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2.
J Craniofac Surg ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34739450

RESUMO

ABSTRACT: Emergence delirium is a common complication after sevoflurane-anesthesia and have a serious impact on children undergoing cleft palate surgery. The aim of this study was to compare the effect of propofol and dexmedetomidine on emergence delirium in children. Ninety children aged 8 to 24 months, underwent cleft palate repair, were enrolled in the study. Children were randomly assigned to 3 groups after the induction: Group C (intravenous infusion 0.9% saline), Group P (intravenous infusion 2 mg/kg/hour propofol), and Group D (intravenous infusion 0.5 µg/kg/hour dexmedetomidine). Emergence delirium was diagnosed using the pediatric anesthesia emergence delirium scale and pain using the face, legs, activity, cry, consolability scale. Heart rate, mean arterial pressure, respiratory recovery time, extubation time, post anesthesia care unit observation time, and adverse events were also evaluated. A total of 86 patients were analyzed. The incidence of emergence delirium was 20.1% in group D, 58.6% in group P and 85.7% in group C (P < 0.05). A lower face, legs, activity, cry, consolability score was seen in group D than in group P and group C (3.9 + 1.1 versus 6.1 ±â€Š0.9 and 7.1 ±â€Š1.0, P < 0.05). The value of heart rate and mean arterial pressure during emergence in group P and group C were significantly higher than that in group D (All P < 0.05). These findings suggest that dexmedetomidine as a sedative, analgesic, and sympatholytic agent was superior to propofol in reducing the incidence of emergence delirium in children undergoing cleft palates surgery with sevoflurane-based anesthesia.

3.
Front Microbiol ; 12: 721399, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759897

RESUMO

Dicer proteins are mainly responsible for generating small RNAs (sRNAs), which are involved in gene silencing in most eukaryotes. In previous research, two DCL proteins in Valsa mali, the pathogenic fungus causing apple tree Valsa canker, were found associated with both the pathogenicity and generation of sRNAs. In this study, the differential expression of small interfering RNAs (siRNAs) and miRNA-like RNAs (milRNAs) was analyzed based on the deep sequencing of the wild type and Vm-DCL2 mutant, respectively. Overall, the generation of 40 siRNAs and 18 milRNAs was evidently associated with Vm-DCL2. The target genes of milRNAs were then identified using degradome sequencing; according to the prediction results, most candidate targets are related to pathogenicity. Further, expression of Vm-PC-3p-92107_6 was confirmed in the wild type but not in the Vm-DCL2 mutant. Moreover, the pathogenicity of Vm-PC-3p-92107_6 deletion mutants (ΔVm-PC-3p-92107_6) and the over-expression transformants (Vm-PC-3p-92107_6-OE) was significantly increased and decreased, respectively. Based on those degradome results, vacuolar protein sorting 10 (Vm-VPS10) was identified as the target of Vm-PC-3p-92107_6. Co-expression analysis in tobacco leaves further confirmed that Vm-PC-3p-92107_6 could suppress the expression of Vm-VPS10. Meanwhile, the expression levels of Vm-PC-3p-92107_6 and Vm-VPS10 displayed divergent trends in ΔVm-PC-3p-92107_6 and Vm-PC-3p-92107_6-OE, respectively. Perhaps most importantly, ΔVm-VPS10 featured a significant reduction in pathogenicity. Taken together, our results indicate that a DCL2-dependent milRNA Vm-PC-3p-92107_6 plays roles in pathogenicity by regulating the expression of Vm-VPS10. This study lays a foundation for the comprehensive analysis of pathogenic mechanisms of V. mali and deepens our understanding of the generation and function of fungal sRNA.

4.
Drug Discov Today ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34767960

RESUMO

The prevalence of obesity is a major cause of many chronic metabolic disorders, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and cancer. Insulin resistance is often associated with metabolic unhealthy obesity (MUO). Therapeutic approaches aiming to improve insulin sensitivity are believed to be central for the prevention and treatment of MUO. However, current antiobesity drugs are reported as multitargeted and their insulin-sensitizing effects remain unclear. In this review, we discuss current understanding of the mechanisms of insulin resistance from the aspects of endocrine disturbance, inflammation, oxidative, and endoplasmic reticulum stress (ERS). We then summarize the antiobesity drugs, focusing on their effects on insulin sensitivity. Finally, we discuss strategies for obesity treatment.

