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BACKGROUND: The KCNQ1+KCNE1 (IKs) potassium channel plays a crucial role in cardiac adaptation to stress, in which ß-adrenergic stimulation phosphorylates the IKs channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death. However, the molecular connection between IKs channel phosphorylation and channel function, as well as why high-risk LQT1 mutations lose cAMP sensitivity, remain unclear. METHODS: Regular patch clamp and voltage clamp fluorometry techniques were utilized to record pore opening and voltage sensor movement of wild-type and mutant KCNQ1/IKs channels. The clinical phenotypic penetrance of each LQT1 mutation was analyzed as a metric for assessing their clinical risk. The patient-specific-induced pluripotent stem-cell model was used to test mechanistic findings in physiological conditions. RESULTS: By systematically elucidating mechanisms of a series of LQT1 variants that lack cAMP sensitivity, we identified molecular determinants of IKs channel regulation by phosphorylation. These key residues are distributed across the N-terminus of KCNQ1 extending to the central pore region of IKs. We refer to this pattern as the IKs channel PKA phosphorylation axis. Next, by examining LQT1 variants from clinical databases containing 10 579 LQT1 carriers, we found that the distribution of the most high-penetrance LQT1 variants extends across the IKs channel PKA phosphorylation axis, demonstrating its clinical relevance. Furthermore, we found that a small molecule, ML277, which binds at the center of the phosphorylation axis, rescues the defective cAMP effects of multiple high-risk LQT1 variants. This finding was then tested in high-risk patient-specific induced pluripotent stem cell-derived cardiomyocytes, where ML277 remarkably alleviates the beating abnormalities. CONCLUSIONS: Our findings not only elucidate the molecular mechanism of PKA-dependent IKs channel phosphorylation but also provide an effective antiarrhythmic strategy for patients with high-risk LQT1 variants.
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OBJECTIVES: To evaluate the value of CT-based whole lung radiomics nomogram for identifying the risk of cardiovascular disease (CVD) in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: A total of 974 patients with COPD were divided into a training cohort (n = 402), an internal validation cohort (n = 172), and an external validation cohort (n = 400) from three hospitals. Clinical data and CT findings were analyzed. Radiomics features of whole lung were extracted from the non-contrast chest CT images. A radiomics signature was constructed with algorithms. Combined with the radiomics score and independent clinical factors, multivariate logistic regression analysis was used to establish a radiomics nomogram. ROC curve was used to analyze the prediction performance of the model. RESULTS: Age, weight, and GOLD were the independent clinical factors. A total of 1218 features were extracted and reduced to 15 features to build the radiomics signature. In the training cohort, the combined model (area under the curve [AUC], 0.731) showed better discrimination capability (p < 0.001) than the clinical factors model (AUC, 0.605). In the internal validation cohort, the combined model (AUC, 0.727) performed better (p = 0.032) than the clinical factors model (AUC, 0.629). In the external validation cohort, the combined model (AUC, 0.725) performed better (p < 0.001) than the clinical factors model (AUC, 0.690). Decision curve analysis demonstrated the radiomics nomogram outperformed the clinical factors model. CONCLUSION: The CT-based whole lung radiomics nomogram has the potential to identify the risk of CVD in patients with COPD. CLINICAL RELEVANCE STATEMENT: This study helps to identify cardiovascular disease risk in patients with chronic obstructive pulmonary disease on chest CT scans. KEY POINTS: ⢠To investigate the value of CT-based whole lung radiomics features in identifying the risk of cardiovascular disease in chronic obstructive pulmonary disease patients. ⢠The radiomics nomogram showed better performance than the clinical factors model to identify the risk of cardiovascular disease in patients with chronic obstructive pulmonary disease. ⢠The radiomics nomogram demonstrated excellent performance in the training, internal validation, and external validation cohort (AUC, 0.731; AUC, 0.727; AUC, 0.725).
