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Predicting and understanding the phenomenon of surface subsidence caused by coal mining in working faces with faults are important issues for safe coal mining and efficient production. In numerical simulation experiments, it was found that the phenomenon of surface subsidence manifests when faults exist, and the degree of influence of faults with different dip angles on surface subsidence varies. This phenomenon is attributed to fault activation. According to the experimental results, the impact of faults with different dip angles on surface subsidence falls into three levels: level I for 35° faults, level II for 45° and 55° faults, and level III for 65° and 75° faults. Similarly, the relationship between the difficulty of fault activation and the dip angle of faults can be categorized as 35° faults prone to activation, 45° and 55° faults difficult to activate, and 65° and 75° faults not prone to activation. The probability integral correction model for fault mining, which integrates the surface subsidence values caused by fault-induced attenuation and the subsidence arising from separation spaces, was introduced, thereby constructing a surface subsidence prediction model. This proposed prediction model can accurately predict surface subsidence, with a root mean square error of 10.74 mm between the predicted and measured values, as validated using DInSAR results from the III 6301 working face in the Jincheng mining area.
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The east route of the South-to-North Water Diversion Project in Jiangsu Province was used as an example to investigate the characteristics of changes in water quality in the area affected by significant water diversion projects. Based on the comprehensive assessment method of the water quality index ï¼WQIï¼, the M-K trend test, and the geographic information system ï¼GISï¼, the spatial and temporal variation characteristics of water quality in the 13 national assessment sections of the east route of the South-to-North Water Diversion Project in Jiangsu Province were evaluated and analyzed from 2013 to 2022. The results showed that the water quality assessment grades in the study area were mainly "medium" and "good." The overall mean value was 74.03, indicating "good" water quality. DO, BOD5, and NH4+-N were the primary indicators of changes in river water quality in the region. Over time, the water quality in the basin had significantly improved from 2013 to 2022. However, there was a rebound in 2021, but this phenomenon was effectively controlled in 2022. Water quality was better during the non-flood season compared to that during the flood season. From a spatial perspective, the water quality in the southern part of the region was superior to that in the north. Furthermore, the rate of improvement was faster in the south. This could be attributed to factors such as precipitation, population density, and the scale of agricultural and livestock activities. However, the water quality of the S11 ï¼Sanduoxi Bridgeï¼ section was generally lower than that of other sections and should be given further attention.
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The rapid transfer and separation of photogenerated electrons is very important for the improvement of photocatalytic efficiency. Here, chiral induced spin selectivity effect (CISS effect) was developed to accelerate electron transfer for efficient photocatalytic hydrogen production. A chiral and achiral racemic supramolecular Pd(II) complex nanofiber was fabricated via supramolecular self-assembly of chiral L-Py or its racemes with Pd(II) and used to modify carbon nitride (g-C3N4). The obtained chiral photocatalyst L-Py-Pd/g-C3N4-4 and achiral photocatalyst Rac-Pd/g-C3N4-4, show enhanced photocatalytic activities with hydrogen evolution rates of 2476 and 1339 µmol g-1 h-1, respectively, while that of pure g-C3N4 is 30.5 µmol g-1 h-1. Chiral photocatalyst has 85% higher activity than achiral one and is 82.5-fold of pure g-C3N4, due to better suppression of the recombination of photogenerated electron-hole pairs in the interface of g-C3N4 contact with chiral molecule. Spectral tests and photoelectrochemical tests proved that the chiral supramolecular Pd(II) complex can act both as an electron spin filter and hydrogen reduction catalytic center to enhance photocatalytic efficiency. This work offers a new route to facilitate electron transfer by the CISS effect for photocatalytic hydrogen evolution.
