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Pancreatic ductal adenocarcinoma (PDAC), a very aggressive tumour, is currently the third leading cause of cancer-related deaths. Unfortunately, many patients face the issue of inoperability at the diagnostic phase leading to a quite dismal prognosis. The onset of metastatic processes has a crucial role in the elevated mortality rates linked to PDAC. Individuals with metastatic advances receive only palliative therapy and have a grim prognosis. It is essential to carefully analyse the intricacies of the metastatic process to enhance the prognosis for individuals with PDAC. Malignancy development is greatly impacted by the process of macrophage efferocytosis. Our current knowledge about the complete range of macrophage efferocytosis activities in PDAC and their intricate interactions with tumour cells is still restricted. This work aims to resolve communication gaps and pinpoint the essential transcription factor that is vital in the immunological response of macrophage populations. We analysed eight PDAC tissue samples sourced from the gene expression omnibus. We utilized several software packages such as Seurat, DoubletFinder, Harmony, Pi, GSVA, CellChat and Monocle from R software together with pySCENIC from Python, to analyse the single-cell RNA sequencing (scRNA-seq) data collected from the PDAC samples. This study involved the analysis of a comprehensive sample of 22,124 cells, which were classified into distinct cell types. These cell types encompassed endothelial and epithelial cells, PDAC cells, as well as various immune cells, including CD4+ T cells, CD8+ T cells, NK cells, B cells, plasma cells, mast cells, monocytes, DC cells and different subtypes of macrophages, namely C0 macrophage TGM2+, C1 macrophage PFN1+, C2 macrophage GAS6+ and C3 macrophage APOC3+. The differentiation between tumour cells and epithelial cells was achieved by the implementation of CopyKat analysis, resulting in the detection and categorization of 1941 PDAC cells. The amplification/deletion patterns observed in PDAC cells on many chromosomes differ significantly from those observed in epithelial cells. The study of Pseudotime Trajectories demonstrated that the C0 macrophage subtype expressing TGM2+ had the lowest level of differentiation. Additionally, the examination of gene set scores related to efferocytosis suggested that this subtype displayed higher activity during the efferocytosis process compared to other subtypes. The most active transcription factors for each macrophage subtype were identified as BACH1, NFE2, TEAD4 and ARID3A. In conclusion, the examination of human PDAC tissue samples using immunofluorescence analysis demonstrated the co-localization of CD68 and CD11b within regions exhibiting the presence of keratin (KRT) and alpha-smooth muscle actin (α-SMA). This observation implies a spatial association between macrophages, fibroblasts, and epithelial cells. There is variation in the expression of efferocytosis-associated genes between C0 macrophage TGM2+ and other macrophage cell types. This observation implies that the diversity of macrophage cells might potentially influence the metastatic advancement of PDAC. Moreover, the central transcription factor of different macrophage subtypes offers a promising opportunity for targeted immunotherapy in the treatment of PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Eferocitosis , Análisis de Expresión Génica de una Sola Célula , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología , Macrófagos/metabolismo , Factores de Transcripción/metabolismo , Microambiente Tumoral , Proteínas de Unión al ADN/genética , Factores de Transcripción de Dominio TEA , Profilinas/genéticaRESUMEN
Electronic health records (EHRs) have been widely used and are gradually replacing paper records. Therefore, extracting valuable information from EHRs has become the focus and hotspot of current research. Clinical named entity recognition (CNER) is an important task in information extraction. Most current research methods used standard supervised learning approaches to fine-tune pre-trained language models (PLMs), which require a large amount of annotated data for model training. However, in realistic medical scenarios, annotated data are scarce, especially in the healthcare field. The process of annotating data in real clinical settings is time-consuming and labour-intensive. In this paper, a language inference-based learning method (LANGIL) is proposed to study clinical NER tasks with limited annotated samples, i.e., in low-resource clinical scenarios. A method based on prompt learning is designed to reformulate the entity recognition task into a language inference-based task. Differing from the standard fine-tuning method, the approach introduced in this paper does not design the additional network layers that train from scratch. This alleviates the gap between pre-training tasks and downstream tasks, allowing the comprehension capabilities of PLMs to be leveraged under the condition of limited training samples. The experiments on four Chinese clinical named entity recognition datasets showed that LANGIL achieves significant improvements in F1-score compared to the former method.