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Doenças Cardiovasculares , Nomogramas , Doença Pulmonar Obstrutiva Crônica , Tomografia Computadorizada por Raios X , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/complicações , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Doenças Cardiovasculares/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Medição de Risco/métodos , Pulmão/diagnóstico por imagem , Fatores de Risco , Estudos Retrospectivos , RadiômicaRESUMO
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is used when standard methods of standard treatment methods are not successful. Obese patients present unique challenges during ECMO due to large body size hindering sufficient flows, difficulties with patient positioning and anatomical landmark identification, and restricted radiology scans. This meta-analysis aims to investigate the impact of obesity on the outcomes of patients undergoing ECMO. METHODS: Databases (PubMed, Embase, and Scopus databases) were searched to identify relevant studies published until July 2023. Data were reported as odds ratios (OR) with 95% confidence interval (CI), and the descriptive data were reported as standard difference of means (SDM) by a random effects model. RESULTS: A literature search identified 345 studies. Of them, 18 studies met the inclusion criteria. The findings from the meta-analysis revealed no significant association between obesity and survival outcomes after ECMO (odds ratio (OR): 0.91, 95% confidence interval (CI): 0.70-1.17, p: 0.46). Moreover, no comparative significant differences were found between obese and non-obese individuals on the duration of ECMO procedure (standardized mean difference (SMD): 0.07, -0.03-0.17), length of hospital stay (-0.03, -0.19 to 0.12), and duration of ventilation support (-0.10, -0.44 to 0.24). CONCLUSION: The meta-analysis findings suggest no significant impact of obesity on the survival outcomes after the ECMO procedure. There was no significant impact of obesity on the duration of ECMO procedures, length of hospital stay, and duration of ventilation support.
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Oxigenação por Membrana Extracorpórea , Obesidade , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Obesidade/complicações , Obesidade/terapia , Tempo de Internação/estatística & dados numéricos , Resultado do TratamentoRESUMO
Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.
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BACKGROUND: Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited. METHODS: We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN. RESULTS: Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model. CONCLUSION: This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.
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Ácidos Aristolóquicos , Nefropatias , Fatores de Transcrição , Ácidos Aristolóquicos/toxicidade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/genética , Animais , Camundongos , Humanos , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo , Mapas de Interação de ProteínasRESUMO
This cross-sectional study was conducted to examine the most effective strategies for managing malodorous and infected wounds in patients who have been diagnosed with advanced cervical cancer. The research was conducted in Liupanshui, China. The study specifically examined demographic profiles, wound characteristics and effectiveness of wound management approaches. The study incorporated the heterogeneous sample of 289 participants who fulfilled the inclusion criteria. Data collection was conducted via structured questionnaires and medical record evaluations. Descriptive statistics and statistical analyses, such as regression analysis, were utilized to evaluate demographic attributes, wound profiles and effects of different approaches to wound management. The findings unveiled the heterogeneous demographic composition of patients, encompassing differences in socioeconomic standing, educational attainment and age. A wide range of wound characteristics were observed, as 65.7% of lesions during the acute phase with diameter between 2 and 5 centimetres, while 41.5% of lesions had this range. The most prevalent types of infections were those caused by fungi (48.4%), followed by bacterial infections lacking resistance (38.1%). A moderate degree of odour intensity was prevalent, affecting 45.0% of the cases. With maximal odour reduction of 80%, a mean healing time of 25 days and patient satisfaction rating of 4.5 out of 5, Negative Pressure Wound Therapy demonstrated itself to be the most efficacious treatment method. Additional approaches, such as photodynamic therapy and topical antibiotic therapy, demonstrated significant effectiveness, as evidenced by odour reductions of 70% and 75%, respectively, and patient satisfaction ratings of 4.3 and 4.2. Thus, the study determined challenges associated with management of malodorous and infected lesions among patients with advanced cervical cancer. The results underscored the significance of individualized care approaches, drew attention to efficacious wound management techniques and identified critical determinants that impacted patient recuperation. The findings of this study hold potential for advancing palliative care for individuals diagnosed with advanced cervical cancer.