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BACKGROUND: Prodromal phases are well recognized in many inflammatory and neurodegenerative diseases, including multiple sclerosis. We evaluated the possibility of a prodrome in aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using health administrative data. METHODS: We investigated individuals with AQP4 + NMOSD and MOGAD, confirmed by medical chart review, in Ontario, Canada. Each NMOSD and MOGAD participant was matched 1:5 to general population controls by sex, birth year, immigrant status, and region. Total outpatient visits and hospitalizations were compared in the 5 years preceding the incident attack in multivariable negative binomial models. RESULTS: We identified 96 people with AQP4 + NMOSD, matched to 479 controls, and 61 people with MOGAD, matched to 303 controls. In the 5 years preceding the incident attack, health care use was elevated for outpatient visits and hospitalizations for the NMOSD cohort (adjusted rate ratio (aRR): 1.47; 95% confidence interval (CI): 1.25-1.73; aRR: 1.67; 95% CI: 1.19-2.36, respectively) but not for MOGAD. Rate ratios steadily increased in NMOSD for outpatient visits in the 2 years preceding the incident attack. CONCLUSION: Our findings support a prodromal phase preceding clinical onset of AQP4 + NMOSD. Earlier recognition and management of NMOSD patients may be possible.
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Aquaporina 4 , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Sintomas Prodrômicos , Humanos , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Aquaporina 4/imunologia , Hospitalização/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ontário/epidemiologia , Autoanticorpos/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologiaRESUMO
Currently, applying lime to cadmium (Cd)-contaminated paddy fields to increase pH and reduce Cd availability is an effective method to control excessive Cd levels in rice grain. However, under hydroponic conditions, the impact of increased pH on Cd accumulation in different rice varieties remains unclear. This study employed three rice varieties (Yuzhenxiang, Shaoxiang 100, Xiangwanxian 12) with different Cd accumulation characteristics under different pH and long-term treatment with 1 µM CdCl2, to study the effect of pH on growth and Cd accumulation in different rice varieties. The result showed that as pH shifted from 5 to 8, the SPAD values, shoot dry weight, and plant height of the three rice varieties significantly decreased. The main root length, root volume, and root dry weight of Yuzhenxiang, and Shaoxiang100 significantly decreased. Conversely, the root architecture indicators of Xiangwanxian 12 did not change significantly. As for element accumulation, increasing the pH significantly increased the content of Mn in both the shoots and roots of all three varieties. Yuzhenxiang significantly reduced Cd content in both the shoots and roots of rice, while Shaoxiang100 significantly increased Cd content in both parts. Xiangwanxian 12 showed a significant increase in Cd content in the shoots but a decrease in the roots. In terms of subcellular distribution, Yuzhenxiang significantly reduced Cd concentrations in the cell wall and organelles of root cells, resulting in lower Cd concentrations in the root tissue. Conversely, Shaoxiang100 significantly increased Cd concentrations in the cell wall, organelles, and soluble fractions of root cells, leading to higher Cd concentrations in the root tissue. Xiangwanxian 12 also exhibited a decrease in Cd concentrations in the cell wall, organelles, and soluble fraction of root cells, resulting in lower Cd concentrations in the root tissue. Additionally, the expression of the OsNRAMP5 and OsHMA3 gene was significantly increased in Shaoxiang 100, while no significantly change in Yuzhenxiang and Xiangwanxian 12. These results provide important guidance on the impact of pH on Cd accumulation during the vegetative growth stage of different rice varieties.
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Cádmio , Hidroponia , Oryza , Raízes de Plantas , Oryza/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/efeitos dos fármacos , Cádmio/metabolismo , Concentração de Íons de Hidrogênio , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/efeitos dos fármacosRESUMO
OBJECTIVE: Spinal cord injury (SCI) severely affects motor, sensory, reflex, and other functions, impacting 250,000 to 500,000 individuals globally each year. Bladder voiding dysfunction, a prevalent and serious complication of SCI, results in significant morbidity and reduced quality of life. This study examines the impact of nurse-led clean intermittent catheterization combined with synchronous health education for family members on improving compliance in patients with SCI and bladder voiding dysfunction. METHODS: Eighty-four patients with urinary dysfunction post-SCI treated in our hospital from January 2023 to January 2024 were selected. Family members were assigned to a control group (n = 40) or an observation group (n = 44) based on their participation in nurse-led health education. Urinary tract management proficiency, satisfaction, compliance, and complications were observed and statistically analyzed in both groups on the 30th day after self-initiated intermittent catheterization. RESULTS: By the 30th day, the observation group exhibited significantly higher cognitive scores in urinary tract management than the control group (p < 0.001). Additionally, the observation group showed greater compliance in daily water intake (p = 0.018), proper timing (p = 0.018), and correct bladder function training (p = 0.004). The incidence of urinary tract infections was lower in the observation group (p = 0.018). Patient satisfaction in the observation group also exceeded that of the control group in all measured aspects and total scores (p < 0.001). CONCLUSIONS: Nurse-led synchronous health education for family members during clean intermittent catheterization significantly enhances patient compliance, reduces complications, and improves patient satisfaction.
