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Herein, we describe a [2+1] annulation reaction of di/trifluorodiazoethane with (alkylidene)malononitriles. This protocol offers a streamlined synthesis of a wide range of stereospecific and densely functionalized difluoromethyl and trifluoromethyl cyclopropane-1,1-dicarbonitriles. Further functional group interconversions or skeletal elaborations afford structurally distinct cyclopropyl variants.
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BACKGROUND: The contribution of bronchoalveolar lavage fluid (BALF) microbiota and mycobiota to silicosis has recently been noticed. However, many confounding factors can influence the accuracy of BALF microbiota and mycobiota studies, resulting in inconsistencies in the published results. In this cross-sectional study, we systematically investigated the effects of "sampling in different rounds of BALF" on its microbiota and mycobiota. We further explored the relationship between silicosis fatigue and the microbiota and mycobiota. METHODS: After obtaining approval from the ethics board, we collected 100 BALF samples from 10 patients with silicosis. Demographic data, clinical information, and blood test results were also collected from each patient. The characteristics of the microbiota and mycobiota were defined using next-generation sequencing. However, no non-silicosis referent group was examined, which was a major limitation of this study. RESULTS: Our analysis indicated that subsampling from different rounds of BALF did not affect the alpha- and beta-diversities of microbial and fungal communities when the centrifuged BALF sediment was sufficient for DNA extraction. In contrast, fatigue status significantly influenced the beta-diversity of microbes and fungi (Principal Coordinates Analysis, P = 0.001; P = 0.002). The abundance of Vibrio alone could distinguish silicosis patients with fatigue from those without fatigue (area under the curve = 0.938, 95% confidence interval [CI] 0.870-1.000). Significant correlations were found between Vibrio and haemoglobin levels (P < 0.001, ρ = -0.64). CONCLUSIONS: Sampling in different rounds of BALF showed minimal effect on BALF microbial and fungal diversities; the first round of BALF collection was recommended for microbial and fungal analyses for convenience. In addition, Vibrio may be a potential biomarker for silicosis fatigue screening.
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Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia. However, given its inherent complexity, few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive. Here, we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors, including anesthesia with surgery (AS), systemic inflammation, and neurotransmission modulation. We found that both bacterial lipopolysaccharide (LPS) and cholinergic receptor antagonist scopolamine (Scop) induction reduced neuronal activities in the delirium-related brain network, with the latter presenting a similar pattern of reduction as found in delirium patients. Consistently, Scop injection resulted in reversible cognitive impairment with hyperactive behavior. No loss of cholinergic neurons was found with treatment, but hippocampal synaptic functions were affected. These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.
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Encefalopatias , Disfunção Cognitiva , Delírio , Animais , Camundongos , Escopolamina/toxicidade , Encefalopatias/veterinária , Encéfalo , Disfunção Cognitiva/induzido quimicamente , Delírio/induzido quimicamenteRESUMO
Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post-translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro-environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl-vWA domain-carrying proteins including integrin ß3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll-like receptor (TLR) family member TLR4 or TLR2 activation. TLR-activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)-mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3-K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle-like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation.
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Neoplasias Pulmonares , Sirtuína 2 , Humanos , Sirtuína 2/genética , Sirtuína 2/metabolismo , Receptor 2 Toll-Like/metabolismo , Processamento de Proteína Pós-Traducional , Acetilação , Microambiente TumoralRESUMO
The new genus and species Pulvinatusiaxuegulaensis (Brassicaceae) are described and illustrated. The species is a cushion plant collected from Xuegu La, Xizang, China. Its vegetative parts are most similar to those of Arenariabryophylla (Caryophyllaceae) co-occurring in the same region, while its leaves and fruits closely resemble those of Xerodrabapatagonica (Brassicaceae) from Patagonian Argentina and Chile. Family-level phylogenetic analyses based on both nuclear ITS and plastome revealed that it is a member of the tribe Crucihimalayeae, but the infra-/intergeneric relationships within the tribe are yet to be resolved.
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BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.