5.
Sci Rep ; 11(1): 22236, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782634

RESUMO

Carotid atherosclerosis (CAS) is a risk factor for cardiovascular and cerebrovascular events, but duplex ultrasonography isn't recommended in routine screening for asymptomatic populations according to medical guidelines. We aim to develop machine learning models to screen CAS in asymptomatic adults. A total of 2732 asymptomatic subjects for routine physical examination in our hospital were included in the study. We developed machine learning models to classify subjects with or without CAS using decision tree, random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM) and multilayer perceptron (MLP) with 17 candidate features. The performance of models was assessed on the testing dataset. The model using MLP achieved the highest accuracy (0.748), positive predictive value (0.743), F1 score (0.742), area under receiver operating characteristic curve (AUC) (0.766) and Kappa score (0.445) among all classifiers. It's followed by models using XGBoost and SVM. In conclusion, the model using MLP is the best one to screen CAS in asymptomatic adults based on the results from routine physical examination, followed by using XGBoost and SVM. Those models may provide an effective and applicable method for physician and primary care doctors to screen asymptomatic CAS without risk factors in general population, and improve risk predictions and preventions of cardiovascular and cerebrovascular events in asymptomatic adults.

6.
Pain Physician ; 24(8): 495-506, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34793634

RESUMO

BACKGROUND: Chronic musculoskeletal pain (CMP) management is a major global public health goal owing to increased social and economic burdens. However, the risk of CMP in smokers compared with nonsmokers remains uncertain. OBJECTIVES: This study aims to determine the magnitude and importance of the relationship between cigarette smoking and risk of CMP. STUDY DESIGN: A meta-analysis of the CMP risk of cigarette smokers. METHODS: We systematically searched PubMed, Embase, and Cochrane library databases from inception to August 2020. Data extraction and quality assessment were performed by 2 independent reviewers using a standardized extraction checklist. Data were pooled using a random-effects model. RESULTS: In this meta-analysis of 32 studies involving 296,109 participants, current smoking was associated with increased CMP risk (OR: 1.23, 95% CI: 1.09-1.40), whereas ever and past smoking did not show such an association (OR: 1.14, 95% CI: 0.95-1.37; OR: 1.06, 95% CI: 0.83-1.35, respectively). Stratified analyses showed that there was a marked significance in almost all strata of current smokers compared with non-smokers, except for mean age (>= 50 years), location of pain (neck pain, sacral pain, and knee pain), smoking frequency (occasionally), study design (cross-sectional), mean follow-up (< 10 years), and adjustment for confounding factors (>= 6). Interestingly, there was statistically negative association between cigarette smoking and knee pain risk in current smokers, ever smokers, and past smokers. LIMITATIONS: The major limitation of this meta-analysis relates to the heterogeneities across included studies. CONCLUSIONS: Cigarette smoking was associated with increased risk of CMP. In view of the high prevalence of smoking in many countries and the increasing number of CMP patients worldwide, reducing tobacco use should be an important public health strategy to prevent and control the global epidemic of CMP. Future research should attempt to establish whether this association is causal and clarify its mechanisms.

7.
Growth Horm IGF Res ; 62: 101441, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34847522

RESUMO

OBJECTIVE: An intrauterine device (IUD) is one of the most effective reversible contraceptive methods currently available. Women who use IUDs may become pregnant, albeit rarely, and many such women continue to use IUDs. Because it is difficult to remove or it may cause miscarriage. This study measured the changes in human leucocyte antigen-G (HLA-G) and insulin-like growth factor II (IGF-II) levels in the decidua and villi to explore the effect of a copper IUD on embryonic development. DESIGN: A total of 54 samples of decidual and villus tissue were collected from pregnant women with IUDs (27 samples) or without IUDs (27 samples). Hematoxylin-eosin staining was used to identify morphological characteristics. Immunohistochemistry was used to detect HLA-G and IGF-II; the protein expression levels were measured via Western blotting. RESULTS: HLA-G was expressed on the membranes of trophoblasts of villus tissues and the glandular epithelium, and in stromal cells of decidual tissues, in both the IUD and control groups. IGF-II was expressed in the glandular epithelium and cytoplasm of trophoblasts and decidual cells in both groups. Compared to the control group, IGF-II expression was significantly reduced in villus tissues of the IUD group (p < 0.05). The mean sac diameter was significantly positively correlated with IGF-II expression in the villi (p < 0.05). CONCLUSIONS: A copper IUD may affect embryonic development by regulating the expression of villus IGF-II.

