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1.
J Am Chem Soc ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637290

RESUMO

Reducing CO2 into fuels via photochemical reactions relies on highly efficient photocatalytic systems. Herein, we report a new and efficient photocatalytic system for CO2 reduction. Driven by electrostatic attraction, an anionic metal-organic framework Cu-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) as host and a cationic photosensitizer [Ru(phen)3]2+ (phen = 1,10-phenanthroline) as guest were self-assembled into a photocatalytic system Ru@Cu-HHTP, which showed high activity for photocatalytic CO2 reduction under laboratory light source (CO production rate of 130(5) mmol g-1 h-1, selectivity of 92.9%) or natural sunlight (CO production rate of 69.5 mmol g-1 h-1, selectivity of 91.3%), representing the remarkable photocatalytic CO2 reduction performance. More importantly, the photosensitizer [Ru(phen)3]2+ in Ru@Cu-HHTP is only about 1/500 in quantity reported in the literature. Theoretical calculations and control experiments suggested that the assembly of the catalysts and photosensitizers via electrostatic attraction interactions can provide a better charge transfer efficiency, resulting in high performance for photocatalytic CO2 reduction.

2.
Pharmazie ; 76(8): 372-378, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34412736

RESUMO

Drug resistance caused by the extreme genetic variability of zhe hepatitis C virus has rendered effective combinations of drugs indispensable in the treatment of chronic hepatitis C (CHC). Herein, we developed a fixed-dose combination (FDC) treatment containing the NS5B inhibitor sofosbuvir (SOF) and the NS5A inhibitor fopitasvir (FOP). Then the dissolution behavior of FOP in FOP/SOF FDC was improved by co-micronizing FOP with lactose. The enhanced dissolution rate of FOP in the FDC was in good agreement with the behavior of the FOP singledrug tablet. In addition, pharmacokinetic studies showed that both FOP and SOF in the FDC exhibited similar characteristics (area under the curve, Cmax, Tmax, and T1/2) as those of tablets containing FOP or SOF alone. These results revealed that the FOP/SOF FDC represents a potential therapeutic option for the treatment of CHC.

3.
J Biomed Sci ; 28(1): 58, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34364371

RESUMO

Transposable elements (TEs) initially attracted attention because they comprise a major portion of the genomic sequences in plants and animals. TEs may jump around the genome and disrupt both coding genes as well as regulatory sequences to cause disease. Host cells have therefore evolved various epigenetic and functional RNA-mediated mechanisms to mitigate the disruption of genomic integrity by TEs. TE associated sequences therefore acquire the tendencies of attracting various epigenetic modifiers to induce epigenetic alterations that may spread to the neighboring genes. In addition to posting threats for (epi)genome integrity, emerging evidence suggested the physiological importance of endogenous TEs either as cis-acting control elements for controlling gene regulation or as TE-containing functional transcripts that modulate the transcriptome of the host cells. Recent advances in long-reads sequence analysis technologies, bioinformatics and genetic editing tools have enabled the profiling, precise annotation and functional characterization of TEs despite their challenging repetitive nature. The importance of specific TEs in preimplantation embryonic development, germ cell differentiation and meiosis, cell fate determination and in driving species specific differences in mammals will be discussed.

4.
Angew Chem Int Ed Engl ; 60(41): 22207-22211, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34396662

RESUMO

Peptidyl asparaginyl ligases (PALs) are powerful tools for peptide macrocyclization. Herein, we report that a derivative of Asn, namely Nγ -hydroxyasparagine or Asn(OH), is an unnatural P1 substrate of PALs. By Asn(OH)-mediated cyclization, we prepared cyclic peptides as new matrix metalloproteinase 2 (MMP2) inhibitors displaying the hydroxamic acid moiety of Asn(OH) as the key pharmacophore. The most potent cyclic peptide (Ki =2.8±0.5 nM) was built on the hyperstable tetracyclic scaffold of rhesus theta defensin-1. The Asn(OH) residue in the cyclized peptides can also be readily oxidized to Asp. By this approach, we synthesized several bioactive Asp-containing cyclic peptides (MCoTI-II, kB2, SFTI, and integrin-targeting RGD peptides) that are otherwise difficult targets for PAL-catalyzed cyclization owing to unfavorable kinetics of the P1-Asp substrates. This study demonstrates that substrate engineering is a useful strategy to expand the application of PAL ligation in the synthesis of therapeutic cyclic peptides.

