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1.
Front Aging Neurosci ; 14: 829573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35462699

RESUMO

Neuronal ceroid lipofuscinosis (NCL) is composed of a group of inherited neurodegenerative diseases, with the hallmark of lipofuscin deposit (a mixture of lipids and proteins with metal materials) inside the lysosomal lumen, which typically emits auto-fluorescence. Adult-onset NCL (ANCL) has been reported to be associated with a mutation in the DNAJC5 gene, including L115R, L116Δ, and the recently identified C124_C133dup mutation. In this study, we reported a novel C128Y mutation in a young Chinese female with ANCL, and this novel mutation caused abnormal palmitoylation and triggered lipofuscin deposits.

2.
Pest Manag Sci ; 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35318795

RESUMO

BACKGROUND: Unmanned aerial vehicles (UAVs) are widely used to improve the efficiency of pesticide applications. Low-volume spraying operations require more efficient deposition of droplets on the target surface. Therefore, pesticide deposition and retention on plant surfaces is a serious challenge for modern precision agriculture. Tank-mix adjuvants have been used to improve spray dilutions performance; however, their effects on the physicochemical properties of spray dilutions, dosage delivery, and pesticide dosage are unclear. RESULTS: Tank-mix adjuvant 8860 significantly improved the physicochemical properties of spray dilutions, inhibited spray droplets rebound, improved the wetting and spreading performance of spray dilutions on wheat leaves, and increased the effective deposition of tebuconazole on wheat leaves. Even when its dosage was reduced by one-third, the spray solution still showed excellent disease control and effective deposition of the active ingredient on wheat leaves. CONCLUSION: The use of appropriate tank-mix adjuvants in UAV-based plant protection for wheat can significantly improve the performance of spray dilutions, increase the efficiency of pesticide dosage delivery, and improve disease control. These adjuvants can also help reduce the pesticide use while ensuring their effectiveness. © 2022 Society of Chemical Industry.

3.
Fish Shellfish Immunol ; 123: 496-505, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35331883

RESUMO

To elucidate the antibacterial role of peroxinectin (referred to as PXN) and its molecular mechanism in Chinese mitten crab Eriocheir sinensis, we analyzed the bacterial binding and removal of the peroxinectin recombinant protein in vitro and the interaction of peroxinectin with integrin and CuZn-SOD through GST-pulldown and bimolecular fluorescence complementation methods. Concurrently, the effect of peroxinectin interference on the expression of other immune-related genes was studied using RNA interference. The results showed that the recombinant peroxinectin protein could bind to Bacillus subtilis, Staphylococcus aureus, Aeromonas hydrophila, and Vibrio parahaemolyticus with different affinities in vitro and could eliminate Vibrio parahaemolyticus in vivo. The findings also indicated that peroxinectin could establish interactions with integrin and CuZn-SOD in vitro. Furthermore, 48 h after the injection of the peroxinectin gene siRNA in vivo, the expression of peroxinectin mRNA decreased significantly (P < 0.05), integrin mRNA expression decreased by 16.8%, and CuZn-SOD mRNA expression decreased by 62.84% (P < 0.01). The expression levels of Dorsal, GPx, GST, PPAF, and Relish (P < 0.01), as well as that of lectin (P < 0.001) were significantly decreased. When peroxinectin siRNA was injected in vivo for 48 h and Aeromonas hydrophila was injected into mitten crabs, the expression of immune-related genes significantly increased. All data indicate that the recombinant peroxinectin protein in Chinese mitten crabs can recognize and bind different bacteria and promote the elimination of Vibrio parahaemolyticus from the body. Furthermore, peroxinectin may establish interactions with integrin and CuZn-SOD to activate the expression of related immune genes to elicit responses to bacterial infections and achieve immune protection.