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Neoplasias do Colo do Útero , Infecção dos Ferimentos , Feminino , Humanos , Neoplasias do Colo do Útero/terapia , Estudos Transversais , Antibacterianos , CicatrizaçãoRESUMO
BACKGROUND: lipopolysaccharide (LPS) can induce nephrotic syndrome-like features such as massive proteinuria, hyperlipidemia, and fusion of glomerular podocytes with foot processes (FPs) in mice. Angiopoietin-like protein 4 (ANGPTL4) neutralized the negative charge of glomerular basement membrane charge and aggravated renal injury. The mechanism of ANGPTL4 aggravating podocyte injury has not been well clarified. In this study, we aimed to investigate the potential role of ANGPTL4 on podocyte FPs fusion and podocyte signal molecules. METHODS: We built angptl4 gene knocked out in C57BL6 mice using CRISPR/Cas9 technique. Nephrotic model was built by LPS in wild type and angptl4-/- mice. Expression of ACTN4, podocin and TRPC6 in the glomerulus were determined by immunohistochemistry. RESULTS: In physical condition, the wild type and angptl4-/- mice showed no significant differences in biochemical indicators and kidney pathology. But in nephrotic condition, compared with wild type mice hyperlipidemia and proteinuria with the angptl4-/- mice was significantly relieved. Moreover, the degree of FPs fusion was notably improved in the nephrotic mice knocked out angptl4 gene. Expression of ACTN4 and podocin decreased drastically in the glomerulus of wild-type nephrotic mice. Different from wild-type, the ACTN4 and podocin expression showed slight weakening in angptl4-/- nephrotic mice. As transient receptor potential cation channel subfamily member, TRPC6 expression had no visible change in glomerulus of each group. CONCLUSIONS: ANGPTL4 induces hyperlipidemia and podocyte injury in nephrotic mice, thereby promoting the formation of proteinuria. Its molecular mechanism may be related to ANGPTL4 down-regulating actin cytoskeletal regulatory signals ACTN4 and podocin.
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Síndrome Nefrótica , Podócitos , Animais , Camundongos , Proteína 4 Semelhante a Angiopoietina/genética , Proteína 4 Semelhante a Angiopoietina/metabolismo , Lipopolissacarídeos/metabolismo , Camundongos Endogâmicos C57BL , Síndrome Nefrótica/genética , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , Podócitos/metabolismo , Proteinúria/patologia , Canal de Cátion TRPC6/metabolismoRESUMO
BACKGROUND: Neuron-specific gene family member 1 (NSG1) is a 21 kDa endosomal protein that is specifically expressed in neurons. AIMS: This study was to explore the expression of NSG1 and possible mechanism in Esophageal Squamous Cell Carcinoma (ESCC). METHODS: The Cancer Genome Atlas (TCGA) database was consulted to analyze the expression of NSG1 in ESCC. Immunohistochemistry (IHC) staining was used to evaluate NSG1 expression in ESCC cancerous tissues and matched paracancerous tissues. The CCK-8 assay, wound-healing assay, and transwell assay were used to detect the cell viability, migration, and invasion of ESCC cells. Western blot was used to assay epithelial-mesenchymal transition (EMT)-related proteins and ERK signaling pathway protein expression. RESULTS: The results showed that the expression of NSG1 in ESCC cancerous tissues was higher than noncancerous tissues. Compared with negative control (NC) group, cell viability, migration. and invasion significantly increased, the expression of p-ERK in ERK signaling pathway was significantly upregulated, the expressions of mesenchymal marker Vimentin and EMT-related transcription factors including snail and slug were significantly upregulated, and the expression of epithelial marker E-cadherin was significantly downregulated in KYSE-150 cells with NSG1 overexpression. However, these effects were reversed by the ERK signaling pathway inhibitor U0126. On the other hand, TE-1 cells with NSG1 knockdown had the changes contrary to that in KYSE-150 cells with NSG1 overexpression. CONCLUSION: NSG1 plays a potential carcinogenic role on the occurrence and progression of ESCC, and aberrant NSG1 expression might promote ESCC cell EMT by the activation of ERK signaling pathway.