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Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Acute kidney injury (AKI) is a life-threatening complication characterized by rapid decline in renal function, which frequently occurs after transplantation surgery. However, the molecular mechanism underlying the development of post-transplant (post-Tx) AKI still remains unknown. An increasing number of studies have demonstrated that certain microRNAs (miRNAs) exert crucial functions in AKI. The present study sought to elucidate the molecular mechanisms in post-Tx AKI by constructing a regulatory miRNA-mRNA network. RESULTS: Based on two datasets (GSE53771 and GSE53769), three key modules, which contained 55 mRNAs, 76 mRNAs, and 151 miRNAs, were identified by performing weighted gene co-expression network analysis (WGCNA). The miRDIP v4.1 was applied to predict the interactions of key module mRNAs and miRNAs, and the miRNA-mRNA pairs with confidence of more than 0.2 were selected to construct a regulatory miRNA-mRNA network by Cytoscape. The miRNA-mRNA network consisted of 82 nodes (48 mRNAs and 34 miRNAs) and 125 edges. Two miRNAs (miR-203a-3p and miR-205-5p) and ERBB4 with higher node degrees compared with other nodes might play a central role in post-Tx AKI. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that this network was mainly involved in kidney-/renal-related functions and PI3K-Akt/HIF-1/Ras/MAPK signaling pathways. CONCLUSION: We constructed a regulatory miRNA-mRNA network to provide novel insights into post-Tx AKI development, which might help discover new biomarkers or therapeutic drugs for enhancing the ability for early prediction and intervention and decreasing mortality rate of AKI after transplantation.
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Injúria Renal Aguda , MicroRNAs , Injúria Renal Aguda/genética , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética , RNA Mensageiro/genéticaRESUMO
A diethylzinc-promoted unconventional annulation reaction of 2,2,2-trifluorodiazoethane with 2H-azirines is described. This transformation involves two [3 + 2] cycloaddition steps and one dinitrogen extrusion process in one pot, thus giving a broad array of 3-trifluoromethyl pyrazolines in good yields with excellent diastereoselectivities. Further transformations provide facile access to 3-trifluoromethyl pyrazoles and 3,5-ditrifluoromethyl pyridazines with good efficiency.
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Knowledge about the impact of altitude and ethnicity on human oral microbiota is currently limited. To obtain the baseline of normal salivary microbiota, we analyzed the bacteria and fungi composition in Tibetan (HY group) and Han population (CD group) living at different altitudes by using next-generation sequencing (NGS) technology combined with PICRUSt and FUNGuild analyses. There were significant differences in oral microbiota composition between the two groups at phylum and genus levels. At the phylum level, the HY group had higher relative abundances of Firmicutes and Ascomycota, whereas the Bacteroidetes and Basidiomycota in the CD group were richer. These changes at the phylum level reflected different dominant genus compositions. Compared with the Han population, Candida, Fusarium, Zopfiella, Streptococcus, Veillonella and Rothia in Tibetan were higher. Surprisingly, the Zopfiella was found almost exclusively in the Tibetan. The PICRUSt and FUNGuild analysis also indicated that the function of the bacterial and fungal communities was altered between the two groups. In conclusion, our results suggest that there are significant differences in oral microbial structure and metabolic characteristics and trophic modes among Tibetan and Han population living at different altitudes. We first established the oral microbiota framework and represented a critical step for determining the diversity of oral microbiota in the Tibetan and Han population.
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Microbiota , Micobioma , Altitude , Bactérias/genética , Fungos/genética , Humanos , Microbiota/genética , TibetRESUMO
BACKGROUND: Since the outbreak of COVID-19, it has been documented that old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, it is unknown whether sarcopenia, a common geriatric syndrome, is associated with poor prognosis among older COVID-19 patients. The aim of our prospective cohort study is to investigate the association between sarcopenia risk and severe disease among COVID-19 patients aged ≥60 years. METHOD: A prospective cohort study of 114 hospitalized older patients (≥60 years) with confirmed COVID-19 pneumonia between 7 February, 2020 and 6 April, 2020. Epidemiological, socio-demographic, clinical and laboratory data on admission and outcome data were extracted from electronic medical records. All patients were assessed for sarcopenia on admission using the SARC-F scale and the outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards model to identify the association between sarcopenia and progression of disease defined as severe cases in a total of 2908 person-days. RESULT: Of 114 patients (mean age 69.52 ± 7.25 years, 50% woman), 38 (33%) had a high risk of sarcopenia while 76 (67%) did not. We found that 43 (38%) patients progressed to severe cases. COVID-19 patients with higher risk sarcopenia were more likely to develop severe disease than those without (68% versus 22%, p < 0.001). After adjustment for demographic and clinical factors, higher risk sarcopenia was associated with a higher hazard of severe condition [hazard ratio = 2.87 (95% CI, 1.33-6.16)]. CONCLUSION: We found that COVID-19 patients with higher sarcopenia risk were more likely to develop severe condition. A clinician-friendly assessment of sarcopenia could help in early warning of older patients at high-risk with severe COVID-19 pneumonia.