Assuntos
Braquiúros , Vibrio parahaemolyticus , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Antibacterianos/farmacologia , China , Hemócitos , Imunidade , Imunidade Inata/genética , Integrinas/metabolismo , Lipopolissacarídeos/farmacologia , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Superóxido Dismutase/metabolismo
4.
Cell ; 185(4): 630-640.e10, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35093192

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here, we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryoelectron microscopy structures of the omicron RBD-hACE2 complex as well as the crystal structure of the delta RBD-hACE2 complex. We found that, unlike alpha, beta, and gamma, omicron RBD binds to hACE2 at a similar affinity to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of omicron RBD-hACE2 and delta RBD-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.


Assuntos
Enzima de Conversão de Angiotensina 2/química , Receptores Virais/química , SARS-CoV-2/química , Sequência de Aminoácidos , Microscopia Crioeletrônica , Humanos , Modelos Moleculares , Mutação/genética , Filogenia , Ligação Proteica , Domínios Proteicos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/ultraestrutura , Eletricidade Estática , Homologia Estrutural de Proteína
5.
Chin J Integr Med ; 28(1): 20-27, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33837482

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (, panaxadiol saponins component, PNDC) in combination with the cyclosporine and androgen for patients with chronic aplastic anemia (CAA). METHODS: A total of 79 CAA patients was randomly divided into 2 groups by a random number table, including PCA group [43 cases, orally PNDC 320 mg/d plus cyclosporine 5 mg/(kg·d) plus andriol 80 mg/d] and CA group [36 cases, orally cyclosporine 5 mg/(kg·d) plus andriol 160 mg/d]. All patients were treated and followed-up for 6 treatment courses over 24 weeks. The complete blood counts, score of Chinese medical (CM) symptoms were assessed and urine routine, electrocardiogram, hepatic and renal function were observed for safety evaluation. Female masculinization rating scale was established according to the actual clinical manifestations to evaluate the accurate degree of masculinization in female CAA patients treated by andriol. RESULTS: The effective rates were 88.1% (37/42) in the PCA group and 77.8% (28/36) in the CA group based on the standard for the therapeutic efficacy evaluation of hematopathy. There was no significant difference in the white blood cell (WBC) counts, platelet counts and hemoglobin concentration of peripheral blood between two groups after 6 months treatment. The masculinization score of female patient in the PCA group was significantly lower than the CA group (P<0.05). The mild abdominal distention was observed in 1 cases in the PCA group. In CA group, the abnormalities in the hepatic function developed in 2 cases and the renal disfunction was found in 1 case. CONCLUSION: The PNDC possesses certain curative effects in the treatment of CAA without obvious side-effects and can partially replace andriol thereby to reduce the degree of masculinization [Registried at Chinese Clinical Trial Registry (ChicTR1900028153)].


Assuntos
Anemia Aplástica , Saponinas , Androgênios , Anemia Aplástica/tratamento farmacológico , China , Feminino , Humanos , Medicamentos sem Prescrição , Saponinas/uso terapêutico
6.
Front Oncol ; 11: 762653, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868978

RESUMO

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

7.
Research (Wash D C) ; 2021: 9854946, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34877539

RESUMO

Isostructural MOFs with similar crystallographic parameter are easily available for MOF-on-MOF growth and possible to form core-shell structure by isotropic growth. However, due to well-matched cell lattice, selective growth in isostructural MOF heterostructures remains a great challenge for engineering atypical MOF heterostructures. Herein, an anisotropic MOF-on-MOF growth strategy was developed to structure a range of multilayer sandwich-like ZIF-L heterostructures via stacking isostructural ZIF-L-Zn and ZIF-L-Co alternately with three-, five-, seven-, and more layer structures. Moreover, these heterostructures with highly designable feature were fantastic precursors for fabricating derivatives with tunable magnetic and catalytic properties. Such strategy explores a novel way of achieving anisotropic MOF-on-MOF growth between isostructural MOFs and opens up new horizons for regulating the properties by MOF modular assembly in versatile functional nanocomposites.