5.
Sci Rep ; 11(1): 14636, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282208

RESUMO

Finding effective and objective biomarkers to inform the diagnosis of schizophrenia is of great importance yet remains challenging. Relatively little work has been conducted on multi-biological data for the diagnosis of schizophrenia. In this cross-sectional study, we extracted multiple features from three types of biological data, including gut microbiota data, blood data, and electroencephalogram data. Then, an integrated framework of machine learning consisting of five classifiers, three feature selection algorithms, and four cross validation methods was used to discriminate patients with schizophrenia from healthy controls. Our results show that the support vector machine classifier without feature selection using the input features of multi-biological data achieved the best performance, with an accuracy of 91.7% and an AUC of 96.5% (p < 0.05). These results indicate that multi-biological data showed better discriminative capacity for patients with schizophrenia than single biological data. The top 5% discriminative features selected from the optimal model include the gut microbiota features (Lactobacillus, Haemophilus, and Prevotella), the blood features (superoxide dismutase level, monocyte-lymphocyte ratio, and neutrophil count), and the electroencephalogram features (nodal local efficiency, nodal efficiency, and nodal shortest path length in the temporal and frontal-parietal brain areas). The proposed integrated framework may be helpful for understanding the pathophysiology of schizophrenia and developing biomarkers for schizophrenia using multi-biological data.

6.
Cardiovasc Res ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259869

RESUMO

AIMS: Interleukin (IL)-5 mediates the development of eosinophils (EOS) that are essential for tissue post-injury repair. It remains unknown whether IL-5 plays a role in heart repair after myocardial infarction (MI). This study aims to test whether IL-5-induced EOS population promotes the healing and repair process post-MI and to reveal the underlying mechanisms. METHOD AND RESULTS: MI was induced by permanent ligation of the left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot and real-time polymerase chain reaction revealed elevated expression of IL-5 in the heart at 5 days post-MI. Immunohistostaining indicated that IL-5 was secreted mainly from macrophages and type 2 innate lymphoid cells in the setting of experimental MI. External supply of recombinant mouse IL-5 (20 min, 1 day, and 2 days after MI surgery) reduced the infarct size and increased ejection fraction and angiogenesis in the border zone. A significant expansion of EOS was detected in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of EOS by TRFK5 pretreatment muted the beneficial effects of IL-5 in MI mice. Mechanistic studies demonstrated that IL-5 increased the accumulation of CD206+ macrophages in infarcted myocardium at 7 days post-MI. In vitro co-culture experiments showed that EOS shifted bone marrow-derived macrophage polarization towards the CD206+ phenotypes. This activity of EOS was abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses demonstrated that EOS promoted the macrophage downstream signal transducer and activator of transcription 6 (STAT6) phosphorylation. CONCLUSION: IL-5 facilitates the recovery of cardiac dysfunction post-MI by promoting EOS accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. TRANSLATIONAL PERSPECTIVE: Accumulating evidence suggests that modulation of innate and adaptive immune responses is a promising therapeutic strategy for myocardial infarction. In this study, we demonstrate that IL-5 exerts cardioprotective effects on infarcted myocardium by promoting eosinophil accumulation and subsequent CD206+ macrophage polarization via the IL-4/STAT6 axis. Hence, regulation of cardiac IL-5 level or eosinophil count may become a therapeutic approach for post-myocardial infarction cardiac repair in humans.

