following standard microbiological procedures. All episodes of E2SKAPE infections and mortality documented among LT recipients were analyzed. FINDINGS: A total of 83 episodes of E2SKAPE infections, including 75 (90.4%) episodes of MDR-E2SKAPE infections, occurred in 23.1% (53/229) of LT recipients. E. faecium was the dominant causative bacterium (37/83; 44.6%). The most common site of infections was the urinary tract (14/53; 26.4%). Sixteen (7%) patients died within 2 months after LT, and 7 deaths were E2SKAPE infections-related. Multivariate logistic regression analysis revealed that female sex [odds ratio (OR) = 3.665, 95% confidence interval (CI): 1.614-8.321, P = 0.002], duration of surgery ≥ 400 min [OR = 2.328, 95%CI: 1.151-4.707, P = 0.019], intraoperative red blood cell (RBC) transfusion ≥ 12U [OR = 2.542, 95%CI: 1.218-5.306, P = 0.013] and indwelling urethral catheter use ≥ 3 days [OR = 3.96, 95%CI: 1.309-11.981, P = 0.015] were independent risk factors for E2SKAPE infections after LT, and that only exposure to more than 2 intravenous antibiotics post-LT [OR = 0.318, 95%CI: 0.15-0.674, P = 0.003] was negatively associated with acquisition of E2SKAPE infections. The predictors of crude mortality included female sex [OR = 4.822, 95%CI: 1.299-17.904, P = 0.019], creatinine on day 3 post-LT > 1.5 mg/dL [OR = 11.014, 95%CI: 2.985-40.637, P < 0.001], mechanical ventilation post-LT [OR = 10.724, 95%CI: 2.695-42.676, P = 0.001] and recipients with E2SKAPE infections [OR = 4.112, 95%CI: 1.169-14.47, P = 0.028]. IMPLICATIONS: A high incidence of E2SKAPE infections was noted in the early post-LT period. The most common infection site was the urinary tract, and the dominant pathogenic bacterium was E. faecium. Female sex, prolonged surgery time, massive RBC transfusion, or delayed urethral catheter removal were associated with E2SKAPE infections. Only exposure to more than 2 intravenous antibiotics post-LT was negatively related to the acquisition of E2SKAPE infections. The predictors of mortality included female sex, creatinine on day 3 post-LT>1.5 mg/dL, mechanical ventilation post-LT, and recipients with E2SKAPE infections.
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Collagen posttranslational processing is crucial for its proper assembly and function. Disruption of collagen processing leads to tissue development and structure disorders like osteogenesis imperfecta (OI). OI-related collagen processing machinery includes prolyl 3-hydroxylase 1 (P3H1), peptidyl-prolyl cis-trans isomerase B (PPIB), and cartilage-associated protein (CRTAP), with their structural organization and mechanism unclear. We determine cryo-EM structures of the P3H1/CRTAP/PPIB complex. The active sites of P3H1 and PPIB form a face-to-face bifunctional reaction center, indicating a coupled modification mechanism. The structure of the P3H1/CRTAP/PPIB/collagen peptide complex reveals multiple binding sites, suggesting a substrate interacting zone. Unexpectedly, a dual-ternary complex is observed, and the balance between ternary and dual-ternary states can be altered by mutations in the P3H1/PPIB active site and the addition of PPIB inhibitors. These findings provide insights into the structural basis of collagen processing by P3H1/CRTAP/PPIB and the molecular pathology of collagen-related disorders.