8.
Front Oncol ; 11: 741341, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722293

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of standard or low-dose chemotherapy followed by HLA-mismatched allogeneic T-cell infusion (allo-TLI) for the treatment of elderly patients with acute myeloid leukemia (AML) and patients with intermediate-2 to high-risk myelodysplastic syndrome (MDS). METHODS: We carried out a prospective, multicenter, single-arm clinical trial. Totally of 25 patients were enrolled, including 17 AML patients and 8 MDS patients. Each patient received four courses of non-ablative chemotherapy, with HLA-mismatched donor CD3+ allo-TLI 24 h after each course. AML patients received chemotherapy with decitabine, idarubicin, and cytarabine, and MDS patients received decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor. RESULTS: A total of 79 procedures were performed. The overall response rates of the AML and MDS patients were 94% and 75% and the 1-year overall survival rates were 88% (61-97%) and 60% (13-88%), respectively. The overall 60-day treatment-related mortality was 8%. Compared with a historical control cohort that received idarubicin plus cytarabine (3 + 7), the study group showed significantly better overall response (94% vs. 50%, P=0.002) and overall survival rates (the 1-year OS rate was 88% vs. 27%, P=0.014). Post-TLI cytokine-release syndrome (CRS) occurred after 79% of allo-TLI operations, and 96% of CRS reactions were grade 1. CONCLUSION: Elderly AML patients and intermediate-2 to high-risk MDS patients are usually insensitive to or cannot tolerate regular chemotherapies, and may not have the opportunity to undergo allogeneic stem cell transplantation. Our study showed that non-ablative chemotherapy followed by HLA-mismatched allo-TLI is safe and effective, and may thus be used as a first-line treatment for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.aspx?proj=20112.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34599699

RESUMO

PURPOSE: Previous reports demonstrated a bleeding avoidance potential of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and ß-blocker. It remains unclear whether early guideline-directed medical therapy [GDMT, i.e., the combined use of ß-blocker, angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) and statin] confers protection against bleeding in the setting of high-intensity antithrombotic therapy. METHODS: We assessed associations between the use of early (within the first 24 h) GDMT and in-hospital major bleeds, ischemic events and mortality among ST-elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. RESULTS: Among 34,538 STEMI patients without contra-indications to GDMT and eligible for analysis, 35.5% received early GDMT. In a 1-to-2 propensity-score matched cohort, compared with non-early GDMT, early GDMT was associated with a 25% reduction in major bleeds [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60-0.94], with parallel reductions in ischemic events (OR 0.60, 95%CI 0.45-0.78) and in-hospital mortality (OR 0.43, 95%CI 0.31-0.61). Early GDMT-associated reduction in major bleeds was generally consistently observed across different major bleeding definitions and in sensitivity analyses. Additionally, no significant interaction was observed in subgroup analyses. CONCLUSION: In a large nationwide registry, early initiation of GDMT was associated with reduced risk for in-hospital major bleeds in STEMI patients treated with PCI. To improve the outcome of STEMI, further effort should be made to reinforce the early use of GDMT in this patient population.

10.
Brain Sci ; 11(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34573225

RESUMO

Nocardia brain abscess is relatively rare, accounting for about 1-2% of all brain abscesses, and its mortality rate is three times higher than of other types of bacterial brain abscesses; thus, early diagnosis and treatment are essential. Nocardia brain abscess generally occurs in immunodeficient patients. We report a case of Nocardia farcinica brain abscess in a multiple myeloma patient treated with proteasome inhibitor (bortezomib and ixazomib), cyclophosphamide, and corticosteroid. The patient was treated with ceftriaxone and trimethoprim-sulfamethoxazole, together with drainage of the brain abscess. Regular brain MRI follow-ups showed that intracranial lesions were gradually absorbed and improved.