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/patologia , Neoplasias Esofágicas/patologia , Transição Epitelial-Mesenquimal , Movimento Celular/genética , Transdução de Sinais , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Invasividade Neoplásica/genéticaRESUMO
BACKGROUND: Since July 2021, some countries and regions have initiated the vaccination of minors against coronavirus disease (COVID-19), and parental COVID-19 vaccine hesitancy will affect the vaccination of minors. We aimed to identify the level of parental hesitancy to vaccinate their children against COVID-19 in Taiwan and the factors associated with vaccine hesitancy. METHODS: We conducted a population-based, self-administered online questionnaire in Taiwan to assess parental hesitancy and the factors influencing their children's vaccination against COVID-19. RESULTS: Among 384 respondents, 64.1% were hesitant to have their children vaccinated against COVID-19. Mothers were more likely to hesitate to vaccinate their teens than their fathers (67.5% vs. 50%, P < 0.005). Multiple regression results showed that parents who were hesitant to vaccinate themselves (OR = 3.81, 95% CI:2.07-7.02) and those who scored lower on their perception of their children's vaccination (OR = 9.73, 95% CI:5.62-16.84) were more hesitant to vaccinate their children with COVID-19 vaccine. CONCLUSIONS: According to the study findings, 64.1% of Taiwanese parents were hesitant to vaccinate their children against COVID-19. Parents who were hesitant to receive the COVID-19 vaccine for themselves and had negative views of the vaccine for their children were more likely to be hesitant to vaccinate their children. An in-depth discussion of the factors affecting vaccine hesitancy and targeted health education is conducive to promoting vaccination in children with COVID-19.
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Vacinas contra COVID-19 , COVID-19 , Adolescente , Criança , Humanos , Vacinas contra COVID-19/uso terapêutico , Taiwan/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pais , VacinaçãoRESUMO
Low-carbon and high-efficiency binder is desirable for sustainable treatment of municipal solid waste incineration fly ash (MSWI FA). In this study, CaO or MgO was used to activate ground granulated blast furnace slag (GGBS) to form calcium silicate hydrate and magnesium silica hydrate gel for stabilization/solidification of hazardous MSWI FA. Experimental results showed that potential toxic elements (PTEs), such as Pb and Zn, significantly inhibited the formation of reaction products in CaO-GGBS system due to the complexation between Ca(OH)2 and PTEs, whereas PTEs only had insignificant inhibition on transformation from MgO to Mg(OH)2 in MgO-GGBS system, resulting in lower leachabilities of PTEs and higher mechanical strengths. Stabilization/solidification experiments demonstrated that MSWI FA (70 wt%) could be recycled by MgO-GGBS binder (30 wt%) into blocks with desirable 28-day compressive strengths (3.9 MPa) and PTEs immobilization efficiencies (99.8% for Zn and 99.7% for Pb). This work provides mechanistic insights on the immobilization mechanisms of PTEs in CaO/MgO-GGBS systems and suggests a promising MgO-GGBS binder for low-carbon treatment of MSWI FA.