7.
Analyst ; 146(15): 4775-4780, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34231558

RESUMO

Cholesterol is an essential compound for human health, and a high or low concentration of cholesterol is closely related to various diseases. Thus, developing a simple method for POCT of cholesterol has great significance in clinical diagnosis. In this work, alginate (Alg) hydrogels with glow-type chemiluminescence (CL) were prepared and applied for rapid and quantitative cholesterol detection via a smartphone. The glow-type CL hydrogels (HRP/COD/luminol/Alg hydrogels) contained luminol as a chemiluminescent reagent, horseradish peroxidase (HRP) and cholesterol oxidase (COD) for enzymatic cascade reactions. The HRP/COD/luminol/Alg hydrogels exhibited outstanding stability, which effectively avoided the enzyme inactivation during long-term storage. Furthermore, the HRP/COD/luminol/Alg hydrogels exhibited longer and more stable glow-type CL. With the help of COD catalytic specificity for cholesterol and bi-enzymatic cascade reactions, the glow-type CL hydrogels realized the specific and sensitive detection of cholesterol. The smartphone was used as a detector instead of a special large instrument for responding to the glow-type CL emission, and a LOD of 7.2 µM was obtained. Therefore, the proposed sensor expands the application of the glow-type CL in POCT and provides an alternative way for cholesterol detection in clinical diagnosis.


Assuntos
Colesterol/análise , Hidrogéis , Testes Imediatos , Peroxidase do Rábano Silvestre , Humanos , Medições Luminescentes , Luminol
8.
Analyst ; 146(16): 5074-5080, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34318784

RESUMO

Diabetes mellitus has received much attention because its complications include liver, kidney, eye, heart and cerebrovascular diseases. Thus, it would be highly significant to develop a rapid and efficient method for glucose detection in biological samples. In this work, a point-of-care testing (POCT) method of glucose detection was proposed using a standard colorimetric card for semi-quantitative determination patterns. In the prepared fluorescence color card for glucose, a good linear relationship was acquired by plotting the ratio of the grayscale value (I/I0) versus the logarithm of glucose concentration within 100.0 to 1000.0 µmol L-1, and the LOD of glucose detection was 1.1 µmol L-1. A large number of actual samples (30 serum and 7 urine) were analyzed and the results demonstrated that this method had good potential to be applied in the primary screening of diabetic patients. In addition, this method is universal and can be applied in the simultaneous detection of multiple small molecules. It provides a new strategy for the primary screening of multiple diseases simultaneously, which presents excellent application potential.


Assuntos
Diabetes Mellitus , Testes Imediatos , Colorimetria , Diabetes Mellitus/diagnóstico , Glucose , Humanos , Sistemas Automatizados de Assistência Junto ao Leito
9.
Food Funct ; 12(12): 5524-5538, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34002173

RESUMO

Given the increasing global trend toward unhealthy lifestyles and dietary decisions, such as "over-consumption of alcohol, and high sugar and fat diets" (ACHSFDs), it is not surprising that metabolic hypertension (MH) is now the most common type of hypertension. There is an urgent, global need for effective measures for the prevention and treatment of MH. Improper diet leads to decreased short-chain fatty acid (SCFA) production in the gut, leading to decreased gastrointestinal function, metabolism, and blood pressure as a result of signaling through G-protein-coupled receptors (GPCRs), ultimately causing MH. Previous studies have suggested that Dendrobium officinale (DO) may improve gastrointestinal function, lower blood pressure, and regulate metabolic abnormalities, but it is not clear whether it acts on MH by increasing SCFA and, if so, how. In this research, it was observed that Dendrobium officinale ultrafine powder (DOFP) could lower blood pressure and improve lipid abnormalities in ACHSFD-induced MH model rats. Moreover, DOFP was found to improve the intestinal flora and increased the SCFA level in feces and serum, as well as increased the expressions of GPCR43/41 and eNOS and the nitric oxide (NO) level. An experiment on isolated aorta rings revealed that DOFP improved the vascular endothelial relaxation function in MH rats, and this effect could be blocked by the eNOS inhibitor l-NAME. These experimental results suggest that DOFP improved the intestinal flora and increased the production, transportation, and utilization of SCFA, activated the intestinal-vascular axis SCFA-GPCR43/41 pathway, improved vascular endothelial function, and finally lowered blood pressure in MH model rats. This research provides a new focus for the mechanism of the effect of DOFP against MH by triggering the enteric-origin SCFA-GPCR43/41 pathway.