11.
PLoS One ; 16(8): e0256810, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34460843

RESUMO

BACKGROUND: To assess the efficacy and safety of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants. METHODS: We searched MEDLINE, EMBASE, and Cochrane database without any language restrictions. The last search was conducted in August 15, 2020. All randomized controlled trials comparing the use of restrictive versus liberal red blood cell transfusion thresholds in very low birth weight (VLBW) infants were selected. Pooled risk ratio (RR) for dichotomous variable with 95% confidence intervals were assessed by a random-effects model. The primary outcome was all-cause mortality. RESULTS: Overall, this meta-analysis included 6 randomized controlled trials comprising 3,483 participants. Restrictive transfusion does not increase the risk of all-cause mortality (RR, 0.99; 95% CI, 0.84 to 1.17; I2 = 0%; high-quality evidence), and does not increase the composite outcome of death or neurodevelopmental impairment (RR, 1.01, 95% CI, 0.93-1.09; I2 = 7%; high-quality evidence) or other serious adverse events. Results were similar in subgroup analyses of all-cause mortality by weight of infants, gestational age, male infants, and transfusion volume. CONCLUSIONS: In very low birth weight infants, a restrictive threshold for red blood cell transfusion was not associated with increased risk of all-cause mortality, in either short term or long term.


Assuntos
Transfusão de Eritrócitos , Recém-Nascido de muito Baixo Peso/sangue , Ensaios Clínicos como Assunto , Transfusão de Eritrócitos/mortalidade , Humanos , Recém-Nascido , Sistema Nervoso/crescimento & desenvolvimento , Avaliação de Resultados em Cuidados de Saúde , Publicações , Risco , Resultado do Tratamento
12.
Atmos Chem Phys ; 21(7): 5549-5573, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-34462630

RESUMO

Epidemiological studies have consistently linked exposure to PM2.5 with adverse health effects. The oxidative potential (OP) of aerosol particles has been widely suggested as a measure of their potential toxicity. Several acellular chemical assays are now readily employed to measure OP; however, uncertainty remains regarding the atmospheric conditions and specific chemical components of PM2.5 that drive OP. A limited number of studies have simultaneously utilised multiple OP assays with a wide range of concurrent measurements and investigated the seasonality of PM2.5 OP. In this work, filter samples were collected in winter 2016 and summer 2017 during the atmospheric pollution and human health in a Chinese megacity campaign (APHH-Beijing), and PM2.5 OP was analysed using four acellular methods: ascorbic acid (AA), dithiothreitol (DTT), 2,7-dichlorofluorescin/hydrogen peroxidase (DCFH) and electron paramagnetic resonance spectroscopy (EPR). Each assay reflects different oxidising properties of PM2.5, including particle-bound reactive oxygen species (DCFH), superoxide radical production (EPR) and catalytic redox chemistry (DTT/AA), and a combination of these four assays provided a detailed overall picture of the oxidising properties of PM2.5 at a central site in Beijing. Positive correlations of OP (normalised per volume of air) of all four assays with overall PM2.5 mass were observed, with stronger correlations in winter compared to summer. In contrast, when OP assay values were normalised for particle mass, days with higher PM2.5 mass concentrations (µgm-3) were found to have lower mass-normalised OP values as measured by AA and DTT. This finding supports that total PM2.5 mass concentrations alone may not always be the best indicator for particle toxicity. Univariate analysis of OP values and an extensive range of additional measurements, 107 in total, including PM2.5 composition, gas-phase composition and meteorological data, provided detailed insight into the chemical components and atmospheric processes that determine PM2.5 OP variability. Multivariate statistical analyses highlighted associations of OP assay responses with varying chemical components in PM2.5 for both mass- and volume-normalised data. AA and DTT assays were well predicted by a small set of measurements in multiple linear regression (MLR) models and indicated fossil fuel combustion, vehicle emissions and biogenic secondary organic aerosol (SOA) as influential particle sources in the assay response. Mass MLR models of OP associated with compositional source profiles predicted OP almost as well as volume MLR models, illustrating the influence of mass composition on both particle-level OP and total volume OP. Univariate and multivariate analysis showed that different assays cover different chemical spaces, and through comparison of mass- and volume-normalised data we demonstrate that mass-normalised OP provides a more nuanced picture of compositional drivers and sources of OP compared to volume-normalised analysis. This study constitutes one of the most extensive and comprehensive composition datasets currently available and provides a unique opportunity to explore chemical variations in PM2.5 and how they affect both PM2.5 OP and the concentrations of particle-bound reactive oxygen species.