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Metais Pesados , Eliminação de Resíduos , Cinza de Carvão , Eliminação de Resíduos/métodos , Material Particulado , Carbono , Óxido de Magnésio , Chumbo , Metais Pesados/análise , Incineração/métodos , Resíduos Sólidos/análiseRESUMO
BACKGROUND & AIMS: Corticosteroids are the mainstay of treatment for hospitalized patients with acute severe ulcerative colitis (ASUC). However, whether the addition/continuation of mesalamine with corticosteroids during hospitalization is superior to corticosteroids alone is unknown. METHODS: This was a randomized controlled, investigator-blinded, clinical trial conducted in 10 centers in 7 countries. Patients hospitalized with ASUC (Lichtiger score ≥10) were eligible. Patients received corticosteroids alone or corticosteroid + mesalamine (4 g/day mesalamine) by a stratified randomization according to mesalamine use before admission. The primary outcome was the percentage of patients who responded to treatment by day 7, defined by a drop >3 points in the Lichtiger score and an absolute score <10 without the need for rescue medications or colectomy. RESULTS: Three hundred forty-six patients were screened, and 149 were included (70/149 female; median age, 41 years). Of these, 73 received corticosteroids + mesalamine, and 76 received corticosteroids alone. For the primary outcome, 53 of 73 patients (72.6%) receiving corticosteroids with mesalamine responded versus 58 of 76 patients (76.3%) on corticosteroids alone (odds ratio, 0.82; 95% confidence interval, 0.39-1.72; P = .60). There was no difference between groups in duration of hospitalization, C-reactive protein normalization rate, or colectomy rate up to day 90. The need for biologics among patients receiving combination of corticosteroids with mesalamine was numerically lower by day 30 (P = .11) and day 90 (P = .07). CONCLUSIONS: In this randomized controlled trial, combination of mesalamine with corticosteroids did not benefit hospitalized patients with ASUC more than corticosteroids alone. An exploratory signal for a reduced need for biologics at 90 days in the mesalamine group merits further evaluation. CLINICALTRIALS: gov ID: NCT01941589.
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Produtos Biológicos , Colite Ulcerativa , Humanos , Feminino , Adulto , Mesalamina/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Anti-Inflamatórios não Esteroides/uso terapêutico , Resultado do Tratamento , Corticosteroides/uso terapêutico , Produtos Biológicos/uso terapêuticoRESUMO
Proton nuclear magnetic resonance (1H NMR) spectroscopy presents a powerful detection tool for studying chemical compositions and molecular structures. In practical chemical and biological applications, 1H NMR experiments are generally confronted with the challenge of spectral congestions caused by abundant observable components and intrinsic limitations of a narrow frequency distribution range and extensive J coupling splitting. Herein, a one-dimensional (1D) general NMR method is proposed to individually extract the signals of targeted proton groups based on their endogenous spin singlet states excited from J coupling interactions, and it is suitable for high-resolution detections on complex chemical and biological samples. The applicability of the proposed method is demonstrated by experimental observations on chemical solutions containing different coupled components, intact grape tissues subjected to crowded resonances, and in vitro pig brain with various metabolites. Moreover, the proposed method is further exploited for magnetic resonance spectroscopy applications by directly combining the spatial localization module, showing promise in in vivo biological metabolite studies.
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Imageamento por Ressonância Magnética , Prótons , Animais , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Soluções , SuínosRESUMO
Lung cancer (LC) remains the leading cause of mortality from malignant tumors worldwide. In our previous study, we surveyed both IgG and IgM-bound serological biomarkers and validated a panel of IgG-bound autoantigens for early LC diagnosis with 50% sensitivity at 90% specificity. To further improve the performance of these serological biomarkers, we surveyed HuProt arrays, comprised of 20,240 human proteins, for IgA-bound autoantigens because IgAs are a major immunoglobulin isotype in the lung. Integrating with IgG-bound autoantigens, we discovered and validated a combined biomarker panel using ELISA-format tests. Specifically, in Phase I, we obtained IgA-based autoimmune profiles of 69 early stage LC patients, 30 healthy subjects and 25 patients with lung benign lesions (LBL) on HuProt arrays and identified 28 proteins as candidate autoantigens that were significantly associated with early stage LC. In Phase II, we re-purified the autoantigens and converted them into an ELISA-format testing to profile an additional large cohort, comprised of 136 early stage LC patients, 58 healthy individuals, and 29 LBL patients. Integration of IgG autoimmune profiles allowed us to identify and validate a biomarker panel of three IgA autoantigens (i.e. BCL7A, and TRIM33 and MTERF4) and three IgG autoantigens (i.e. CTAG1A, DDX4 and MAGEC2) for diagnosis of early stage LC with 73.5% sensitivity at >85% specificity. In Phase III, the performance of this biomarker panel was confirmed with an independent cohort, comprised of 88 early stage LC patients, 18 LBL patients, and 36 healthy subjects. Finally, a blind test on 178 serum samples was conducted to confirm the performance of the biomarker panel. In summary, this study demonstrates for the first time that an integrated panel of IgA/IgG autoantigens can serve as valuable biomarkers to further improve the performance of early diagnosis of LC.