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Almacenamiento y Recuperación de la Información , Lenguaje , Caballos , Animales , Registros Electrónicos de Salud , Procesamiento de Lenguaje Natural , ChinaRESUMEN
Increasing evidence has suggested a strong association of hepatocellular carcinoma (HCC) susceptibility and Gln223Arg (rs1137101) and Lys109Arg (rs1137100) polymorphisms in leptin receptor (LEPR) genes. To provide a quantitative assessment for such correlation, we reviewed all related systems and conducted meta-analysis for case and control researches. A literature search of Web of Science, EMBASE, PubMed, Scopus as well as China National Knowledge Infrastructure databases was collected. 95% confidence intervals (95% CIs) together with odds ratios (ORs) were calculated. Five case-control researches consisting of 1323 cases and 1919 control cases were incorporated into meta-analysis. Researches indicated A-allelic and AA genotype of rs1137101 were substantially related to boosted susceptibility of hepatitis B virus (HBV)-related HCC (mutant model, OR = 1.81, 95% CI = 1.36-2.41, p < .001; allelic model, OR = 1.55, 95% CI = 1.32-1.83, p < .001). On the contrary, we observed GG genotype of rs1137101 substantially related to reduced risk of HBV-related HCC (wild model, OR 0.59, 95%CI = 0.46-0.75, p < .001). We observed AA genotype of rs1137100 relevant to boosted HCC risk (mutant model, OR = 1.51, 95%CI = 1.14-2.01, p = .005) as well as in those with HBV-related HCCs (homozygous model, OR = 2.12, 95%CI = 1.49-3.02, p < .001; mutant model, OR = 1.67, 95%CI = 1.23-2.26, p = .001). G-allele and AA genotype of rs1137101 might be in connection with boosted HBV-related HCC susceptibility, and wild-type GG genotype might prevent diseases. AA genotype of rs1137100 might also improve HBV-related HCC susceptibility. Such conclusions ought to be validated by larger and better-designed researches.
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BACKGROUND: We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients. METHODS: A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92-0.98), Q3 (0.98-1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4-5) separately on discharge in AIS patients. RESULTS: Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge. CONCLUSIONS: High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Pronóstico , Tiempo de Protrombina , Relación Normalizada Internacional , Accidente Cerebrovascular/complicaciones , Isquemia Encefálica/complicaciones , Pueblos del Este de AsiaRESUMEN
Filoviruses cause high-consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterized animal models for the assessment of antiviral agents and vaccines. Following large-scale Ebola virus (EBOV) disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterization of the ferret as a model for Ebola virus infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral, and rectal swabs and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long-term EBOV persistence in immune-privileged sites. IMPORTANCE Recent reemergence of Ebola in Guinea that caused over 28,000 cases between 2013 and 2016 has been linked to the original virus from that region. It appears the virus has remained in the region for at least 5 years and is likely to have been maintained in humans. Persistence of Ebola in areas of the body for extended periods of time has been observed, such as in the eye and semen. Despite the importance of reintroduction of Ebola from this route, such events are rare in the population, which makes studying medical interventions to clear persistent virus difficult. We studied various doses of Ebola in ferrets and detected virus in the eyes of most ferrets. We believe this model will enable the study of medical interventions that promote clearance of Ebola virus from sites that promote persistence.
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Ebolavirus/genética , Evolución Molecular , Ojo/virología , Fiebre Hemorrágica Ebola/fisiopatología , Fiebre Hemorrágica Ebola/virología , Animales , Anticuerpos Antivirales/inmunología , Modelos Animales de Enfermedad , Ebolavirus/inmunología , Femenino , Hurones/inmunología , Fiebre Hemorrágica Ebola/inmunología , Masculino , ARN Viral/genéticaRESUMEN
Protonated water-hydrogen clusters [H+(H2O)n·m(H2)] present an interesting model for fundamental water research, but their formation and isolation presents considerable experimental challenges. Here, we report the detection of [H+(H2O)n·m(H2)] (2 ≤ n ≤ 3, m ≤ 2) clusters alongside protonated water clusters H+(H2O)n (2 ≤ n ≤ 3) in a linear ion trap mass spectrometer under two different experimental conditions: (1) when water vapor was ionized by +5.5 kV ambient corona discharge in front of the mass spectrometer inlet; (2) when isolated H+(H2O)n clusters were exposed to H2 gas inside the linear trap. Chemical assignment of [H+(H2O)n·m(H2)] clusters was confirmed using reference experiments with isotopically labeled water and deuterium. Also, the formation of H2 gas in the corona discharge area was indicated by a flame test. Overall, our findings clearly indicate that [H+(H2O)n·m(H2)] clusters can be produced at room temperature through the association of protonated water clusters H+(H2O)n with H2 gas, without any cooling necessary. A mechanism for the formation of the protonated water-hydrogen complexes was proposed. Our results also suggest that the association of water ions with H2 gas may play a notable role in corona discharge ionization processes, such as atmospheric pressure chemical ionization, and may be partially responsible for the stabilization of reactive radical species occasionally reported in corona discharge ionization experiments.