13.
Stroke ; 52(10): e614-e617, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34281381

RESUMO

Background and Purpose: Chronic liver disease (CLD) is a risk factor for increased morbidity and mortality in acutely ill patients. For patients with aneurysmal subarachnoid hemorrhage (aSAH), the association between CLD and mortality remains unknown. Methods: In this retrospective cohort study, we analyzed consecutive aSAH patients admitted to the West China Hospital between 2009 and 2019. The primary outcome was in-hospital all-cause mortality. Results: This study included 6228 cases of aSAH, 489 (7.9%) of whom also had CLD. In a propensity-matched analysis, CLD was associated with increased mortality in patients with aSAH compared with non-CLD (odds ratio, 2.04 [95% CI, 1.43­2.92]). In aSAH patients with CLD, a high Model for End-Stage Liver Disease score was still associated with an increased odds of mortality. Conclusions: Among aSAH patients, CLD was associated with increased mortality compared with non-CLD. Among aSAH patients with CLD, a higher Model for End-Stage Liver Disease score was associated with an increased odds of mortality.


Assuntos
Hepatopatias/complicações , Hepatopatias/mortalidade , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/mortalidade , Adulto , Idoso , China/epidemiologia , Doença Crônica , Estudos de Coortes , Doença Hepática Terminal/complicações , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
J Am Chem Soc ; 143(29): 11141-11151, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34279908

RESUMO

Small-ring silacycles are important organosilane species in main-group chemistry and have found numerous applications in organic synthesis. 3-Silaazetidine, a unique small silacycle bearing silicon and nitrogen atoms, has not been adequately explored due to the lack of a general synthetic scheme and its sensitivity to air. Here, we describe that 3-silaazetidine can be easily prepared in situ from diverse air-stable precursors (RSO2NHCH2SiR12CH2Cl). 3-Silaazetidine shows excellent functional group tolerance in a palladium-catalyzed ring expansion reaction with terminal alkynes, giving 3-silatetrahydropyridines and diverse silaazacycle derivatives, which are promising ring frameworks for the discovery of Si-containing functional molecules.

15.
Cell ; 184(13): 3438-3451.e10, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34139177

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading worldwide, causing a global pandemic. Bat-origin RaTG13 is currently the most phylogenetically related virus. Here we obtained the complex structure of the RaTG13 receptor binding domain (RBD) with human ACE2 (hACE2) and evaluated binding of RaTG13 RBD to 24 additional ACE2 orthologs. By substituting residues in the RaTG13 RBD with their counterparts in the SARS-CoV-2 RBD, we found that residue 501, the major position found in variants of concern (VOCs) 501Y.V1/V2/V3, plays a key role in determining the potential host range of RaTG13. We also found that SARS-CoV-2 could induce strong cross-reactive antibodies to RaTG13 and identified a SARS-CoV-2 monoclonal antibody (mAb), CB6, that could cross-neutralize RaTG13 pseudovirus. These results elucidate the receptor binding and host adaption mechanisms of RaTG13 and emphasize the importance of continuous surveillance of coronaviruses (CoVs) carried by animal reservoirs to prevent another spillover of CoVs.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Sítios de Ligação/fisiologia , COVID-19/metabolismo , Quirópteros/virologia , SARS-CoV-2/patogenicidade , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , COVID-19/imunologia , Quirópteros/imunologia , Quirópteros/metabolismo , Especificidade de Hospedeiro/imunologia , Humanos , Filogenia , Ligação Proteica/fisiologia , Receptores Virais/metabolismo , SARS-CoV-2/imunologia , Alinhamento de Sequência
16.
Stroke ; 52(10): 3266-3275, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34167330