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Autoantígenos/imunologia , Biomarcadores Tumorais/imunologia , Detecção Precoce de Câncer , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Neoplasias Pulmonares/diagnóstico , Idoso , Biomarcadores Tumorais/sangue , Feminino , Humanos , Pulmão/imunologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Telemedicine plays an important role in the management of inflammatory bowel disease (IBD), particularly during a pandemic such as COVID-19. However, the effectiveness and efficiency of telemedicine in managing IBD are unclear. OBJECTIVE: This systematic review and meta-analysis aimed to compare the impact of telemedicine with that of standard care on the management of IBD. METHODS: We systematically searched the PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus databases on April 22, 2020. Randomized controlled trials comparing telemedicine with standard care in patients with IBD were included, while conference abstracts, letters, reviews, laboratory studies, and case reports were excluded. The IBD-specific quality of life (QoL), disease activity, and remission rate in patients with IBD were assessed as primary outcomes, and the number of in-person clinic visits per patient, patient satisfaction, psychological outcome, and medication adherence were assessed as secondary outcomes. Review Manage 5.3 and Stata 15.1 were used for data analysis. RESULTS: A total of 17 randomized controlled trials (2571 participants) were included in this meta-analysis. The telemedicine group had higher IBD-specific QoL than the standard care group (standard mean difference 0.18, 95% CI 0.01 to 0.34; P.03). The number of clinic visits per patient in the telemedicine group was significantly lower than that in the standard care group (standard mean difference -0.71, 95% CI -1.07 to -0.36; P<.001). Subgroup analysis showed that adolescents in the telemedicine group had significantly higher IBD-specific QoL than those in the standard care group (standard mean difference 0.42, 95% CI 0.15 to 0.69; I2=0; P.002), but there was no significant difference between adults in the 2 groups. There were no significant differences in disease activity, remission rate, patient satisfaction, depression, self-efficacy, generic QoL, and medication adherence outcomes between the telemedicine and standard care groups. CONCLUSIONS: Telemedicine intervention showed a promising role in improving IBD-specific QoL among adolescents and decreased the number of clinic visits among patients with IBD. Further research is warranted to identify the group of patients with IBD who would most benefit from telemedicine.
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COVID-19 , Doenças Inflamatórias Intestinais , Telemedicina , Adolescente , Adulto , Humanos , Doenças Inflamatórias Intestinais/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Benefitting from the capability of recording scalar (J) couplings and bonding information, 2D J-resolved NMR spectroscopy constitutes an important tool for molecular structure analysis and mixture component identification. Unfortunately, conventional 2D J-resolved experiments generally encounter challenges of insufficient spectral resolution and strong coupling artifacts. In this study, a general NMR approach is exploited to record absorption-mode artifact-free 2D J-resolved spectra. This proposal adopts the advanced triple-spin-echo pure shift yielded by chirp excitation element to eliminate J coupling splittings and preserve chemical shifts along the F2 dimension, and it additionally utilizes the echo-train J acquisition to reveal the multiplet structure along the F1 dimension in accelerated experimental acquisition. Thus, it permits one to extract multiplet structure information from crowded spectral regions in one-shot experiments, with considerable resolution advantage resulting from completely decoupling F2 dimension and absorption-mode presentation, thus facilitating analysis on complex samples. More importantly, this method grants the superior performance on suppressing strong coupling artifacts, which have been affirmed by experiments on a series of chemical samples. As a consequence, this proposed method serves as a useful tool for J coupling measurements and multiplet structure analyses on complex samples that contain crowded NMR resonances and strong coupling spin systems, and it may exhibit broad application potentials in fields of physics, chemistry, and medical science, among others.