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Cateterismo Uretral Intermitente , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/complicações , Cateterismo Uretral Intermitente/efeitos adversos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Educação em Saúde , Transtornos Urinários/etiologia , Transtornos Urinários/terapia , Cooperação do Paciente , Padrões de Prática em EnfermagemRESUMO
The diseases caused by excessive sodium intake derived from NaCl consumption have attracted widespread attention worldwide, and many researchers are committed to finding suitable ways to reduce sodium intake during the dietary process. Salt substitute is considered an effective way to reduce sodium intake by replacing all/part of NaCl in food without reducing the saltiness while minimizing the impact on the taste and acceptability of the food. Plant-derived natural ingredients are generally considered safe and reliable, and extensive research has shown that certain plant extracts or specific components are effective salt substitutes, which can also give food additional health benefits. However, these plant-derived salt substitutes (PSS) have not been systematically recognized by the public and have not been well adopted in the food industry. Therefore, a comprehensive review of PSS, including its material basis, flavor characteristics, and taste mechanism is helpful for a deeper understanding of PSS, accelerating its research and development, and promoting its application.
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Cloreto de Sódio na Dieta , Paladar , Humanos , Cloreto de Sódio na Dieta/análise , Extratos VegetaisRESUMO
Malignant mesothelioma is a rare tumour caused by asbestos exposure that originates mainly from the pleural lining or the peritoneum. Treatment options are limited, and the prognosis is dismal. Although immune checkpoint blockade (ICB) can improve survival outcomes, the determinants of responsiveness remain elusive. Here, we report the outcomes of a multi-centre phase II clinical trial (MiST4, NCT03654833) evaluating atezolizumab and bevacizumab (AtzBev) in patients with relapsed mesothelioma. We also use tumour tissue and gut microbiome sequencing, as well as tumour spatial immunophenotyping to identify factors associated with treatment response. MIST4 met its primary endpoint with 50% 12-week disease control, and the treatment was tolerable. Aneuploidy, notably uniparental disomy (UPD), homologous recombination deficiency (HRD), epithelial-mesenchymal transition and inflammation with CD68+ monocytes were identified as tumour-intrinsic resistance factors. The log-ratio of gut-resident microbial genera positively correlated with radiological response to AtzBev and CD8+ T cell infiltration, but was inversely correlated with UPD, HRD and tumour infiltration by CD68+ monocytes. In summary, a model is proposed in which both intrinsic and extrinsic determinants in mesothelioma cooperate to modify the tumour microenvironment and confer clinical sensitivity to AtzBev. Gut microbiota represent a potentially modifiable factor with potential to improve immunotherapy outcomes for individuals with this cancer of unmet need.