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Epilepsy is one of the most common neurological diseases with spontaneous recurrent seizures. Long noncoding RNAs (lncRNAs) are crucial modulators in numerous diseases, including epilepsy. However, the functional role and potential mechanism of lncRNA Nespas in epilepsy remain unknown. Our study clarified that Nespas was underexpressed in epileptiform hippocampal tissues and neurons. Furthermore, Nespas promoted hippocampal neuron viability and proliferation, and inhibited hippocampal neuron apoptosis. Mechanistically, Nespas interacted with microRNA 615-3p (miR-615-3p) in epileptiform hippocampal neurons. 26S proteasome non-ATPase regulatory subunit 11 (Psmd11) was a downstream target of miR-615-3p, and Nespas elevated Psmd11 expression via competitively binding to miR-615-3p in epileptiform hippocampal neurons. In addition, rescue assays suggested that Nespas promoted hippocampal neuron viability and proliferation, and suppressed hippocampal neuron apoptosis by upregulation of Psmd11. Furthermore, Nespas suppressed the PI3K/Akt/mTOR pathway via upregulating Psmd11 in epileptiform hippocampal neurons. This report explored the function and regulatory mechanism of Nespas in epileptiform hippocampal neurons for the first time. Our findings revealed that Nespas suppressed the apoptosis of epileptiform hippocampal neurons by inhibiting the PI3K/Akt/mTOR pathway via upregulation of Psmd11 at a miR-615-3p dependent way, indicating that Nespas may offer a new direction for the treatment of epilepsy.
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Hipocampo/metabolismo , Neuronas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Apoptosis , Hipocampo/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/patología , ARN Largo no Codificante/genéticaRESUMEN
Rationale: In life-threatening coronavirus disease (COVID-19), corticosteroids reduce mortality, suggesting that immune responses have a causal role in death. Whether this deleterious inflammation is primarily a direct reaction to the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or an independent immunopathologic process is unknown.Objectives: To determine SARS-CoV-2 organotropism and organ-specific inflammatory responses and the relationships among viral presence, inflammation, and organ injury.Methods: Tissue was acquired from 11 detailed postmortem examinations. SARS-CoV-2 organotropism was mapped by using multiplex PCR and sequencing, with cellular resolution achieved by in situ viral S (spike) protein detection. Histologic evidence of inflammation was quantified from 37 anatomic sites, and the pulmonary immune response was characterized by using multiplex immunofluorescence.Measurements and Main Results: Multiple aberrant immune responses in fatal COVID-19 were found, principally involving the lung and reticuloendothelial system, and these were not clearly topologically associated with the virus. Inflammation and organ dysfunction did not map to the tissue and cellular distribution of SARS-CoV-2 RNA and protein between or within tissues. An arteritis was identified in the lung, which was further characterized as a monocyte/myeloid-rich vasculitis, and occurred together with an influx of macrophage/monocyte-lineage cells into the pulmonary parenchyma. In addition, stereotyped abnormal reticuloendothelial responses, including excessive reactive plasmacytosis and iron-laden macrophages, were present and dissociated from viral presence in lymphoid tissues.Conclusions: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease. Our data highlight novel immunopathologic mechanisms and validate ongoing and future efforts to therapeutically target aberrant macrophage and plasma-cell responses as well as promote pathogen tolerance in COVID-19.