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Colágeno , Microscopía por Crioelectrón , Ciclofilinas , Proteínas de la Matriz Extracelular , Humanos , Colágeno/metabolismo , Colágeno/química , Proteínas de la Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/química , Proteínas de la Matriz Extracelular/genética , Ciclofilinas/metabolismo , Ciclofilinas/química , Ciclofilinas/genética , Dominio Catalítico , Isomerasa de Peptidilprolil/metabolismo , Isomerasa de Peptidilprolil/química , Isomerasa de Peptidilprolil/genética , Procesamiento Proteico-Postraduccional , Sitios de Unión , Unión Proteica , Autoantígenos/metabolismo , Autoantígenos/química , Autoantígenos/genética , Modelos Moleculares , Mutación , Osteogénesis Imperfecta/metabolismo , Osteogénesis Imperfecta/genética , Procolágeno-Prolina Dioxigenasa/metabolismo , Procolágeno-Prolina Dioxigenasa/genética , Procolágeno-Prolina Dioxigenasa/química , Glicoproteínas de Membrana , Proteoglicanos , Chaperonas Moleculares , Prolil HidroxilasasRESUMEN
BACKGROUND: Leukemia is the tenth most common cause of cancer death worldwide and one of the most important causes of disability. To understand the current status and changing trends of the disease burden of leukemia at the global, regional, and national levels, and to provide a scientific basis for the development of leukemia prevention and treatment strategies. METHODS: Based on open data from the Global Burden of Disease Study 2019 (GBD 2019), R software was used to calculate estimated annual percentage changes to estimate trends in the age-standardized incidence (ASIR) and the age-standardized disability-adjusted life years (DALY) rate due to leukemia and its major subtypes from 1990 to 2019. RESULTS: In 2019, globally, the number of incidences and DALYs of leukemia were 643.6 × 103 (587.0 × 103, 699.7 × 103) and 11,657.5 × 103 (10529.1 × 103, 12700.7 × 103), respectively. The ASIR (estimated annual percentage change (EAPC) = -0.37, 95%UI -0.46 to -0.28) and the age-standardized DALY rate (EAPC = -1.72, 95%UI -1.80 to -1.65) of leukemia showed a decreasing trend from 1990 to 2019. The APC model analysis showed that the age effect of leukemia risk was a "U"-shaped distribution of relative risk (RR) with increasing age from 1990 to 2019, globally. The time effect was an increase in incidence rate with increasing years but a decrease in DALY rate with increasing years. The cohort effects of both incidence and DALY rates tended to increase and then decrease with the development of the birth cohort. In 1990 and 2019, smoking, high body-mass index, occupational exposure to benzene, and occupational exposure to formaldehyde were risk factors for DALY in leukemia, especially in areas with high SDI. CONCLUSIONS: From 1990 to 2019, the disease burden of leukemia showed a decreasing trend, but it is worth noting that its overall severity is still very high. The disease burden of leukemia varies greatly from region to region, and exclusive strategies for the prevention and treatment of leukemia should be developed according to the economic and cultural development of each region.
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Años de Vida Ajustados por Discapacidad , Carga Global de Enfermedades , Leucemia , Humanos , Carga Global de Enfermedades/tendencias , Leucemia/epidemiología , Incidencia , Masculino , Femenino , Salud Global , Adulto , Persona de Mediana Edad , Anciano , Adolescente , Adulto JovenRESUMEN
Background: Diabetic kidney disease (DKD) is the primary contributor to renal failure and poses a severe threat to human health. Accumulating studies demonstrated that competing endogenous RNA (ceRNA) network is involved in cuproptosis and DKD progression. However, the role of cuproptosis-associated ceRNA network and immune infiltration in DKD remains largely unclear. This study aimed to investigate the cuproptosis-related ceRNA regulation network and immune infiltration in DKD. Methods: The rat model of DKD was induced by combining the nephrectomy of the left kidney, high-fat diet, and streptozotocin. Differentially expressed genes (DEGs), miRNAs (DEMs), and lncRNAs (DELs) between normal and DKD rats were obtained. DEGs were intersected with cuproptosis-related genes (CRGs) to obtain DE-CRGs. LncRNAs and miRNAs were predicted based on the DE-CRGs, and they were intersected with DEMs and DELs, respectively. Subsequently, a cuproptosis-associated lncRNA-miRNA-mRNA network was established in DKD. In addition, the relative proportion of 22 infiltrating immune cell types in each sample was calculated, and the relationship between hub DE-CRGs and immune cells was explored. Results: In total, there were 429 DEGs, 22 DEMs, and 48 DELs between CON and MOD groups. Then, 73 DE-CRGs were obtained, which were significantly enriched in 22 pathways, such as MAPK signaling pathway, IL-17 signaling pathway, and TNF signaling pathway. In addition, a core cuproptosis-related ceRNA network that included one lncRNA (USR0000B2476D), one miRNA (miR-34a-3p), and eight mRNAs (Mmp9, Pik3c3, Prom1, Snta1, Slc51b, Ntrk3, Snca, Egf) was established. In addition, 18 hub DE-CRGs were obtained. CIBERSORT algorithms showed that resting dendritic cells and resting NK cells were more infiltrated whereas regulatory T cells were less infiltrated in DKD rats than in normal rats. Spearman's correlation analysis revealed that hub DE-CRGs showed significant positive or negative correlations with naive B cells, regulatory T cells, resting NK cells, M0 macrophages, resting dendritic cells, and resting mast cells. Conclusion: A ceRNA network was comprehensively constructed, and 18 hub DE-CRGs were obtained, which will provide novel insights into the pathologic mechanism elucidation and targeted therapy development of DKD.