8.
Mol Biomed ; 2(1): 11, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34806028

RESUMO

Regulatory T cells (Tregs) are essential in the maintenance of immunity, and they are also a key to immune suppressive microenvironment in solid tumors. Many studies have revealed the biology of Tregs in various human pathologies. Here we review recent understandings of the immunophenotypes and suppressive functions of Tregs in melanoma, including Treg recruitment and expansion in a tumor. Tregs are frequently accumulated in melanoma and the ratio of CD8+ T cells versus Tregs in the melanoma is predictive for patient survival. Hence, depletion of Tregs is a promising strategy for the enhancement of anti-melanoma immunity. Many recent studies are aimed to target Tregs in melanoma. Distinguishing Tregs from other immune cells and understanding the function of different subsets of Tregs may contribute to better therapeutic efficacy. Depletion of functional Tregs from the tumor microenvironment has been tested to induce clinically relevant immune responses against melanomas. However, the lack of Treg specific therapeutic antibodies or Treg specific depleting strategies is a big hurdle that is yet to be overcome. Additional studies to fine-tune currently available therapies and more agents that specifically and selectively target tumor infiltrating Tregs in melanoma are urgently needed.

9.
Environ Sci Technol ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34813313

RESUMO

Disinfection byproduct (DBP) exposure has been associated with birth size, pregnancy oxidative stress, and other adverse perinatal outcomes. However, little is known about the potential effect of prenatal DBP exposure on intrauterine growth. The present study included 1516 pregnant women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort who were measured for four blood trihalomethanes [i.e., chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and two urinary haloacetic acids [i.e., dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)] across pregnancy trimesters. Second- and third-trimester fetal ultrasound measures of the abdominal circumference (AC), head circumference, biparietal diameter, femur length, and estimated fetal weight and birth weight were converted into z-scores. After adjusting for potential confounders, linear mixed models showed a decreasing AC z-score across tertiles of blood brominated THM (Br-THMs, the sum of BDCM, DBCM, and TBM) and total THM (THM4, the sum of Br-THMs and TCM) concentrations (both p for trend <0.01). We also observed a decreasing AC z-score across categories of blood TBM during pregnancy trimesters (p for trend = 0.03). Urinary haloacetic acids were unrelated to fetal growth parameters. In summary, prenatal exposure to THMs, particularly during the first trimester, was associated with reduced fetal abdominal circumference.

10.
MedComm (Beijing) ; 2(1): 17-26, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34766134

RESUMO

Small extracellular vesicles (sEVs) are extracellular nanovesicles that contain bioactive proteins, lipids, RNA, and DNA. A variety of biological process is regulated with sEVs. sEVs are an intercellular messenger regulating recipient cell function and play a role in disease initiation and progression. sEVs derived from certain cells, such as mesenchymal stem cells and immune cells, have the potential for clinical therapy as they possess the characteristics of their parental cells. With better understanding of sEVs biogenesis, their transportation properties, extended circulatory capability, and exceptional biocompatibility, sEVs emerge as a potential therapeutic tool in the clinic. Here, we summarize applications of sEVs-based therapies in different diseases and current knowledge about the strategies in bioengineered sEVs, as well as the challenges for their use in clinical settings.

11.
Nat Sci Sleep ; 13: 1797-1806, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675727

RESUMO

Background: Existing evidence suggested that sleep duration may be involved in hypertension; however, the conclusions were still controversial. This study aimed to examine the association of longitudinal trajectory of sleep duration with hypertension and to explore the role of the inflammation in such associations. Methods: A total of 3178 subjects over 30 years of age without hypertension were enrolled in 2004, and they were followed until 2009. Self-reported sleep duration was recorded, and inflammation was measured by highly sensitive C reactive protein (hs-CRP). Log-binomial regression models were applied to examine the association of sleep duration trajectory and inflammation with the risk of hypertension. The mediating effect of elevated hs-CRP was examined by the bootstrap and the process software. Results: The prevalence of persistent short (≤7 hours/day), normal (8-9 hours/day), and long (>9 hours/day) sleep duration over 5 years were 9.1%, 37.7%, and 2.3%, respectively. The incidence of hypertension was 26.6% during the follow-up period. Compared with those who persistently slept 8-9 hours/day from baseline to follow-up, those who persistently slept ≤7 hours/day, persistently slept ≥10 hours/day, and those whose sleep duration changed have higher risks of hypertension by 1.375-fold (95% CI: 1.121, 1.686), 1.557-fold (95% CI: 1.171, 2.069) and 1.299-fold (95% CI: 1.135, 1.487), respectively. In addition, persistently slept ≤7 hours/day was found to be associated with higher risk of inflammation (RR: 1.285, 95% CI: 1.008, 1.638). The mediation analysis did not find significant mediating effect of elevated CRP on the association between sleep duration trajectory and hypertension. Conclusion: Experiencing both a short or long sleep duration, especially for a long time, could lead to higher risk of hypertension. Persistent exposure to short sleep duration was also associated with inflammation. However, the higher risk of hypertension caused by persistent short sleep duration does not seem to be directly mediated through inflammation.