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COVID-19/inmunología , Inflamación/virología , Pulmón/inmunología , Insuficiencia Multiorgánica/virología , SARS-CoV-2/inmunología , Anciano , Anciano de 80 o más Años , Autopsia , Biopsia , COVID-19/patología , COVID-19/virología , Prueba de Ácido Nucleico para COVID-19 , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Inflamación/inmunología , Inflamación/patología , Pulmón/patología , Pulmón/virología , Masculino , Insuficiencia Multiorgánica/inmunología , Insuficiencia Multiorgánica/patología , SARS-CoV-2/patogenicidad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: We investigated the association between international normalised ratio (INR) and prothrombin time (PT) levels on hospital admission and in-hospital outcomes in acute ischaemic stroke (AIS) patients. METHODS: A total of 3175 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included. We divided patients into four groups according to their level of admission INR: (<0.92), Q2 (0.92-0.98), Q3 (0.98-1.04) and Q4 (≥1.04) and PT. Logistic regression models were used to estimate the effect of INR and PT on death or major disability (modified Rankin Scale score (mRS)>3), death and major disability (mRS scores 4-5) separately on discharge in AIS patients. RESULTS: Having an INR level in the highest quartile (Q4) was associated with an increased risk of death or major disability (OR 1.69; 95% CI 1.23 to 2.31; P-trend = 0.001), death (OR, 2.64; 95% CI 1.12 to 6.19; P-trend = 0.002) and major disability on discharge (OR, 1.56; 95% CI 1.13 to 2.15; P-trend = 0.008) in comparison to Q1 after adjusting for potential covariates. Moreover, in multivariable logistic regression models, having a PT level in the highest quartile also significantly increased the risk of death (OR, 2.38; 95% CI 1.06 to 5.32; P-trend = 0.006) but not death or major disability (P-trend = 0.240), major disability (P-trend = 0.606) on discharge. CONCLUSIONS: High INR at admission was independently associated with death or major disability, death and major disability at hospital discharge in AIS patients and increased PT was also associated with death at hospital discharge.
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BACKGROUND Intraoperative intact parathyroid hormone (IO-iPTH) monitoring has not reached a consensus in predicting surgical outcomes of secondary hyperparathyroidism. Here, we explore the predictive effect of IO-iPTH monitoring on surgical outcomes of secondary hyperparathyroidism as a potentially effective standard. MATERIAL AND METHODS We enrolled 119 patients who underwent total parathyroidectomy with autotransplantation from January 2016 to August 2019. Intact parathyroid hormone (iPTH) levels were tested 1 day before surgery (iPTHpre), 10 min after glands resection (iPTH10min), and 1 and 7 days after the operation (iPTHd1, iPTHd7). According to iPTHpre levels, patients were divided into a <2000 pg/ml group and a ≥2000 pg/ml group, and the cutoff values were compared. In patients with successful parathyroidectomy, the value of iPTHpre minus iPTH10min (iPTHdec) and relative-iPTH10min were compared between groups. RESULTS Using cutoff values, the predictive criterion was defined as iPTH10min ≤314.5 pg/ml or relative-iPTH10min ≤12.4%. In the iPTHpre ≥2000 pg/ml group, iPTH10min had a higher predictive value (318 pg/ml vs 218 pg/ml) whereas relative-iPTH10min had a lower predictive value (12.1% vs 20.3%). In patients with successful PTX, the iPTHdec value of the iPTHpre ≥2000 pg/ml group was significantly higher than that of the <2000 pg/ml group. Additionally, the relative-iPTH10min was significantly lower in the ≥2000 pg/ml group than in the <2000 pg/ml group. CONCLUSIONS An intraoperative predictive criterion of iPTH10min ≤314.5 pg/ml or relative-iPTH10min ≤12.4% is associated with effectively predicting surgical success of secondary hyperparathyroidism. The predictive value is affected by iPTHpre level; therefore, a variable prediction standard based on iPTHpre levels shall be established.
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Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/cirugía , Monitoreo Intraoperatorio/métodos , Hormona Paratiroidea/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: High white blood cell (WBC) count and high blood glucose level are risk factors for mortality and pneumonia after acute ischemic stroke (AIS). We investigated the combined effect of high WBC count and high blood glucose level on hospital admission and in-hospital mortality and pneumonia in acute AIS patients. METHODS: A total of 3124 AIS patients enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city were included in the present study. We divided patients into four groups according to their level of WBC count and blood glucose: NWNG (normal WBC count and normal glucose), NWHG (normal WBC count and higher glucose), HWNG (higher WBC count and normal glucose), and HWHG (higher WBC count and higher glucose). Cox proportional hazard model and logistic regression model were used to estimate the combined effect of WBC count and blood glucose on all-cause in-hospital mortality and pneumonia in AIS patients. RESULTS: HWHG was associated with a 2.22-fold increase in the risk of in-hospital mortality in comparison to NWNG (adjusted hazard ratio [HR] 2.22; 95% confidence interval [CI], 1.21-4.07; P trend = 0.003). The risk of pneumonia was significantly higher in patients with HWHG compared to those with NWNG (adjusted odds ratio [OR] 2.61; 95% CI, 1.66-4.10; P trend < 0.001). The C-statistic for the combined WBC count and blood glucose was higher than WBC count or blood glucose alone for prediction of in-hospital mortality and pneumonia (all p < 0.01). CONCLUSIONS: High WBC count combined with high blood glucose level at admission was independently associated with in-hospital mortality and pneumonia in AIS patients. Moreover, the combination of WBC count and blood glucose level appeared to be a better predictor than WBC count or blood glucose alone.