RESUMO

Background and Purpose: Systemic inflammation is recognized as a hallmark of stroke. We aimed to evaluate the prognostic value of various inflammatory factors using blood at admission in patients with aneurysmal subarachnoid hemorrhage. Methods: In a multicenter observational study of patients with aneurysmal subarachnoid hemorrhage, the counts of neutrophil, platelet, and lymphocyte were collected on admission. Patients were stratified based on neutrophil counts with propensity score matching to minimize confounding. We calculated the adjusted odds ratios with 95% CIs for the primary outcome of in-hospital mortality and hospital-acquired infections. Results: A total of 6041 patients were included in this study and 344(5.7%) of them died in hospital. Propensity score matching analyses indicated that compared with the lower neutrophil counts, higher neutrophil counts were associated with increased risk of in-hospital mortality (odds ratio, 1.53 [95% CI, 1.14­2.06]), hospital-acquired infections (odds ratio, 1.61 [95% CI, 1.38­1.79]), and delayed neurological ischemic deficits (odds ratio, 1.52 [95% CI, 1.09­1.97]). Moreover, out of all the inflammatory factors studied, neutrophil counts demonstrated the highest correlation with in-hospital mortality and hospital-acquired infections. Conclusions: Among patients with aneurysmal subarachnoid hemorrhage, high neutrophil counts at admission were associated with increased mortality and hospital-acquired infections. The neutrophil count is a simple, useful marker with prognostic value in patients with aneurysmal subarachnoid hemorrhage.


Assuntos
Contagem de Leucócitos , Neutrófilos , Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/mortalidade , Adulto , Idoso , Biomarcadores , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , AVC Isquêmico/epidemiologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
17.
J Clin Lab Anal ; 35(5): e23769, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33942367

RESUMO

OBJECTIVE: Denys-Drash syndrome (DDS) is defined by the triad of Wilms tumor, nephrotic syndrome, and/or ambiguous genitalia. Genetic testing may help identify new gene mutation sites and play an important role in clinical decision-making. METHODS: We present a patient with an XY karyotype and female appearance, nephropathy, and Wilms tumor in the right kidney. Genomic DNA was extracted from peripheral blood cells according to standard protocols. "Next-generation" sequencing (NGS) was performed to identify novel variants. The variant was analyzed with Mutation Taster, and its function was explored by a cell growth inhibition assay. RESULTS: We found the first case of Denys-Drash syndrome with the uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene. In silico analysis, the variant was predicted "disease-causing" by Mutation Taster. The mutated variant showed a weaker effect in inhibiting tumor cells than wild-type WT1. CONCLUSIONS: The uncommon missense mutation (c.1420C>T, p.His474 Tyr) in the WT1 gene may be a crucial marker in DDS.


Assuntos
/genética , Síndrome de Denys-Drash/genética , Proteínas WT1/genética , Tumor de Wilms/genética , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular Tumoral , China , Simulação por Computador , Feminino , Seguimentos , Humanos , Lactente , Laparoscopia , Mutação , Linhagem , Tomografia Computadorizada por Raios X , Proteínas WT1/química , Tumor de Wilms/diagnóstico , Tumor de Wilms/diagnóstico por imagem
18.
Int J Nurs Stud ; 118: 103924, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33774265