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Anticorpos Monoclonais Humanizados , Antígeno B7-H1 , Bevacizumab , Microbioma Gastrointestinal , Inibidores de Checkpoint Imunológico , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Bevacizumab/uso terapêutico , Bevacizumab/farmacologia , Masculino , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Pessoa de Meia-Idade , Idoso , Mesotelioma Maligno/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Mesotelioma/imunologia , Mesotelioma/tratamento farmacológico , Mesotelioma/microbiologia , Mesotelioma/patologia , Microambiente Tumoral/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/microbiologia , Resultado do TratamentoRESUMO
This study aimed to explore the potential of a fermentation technology to reduce off-flavour perception and its underlying mechanisms. Results revealed that yeast fermentation (YF) significantly ameliorated the off-flavour of pig liver (p < 0.05). Specifically, YF pre-treatment decreased the relative abundance of α-helix and fluorescence intensity while increasing the surface hydrophobicity and SS level and loosening the microstructure of myofibrillar proteins (MPs) in pig liver. Additionally, the appropriate fermentation treatments enhanced the MP-aldehyde binding capacity by 0.25-1.30 times, demonstrating that YF-induced conformational modifications in pig liver proteins made them more prone to interacting with characteristic aldehydes. Moreover, molecular docking results confirmed that hydrophobic interactions are the primary drivers of MP-aldehyde binding. These findings suggest that YF technology holds immense promise for modulating off-flavour perception in liver products by altering protein conformation.
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Aldeídos , Fermentação , Fígado , Saccharomyces cerevisiae , Animais , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/química , Suínos , Fígado/metabolismo , Fígado/química , Aldeídos/metabolismo , Aldeídos/química , Simulação de Acoplamento Molecular , Conformação Proteica , Interações Hidrofóbicas e HidrofílicasRESUMO
Importance: 5-alpha-reductase-inhibitors (5-ARIs) are approved for treating benign prostatic hyperplasia (BPH) and have been found to reduce prostate cancer (PCa) risk by 25%. However, trials also have shown 5-ARIs to be associated with high-grade PCa. Whether 5-ARIs increase mortality among those with a diagnosis of PCa remains unclear. Objective: To determine long-term outcomes of clinically localized PCa arising in individuals taking 5-ARIs compared with nonusers. Design, Setting, and Participants: This population-based cohort study was conducted between January 2003 and October 2017. Eligible participants were men aged 65 years or older in Ontario, Canada, who developed clinically localized PCa with complete pathological abstraction from the Ontario Health Administrative Databases. Data analysis occurred from November 2017 to November 2022. Exposure: 5-ARIs before PCa diagnosis. Main Outcomes and Measures: The primary outcomes were overall mortality and PCa-specific mortality. Cause-specific hazard models with inverse probability treatment weights (IPTW) were used to examine associations of 5-ARI use with mortality outcomes. Sensitivity analyses based on prediagnostic 5-ARI use, Gleason score, comorbidity, 5-ARI indication, prostate-specific antigen modeling, and statin use were also performed. Results: The cohort included 19â¯938 patients with PCa. Of these, 2112 (10.6%; median [IQR] age, 74 [70-79] years) were 5-ARI users and 17â¯826 (89.4%; median [IQR] age, 71 [68-76] years) were nonusers. During a median (IQR) follow-up of 8.96 (6.28-12.17) years, 6053 (30.4%) died, including 1047 (5.3%) from PCa. 5-ARI use appeared to be associated with increased overall and PCa specific mortality in crude analyses; however, after IPTW, 5-ARI use was not associated with overall mortality (hazard ratio, 0.98; 95% CI, 0.90-1.07; P = .77) or PCa-specific mortality (hazard ratio, 1.02; 95% CI, 0.83-1.25; P = .84). Conclusions and Relevance: In this population-based cohort study of 5-ARI use prior to PCa diagnosis including long-term follow-up and clinicopathologic details, prediagnostic 5-ARI use was not associated with PCa-specific or all-cause mortality. This study offers reassuring safety data for patients using 5-ARIs before PCa diagnosis for both BPH and chemopreventive reasons.
