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Stem cells can generate a diversity of cell types during development, regeneration and adult tissue homeostasis. Differentiation changes not only the cell fate in terms of gene expression but also the physical properties and functions of cells, e.g. the secretory activity, cell shape, or mechanics. Conversely, these activities and properties can also regulate differentiation itself. Membrane trafficking is known to modulate signal transduction and thus has the potential to control stem cell differentiation. On the other hand, membrane trafficking, particularly from and to the plasma membrane, depends on the mechanical properties of the cell surface such as tension within the plasma membrane or the cortex. Indeed, recent findings demonstrate that cell surface mechanics can also control cell fate. Here, we review the bidirectional relationships between these three fundamental cellular functions, i.e. membrane trafficking, cell surface mechanics, and stem cell differentiation. Furthermore, we discuss commonly used methods in each field and how combining them with new tools will enhance our understanding of their interplay. Understanding how membrane trafficking and cell surface mechanics can guide stem cell fate holds great potential as these concepts could be exploited for directed differentiation of stem cells for the fields of tissue engineering and regenerative medicine.
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Medicina Regenerativa , Células-Tronco , Adulto , Humanos , Membrana Celular , Diferenciação Celular , Forma CelularRESUMO
This study aimed to develop a pharmacokinetic model of linezolid in premature neonates and evaluate and optimize the administration regimen. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the blood concentration data of 54 premature neonates after intravenous administration of linezolid, and the relevant clinical data were collected. The population pharmacokinetic (PPK) model was established by nonlinear mixed effects modeling. Based on the final model parameters, the optimal administration regimen of linezolid in premature neonates with different body surface areas (BSA) was simulated and evaluated. The pharmacokinetic properties of linezolid in premature neonates are best described by a single-compartment model with primary elimination. The population typical values for apparent volume of distribution and clearance were 0.783 L and 0.154 L/h, respectively. BSA was a statistically significant covariate with clearance (CL) and volume of distribution (Vd). Monte Carlo simulations showed that the optimal administration regimen for linezolid in premature neonates was 6 mg/kg q8h for BSA 0.11 m2, 7 mg/kg q8h for BSA 0.13 m2, and 9 mg/kg q8h for BSA 0.15 m2 with minimum inhibitory concentration (MIC) ≤1 mg/L, 7 mg/kg q8h for BSA 0.11 m2, 8 mg/kg q8h for BSA 0.13 m2, and 10 mg/kg q8h for BSA 0.15 m2 with MIC = 2 mg/L. A pharmacokinetic model was developed to predict the blood concentration on linezolid in premature neonates. Based on this model, the optimal administration regimen of linezolid in premature neonates needs to be individualized according to different BSA levels.
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Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.
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This study aimed at investigating the mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus(GX) in treating cardiovascular diseases in rats with the syndrome of combined phlegm and stasis. The rat model was established by a high-fat diet, ice-water bath combined with subcutaneous injection of adrenalin hydrochloride, and the syndrome score was determined. The serum samples of rats in the control, model, and GX groups were collected. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to analyze the metabolic profiles of the serum samples. The differential metabolites were screened and identified by partial least squares-discriminant analysis(PLS-DA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). The intervention targets of GX-regulated metabolites and their metabolic pathways were searched against MetaboAnalyst. Gene Ontology enrichment was carried out to predict the biological pathways associated with the intervention targets of metabolic pathways. A total of 129 potential biomarkers were detected in the rat model with the syndrome of combined phlegm and stasis via metabolomics, and GX regulated 54 metabolites in several metabolic pathways such as linoleic acid metabolism, sphingolipid metabolism, and tricarboxylic acid cycle. The further screening against MetaboAnalyst showed that GX recovered the levels of nine metabolites associated with cardiovascular diseases with the syndrome of combined phlegm and stasis, which involved 69 targets in the pathways regarding cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism. The above-mentioned results suggested that GX can alleviate the symptoms of the rat model of cardiovascular diseases with the syndrome of combined phlegm and stasis by regulating the metabolism of linoleic acid, sphingosine, docosahexaenoic acid, rosemary acid, succinic acid, adenine, L-phenylalanine, L-valine and modulating the biological pathways such as cholesterol metabolism, fatty acid metabolism, inflammatory response, and glucose homeostasis and metabolism.