RESUMO

BACKGROUND: The role of conservative versus liberal oxygen therapy for acutely ill patients remains controversial. OBJECTIVE: To systematically review the available evidence regarding the efficacy and safety of conservative oxygen therapy compared with liberal oxygen therapy for acutely ill patients. METHODS: A systematic search of Medline, Embase, and the Cochrane Central Register was conducted from their inception until April 5, 2020. Randomized clinical trials evaluating a high-target (liberal) or a low-target (conservative) oxygenation strategy in adults with an acutely ill condition were eligible for inclusion. A meta-analysis using random-effects models was conducted to calculate the risk ratio with corresponding 95% confidence intervals. Heterogeneity and publication bias were evaluated. RESULTS: The analyses included 33 randomized clinical trials with a total of 17,780 participants. Compared with conservative oxygen therapy, liberal oxygen therapy was not associated with increased mortality at 30 days (risk ratio 1.09, 95% confidence intervals 0.98-1.22; I2=0%), at 90 days (risk ratio 1.00, 95% confidence intervals 0.88-1.13, I2=37%), or at the longest follow-up (risk ratio 1.04, 95% confidence intervals 0.96-1.12, I2=0%). Good functional outcome was similar between groups. Findings were robust to trial sequential, subgroup, and sensitivity analyses. CONCLUSIONS: Compared with liberal oxygen therapy, conservative oxygen therapy was not associated with decreased mortality. Tweetable abstract: Compared with liberal oxygen therapy, conservative oxygen therapy was not associated with decreased mortality.


Assuntos
Oxigenoterapia , Oxigênio , Adulto , Humanos
19.
Environ Sci Pollut Res Int ; 28(24): 31838-31849, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33616822

RESUMO

Investigations of ventilation in an immersed tunnel have recently drawn greater research attentions; however, analyses on the influence of vent design and tunnel width on ventilation performance have rarely been addressed. For the sake of the security of evacuees in an immersed tunnel fire, the influence of three vent designs and two immersed tunnel widths on mechanical ventilation performance during tunnel fires were numerically investigated using large eddy simulation. The pollutant gas flow characteristics in the tunnel after a fire were analyzed, and the pollutant gas exhaust efficiency based on the mass conservation of carbon monoxide in the smoke was proposed in this study. By comparing the smoke propagation, smoke distribution, and exhaust efficiency between three different vent designs, it was determined that the Top Vent Design has the best smoke exhaust effect, and the Sidewall Vent Design (with an activated vertical smoke screen) has a better smoke exhaust effect than the Sidewall Vent Design. The influences of the tunnel width and heat release rate of the fire on the ventilation effect were also investigated.


Assuntos
Incêndios , Ventilação , Monóxido de Carbono , Simulação por Computador , Emissões de Veículos
20.
Artigo em Inglês | MEDLINE | ID: mdl-33581340

RESUMO

As a novel post-translational modification (PTM), lysine 2-hydroxyisobutyrylation (Khib) was considered to regulate gene transcriptional activity in eukaryotic cells and yeast, but the function of Khib proteins in plants remains unknown. Here, we report that Khib is an evolutionarily-conserved PTM in wheat and its donators. Proteomic analysis shows that there are 3348 Khib lysine modification sites from 1074 proteins in common wheat (Triticum aestivum L.) using affinity purification and mass spectroscopy of 2-hydroxyisobutyrylome. Bioinformatic data indicates that Khib proteins participate in a wide variety of biological and metabolic pathways. Immunoprecipitation (IP) confirmed that Khib proteins have an in vivo origin. A comparison of Khib and other major PTMs shows that Khib proteins are simultaneously modified by multiple PTMs. Using mutagenesis experiments and Co-IP, we demonstrate that Khib on K206 is a key regulatory modification of phosphoglycerate kinase (PGK) enzymatic activity, and mutation of the Khib site affects protein interactions of PGK and its substrates. Furthermore, Khib production of low-molecular-weight proteins is a response to the deacetylase inhibitors nicotinamide and trichostatin. This study provides evidence that enhances our current understanding of Khib in wheat plants, including the cooperation between this PTM and its metabolic regulation.

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