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Inibidores de 5-alfa Redutase , Neoplasias da Próstata , Humanos , Masculino , Inibidores de 5-alfa Redutase/uso terapêutico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/tratamento farmacológico , Idoso , Ontário/epidemiologia , Estudos de Coortes , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/mortalidade , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Oxidative stress is an unavoidable process in kidney transplantation and is closely related to the development of acute rejection after kidney transplantation. This study aimed to investigate the biomarkers associated with oxidative stress and their potential biological functions during acute rejection of kidney transplants. METHODS: We identified Hub genes using five machine learning algorithms based on differentially expressed genes (DEGs) in the kidney transplant acute rejection dataset GSE50058 and oxidative stress-related genes (OS) obtained from the MSigDB database, and validated them with the datasets GSE1563 and GSE9493, as well as with animal experiments; Subsequently, we explored the potential biological functions of Hub genes using single-gene GSEA enrichment analysis; The Cibersort algorithm was used to explore the altered levels of infiltration of 22 immune cells during acute rejection of renal transplantation, and a correlation analysis between Hub genes and immune cells was performed; Finally, we also explored transcription factors (TFs), miRNAs, and potential drugs that regulate Hub genes. RESULTS: We obtained a total of 57 genes, which we defined as oxidative stress-associated differential genes (DEOSGs), after intersecting DEGs during acute rejection of kidney transplants with OSs obtained from the MSigDB database; The results of enrichment analysis revealed that DEOSGs were mainly enriched in response to oxidative stress, response to reactive oxygen species, and regulation of oxidative stress and reactive oxygen species; Subsequently, we identified one Hub gene as APOD using five machine learning algorithms, which were validated by validation sets and animal experiments; The results of single-gene GSEA enrichment analysis revealed that APOD was closely associated with the regulation of immune signaling pathways during acute rejection of kidney transplants; The Cibersort algorithm found that the infiltration levels of a total of 10 immune cells were altered in acute rejection, while APOD was found to correlate with the expression of multiple immune cells; Finally, we also identified 154 TFs, 12 miRNAs, and 12 drugs or compounds associated with APOD regulation. CONCLUSION: In this study, APOD was identified as a biomarker associated with oxidative stress during acute rejection of kidney transplants using multiple machine learning algorithms, which provides a potential therapeutic target for mitigating oxidative stress injury and reducing the incidence of acute rejection in kidney transplantation.
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Algoritmos , Biomarcadores , Rejeição de Enxerto , Transplante de Rim , Aprendizado de Máquina , Estresse Oxidativo , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/genética , Rejeição de Enxerto/diagnóstico , Animais , Biomarcadores/metabolismo , Humanos , Camundongos , Perfilação da Expressão Gênica , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Bases de Dados GenéticasRESUMO
We evaluated the effectiveness of COVID-19 vaccines among South Asians living in Ontario, Canada compared to non-South Asians and compared the odds of symptomatic COVID-19 infection and related hospitalizations and deaths among non-vaccinated South Asians and non-South Asians. This was a test negative design study conducted in Ontario, Canada between December 14, 2020 and November 15, 2021. All eligible individuals >18 years with symptoms of COVID-19 were subdivided by ethnicity (South Asian vs other) and vaccination status (vaccinated versus not). The primary outcome was vaccine effectiveness as defined by COVID-19 infections, hospitalizations, and deaths, and secondary outcome was the odds of COVID-19 infections, hospitalizations, and death comparing non-vaccinated South Asians to non-vaccinated non-South Asians. 883,155 individuals were included. Among South Asians, two doses of COVID-19 vaccine prevented 93.8% (95% CI 93.2, 94.4) of COVID-19 infections and 97.5% (95% CI 95.2, 98.6) of hospitalizations and deaths. Among non-South Asians, vaccines prevented 86.6% (CI 86.3, 86.9) of COVID-19 infections and 93.1% (CI 92.2, 93.8) of hospitalizations and deaths. Non-vaccinated South Asians had higher odds of symptomatic SARS-CoV-2 infection compared to non-vaccinated non-South Asians (OR 2.35, 95% CI 2.3, 2.4), regardless of their immigration status. COVID-19 vaccines are effective in preventing infections, hospitalizations and deaths among South Asians living in Canada. The observation that non-vaccinated South Asians have higher odds of symptomatic COVID-19 infection warrants further investigation.