10.
Clin Biochem ; 93: 50-58, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33861985

RESUMO

OBJECTIVE: C1q has been shown to be associated with coronary heart disease (CAD) and can co-deposit with C-reactive protein (CRP) in atherosclerotic plaques. However, few studies have been conducted between C1q, CRP parameters and CAD. The aim of this study is to explore the relationship between C1q and CRP parameters and assess their clinical significance in CAD. METHODS: 238 total patients who underwent coronary artery angiography were enrolled and divided into control group (n = 65), stable CAD group (n = 47) and unstable angina group (UA group, n = 126). Patients' data were collected from self-administered questionnaires and electrical medical records. The severity of coronary stenosis was presented by Gensini score. The relationship between C1q, CRP parameters and CAD were evaluated by multivariate regression analysis and their predicting performance were assessed by ROC analysis and odds ratio analysis. RESULTS: Compared with control group, C1q was showed significantly lower in stable CAD (P = 0.004) and UA groups (P = 0.008), while hsCRP was higher in UA group (P = 0.024). Serum C1q was weakly positively associated with hsCRP (r = 0.24, P < 0.001) but not correlated with Gensini score. Logistic regression identified C1q (OR: 0.87 per 10 mg/L, 95% CI: 0.79-0.95, P = 0.001) and hsCRP (OR: 1.08 mg/L, 95% CI: 1.01-1.15, P = 0.032) as independent determinants of CAD. Furthermore, combined C1q and hsCRP level showed higher discriminatory accuracy in predicting CAD than C1q (AUC: 0.676 vs 0.585, P = 0.101; NRI: 10.4%, P = 0.049; IDI: 3.9%, P < 0.001) or hsCRP (AUC: 0.676 vs 0.585, P = 0.101; NRI: 16.7%, P = 0.006; IDI: 5.8%, P < 0.001). CONCLUSIONS: Reduced serum C1q and increased hsCRP are independently associated with CAD and could be potential predictors for CAD diagnosis. Furthermore, combined C1q and hsCRP showed better performance in predicting CAD than using single one.


Assuntos
Proteína C-Reativa/metabolismo , Complemento C1q/metabolismo , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Idoso , Angina Instável/diagnóstico , Angina Instável/metabolismo , Biomarcadores/sangue , Angiografia Coronária , Estenose Coronária/diagnóstico , Estenose Coronária/metabolismo , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas
11.
J Dairy Sci ; 104(6): 6415-6430, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33741171

RESUMO

Depression is a prevalent, stress-related mental disorder that can lead to serious psychiatric diseases with morbidity and high mortality. Although some functional fermented dairy drinks have promising anxiolytic and antidepressant effects, the mechanism is still not clear. To determine the antidepressant-like effect and the potential molecule mechanism of kefir peptides (KP), various behavioral tests, including the elevated plus maze test, open field test, forced swimming test, and tail suspension test, were used. Administration of 150 mg/kg KP in mice reduced the duration of immobility in the forced swimming test and tail suspension test, elevated the time spent in the open arm and center zone in the elevated plus maze test, and increased the total distance traveled, average speed, and time spent in the center zone in the open field test compared with the mock group. These results indicated that KP dramatically ameliorated the depression-like behaviors. Kefir peptides were further isolated and identified using high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry, from which 3 peptides were identified and designated KFP-1, KFP-3, and KFP-5. Among these peptides, administration of KFP-3 (15 AA residues) remarkably decreased immobility time in the forced swimming test and increased mobility time in the tail suspension test. Therefore, KFP-3 may be the major active peptide with antidepressant activity in KP. Overexpression of brain-derived neurotrophic factor, phosphorylated tropomyosin receptor kinase B, and phosphorylated ERK1/2 protein levels could be detected in the hippocampus under KP administration. Therefore, we suggest that KP improves depressive-like behaviors by activating the brain-derived neurotrophic factor-phosphorylated tropomyosin receptor kinase B signaling pathway. Kefir peptides may serve as a new type of antidepressant dairy product and may provide potent antidepressant effects for clinical use.