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COVID-19 , Sarcopenia , Idoso , Feminino , Avaliação Geriátrica , Humanos , Modelos de Riscos Proporcionais , Estudos Prospectivos , SARS-CoV-2 , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs. PURPOSE: To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method. METHODS: The chemical profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle analysis under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical analysis on the chemical composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, respectively. RESULTS: Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical analysis uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/ml differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/ml (IC50) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration. The spectrum-effect relationship analysis revealed that 44 compounds were positively correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen positively correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, ß-elemene and ß-caryophyllene. CONCLUSION: Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs.
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Antineoplásicos Fitogênicos/farmacologia , Biomarcadores/análise , Curcuma/química , Medicamentos de Ervas Chinesas/química , Células A549 , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Biomarcadores/química , Medicamentos de Ervas Chinesas/farmacologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Óleos Voláteis/química , Sesquiterpenos Policíclicos/análise , Sesquiterpenos Policíclicos/farmacologia , Controle de Qualidade , Rizoma/química , Sesquiterpenos/análise , Sesquiterpenos/farmacologiaRESUMO
OBJECTIVE: To identify the associations between sleep quality, sleep duration and nutritional status in older adults. METHODS: Data from a total of 6792 community-dwellings adults aged 50 and over from the baseline of the West China Health and Aging Trend (WCHAT) study were analyzed. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). PSQI scores >5 were categorized as poor sleep quality. Duration of sleep was classified as <6â¯h, 6-7â¯h, 7-8â¯h, 8-9â¯h and ≥9â¯h. The Mini Nutritional Assessment Short Form (MNA-SF) was used to assess nutritional status and a score <12 was identified as indicating a risk of malnutrition. Logistic regression models were used to explore the associations. RESULTS: Of 6792 participants (mean age 62.4⯱â¯8.3 years, 62.5 % women), 1831 (27.0 %) were at risk of malnutrition. The prevalence of poor sleep quality was 47.1 %. In the logistic regression model adjusted for potential confounders, poor sleep quality was significantly associated with a risk of malnutrition (ORâ¯=â¯1.62, 95 %CIâ¯=â¯1.44, 1.82). Sleep durations of less than 6â¯h and of more than 9â¯h were shown to increase the odds of malnutrition risk (ORâ¯=â¯1.42, 95 %CIâ¯=â¯1.16, 1.73 and ORâ¯=â¯1.24, 95 %CIâ¯=â¯1.05, 1.47, respectively). CONCLUSIONS: Sleep disorders were significantly associated with malnutrition risk among older adults. Our results highlight the importance of good sleep quality and enough sleep in order to maintain good nutritional status in older adults.
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Desnutrição/epidemiologia , Estado Nutricional , Transtornos do Sono-Vigília/epidemiologia , Sono , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Increased evidence suggests chronic inflammation is significant in the progression of sarcopenia in older adults. In this study, we aimed to compare the level of systemic inflammation markers (White blood cells, neutrophils, lymphocytes, platelets and their derived ratios) between sarcopenic and non-sarcopenic individuals and investigate the association of these inflammatory markers with sarcopenia. METHODS: This cross-sectional study included 4224 adults (1514 men and 2710 women) from the West China Health and Aging Trend (WCHAT) study. Sarcopenia was defined according to the recommended diagnostic algorithm of the Asia Working Group for Sarcopenia (AWGS). The value of systemic inflammatory markers was based on laboratory data. Multiple logistic regression analysis was used to explore the association between inflammatory markers and sarcopenia after adjusting for covariates. RESULTS: Among 4224 participants (mean age 62.3⯱â¯8.2 years, 64.2 % women), 814 (19.3 %) were diagnosed as sarcopenia. After adjusting for potential confounders, logistic regression analysis indicated that neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII) were significantly associated with sarcopenia. Participants in the highest NLR, PLR and SII value group had higher odds for sarcopenia than those in the lowest value group (OR [95 %CI]: 1.233 [1.002,1.517], 1.455 [1.177,1.799] and 1.268 [1.029,1.561], respectively). CONCLUSIONS: Higher NLR, PLR, and SII level are associated with an increased prevalence of sarcopenia in middle-aged and older adults. Since these systemic inflammatory markers are inexpensive and can be obtained easily from routine blood tests, regular follow-up of NLR, PLR and SII may be an effective strategy in sarcopenia screening and management.