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BACKGROUND: The SET domain group (SDG) genes encode histone lysine methyltransferases, which regulate gene transcription by altering chromatin structure and play pivotal roles in plant flowering determination. However, few studies have investigated their role in the regulation of flowering in upland cotton. RESULTS: A total of 86 SDG genes were identified through genome-wide analysis in upland cotton (Gossypium hirsutum). These genes were unevenly distributed across 25 chromosomes. Cluster analysis revealed that the 86 GhSDGs were divided into seven main branches. RNA-seq data and qRTâPCR analysis revealed that lysine methyltransferase 3 (KMT3) genes were expressed at high levels in stamens, pistils and other floral organs. Using virus-induced gene silencing (VIGS), functional characterization of GhKMT3;1a and GhKMT3;2a revealed that, compared with those of the controls, the GhKMT3;1a- and GhKMT3;2a-silenced plants exhibited later budding and flowering and lower plant heightwere shorter. In addition, the expression of flowering-related genes (GhAP1, GhSOC1 and GhFT) significantly decreased and the expression level of GhSVP significantly increased in the GhKMT3;1a- and GhKMT3;2a-silenced plants compared with the control plants. CONCLUSION: A total of 86 SDG genes were identified in upland cotton, among which GhKMT3;1a and GhKMT3;2a might regulate flowering by affecting the expression of GhAP1, GhSOC1, GhFT and GhSVP. These findings will provide genetic resources for advanced molecular breeding in the future.
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Flores , Regulação da Expressão Gênica de Plantas , Gossypium , Histona-Lisina N-Metiltransferase , Proteínas de Plantas , Gossypium/genética , Gossypium/enzimologia , Gossypium/fisiologia , Flores/genética , Flores/crescimento & desenvolvimento , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Genes de Plantas , Inativação GênicaRESUMO
Obesity is a multifactorial chronic inflammatory metabolic disorder, with pathogenesis influenced by genetic and non-genetic factors such as environment and diet. Intestinal microbes and their metabolites play significant roles in the occurrence and development of obesity by regulating energy metabolism, inducing chronic inflammation, and impacting intestinal hormone secretion. Epigenetics, which involves the regulation of host gene expression without changing the nucleotide sequence, provides an exact direction for us to understand how the environment, lifestyle factors, and other risk factors contribute to obesity. DNA methylation, as the most common epigenetic modification, is involved in the pathogenesis of various metabolic diseases. The epigenetic modification of the host is induced or regulated by the intestinal microbiota and their metabolites, linking the dynamic interaction between the microbiota and the host genome. In this review, we examined recent advancements in research, focusing on the involvement of intestinal microbiota and DNA methylation in the etiology and progression of obesity, as well as potential interactions between the two factors, providing novel perspectives and avenues for further elucidating the pathogenesis, prevention, and treatment of obesity.
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OBJECTIVES: The risk factors and outcomes associated with persistent bacteraemia in Gram-negative bloodstream infection (GN-BSI) are not well described. We conducted a follow-on analysis of a retrospective population-wide cohort to characterize persistent bacteraemia in patients with GN-BSI. METHODS: We included all hospitalized patients >18 years old with GN-BSI between April 2017 and December 2021 in Ontario who received follow-up blood culture (FUBC) 2-5 days after the index positive blood culture. Persistent bacteraemia was defined as having a positive FUBC with the same Gram-negative organism as the index blood culture. We identified variables independently associated with persistent bacteraemia in a multivariable logistic regression model. We evaluated whether persistent bacteraemia was associated with increased odds of 30- and 90-day all-cause mortality using multivariable logistic regression models adjusted for potential confounders. RESULTS: In this study, 8807 patients were included; 600 (6.8%) had persistent bacteraemia. Having a permanent catheter, antimicrobial resistance, nosocomial infection, ICU admission, respiratory or skin and soft tissue source of infection, and infection by a non-fermenter or non-Enterobacterales/anaerobic organism were associated with increased odds of having persistent bacteraemia. The 30-day mortality was 17.2% versus 9.6% in those with and without persistent bacteraemia (aOR 1.65, 95% CI 1.29-2.11), while 90-day mortality was 25.5% versus 16.9%, respectively (aOR 1.53, 95% CI 1.24-1.89). Prevalence and odds of developing persistent bacteraemia varied widely depending on causative organism. CONCLUSIONS: Persistent bacteraemia is uncommon in GN-BSI but is associated with poorer outcomes. A validated risk stratification tool may be useful to identify patients with persistent bacteraemia.