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Glucemia/metabolismo , Hospitalización , Recuento de Leucocitos/métodos , Leucocitos/patología , Accidente Cerebrovascular/sangre , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/sangre , Isquemia Encefálica/complicaciones , Femenino , Estudios de Seguimiento , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapiaRESUMEN
BACKGROUND: The clinical impacts of serum alkaline phosphatase (ALP) and phosphate on early death are not fully understood in patients with acute ischemic stroke. We examined the associations between serum ALP, phosphate, and in-hospital mortality after ischemic stroke. METHODS: Serum ALP and phosphate were measured in 2944 ischemic stroke patients from 22 hospitals in Suzhou City from December 2013 to May 2014. Cox proportional hazard models and restricted cubic splines were used to estimate the relationships between serum ALP and phosphate (both as categorical and continuous variables) and risk of in-hospital mortality. RESULTS: During hospitalization, 111 patients (3.7%) died from all causes. After multivariable adjustment, the hazard ratio (HR) of the highest quartile compared with the lowest quartile of ALP was 2.19 (95% confidence interval [CI], 1.20-4.00) for early death. Restricted cubic spline analysis indicated a significant linear association between ALP and death (P-linearity = .017). A U-shaped association of phosphate with in-hospital mortality was observed (P-nonlinearity = .011). Compared with the third quartile of phosphate (1.08-1.21 mmol/L), HRs of the lowest and highest quartiles for early death were 2.17 (1.15-4.08) and 1.70 (.88-3.30), respectively. Sensitivity analyses further confirmed our findings. CONCLUSIONS: We observed a graded relationship between serum ALP levels and risk of early death in patients with acute ischemic stroke. There was a U-shaped association between phosphate and all-cause mortality with significantly increased risk among patients with lower phosphate levels.
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Fosfatasa Alcalina/sangre , Isquemia Encefálica/sangre , Isquemia Encefálica/mortalidad , Mortalidad Hospitalaria , Fosfatos/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/mortalidad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Isquemia Encefálica/diagnóstico , Distribución de Chi-Cuadrado , China/epidemiología , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Dinámicas no Lineales , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Factores de TiempoRESUMEN
This study was conducted to investigate the role of different homocysteine metabolism-related vitamin (HMRV) levels in the correlation between hyperhomocysteinemia (HHCY) and ischemic stroke (IS) subtypes. Three hundred and forty-eight IS patients manifesting different vascular subtypes were subclassified on the basis of HMRV deficiencies. Correlation between HHCY and IS subtypes was investigated in all the subgroups. In this study, HHCY was significantly correlated with the IS subtypes in large artery atherosclerosis (OR 1.126, 95%CI: 1.051 ~ 1.206, P = 0.001) and small artery occlusion (OR 1.105, 95%CI: 1.023 ~ 1.193, P = 0.012). Subgroup analysis revealed a correlation between HHCY and IS subgroup (OR 1.201, 1.178, 95%CI: 1.081 ~ 1.334, 1.058 ~ 1.313, P = 0.001, P = 0.003, respectively) in HMRV deficiency, but not significantly with the IS subgroup in normal HMRV levels. Serum vitamin B12 concentrations are inversely correlated with both IS subtypes in HMRV deficiency subgroups (OR 0.992, 0.995, 95%CI: 0.987 ~ 0.996, 0.991 ~ 0.999, P < 0.001, P = 0.007, respectively), which may contribute to HHCY incidence in these populations. The correlation between HHCY and IS subtypes is affected by HMRV levels in this case-control study. Our findings are helpful to understand the inconsistency in prior homocysteine studies. Serum vitamin B12 levels may play a critical role in HHCY incidence in this Chinese population.Cerebrovascular disease has emerged as the leading cause of disability and mortality in both urban and rural areas of China (Neurology branch of Chinese Medical Association 2015). Ischemic stroke (IS) constitutes 60% to 80% of all cerebrovascular disease (Neurology branch of Chinese Medical Association 2014). Among a variety of risk factors, hyperhomocysteinemia (HHCY) has been closely correlated with IS due to intracranial small-vessel disease and extracranial large-artery disease (Selhub et al. 1995; Eikelboom et al. 2000; Alvarez et al. 2012; Jeon et al. 2014). However, the failure to lower homocysteine (HCY) via homocysteine metabolism-related vitamin (HMRV, including folic acid and vitamin B12 but not vitamin B6 in this study) supplementation to reduce stroke morbidity questions the role of HCY as a risk factor for stroke (Lonn et al. 2006; Hankey et al. 2010). Theoretically, HMRV supplementation merely lowers the incidence of stroke induced by HHCY resulting from HMRV deficiency, whereas HHCY-induced stroke concomitant with normal HMRV levels may be refractory to treatment. The correlation between HCY varying with HMRV levels and IS subtypes is still unclear. In this study, we investigated the impact of variation in HMRV levels on the correlation between HHCY and IS subtypes in 348 acute IS patients with large and small vessel diseases. We sought to determine the factors underlying the conflicting results associated with lowering HCY by HMRV supplementation to reduce stroke incidence.