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Sarcopenia , Idoso , Envelhecimento , Plaquetas , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Estudos Retrospectivos , Sarcopenia/diagnóstico , Sarcopenia/epidemiologiaRESUMO
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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Quimioprevenção/métodos , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Adulto , Betacoronavirus , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Alta do Paciente/normas , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Guias de Prática Clínica como Assunto , SARS-CoV-2RESUMO
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients
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Humanos , Adulto , Plasma/imunologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Cloroquina/uso terapêutico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Quimioprevenção/métodos , Receptores de Interleucina-6/uso terapêutico , Antirretrovirais/uso terapêutico , Pandemias/prevenção & controle , Lopinavir/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Hidroxicloroquina/uso terapêutico , Prática Clínica Baseada em Evidências/métodosRESUMO
Objective: To investigate whether the increased expression of thioredoxin interacting protein (TXNIP) in diabetes affects the senescence of islet ß cells. Methods: Six normal mice (db/m) and six diabetic mice (db/db) were randomly selected. Fasting blood glucose was measured by blood sugar meter, the expression levels of TXNIP protein, p16, p21 and Rb in pancreatic tissues were detected by Western blot, senescence-associated beta-galactosidase activity in pancreatic tissue was determined by immunochemical staining. INS-1 islet beta cells were randomly divided into 7 groups (n=6), and transfected with lentiviruses (30 µl) for 4 to 6 hours, then was screened with puromycin (PM, 3 µg/m) for 7 days to construct normal group, scramble ShRNA group (interference with airborne poison group), TXNIP-ShRNA-1 group (TXNIP silence group-1), TXNIP-ShRNA-2 group (TXNIP silence group 2), TXNIP-ShRNA-3 group (TXNIP silence group 3), Ad-GFP group (overexpression of the air virus group), Ad-TXNIP-GFP group (TXNIP overexpression group) stably transferred INS-1 islet beta cell line. TXNIP protein expression was detected by Western blot, aging-related beta-galactosidase activity was detected by immunochemical staining, the changes of expression of p16, p21 and Rb was determined by Western blot. Results: Compared with normal mice, the fasting blood glucose of db/db group was increased significantly (Pï¼0. 01), the expression of TXNIP protein was increased significantly in pancreatic tissues(Pï¼0. 05), positive staining rate of ß- galactosidase was increased significantly in pancreatic tissues, p16/p21/Rb protein expression levels were increased significantly (Pï¼0. 05). Compared with Ad-GFP group, the positive staining rate of ß- galactosidase in Ad-TXNIP-GFP group was increased significantly, p16/p21/Rb protein expression levels were increased significantly (Pï¼0. 01). Compared to the scramble ShRNA group, the positive staining rate of ß- galactosidase in TXNIP-ShRNA group was decreased, p16/p21/Rb protein expression levels were decreased significantly (Pï¼0. 05). Conclusion: Diabetes can induce islet ß-cell senescence by up-regulating TXNIP expression.
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Proteínas de Transporte/metabolismo , Senescência Celular , Diabetes Mellitus Experimental , Ilhotas Pancreáticas/citologia , Tiorredoxinas/metabolismo , Animais , Proteínas de Transporte/genética , CamundongosRESUMO
Importance: Postoperative delirium (POD) is a common condition for older adults, contributing to their functional decline. Objective: To investigate the effectiveness of the Tailored, Family-Involved Hospital Elder Life Program (t-HELP) for preventing POD and functional decline in older patients after a noncardiac surgical procedure. Design, Setting, and Participants: A 2-arm, parallel-group, single-blind, cluster randomized clinical trial was conducted from August 24, 2015, to February 28, 2016, on 6 surgical floors (gastric, colorectal, pancreatic, biliary, thoracic, and thyroid) of West China Hospital in Chengdu, China. Eligible participants (n = 281) admitted to each of the 6 surgical floors were randomized into a nursing unit providing t-HELP (intervention group) or a nursing unit providing usual care (control group). All randomized patients were included in the intention-to-treat analyses for the primary outcome of POD incidence. Statistical analysis was performed from April 3, 2016, to December 30, 2017. Interventions: In addition to receiving usual care, all participants in the intervention group received the t-HELP protocols, which addressed each patient's risk factor profile. Besides nursing professionals, family members and paid caregivers were involved in the delivery of many of the program interventions. Main Outcomes and Measures: The primary outcome was the incidence of POD, evaluated with the Confusion Assessment Method. Secondary outcomes included the pattern of functional and cognitive changes (activities of daily living [ADLs], instrumental activities of daily living [IADLs], Short Portable Mental Status Questionnaire [SPMSQ]) from hospital admission to 30 days after discharge, and the length of hospital stay (LOS). Results: Of the 475 patients screened for eligibility, 281 (171 [60.9%] male, mean [SD] age 74.7 [5.2] years) were enrolled and randomized to receive t-HELP (n = 152) or usual care (n = 129). Postoperative delirium occurred in 4 participants (2.6%) in the intervention group and in 25 (19.4%) in the control group, with a relative risk of 0.14 (95% CI, 0.05-0.38). The number needed to treat to prevent 1 case of POD was 5.9 (95% CI, 4.2-11.1). Participants in the intervention group compared with the control group showed less decline in physical function (median [interquartile range] for ADLs: -5 [-10 to 0] vs -20 [-30 to -10]; P < .001; for IADLs: -2 [-2 to 0] vs -4 [-4 to -2]; P < .001) and cognitive function (for the SPMSQ level: 1 [0.8%] vs 8 [7.0%]; P = .009) at discharge, as well as shorter mean (SD) LOS (12.15 [3.78] days vs 16.41 [4.69] days; P < .001). Conclusions and Relevance: The findings suggest that t-HELP, with family involvement at its core, is effective in reducing POD for older patients, maintaining or improving their physical and cognitive functions, and shortening the LOS. The results of this t-HELP trial may improve generalizability and increase the implementation of this program. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-POR-15006944.