Assuntos
Kefir , Doenças dos Roedores , Animais , Antidepressivos , Fator Neurotrófico Derivado do Encéfalo , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Glicoproteínas de Membrana , Camundongos , Peptídeos , Proteínas Tirosina Quinases , Estresse Psicológico
12.
Infect Dis Poverty ; 10(1): 32, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33736710

RESUMO

BACKGROUND: World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis (DR-TB) should develop and implement a system for active pharmacovigilance that allows for detection, reporting and management of adverse events. The aim of the study is to evaluate the frequency and severity of adverse events (AEs) of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant (MDR)/extensively drug-resistant (XDR)-TB based on active drug safety monitoring (aDSM) system of New Drug Introduction and Protection Program (NDIP). METHODS: AEs were prospectively collected with demographic, bacteriological, radiological and clinical data from 54 sites throughout China at patient enrollment and during treatment between February, 2018 and December, 2019. This is an interim analysis including patients who are still on treatment and those that have completed treatment. A descriptive analysis was performed on the patients evaluated in the cohort. RESULTS: By December 31, 2019, a total of 1162 patients received bedaquiline-containing anti-TB treatment. Overall, 1563 AEs were reported, 66.9% were classified as minor (Grade 1-2) and 33.1% as serious (Grade 3-5). The median duration of bedaquiline treatment was 167.0 [interquartile range (IQR): 75-169] days. 86 (7.4%) patients received 36-week prolonged treatment with bedaquiline. The incidence of AEs and serious AEs was 47.1% and 7.8%, respectively. The most frequently reported AEs were QT prolongation (24.7%) and hepatotoxicity (16.4%). There were 14 (1.2%) AEs leading to death. Out of patients with available corrected QT interval by Fridericia's formula (QTcF) data, 3.1% (32/1044) experienced a post-baseline QTcF ≥ 500 ms, and 15.7% (132/839) had at least one change of QTcF ≥ 60 ms from baseline. 49 (4.2%) patients had QT prolonged AEs leading to bedaquiline withdrawal. One hundred and ninety patients reported 361 AEs with hepatotoxicity ranking the second with high occurrence. Thirty-four patients reported 43 AEs of hepatic injury referred to bedaquiline, much lower than that referred to protionamide, pyrazinamide and para-aminosalicylic acid individually. CONCLUSIONS: Bedaquiline was generally well-tolerated with few safety concerns in this clinical patient population without any new safety signal identified. The mortality rate was generally low. These data inform significant positive effect to support the WHO recent recommendations for the wide use of bedaquiline.


Assuntos
Antituberculosos/efeitos adversos , Antituberculosos/uso terapêutico , Diarilquinolinas/efeitos adversos , Diarilquinolinas/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , Antituberculosos/administração & dosagem , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segurança
13.
Aging (Albany NY) ; 13(7): 9732-9747, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33744860

RESUMO

We analyzed the effects of ginsenoside Rb1 on hyperlipidemic in model mice. Using stool, plasma and hepatic tissue samples, we observed that the genera Blautia and Allobaculum were increased and Turicibacter was decrease in Rb1-treated mice as compared to untreated model mice. Ether lipid metabolism, glycerolipid metabolism, and glyoxylate and dicarboxylate metabolism were differentially enriched between the Rb1 and model groups. Lipidomics revealed 169 metabolites differentially expressed between the model and Rb1 groups in a positive ion model and 58 in a negative ion model. These metabolites mainly participate in glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism. The main metabolites enriched in these three pathways were phosphatidylcholine, diacylglycerol and ceramide, respectively. In a transcriptome analysis, 766 transcripts were differentially expressed between the Rb1 and model groups. KEGG analysis revealed lysine degradation, inositol phosphate metabolism, and glycerophospholipid metabolism to be the main enriched pathways. Multiomics analysis revealed glycerophospholipid metabolism to be a common pathway and phosphatidylcholine the main metabolite differentially enriched between the Rb1 and model groups. Results from fecal transplanted germ-free mice suggest that to suppress hyperlipidemia, Rb1 regulates gut microbiota by regulating the synthesis and decomposition of phosphatidylcholine in glycerophospholipid metabolism, which in turn decreases serum total cholesterol.