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Ácido Fólico/sangre , Homocisteína/sangre , Hiperhomocisteinemia/sangre , Arteriosclerosis Intracraneal/sangre , Riñón/fisiología , Accidente Cerebrovascular/sangre , Vitamina B 12/sangre , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Estudios de Casos y Controles , Trastornos Cerebrovasculares/sangre , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/epidemiología , China/epidemiología , Femenino , Humanos , Hiperhomocisteinemia/diagnóstico por imagen , Hiperhomocisteinemia/epidemiología , Arteriosclerosis Intracraneal/diagnóstico por imagen , Arteriosclerosis Intracraneal/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/epidemiologíaRESUMEN
Siliva as a kind of biomarker containing a variety of bioactive components can be used to help disease diagnosis. Compared with the urine and blood, the collection of saliva is more simple and convenient while the collection process is completely non-invasive. Therefore, saliva detection attracts more and more attention in non-invasive disease diagnosis. Histatins are a family of small, cationic, histidine-rich peptides, which secreted by salivary bringing innate defense of the oral cavity. It has been reported that histatins are related to many other diseases, such as HIV and AIDs. Thus the detection of histatins in saliva is significantly important for oral healthy monitoring and disease diagnosis. In this paper, a new label free method for rapid detection of histidine-rich peptides was developed based on the fact that histidine-rich peptides can interact with 3-azidocoumarin through hydrogen bonds which decreases the electron-donating ability of the azido group and results in fluorescence enhancement of the system. The results showed that the fluorescence intensities were dramatically increased when histatin 5 were incubation with 3-azidocoumarin. There is a good relationship with the linear co r of 0.994 between the enhanced fluorescence and histatin 5 concentration ranging from 0.23 to 31.05 µmol·L-1, and the limit of detection is 72 nmol·L-1 (3σ/k). Moreover, the detection of histidine-rich peptides in saliva was successfully achieved by the new developed label free method since amino acids and proteins in saliva will not be interfered with the detection with the recoveries between 96.7%~111.6%. Compared with the existing saliva analysis methods, this method has the advantage of simple, fast and low cost. It might be applied in non-invasive disease diagnosis.
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Saliva , Secuencia de Aminoácidos , Histatinas , Histidina , Proteínas y Péptidos SalivalesRESUMEN
BACKGROUND: Until 2021, colon cancer was a leading cancer globally. Early detection improves outcomes; however, advanced cases still having poor prognosis. Therefore, an understanding of associated molecular mechanisms is crucial for developing new preventive and therapeutic strategies for colon cancer. METHODS: The TCGA database was analyzed to assess melanocortin 1receptor (MC1R) expression in colon cancer and its link with patient prognosis. Further, models and diverse experimental techniques were employed to investigate the impact of MC1R on colon cancer progression and its underlying mechanism was elucidated. RESULTS: In a follow-up study of clinical patients, the important role of MC1R was identified in the development of colon cancer. First, MC1R was expressed more highly in colon tumor tissues than in adjacent tissues. In addition, MC1R was associated with colon cancer prognosis, and higher expression of MC1R tended to predict a worse prognosis. This conclusion was verified in MC1R-/- mice, which showed a greater resistance to tumor growth than wild-type mice, as expected. Further investigation revealed a significant change in the portion of Tregs in MC1R-/- mice, while the portion of CD4 + and CD8 + T cells remained unchanged. The in vitro experiments revealed a weaker ability of the MC1R-/- T cells to differentiate into Tregs. Previous studies report that the functional integrity of Tregs is interwoven with cellular metabolism. Therefore, MC1R was deduced to regulate the differentiation of Tregs by reprogramming the metabolism. As expected, MC1R-/- T cells exhibited weaker mitochondrial function and a lower aerobic oxidation capacity. Concurrently, the MC1R-/- T cells had stronger limiting effects on colon cancer cells. According to these results, the MC1R inhibitor was hypothesized as a potential therapeutic agent to suppress colon cancer. The results showed that upon MC1R suppression, the tumors in the mice developed more slowly, and the mice survived longer, potentially providing a novel strategy to treat clinical colon cancer. CONCLUSION: By regulating Tregs differentiation, MC1R overexpression in colon cancer correlates with poor prognosis, while MC1R inhibition shows potential as a therapeutic approach to slow tumor growth and enhance survival.