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Bacteriemia , Infecções por Bactérias Gram-Negativas , Humanos , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Ontário/epidemiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/mortalidade , Infecções por Bactérias Gram-Negativas/microbiologia , Fatores de Risco , Bactérias Gram-Negativas/isolamento & purificação , Adulto , Hemocultura , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Relevância ClínicaRESUMO
Background: Kidney transplantation (KT) is the best treatment for end-stage renal disease. Although long and short-term survival rates for the graft have improved significantly with the development of immunosuppressants, acute rejection (AR) remains a major risk factor attacking the graft and patients. The innate immune response plays an important role in rejection. Therefore, our objective is to determine the biomarkers of congenital immunity associated with AR after KT and provide support for future research. Materials and Methods: A differential expression genes (DEGs) analysis was performed based on the dataset GSE174020 from the NCBI gene Expression Synthesis Database (GEO) and then combined with the GSE5099 M1 macrophage-related gene identified in the Molecular Signatures Database. We then identified genes in DEGs associated with M1 macrophages defined as DEM1Gs and performed gene ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. Cibersort was used to analyze the immune cell infiltration during AR. At the same time, we used the protein-protein interaction (PPI) network and Cytoscape software to determine the key genes. Dataset, GSE14328 derived from pediatric patients, GSE138043 and GSE9493 derived from adult patients, were used to verify Hub genes. Additional verification was the rat KT model, which was used to perform HE staining, immunohistochemical staining, and Western Blot. Hub genes were searched in the HPA database to confirm their expression. Finally, we construct the interaction network of transcription factor (TF)-Hub genes and miRNA-Hub genes. Results: Compared to the normal group, 366 genes were upregulated, and 423 genes were downregulated in the AR group. Then, 106 genes related to M1 macrophages were found among these genes. GO and KEGG enrichment analysis showed that these genes are mainly involved in cytokine binding, antigen binding, NK cell-mediated cytotoxicity, activation of immune receptors and immune response, and activation of the inflammatory NF-κB signaling pathway. Two Hub genes, namely CCR7 and CD48, were identified by PPI and Cytoscape analysis. They have been verified in external validation sets, originated from both pediatric patients and adult patients, and animal experiments. In the HPA database, CCR7 and CD48 are mainly expressed in T cells, B cells, macrophages, and tissues where these immune cells are distributed. In addition to immunoinfiltration, CD4+T, CD8+T, NK cells, NKT cells, and monocytes increased significantly in the AR group, which was highly consistent with the results of Hub gene screening. Finally, we predicted that 19 TFs and 32 miRNAs might interact with the Hub gene. Conclusions: Through a comprehensive bioinformatic analysis, our findings may provide predictive and therapeutic targets for AR after KT.
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Antígeno CD48 , Rejeição de Enxerto , Transplante de Rim , Macrófagos , Mapas de Interação de Proteínas , Receptores CCR7 , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/genética , Transplante de Rim/efeitos adversos , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Criança , Ratos , Receptores CCR7/genética , Receptores CCR7/metabolismo , Antígeno CD48/genética , Antígeno CD48/metabolismo , Perfilação da Expressão Gênica , Biomarcadores , Biologia Computacional/métodos , Masculino , Redes Reguladoras de Genes , Bases de Dados Genéticas , Ontologia Genética , Modelos Animais de Doenças , Feminino , MicroRNAs/genéticaRESUMO
Allicin (AL) is one of garlic-derived organosulfides and has a variety of pharmacological effects. Studies have reported that AL has notable inhibitory effects on liver cancer, gastric cancer, breast cancer, and other cancers. However, there are no relevant reports about its role in human nasopharyngeal carcinoma. Ferroptosis is an iron-dependent form of non-apoptotic regulated cell death. Increasing evidence indicates that induction of ferroptosis can inhibit the proliferation, migration, invasion, and survival of various cancer cells, which act as a tumor suppressor in cancer. In this study, we confirmed that AL can inhibit cell proliferation, migration, invasion, and survival in human nasopharyngeal carcinoma cells. Our finding shows that AL can induce the ferroptosis axis by decreasing the level of GSH and GPX4 and promoting the induction of toxic LPO and ROS. AL-mediated cytotoxicity in human nasopharyngeal carcinoma cells is dependent on ferroptosis. Therefore, AL has good anti-cancer properties and is expected to be a potential drug for the treatment of nasopharyngeal carcinoma.