Assuntos
Ginsenosídeos/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Ginsenosídeos/farmacologia , Hiperlipidemias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Proteômica
14.
JAMA Oncol ; 7(4): 525-533, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33630025

RESUMO

Importance: Use of next-generation sequencing (NGS) to identify clinically actionable genomic targets has been incorporated into routine clinical practice in the management of advanced solid tumors; however, the clinical utility of this testing remains uncertain. Objective: To determine which patients derived the greatest degree of clinical benefit from NGS profiling. Design, Setting, and Participants: Patients in this cohort study underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA (whole-exome or targeted-exome capture with analysis of 1700 genes) and tumor transcriptome (RNA) sequencing. Somatic and germline genomic alterations were annotated and classified according to degree of clinical actionability. Results were returned to treating oncologists. Data were collected from May 1, 2011, to February 28, 2018, and analyzed from May 1, 2011, to April 30, 2020. Main Outcomes and Measures: Patients' subsequent therapy and treatment response were extracted from the medical record to determine clinical benefit rate from NGS-directed therapy at 6 months and exceptional responses lasting 12 months or longer. Results: During the study period, NGS was attempted on tumors from 1138 patients and was successful in 1015 (89.2%) (MET1000 cohort) (538 men [53.0%]; mean [SD] age, 57.7 [13.3] years). Potentially clinically actionable genomic alterations were discovered in 817 patients (80.5%). Of these, 132 patients (16.2%) received sequencing-directed therapy, and 49 had clinical benefit (37.1%). Exceptional responses were observed in 26 patients (19.7% of treated patients). Pathogenic germline variants (PGVs) were identified in 160 patients (15.8% of cohort), including 49 PGVs (4.8% of cohort) with therapeutic relevance. For 55 patients with carcinoma of unknown primary origin, NGS identified the primary site in 28 (50.9%), and sequencing-directed therapy in 13 patients resulted in clinical benefit in 7 instances (53.8%), including 5 exceptional responses. Conclusions and Relevance: The high rate of therapeutically relevant PGVs identified across diverse cancer types supports a recommendation for directed germline testing in all patients with advanced cancer. The high frequency of therapeutically relevant somatic and germline findings in patients with carcinoma of unknown primary origin and other rare cancers supports the use of comprehensive NGS profiling as a component of standard of care for these disease entities.

15.
Neuroscience ; 460: 1-12, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588002

RESUMO

Emerging evidence suggests that the coupling relating the structural connectivity (SC) of the brain to its functional connectivity (FC) exhibits remarkable changes during development, normal aging, and diseases. Although altered structural-functional connectivity couplings (SC-FC couplings) have been previously reported in schizophrenia patients, the alterations in SC-FC couplings of different illness stages of schizophrenia (SZ) remain largely unknown. In this study, we collected structural and resting-state functional MRI data from 73 normal controls (NCs), 61 first-episode (FeSZ) and 78 chronic (CSZ) schizophrenia patients. Positive and negative syndrome scale (PANSS) scores were assessed for all patients. Structural and functional brain networks were constructed using gray matter volume (GMV) and resting-state magnetic resonance imaging (rs-fMRI) time series measurements. At the connectivity level, the CSZ patients showed significantly increased SC-FC coupling strength compared with the FeSZ patients. At the node strength level, significant decreased SC-FC coupling strength was observed in the FeSZ patients compared to that of the NCs, and the coupling strength was positively correlated with negative PANSS scores. These results demonstrated divergent alterations of SC-FC couplings in FeSZ and CSZ patients. Our findings provide new insight into the neuropathological mechanisms underlying the developmental course of SZ.