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Diferenciación Celular , Neoplasias del Colon , Receptor de Melanocortina Tipo 1 , Linfocitos T Reguladores , Animales , Neoplasias del Colon/patología , Neoplasias del Colon/genética , Neoplasias del Colon/inmunología , Linfocitos T Reguladores/inmunología , Humanos , Receptor de Melanocortina Tipo 1/genética , Receptor de Melanocortina Tipo 1/metabolismo , Ratones , Ratones Noqueados , Masculino , Pronóstico , Ratones Endogámicos C57BL , Femenino , Línea Celular Tumoral , Reprogramación MetabólicaRESUMEN
Laparoscopic surgery is extensively applied in the treatment of hepatobiliary diseases. Hepatic artery pseudoaneurysm (HAP) is a rare complication following hepatic biliary surgery through laparoscopy. The clinical manifestations of HAP are diverse and can be fatal. Given its severity, rapid assessment and management are crucial to ensuring a good prognosis. Here, we report three cases of HAP; two underwent laparoscopic surgery due to cholelithiasis, and another caused by trauma. The first case exhibited a pseudoaneurysm involving the distal portion of the right hepatic artery main trunk. The second patient had a pseudoaneurysm at the bifurcation of the left and right hepatic arteries. The third case involved a patient with a pseudoaneurysm involving a branch of the right hepatic artery. The main clinical manifestations of all three cases were bleeding from the biliary tract (the first two cases showed postoperative bleeding in the T-tube, while the third case exhibited gastrointestinal bleeding). The final diagnosis was obtained through digital subtraction angiography. The three patients underwent successful transcatheter arterial embolization operation and a follow-up revealed they were disease-free and alive. This article aims to highlight a rare complication of laparoscopic hepatobiliary surgery and share our experience in early diagnosis and treatment of HAP.
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Photocatalytic antimicrobials, as emerging advanced oxidative antimicrobial materials, have the advantages of low price and long-lasting antimicrobial properties. Nevertheless, with catalysts increasingly trending toward nanoscale dimensions, the environmental challenge of catalyst recycling becomes more pronounced. In this paper, we propose utilizing one-dimensional carbon fiber as a substrate, employing the nucleating agent method to induce Titanium dioxide (TiO2) growth on the fiber surface. Furthermore, the material's band gap underwent modification through hydrogen calcination, thus resulting in the attainment of hierarchical black TiO2/carbon fiber composites with visible light-driven capabilities. The characterization of the materials was conducted via scanning electron microscope (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS). The results revealed that when the black hydrogenated TiO2 was composited with carbon fiber, the Schottky heterojunction was formed, and thus effectively improved the photocatalytic effect of the composites. Notably, the degradation rate of methylene blue achieved 96.25% within 150 min when utilizing black TiO2/carbon fiber composites, while the inactivation rate of Escherichia coli (E. coli) reached 97.58% within 0.5 h and attained complete inactivation within 60 min.