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Proliferação de Células , Dissulfetos , Ferroptose , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Espécies Reativas de Oxigênio , Ácidos Sulfínicos , Humanos , Ferroptose/efeitos dos fármacos , Dissulfetos/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Proliferação de Células/efeitos dos fármacos , Ácidos Sulfínicos/farmacologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Movimento Celular/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Glutationa/metabolismo , Sobrevivência Celular/efeitos dos fármacosRESUMO
In the original publication [...].
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AIM: To compare high or low concentration of hyaluronic acid eye drops (HY) for dry eye syndromes (DES). METHODS: Randomized controlled trials (RCTs) comparing various concentrations of HY were searched in PubMed, Embase, Web of Science, Cochrane, SinoMed, CNKI, Wanfang Database, CQVIP, and Chinese journals databases between inception and July 2023. Pooled standardized mean differences (SMD) or weighted mean difference (WMD) with 95% confidence intervals (CI) from RCTs evaluating Schirmer's I test (SIT), corneal fluorescein staining score (CFS), tear breakup time (TBUT), DES score (DESS), and Ocular Surface Disease Index (OSDI) were calculated. Sensitivity analysis, Egger's test and Meta-regression analysis were performed for all indicators. RESULTS: We conducted a Meta-analysis of 10 RCTs that met the inclusion criteria, involving 1796 cases. High-concentrations group significantly improved the outcome of CFS according to random effects modelling (SMD, -3.37; 95%CI, -5.25 to -1.48; P=0.0005). The rest of the results were not statistically significant, including indicators such as SIT, TBUT, DESS and OSDI. CONCLUSION: For dry eyes with positive corneal staining, a high concentration of HY is recommended, whereas in other cases, a high concentration of HY does not offer a more pronounced advantage over a low concentration of HY in the treatment of dry eyes.
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OBJECTIVES: To investigate the long-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for multiple uterine fibroids and the factors associated with recurrence. MATERIALS AND METHODS: Five hundred and forty-nine patients with multiple uterine fibroids treated with USgHIFU from June 2017 to June 2019 were retrospectively analyzed. The Pictorial Blood Loss Assessment Chart (PBAC) was used to assess menstrual blood loss. The patients were asked to undergo pre- and post-USgHIFU magnetic resonance imaging (MRI) and complete routine follow-up after USgHIFU. Cox regression analysis was used to investigate the risk factors associated with recurrence. RESULTS: The median number of fibroids per patient was 3 (interquartile range: 3-4), and a total of 1371 fibroids were treated. Among them, 446 patients completed 3 years follow-up. Recurrence, defined as PBAC score above or equal to 100 and/or the residual fibroid volume increased by 10%, was detected in 90 patients within 3 years after USgHIFU, with a cumulative recurrence rate of 20.2% (90/446). The multi-factor Cox analysis showed that age was a protective factor for recurrence. Younger patients have a greater chance of recurrence than older patients. Mixed hyperintensity of fibroids on T2WI and treatment intensity were risk factors for recurrence. Patients with hyperintense uterine fibroids and treated with lower treatment intensity were more likely to experience recurrence than other patients after USgHIFU. No major adverse effects occurred. CONCLUSIONS: USgHIFU can be used to treat multiple uterine fibroids safely and effectively. The age, T2WI signal intensity and treatment intensity are factors related to recurrence.