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Purpose: Our pilot study in a small cohort by ELISA showed that the levels and positive rates of serum IgG autoantibodies against p53, HRAS and NSG1, and IgA autoantibody against TIF1γ in early colon cancer (CC) group were significantly higher than that of colon benign lesion (CBL) group / healthy control (HC) group (P <0.01), which suggested that four autoantibodies might be valuable for the diagnosis of patients with CC at early stage. On the basis of pilot study, we intend to comprehensively elucidate the performance of four autoantibodies for the early diagnosis of CC in a large sample cohort, and explore the optimal panel of autoantibodies in the diagnosis of patients with CC at early stage. Methods: Western blot was used to define the ELISA results of serum anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA. The performances of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA were evaluated by ELISA for the early diagnosis of CC with 601 serum samples of 157 patients with CC at early stage, 144 patients with CC at advanced stage, 130 patients with CBL, and 170 HC, and then the performances of different combinations of four autoantibodies were analyzed for the development of an optimal panel for the early diagnosis of CC. Results: The results of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA in western blotting were consistent with that in ELISA. The levels and positive rates of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA in early CC group were significantly higher than that in CBL group/HC group (P <0.01), while had no significant difference from that in advanced CC group (P >0.05), of which anti-TIF1γ-IgA showed the highest area under the receiver operating characteristic curve (AUC) of 0.716 for the patients with CC at early stage, with 25.5% sensitivity and specificity at 96.7%. Additionally, a panel of anti-p53, HRAS-IgG and anti-TIF1γ-IgA showed the highest AUC among all possible combinations of four autoantibodies, up to 0.737, with 47.1% sensitivity at 92.0% specificity. Conclusions: Serum IgG autoantibodies against p53, HRAS and NSG1, and IgA autoantibody against TIF1γ show the diagnostic value for the patients with CC at early stage, of which anti-TIF1γ-IgA is demonstrated to be a preferable biomarker, and an optimal panel comprised of anti-p53, HRAS-IgG and anti-TIF1γ-IgA might contribute to the further improvement of early diagnosis for CC.
Assuntos
Autoanticorpos/sangue , Biomarcadores Tumorais/sangue , Neoplasias do Colo/diagnóstico , Detecção Precoce de Câncer/métodos , Idoso , Autoanticorpos/imunologia , Biomarcadores Tumorais/imunologia , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias do Colo/sangue , Neoplasias do Colo/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Voluntários Saudáveis , Humanos , Imunoglobulina A/sangue , Imunoglobulina A/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Projetos Piloto , Curva ROCRESUMO
Objective: The aberrant expression of tumor-associated antigens (TAAs) is responsible for the release of large amounts of autoantibodies in sera, and serum autoantibody detection has been demonstrated to contribute to the early diagnosis of malignancies. Recent studies showed the closely correlation of transcriptional intermediary factor-1γ (TIF1γ) with some malignancies. In our pilot study, we found aberrantly high expression of TIF1γ protein existed in cancer tissues other than matched paracancerous tissues of patients with lung cancer (LC) at early stage by immunohistochemistry (IHC) staining. As a result, this study aims to detect the expression of autoantibodies against TIF1γ in sera of patients with LC at early stage by using enzyme-linked immunosorbent assay (ELISA) and investigate its potential value for the early diagnosis of LC. Methods: The expressions of TIF1γ protein in 60 pairs of LC tissues and matched paracancerous tissues were detected by IHC staining. The levels of anti-TIF1γ-IgA, IgG, IgM, and IgE in the sera of 248 patients with LC at early stage, 200 patients with lung benign lesions (LBL), and 218 healthy controls (HC) were detected by ELISA, respectively. Western blot was used to validate the ELISA results of serum autoantibodies against TIF1γ. Results: The positive rate of TIF1γ protein expression in LC tissues was 83.33%, which was significantly higher