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BACKGROUND: Cystathionine accumulates selectively in 1p/19q-codeleted gliomas, and can serve as a possible noninvasive biomarker. This study aims to optimize the echo time (TE) of point-resolved spectroscopy (PRESS) for cystathionine detection in gliomas, and evaluate the diagnostic accuracy of PRESS for 1p/19q-codeletion identification. METHODS: The TE of PRESS was optimized with numerical and phantom analysis to better resolve cystathionine from the overlapping aspartate multiplets. The optimized and 97 ms TE PRESS were then applied to 84 prospectively enrolled patients suspected of glioma or glioma recurrence to examine the influence of aspartate on cystathionine quantification by fitting the spectra with and without aspartate. The diagnostic performance of PRESS for 1p/19q-codeleted gliomas were assessed. RESULTS: The TE of PRESS was optimized as (TE1, TE2) = (17 ms, 28 ms). The spectral pattern of cystathionine and aspartate were consistent between calculation and phantom. The mean concentrations of cystathionine in vivo fitting without aspartate were significantly higher than those fitting with full basis-set for 97 ms TE PRESS (1.97 ± 2.01 mM vs. 1.55 ± 1.95 mM, p < 0.01), but not significantly different for 45 ms method (0.801 ± 1.217 mM and 0.796 ± 1.217 mM, p = 0.494). The cystathionine concentrations of 45 ms approach was better correlated with those of edited MRS than 97 ms counterparts (r = 0.68 vs. 0.49, both p < 0.01). The sensitivity and specificity for discriminating 1p/19q-codeleted gliomas were 66.7% and 73.7% for 45 ms method, and 44.4% and 52.5% for 97 ms method, respectively. CONCLUSION: The 45 ms TE PRESS yields more precise cystathionine estimates than the 97 ms method, and is anticipated to facilitate noninvasive diagnosis of 1p/19q-codeleted gliomas, and treatment response monitoring in those patients. Medium diagnostic performance of PRESS for 1p/19q-codeleted gliomas were observed, and warrants further investigations.
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Neoplasias Encefálicas , Cistationina , Glioma , Humanos , Glioma/diagnóstico por imagen , Masculino , Cistationina/análisis , Femenino , Neoplasias Encefálicas/diagnóstico por imagen , Persona de Mediana Edad , Adulto , Estudios Prospectivos , Fantasmas de Imagen , Anciano , Espectroscopía de Resonancia Magnética/métodos , Adulto Joven , Biomarcadores de Tumor/análisis , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisisRESUMEN
Wastewater-based epidemiology (WBE) is a reliable means to estimate drug consumption in a specific population. By measuring the concentration of drug residues or metabolites in wastewater, the consumption behavior pattern of a specific population can be deduced. Using the WBE method, the present study, for the first time, continuously monitored the differences in the consumption of morphine (MOR), codeine (CODE), and methamphetamine (METH) in three wastewater-treatment plants in a city and two surrounding villages in Xinjiang, China during International Workers' Day and the following week. The wastewater samples were pretreated by solid-phase extraction and then analyzed by high-performance liquid chromatography-tandem mass spectrometry. Methamphetamine was not detected in rural areas and was detected only on International Workers' Day in urban areas. According to the estimation of per capita consumption, the per capita consumption of MOR, CODE, and METH in urban inhabitants was 12.04 to 23.39, 10.44 to 16.39, and 1.31 mg/day/1000 inhabitants. The per capita consumption of MOR and CODE in rural areas was 5.19 to 8.35 and 2.56 to 3.52 mg/day/1000 inhabitants. The consumption of MOR in urban and rural areas was significantly higher than that of CODE and METH. During International Workers' Day, workdays, and weekends, the consumption of MOR and CODE in urban areas is significantly higher than that in rural areas. Compared with those on weekends, the consumption of urban MOR and CODE increased more during International Workers' Day. The consumption of MOR in urban areas showed a weekend effect. The present study can provide information for subsequent research and government departments. Environ Toxicol Chem 2024;00:1-9. © 2024 SETAC.
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Lung cancer is one of the most common malignant tumors. Despite decades of research, the treatment of lung cancer remains challenging. Non-small cell lung cancer (NSCLC) is the primary type of lung cancer and is a significant focus of research in lung cancer treatment. The deubiquitinase ubiquitin-specific protease 28 (USP28) plays a role in the progression of various tumors and serves as a potential therapeutic target. This study aims to determine the role of USP28 in the progression of NSCLC. We examined the impact of the USP28 inhibitor AZ1 on the cell cycle, apoptosis, DNA damage response, and cellular immunogenicity in non-small cell lung cancer. We observed that AZ1 and siUSP28 induce DNA damage, leading to the activation of Noxa-mediated mitochondrial apoptosis. The dsDNA and mtDNA released from DNA damage and mitochondrial apoptosis activate tumor cell immunogenicity through the cGAS-STING signaling pathway. Simultaneously, targeting USP28 promotes the degradation of c-MYC, resulting in cell cycle arrest and inhibition of DNA repair. This further promotes DNA damage-induced cell apoptosis mediated by the Noxa protein, thereby enhancing tumor cell immunogenicity mediated by dsDNA and mtDNA. Moreover, we found that the combination of AZ1 and cisplatin (DDP) can enhance therapeutic efficacy, thereby providing a new strategy to overcome cisplatin resistance in NSCLC. These findings suggest that targeting USP28 and combining it with cisplatin are feasible strategies for treating NSCLC.