12.
Front Plant Sci ; 12: 741342, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691119

RESUMO

To successfully colonize the plants, the pathogenic microbes secrete a mass of effector proteins which manipulate host immunity. Apple valsa canker is a destructive disease caused by the weakly parasitic fungus Valsa mali. A previous study indicated that the V. mali effector protein 1 (VmEP1) is an essential virulence factor. However, the pathogenic mechanism of VmEP1 in V. mali remains poorly understood. In this study, we found that the apple (Malus domestica) pathogenesis-related 10 proteins (MdPR10) are the virulence target of VmEP1 using a yeast two-hybrid screening. By bimolecular fluorescence (BiFC) and coimmunoprecipitation (Co-IP), we confirmed that the VmEP1 interacts with MdPR10 in vivo. Silencing of MdPR10 notably enhanced the V. mali infection, and overexpression of MdPR10 markedly reduced its infection, which corroborates its positive role in plant immunity against V. mali. Furthermore, we showed that the co-expression of VmEP1 with MdPR10 compromised the MdPR10-mediated resistance to V. mali. Taken together, our results revealed a mechanism by which a V. mali effector protein suppresses the host immune responses by interfering with the MdPR10-mediated resistance to V. mali during the infection.

13.
Stem Cells Int ; 2021: 9981589, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34707661

RESUMO

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by pulmonary microvascular endothelial barrier dysfunction. Mesenchymal stem cell-secreted hepatocyte growth factor (HGF) has positive effects of lipopolysaccharide- (LPS-) induced pulmonary endothelial barrier. Studies have exhibited the mammalian TORC1 (mTORC1) signaling is of potent angiogenesis effects. The mTOR protein kinase has two distinct multiprotein complexes mTORC1 and mTORC2 that regulate different branches of the mTOR network. However, detailed mTORC2 mechanisms of HGF protective effects remain poorly defined. Therefore, the aim of this study was to determine whether mTORC2 mediated protective effects of MSC-secreted HGF against LPS-induced pulmonary microvascular endothelial barrier dysfunction activated like mTORC1 activation. We introduced MSC-PMVEC coculture transwell system and recombinant murine HGF on LPS-induced endothelial cell barrier dysfunction in vitro and then explored potential mechanisms by lentivirus vector-mediated HGF, mTORC1 (raptor), and mTORC2 (rictor) gene knockdown modification. Endothelial paracellular and transcellular permeability, adherent junction protein (VE-Cadherin), cell proliferation, apoptosis, and mTOR-associated proteins were tested. These revealed that HGF could promote quick reestablishment of adherent junction VE-cadherin and decrease endothelial paracellular and transcellular permeability during LSP-induced endothelial dysfunction with the involvement of mTORC2 (rictor) and mTORC1 (raptor) pathways. Raptor and rictor knockdown in LPS-induced PMEVECs with stimulation of HGF increased apoptosis ratio, activated Cleaved-Caspase-3 expression, and downregulated cell proliferation. Moreover, mTORC2/Akt but not mTORC2/PKC had significance on HGF endothelial protective effects. Taken together, these highlight activation mTORC2 pathway could also contribute to vascular endothelial barrier recovery by MSC-secreted HGF in LPS stimulation.