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BACKGROUND: The correlation between the preoperative albuminalkaline phosphatase ratio (AAPR) and the prognosis of hepatocellular carcinoma (HCC) patients after radical resection is still not comprehensive. OBJECTIVE: This study aims to observe the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. METHODS: We constructed a retrospective cohort study and included 656 HCC patients who underwent radical resection. The patients were grouped after determining an optimum AAPR cut-off value. We used the Cox proportional regression model to assess the correlation between preoperative AAPR and the prognosis of HCC patients after radical resection. RESULTS: The optimal cut-off value of AAPR for assessing the prognosis of HCC patients after radical resection was 0.52 which was acquired by using X-tile software. Kaplan-Meier analysis curves showed that a low AAPR (⩽ 0.52) had a significantly lower rate of overall survival (OS) and recurrence-free survival (RFS) (P< 0.05). Multiple Cox proportional regression showed that an AAPR > 0.52 was a protective factor for OS (HR = 0.66, 95%CI 0.45-0.97, p= 0.036) and RFS (HR = 0.70, 95% CI 0.53-0.92, p= 0.011). CONCLUSIONS: The preoperative AAPR level was related to the prognosis of HCC patients after radical resection and can be used as a routine preoperative test, which is important for early detection of high-risk patients and taking personalized adjuvant treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Fosfatasa Alcalina , Estudios Retrospectivos , Neoplasias Hepáticas/cirugía , Pronóstico , AlbúminasRESUMEN
Outbreaks of hepatitis-hydropericardium syndrome (HHS) caused by fowl adenovirus serotype 4 (FAdV-4) have resulted in huge economic losses to the poultry industry in China since 2015. However, commercially available vaccines against the FAdV-4 infection remain scarce. In our study, subunit vaccine candidates derived from the bacterially expressed recombinant Fiber1 knob domain and Fiber2 knob domain fusion protein (termed as Fiber1/2 knob subunit vaccine) and Fiber2 protein (termed as Fiber2 subunit vaccine) of the FAdV-4 SDSX strain were developed. Immunogenicity evaluation showed that the Fiber1/2 knob subunit vaccine induced the production of antibodies at 7 d postvaccination (dpv), earlier than the Fiber2 subunit vaccine. Moreover, the neutralizing antibody level of the Fiber1/2 subunit vaccine group was higher than the Fiber2 subunit vaccine group, showing significant differences at 14, 21, and 28 dpv. Immune protection test results revealed that both Fiber1/2 knob subunit and Fiber2 subunit vaccines could protect chickens from death against FAdV-4 challenge, although the weight of chickens in the Fiber1/2 knob subunit vaccine group decreased less. Furthermore, analysis of plasma Glutamic oxaloacetic transaminase (AST) and blood glutamic pyruvic transaminase (ALT) levels suggested that the Fiber1/2 subunit vaccine can significantly inhibit liver damage caused by FAdV-4 infection and is more effective in blocking the pathogenicity of FAdV-4 in target organs. In addition, the Fiber1/2 knob subunit vaccine further reduced the viral load in different tissues and virus shedding in chickens than the Fiber2 subunit vaccine. Overall, the Fiber1/2 knob subunit vaccine was more effective than the Fiber2 subunit vaccine. These findings lay the foundation for the development of more effective FAdV-4 subunit vaccines.
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Infecciones por Adenoviridae , Aviadenovirus , Pollos , Enfermedades de las Aves de Corral , Vacunas de Subunidad , Animales , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Infecciones por Adenoviridae/veterinaria , Infecciones por Adenoviridae/prevención & control , Infecciones por Adenoviridae/virología , Infecciones por Adenoviridae/inmunología , Aviadenovirus/inmunología , Vacunas Virales/inmunología , SerogrupoRESUMEN
Climate change is often closely related to vegetation dynamics; time lag (Tlag) and accumulative effects (Tacc) are non-negligible phenomena when studying the interaction between climate and vegetation. But, amidst the escalating frequency of extreme climatic events, the quantification of temporal effects (Teffects) of such extremes on vegetation remains scarce. This research quantifies the Tlag and Tacc responses of China's vegetation to episodes of extreme temperature and precipitation since the early 2000s, utilizing daily meteorological data series. Overall, the precipitation in China has become wetter, and nighttime temperatures have risen significantly. The proportion of areas with Teffects ranged from 1.15 % to 15.95 %, and the correlation coefficient between the climate indices and the Normalized Difference Vegetation Index (NDVI) increased by 0.05 to 0.38 when considering the Teffects, compared to not considering it. The Tacc of vegetation had the strongest response (70.74-88.01 %) to extreme events among all the tested climate indices. Moreover, the Tacc of consecutive climate events had a greater impact on vegetation growth than individual climate event. The average Tacc for extreme temperature and extreme precipitation was 1.7-3.09 months and 2.17-3.25 months, respectively. Events like the over 95 % (R95p) and 99 % (R99p) percentile heavy precipitation and the maximum precipitation amount in one day (Rx1day) caused significant Teffects on NDVI. In addition, 90 % of grasslands exhibit Tacc, mainly contributed by the extreme precipitation indices (55.7 %), while the Teffects of forests were stronger than those of extreme temperature. Furthermore, NDVI was more affected by annual precipitation than by extreme precipitation, but the opposite was true for temperature. The results of this study highlight the importance of considering the Tlag and Tacc when predicting the effects of climate change on vegetation dynamics.