Assuntos
Esquizofrenia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem
16.
Chemosphere ; 271: 129520, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33445021

RESUMO

Monochlorobenzene (MCB), a solvent and synthetic intermediate, has been widely detected in groundwater at industrial contaminated sites. Cysteine (Cys) enhanced Fe2+/persulfate (Fe2+/Cys/PS) process with high degradation efficiency of organic pollutants has the potential for in-situ chemical oxidation of MCB. In this study, we systematically explored the impacts of common anions (CO32-, HCO3-, SO42-, NO3-, NO2-, PO43-, HPO42-, H2PO4-, Cl-, Br-), cations (NH4+, Mg2+, Al3+, Mn2+, Cu2+) and natural organic matter (NOM) on the degradation kinetics of MCB by the novel Fe2+/Cys/PS process and evaluated the ecotoxicity. The results showed that the removal of MCB in absence of matrices was enhanced by Cys due to its reduction and complexation ability. All of the anions inhibited the MCB degradation through the scavenging of SO4•- and HO•, though the inhibition degree of SO42-and NO3- was slight. Cations such as NH4+, Mg2+ and Al3+ hardly interfered with the reaction. Low concentrations of Cu2+ and NOM promoted the MCB oxidation, but the promotion strength weakened and turned into inhibition with the increased concentration of Cu2+ and NOM. The toxicity assessment of the transformation products (TPs) in the presence of Cl- and Br- based on the quantitative structure-activity relationships model showed the potentially higher toxicity of some TPs than their parent MCB. These results indicate that groundwater matrices may interfere with the MCB oxidation process. To accurately evaluate the effects of groundwater matrices on Fe2+/Cys/PS process for MCB oxidation and its potential toxicity, the field tests should be carried out in the future.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Clorobenzenos , Cisteína , Ferro , Cinética , Oxirredução , Sulfatos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
17.
J Psychopharmacol ; 35(2): 159-167, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32720857

RESUMO

BACKGROUND: Ketamine produces significant rapid-onset and robust antidepressant effects in patients with major depressive disorder. However, this drug also has transient cardiovascular stimulatory effects, and there are limited data about potential predictors of these cardiovascular effects. METHODS: A total of 135 patients with unipolar and bipolar depression received a total of 741 ketamine infusions (0.5 mg/kg over 40 min). Blood pressure and pulse were monitored every 10 min during the infusions and 30 min after the infusions. Depressive, psychotomimetic and dissociative symptom severity was assessed at baseline and 4 hours after each infusion. RESULTS: The maximum blood pressure and pulse values were observed at 30-40 min during infusions. The largest mean systolic/diastolic blood pressure increases were 7.4/6.0 mmHg, and the largest mean pulse increase was 1.9 beats per min. No significant change in blood pressure and pulse was found in the second to sixth infusions compared with the first infusion. Patients who were older (age⩾50 years), hypertensive and receiving infusions while exhibiting dissociative symptoms showed greater maximal changes in systolic and diastolic blood pressure than patients who were younger (age<50 years), normotensive and without dissociative symptoms (all p < 0.05). Hypertensive patients had less elevation of pulse than normotensive patients (p < 0.05). Ketamine dosage was positively correlated with changes in systolic and diastolic blood pressure (all p < 0.05). CONCLUSIONS: Blood pressure and pulse elevations following subanaesthetic ketamine infusions are transient and do not cause serious cardiovascular events. Older age, hypertension, large ketamine dosage and dissociative symptoms may predict increased ketamine-induced cardiovascular effects.

18.
Psychiatr Q ; 92(1): 311-320, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32661940

RESUMO

Nonconvulsive electrotherapy (NET) defined as electrical brain stimulation administered like standard electroconvulsive therapy (ECT), but below seizure threshold, could be effective for patients with treatment-refractory depression (TRD) with fewer adverse neurocognitive outcomes. However, there is a lack of studies in Chinese patients with TRD. Thus, this study was conducted to examine the efficacy and safety of adjunctive NET for Chinese patients with TRD. Twenty TRD patients were enrolled and underwent six NET treatments. Depressive symptoms, response, and remission were assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 1, 3, and 6 NET treatments. Neurocognitive function was assessed by the Wisconsin Card Sorting Test (WCST) at baseline and after the completion of six NET treatments. Mean HAMD-17 scores declined significantly from 26.2 to 10.4 (p < 0.001) after post-NET. The rates of response and remission were 60.0% (95% CI: 36.5-83.5) and 10.0% (95% CI: 0-24.4), respectively. Neurocognitive performance improved following a course of NET. No significant association was found between changes in depressive symptoms and baseline neurocognitive function. Adjunctive NET appeared to be effective for patients with TRD, without adverse neurocognitive effects. Randomized controlled studies were warranted to confirm these findings.