14.
J Fungi (Basel) ; 7(10)2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34682251

RESUMO

Necrosis and ethylene-inducing peptide 1(Nep1)-like protein (NLP) is well known for its cytotoxicity and immunogenicity on dicotyledonous, and it has attracted large attention due to its gene expansion and functional diversification in numerous phytopathogens. Here, two NLP family proteins, VmNLP1 and VmNLP2, were identified in the pathogenic fungus Valsa mali. We showed that VmNLP2 but not VmNLP1 induced cell death when transiently expressed in Nicotiana benthamiana. VmNLP2 was also shown to induce cell death in apple leaves via the treatment of the Escherichia coli-produced recombinant protein. VmNLP1 and VmNLP2 transcripts were drastically induced at the early stage of V. mali infection, whereas only VmNLP2 was shown to be essential for pathogen virulence. We also found that VmNLP1 and VmNLP2 are required for maintaining the integrity of cell membranes, and they differentially contribute to V. mali tolerance to salt- and osmo-stresses. Notably, multiple sequence alignment revealed that the second histidine (H) among the conserved heptapeptide (GHRHDWE) of VmNLP2 is mutated to tyrosine (Y). When this tyrosine (Y) was substituted by histidine (H), the variant displayed enhanced cytotoxicity in N. benthamiana, as well as enhanced virulence on apple leaves, suggesting that the virulence role of VmNLP2 probably correlates to its cytotoxicity activity. We further showed that the peptide among VmNLP2, called nlp25 (VmNLP2), triggered strong immune response in Arabidopsis thaliana. This work demonstrates that NLPs from V. mali involve multiple biological roles, and shed new light on how intricately complex the functions of NLP might be.

15.
Front Endocrinol (Lausanne) ; 12: 717544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512549

RESUMO

Liver-expressed antimicrobial peptide 2 (LEAP-2), originally described as an antimicrobial peptide, has recently been recognized as an endogenous blocker of growth hormone secretagogue receptor 1a (GHS-R1a). GHS-R1a, also known as ghrelin receptor, is a G protein-coupled receptor (GPCR) widely distributed on the hypothalamus and pituitary gland where it exerts its major functions of regulating appetite and growth hormone (GH) secretion. The activity of GHS-R1a is controlled by two counter-regulatory endogenous ligands: Ghrelin (activation) and LEAP-2 (inhibition). Ghrelin activates GHS-R1a on the neuropeptide Y/Agouti-related protein (NPY/AgRP) neurons at the arcuate nucleus (ARC) to promote appetite, and on the pituitary somatotrophs to stimulate GH release. On the flip side, LEAP-2, acts both as an endogenous competitive antagonist of ghrelin and an inverse agonist of constitutive GHS-R1a activity. Such a biological property of LEAP-2 vigorously blocks ghrelin's effects on food intake and hormonal secretion. In circulation, LEAP-2 displays an inverse pattern as to ghrelin; it increases with food intake and obesity (positive energy balance), whereas decreases upon fasting and weight loss (negative energy balance). Thus, the LEAP-2/ghrelin molar ratio fluctuates in response to energy status and modulation of this ratio conversely influences energy intake. Inhibiting ghrelin's activity has shown beneficial effects on obesity in preclinical experiments, which sheds light on LEAP-2's anti-obesity potential. In this review, we will analyze LEAP-2's effects from a metabolic point of view with a focus on metabolic hormones (e.g., ghrelin, GH, and insulin), and discuss LEAP-2's potential as a promising therapeutic target for obesity.

16.
Lancet Infect Dis ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536349

RESUMO

BACKGROUND: Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3-17 years. METHODS: A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3-5 years, 6-12 years, or 13-17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 µg, 4 µg, or 8 µg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing. FINDINGS: Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=72, 24 for each age cohort [3-5, 6-12, and 13-17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=180, 60 for each age cohort [3-5, 6-12, and 13-17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3-5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13-17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3-5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13-17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3-5 years cohort, 84·1 to 168·6 in the 6-12 years cohort, and 88·0 to 155·7 in the 13-17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3-5 years cohort, 127 to 184·8 in the 6-12 years cohort, and 150·7 to 199 in the 13-17 years cohort on day 28 after the third vaccination. INTERPRETATION: The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3-17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 µg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

17.
J Intensive Care Med ; : 8850666211037326, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34550036

RESUMO

BACKGROUND: The potential protective role of eosinophils in the COVID-19 pandemic has aroused great interest, given their potential virus clearance function and the infection resistance of asthma patients to this coronavirus. However, it is unknown whether eosinophil counts could serve as a predictor of the severity of COVID-19. METHODS: A total of 1004 patients with confirmed COVID-19 who were admitted to Leishenshan Hospital in Wuhan, China, were enrolled in this study, including 905 patients in the general ward and 99 patients in the intensive care unit (ICU). We reviewed their medical data to analyze the association between eosinophils and ICU admission and death. RESULTS: Of our 1004 patients with COVID-19, low eosinophil counts/ratios were observed in severe cases. After adjusting for confounders that could have affected the outcome, we found that eosinophil counts might not be a predictor of ICU admission. In 99 ICU patients, 58 of whom survived and 41 of whom died, low eosinophil level was an indicator of death in severe COVID-19 patients with a cutoff value of 0.04 × 109/L, which had an area under the curve of 0.665 (95% CI = 1.089-17.839; P = .045) with sensitivity and specificity of 0.569 and 0.7317, respectively. CONCLUSION: Our research revealed that a low eosinophil level is a predictor of death in ICU patients rather than a cause of ICU admission.