than 25.00% in paracancerous tissues (P<0.01). The levels and positive rates of serum anti-TIF1γ-IgM and anti-TIF1γ-IgE in early LC group had no significant difference from that in LBL group and HC group (P>0.05), while the levels and positive rates of anti-TIF1γ-IgA and anti-TIF1γ-IgG were significantly higher than that in LBL group and HC group (P<0.01), of which anti-TIF1γ-IgA showed the area under the receiver operating characteristic curve (AUC) of 0.704 for the patients with LC at early stage, with 28.20% sensitivity at 95.93% specificity, and anti-TIF1γ-IgG showed the AUC of 0.622 for the patients with LC at early stage, with 18.54% sensitivity at 94.25% specificity. The results of anti-TIF1γ-IgA and anti-TIF1γ-IgG in western blot were consistent with that in ELISA. Additionally, the combination of anti-TIF1γ-IgA and anti-TIF1γ-IgG improved the AUC to 0.734, with 38.31% sensitivity at 92.34% specificity. Conclusions: There is a strong humoral immune response to autologous TIF1γ existing in patients with early LC. Both serum anti-TIF1γ-IgA and anti-TIF1γ-IgG show the diagnostic value for the patients with LC at early stage, of which anti-TIF1γ-IgA is donstrated to be a preferable biomarker, and the combined detection of anti-TIF1γ-IgA and anti-TIF1γ-IgG might contribute to the further improvement of early diagnosis for LC.
Assuntos
Autoanticorpos/imunologia , Biomarcadores Tumorais/imunologia , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Anticorpos Anti-Idiotípicos/imunologia , Western Blotting , Detecção Precoce de Câncer , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina E/imunologia , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
AIMS: To investigate control measures for COVID-19 pandemic in GIE centers in China. METHODS: This is a retrospective multi-center research, including seven centers. Data collection was from 1 February to 31 March 2020 and the same period in 2019. RESULTS: There were a total of 28 COVID-19 definite cases in these hospitals. Six out of seven GIE centers were arranged to shut down on 1 February, with a mean number of shutdown days of 23.6 ± 5.3. The actual workloads were only 10.3%-62.9% compared to those last year. All centers had a preoperative COVID-19 screening process. Epidemiological questionnaire, temperature taking and QR-code of journey were conducted. Chest CT scan was conducted during the shutdown period and continued in five centers after return to work. Antibody and nucleic acid test were applied in one to three centers. All endoscopists had advanced PPE. Five centers used surgical mask and the rest used N95 mask. Six centers used goggles or face shield. Five centers selected isolation gowns and the rest selected protective suits. The change frequency of these PPE was 4 h. Sterilizing measures were improved in six centers. Five centers utilized ultraviolet and six centers strengthened natural ventilation. Four and six centers used peracetic acid during the period of shutdown and return to work, alone or matched with OPA or acidified water. CONCLUSIONS: Many effective control measures were conducted in GIE centers during the outbreak, including patients' volume limitation, preoperative COVID-19 screening, advanced PPE and disinfection methods.
Assuntos
COVID-19/prevenção & controle , Endoscopia Gastrointestinal , Controle de Infecções/normas , COVID-19/epidemiologia , China/epidemiologia , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
Longitudinal spin-lattice relaxation (T1) and transverse spin-spin relaxation (T2) reveal valuable information for studying molecular dynamics in NMR applications. Accurate relaxation measurements from conventional 1D proton spectra are generally subject to challenges of spectral congestion caused by J coupling splittings and spectral line broadenings due to magnetic field inhomogeneity. Here, we present an NMR relaxation method based on real-time pure shift techniques to overcome these two challenges and achieve accurate measurements of T1 and T2 relaxation times from complex samples that contain crowded NMR resonances even under inhomogeneous magnetic fields. Both theoretical analyses and detailed experiments are performed to demonstrate the effectiveness and ability of the proposed method for accurate relaxation measurements on complex samples and its practicability to non-ideal magnetic field conditions.