19.
Cardiovasc Drugs Ther ; 35(3): 599-612, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32495070

RESUMO

PURPOSE: Hypothyroidism (HT) is associated with accelerated atherosclerosis (AS). The efficacy of traditional strategies of hypothyroid AS remains controversial. Here, we aimed to deepen the understanding of the HT-induced acceleration of AS, to decrease the residual risk of coronary artery disease (CAD) and to find a new therapeutic target. METHODS: We collected peripheral venous blood samples from 20 patients and divided them into 4 groups, namely, the normal group, the HT group, the CAD group and the HT + CAD group. Then we performed mRNA microarray analysis and bioinformatics analysis to screen the differentially expressed genes and pathways, and we also conducted validations on ApoE knockout mice models and Raw264.7 cell models. RESULTS: In short, (1) in the analysis between the CAD group and the HT + CAD group, we found a total of 1218 differentially expressed genes, 11 upregulated pathways and 40 downregulated pathways. (2) We validated that patients with HT and CAD had a significantly decreased expression of MAP3K7 (encoding transforming growth factor-ß-activated kinase 1, TAK1) gene than normal subjects. (3) In animal and cell experiments, we found the decreased expression of TAK1 and the reduced phosphorylation of AMP-activated protein kinase (AMPK) under the hypothyroid and atherosclerotic condition. (4) Changes in the expressions of TAK1 may affect the progression of AS. CONCLUSION: Taken together, these data suggest that the accelerated AS in hypothyroid patients may be due to the suppression of TAK1-AMPK pathway in macrophages. This new finding may become a novel therapeutic target in hypothyroid AS.

20.
Hu Li Za Zhi ; 67(6): 61-69, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33274427

RESUMO

BACKGROUND: The author of this paper works in the critical care ward of an internal medicine department. During the study period, current trainees in a nurse post graduate year (NPGY) program joined our nurse team. While at our ward, they were required to demonstrate clinical nursing competencies in intensive care units in the facets of nursing knowledge, equipment use, prediction of emergencies, emergency response, and patient evaluation and management. The ability to interpret arrhythmias is critical to connecting and coordinating these competencies. However, arrhythmia interpretation is usually the most difficult skill for nurses to master. PURPOSE: This study was developed to improve the knowledge of NPGY trainees regarding arrhythmia interpretation, the accuracy of their arrhythmia interpretation and management, and their confidence in caring for patients with arrhythmia. RESOLUTION: The period of this study spanned from April 5th to June 18th, 2018. After surveying the current capabilities of the NPGY trainees to provide a reference for improvement, several teaching strategies were adopted. These strategies included: (1) provision of arrhythmia clinical scenarios; (2) establishment of multimedia teaching and interactive e-books; (3) development of memory strategies; and (4) mind mapping. RESULTS: The accuracy of the trainees' knowledge regarding arrhythmia interpretation increased from 52.5% pretest to 92.5% posttest, while their arrhythmia interpretation skill improved from 56.3% pretest to 92.5% posttest. Furthermore, their caring-for-patients-with-arrhythmia confidence score increased from 5.5 to 9.1. All of the objectives of this study were achieved. CONCLUSIONS: The diverse teaching approach employed in this study enhanced the ability of trainees to remember and recall relevant theories as well as improved their related practical skills. Furthermore, posttest, the trainees were significantly less nervous during encounters with patients with arrhythmia and demonstrated improved problem-solving abilities. Participation in this intervention significantly improved the confidence of trainees to serve as critical care nurses and to pursue a career in critical care nursing.


Assuntos
Arritmias Cardíacas/enfermagem , Competência Clínica , Estudantes de Enfermagem/psicologia , Educação em Enfermagem , Humanos , Medicina Interna , Conhecimento , Leitura
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