18.
Biomed Chromatogr ; : e5234, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477231

RESUMO

Maternal lipopolysaccharide (LPS) exposure during pregnancy induces metabolic abnormalities in male offspring, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of maternal LPS exposure during pregnancy on metabolic profiling of maternal serum and male fetal liver using Liquid Chromatograph Mass Spectrometer techniques. From day 15 to day 17 of gestation, pregnant mice were administered intraperitoneal LPS (experimental group) (50 µg/kg/d) or saline (control group). On day 18 of gestation, maternal serum and male fetal liver were collected. After LPS exposure, levels of 38 and 75 metabolites, mainly glycerophospholipid and fatty acid metabolites, were altered in maternal serum and male fetal liver, respectively. It was found that in maternal serum and male fetal livers, the glycerophospholipids containing saturated fatty acids (SFAs) and the SFAs were upregulated, while the glycerophospholipids containing polyunsaturated fatty acids (PUFAs) and the PUFAs were downregulated. This concordance between maternal and fetal alterations in glycerophospholipid and fatty acid metabolites may be a metabolomic signature of the early intrauterine period and may provide insight into the mechanisms by which maternal LPS exposure induces disorders of glucose metabolism in male offspring.

19.
Oxid Med Cell Longev ; 2021: 8532940, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539975

RESUMO

Accumulating evidence shows that elevated levels of reactive oxygen species (ROS) are associated with cancer initiation, growth, and response to therapies. As concentrations increase, ROS influence cancer development in a paradoxical way, either triggering tumorigenesis and supporting the proliferation of cancer cells at moderate levels of ROS or causing cancer cell death at high levels of ROS. Thus, ROS can be considered an attractive target for therapy of cancer and two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to treat cancer. Despite tremendous resources being invested in prevention and treatment for cancer, cancer remains a leading cause of human deaths and brings a heavy burden to humans worldwide. Chemotherapy remains the key treatment for cancer therapy, but it produces harmful side effects. Meanwhile, the process of de novo development of new anticancer drugs generally needs increasing cost, long development cycle, and high risk of failure. The use of ROS-based repurposed drugs may be one of the promising ways to overcome current cancer treatment challenges. In this review, we briefly introduce the source and regulation of ROS and then focus on the status of repurposed drugs based on ROS regulation for cancer therapy and propose the challenges and direction of ROS-mediated cancer treatment.

20.
Neurol Res ; : 1-8, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581662

RESUMO

OBJECTIVE: To precisely prevent stroke, we evaluated three platelet function tests and their associations with clinical outcomes in ischemic stroke patients. METHODS: On-treatment platelet reactivity of acute minor stroke patients taking aspirin plus clopidogrel was tested by light transmittance aggregometry (LTA), thromboelastography (TEG) and platelet function analyzer (PFA). Mann-Whitney U tests and receiver operating characteristic (ROC) curve analysis were used to assess their associations with recurrent events and clinical outcome prediction. RESULTS: 127 acute minor stroke patients were stringently selected and followed for 13 months. Eight patients (6.3%) self-reported the recurrence and 13 (10.2%) patients self-reported bleeding. Recurrent patients displayed significantly higher on-treatment platelet reactivity when measured with LTA (p = 0.030) and PFA (p < 0.001). Further ROC analysis demonstrated that LTA and PFA had modest-to-fair ability to predict stroke recurrence (LTA: area under the curve [AUC], 0.765; 95% CI, 0.584-0.945, PFA: AUC, 0.832; 95% CI, 0.658-1.000). However, TEG (measured by the platelet inhibition rate) could not detect the difference between recurrent patients and non-recurrent patients (p = 0.515) and predict recurrent events (AUC, 0.569; 95% CI, 0.368-0.770). None of the tests were associated with bleeding except for PFA (p < 0.001), with AUC of PFA reaching 0.772 (0.726-0.818). CONCLUSIONS: Of the three tests assessed, the predictive accuracies of PFA and LTA were satisfying for aspirin secondary prevention, while TEG's performance was poor. Only PFA could provide accurate prognostic information for bleeding.

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