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Atividades Cotidianas , Cognição/fisiologia , Delírio/epidemiologia , Hospitalização/tendências , Hospitais/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Idoso , China/epidemiologia , Delírio/etiologia , Feminino , Humanos , Incidência , Masculino , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Método Simples-CegoRESUMO
Metal-organic framework is an extended coordination compound with repeating coordination entities and voids, which shows potential applications in gas storage, separation, catalysis, and etc. This work reports the synthesis of a new functional metal-organic framework of pyromellitic acid and europium, and its application in fluorescence sensing of doxycycline, a broad-spectrum polyketide antibiotic on the basis of fluorescence turn-on method. The metal-organic framework was initially non-fluorescent, however, with the addition of doxycycline, the system exhibited significant fluorescence enhancement at 526â¯nm and 617â¯nm, where both fluorescence intensities showed good linear correlations with the doxycycline concentration, suggesting the possibility for direct two-channel detection without any sensitization materials such as metal particles or surface-modified quantum dots. More interestingly, the unique fluorescence response of the system could discriminate doxycycline from other tetracycline antibiotics with high selectivity, and a limit of detection (LOD) was estimated to be 47â¯nM. It has been further demonstrated that the material has been successfully applied as sensing materials for selective determination of doxycycline in real samples of fish and urine.
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The use of anion redox reactions is gaining interest for increasing rechargeable capacities in alkaline ion batteries. Although anion redox coupling of S2- and (S2)2- through dimerization of S-S in sulfides have been studied and reported, an anion redox process through electron hole formation has not been investigated to the best of our knowledge. Here, we report an O3-NaCr2/3Ti1/3S2 cathode that delivers a high reversible capacity of ~186 mAh g-1 (0.95 Na) based on the cation and anion redox process. Various charge compensation mechanisms of the sulfur anionic redox process in layered NaCr2/3Ti1/3S2, which occur through the formation of disulfide-like species, the precipitation of elemental sulfur, S-S dimerization, and especially through the formation of electron holes, are investigated. Direct structural evidence for formation of electron holes and (S2)n- species with shortened S-S distances is obtained. These results provide valuable information for the development of materials based on the anionic redox reaction.
RESUMO
OBJECTIVE: To determine the prevalence of sarcopenia in community-dwelling elderly populations in Chengdu and its associated risk factors. METHODS: A total of 947 community dwelling residents aged ≥60 yr. in Chengdu participated in this study. Their appendicular skeletal muscle mass was measured through bioelectrical impedance analyses. Sarcopenia was defined using the diagnostic algorithm recommended by the Asia Working Group (AWGS) for Sarcopenia. Data in relation to the demographic characteristics, chronic diseases and life style of the participants were obtained through a questionnaire survey, which included the 15-item geriatric depression scale (GDS-15) and the mini nutritional assessment (MNA). RESULTS: Overall, 10.5% of the elderly participants were identified with sarcopenia: 8.4% in men and 12.5% in women. The prevalence of sarcopenia increased with age: 2.3% in the 60-64 yr., 5.6% in the 65-74 yr., 19.7% in the ≥75 yr.. Age [odds ratio (OR)=1.109, 95% confldence interval (CI):1.054-1.168], smoking (OR=3.482, 95%CI:1.356-8.938) and Malnorishment (OR=5.598, 95%CI:2.677-11.709) are significant predictors of sarcopenia after adjustment for potential confounders. CONCLUSION: Approximately 10% community-dwelling elderly in Chengdu have sarcopenis. Age, smoking, malnutrition are risk factors of sarcopenia.