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Doenças Cardiovasculares , Cebolinha-Francesa , Medicamentos de Ervas Chinesas , Ratos , Animais , Doenças Cardiovasculares/tratamento farmacológico , Ácido Linoleico , Cromatografia Líquida de Alta Pressão/métodos , Metabolômica/métodos , Biomarcadores , Colesterol , GlucoseRESUMO
Chronic visceral pain is a common symptom of irritable bowel syndrome (IBS). Exosomes are involved in the development of pain. Rab27a can mediate the release of exosomes. The purpose of this study is to investigate how Rab27a-mediated exosome secretion in the anterior cingulate cortex (ACC) regulates visceral hyperalgesia induced with neonatal maternal deprivation (NMD) in adult mice. The colorectal distension method was adopted to measure visceral pain. The BCA protein assay kit was applied to detect the exosome protein concentration. Western blotting, quantitative PCR, and immunofluorescence technique were adopted to detect the expression of Rab27a and the markers of exosomes. Exosomes extracted from ACC were more in NMD mice than in control (CON) mice. Injection of the exosome-specific inhibitor GW4869 in ACC attenuated colorectal visceral pain of NMD mice. Injection of NMD-derived exosomes produced colorectal visceral pain in CON mice. Rab27a was upregulated in ACC of NMD mice. Rab27a was highly expressed in ACC neurons of NMD mice, rather than astrocytes and microglia. Injection of Rab27a-siRNA reduced the release of exosomes and attenuated the colorectal visceral pain in NMD mice. This study suggested that overexpression of Rab27a increased exosome secretion in ACC neurons, thus contributing to visceral hyperalgesia in NMD mice.NEW & NOTEWORTHY This work demonstrated that the expression of Rab27a in the anterior cingulate cortex was upregulated, which mediated multivesicular bodies trafficking to the plasma membrane and led to the increased release of neuronal exosomes, thus contributing to colorectal visceral pain in neonatal maternal deprivation (NMD) mice. Blocking the release of exosomes or downregulation of Rab27a could alleviate colorectal visceral pain in NMD mice. These data may provide a promising strategy for the treatment of visceral pain in irritable bowel syndrome patients.
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Neoplasias Colorretais , Exossomos , Síndrome do Intestino Irritável , Dor Visceral , Camundongos , Animais , Giro do Cíngulo , Dor Visceral/metabolismo , Hiperalgesia/etiologia , Privação Materna , Exossomos/metabolismo , Proteínas rab27 de Ligação ao GTP/genética , Proteínas rab27 de Ligação ao GTP/metabolismoRESUMO
The Omicron variant has been reported to present with milder disease compared with Delta, although this may be due to immunity from vaccination and prior exposure. Predictors of severity with recent strains have not been well characterized. We retrospectively examined consecutive cases of moderate-to-severe COVID-19 (defined as requiring supplemental oxygenation, intensive care or mortality) admitted to seven tertiary hospitals across Singapore in April 2023. Whole genome sequencing was performed on each isolate to determine the sublineage, while baseline clinical, laboratory data and outcomes were tabulated. We reviewed 182 patients with moderate-to-severe illness and 466 controls hospitalized at the same time. Advanced age and presence of chronic kidney disease predicted adverse outcome. Previously reported markers such as radiographic evidence of pneumonia, elevated C-reactive protein and serum creatinine levels at presentation also correlated with adverse outcomes. There were no observable differences in outcomes with any specific Omicron XBB sublineage. We did not find any specific Omicron XBB sublineage that was associated with worse outcomes. Larger multinational studies would be important to track the clinical evolution of the virus in its current endemic state.
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COVID-19 , Humanos , COVID-19/diagnóstico , Gravidade do Paciente , Estudos Retrospectivos , SARS-CoV-2/genéticaRESUMO
To improve the interfacial bonding of dissimilar composites, the interaction mechanism between the surface state and severe plastic deformation to strengthen the interfacial bonding strength was revealed. In this study, the different surface states of the steel strip were designed by louver blade grinding (LBG) and diamond bowl grinding (DBG), and the cold-rolled composite method was developed to prepare the brass/carbon steel composite strips. The results show that the steel surface after DBG has a large roughness of 9.79 µm, a hard hardening layer of 6.2 GPa, and high cleanliness of 1.34 atomic % oxygen content, while that after LBG has a roughness of 1.31 µm, a hardening layer of 4.2 GPa, and an oxygen content of 2.37 atomic %. The large roughness promotes the breaking of the hardening layer; the hardening layer is beneficial to obtain sufficient interfacial stress to expose the fresh metal; and the high cleanliness reduces the barrier to the fresh metal and contributes to the bonding of the fresh metal. The interface of the cold-rolled brass/carbon steel composite strip after LBG and DBG is mechanical bonding and metallurgical bonding, respectively. In the process of the cold-rolling composite, large shear deformation occurs at the interface of brass and steel, resulting in a high concentration of vacancy and dislocation defects, which provides a channel for interdiffusion of atoms at the interface. Under the diffusion driving force provided by the cold-rolling shear deformation heat, a nanodiffusion layer with a thickness of 60 nm and high interfacial bond strength was formed.
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The perfluoroalkylthiolation/decarbonylation reactions of 1,3-dicarbonyl compounds with in situ formed perfluoroalkanesulfenic acids were achieved. Using trifluoromethanesulfonic acid as an additive, a series of α-perfluoroalkylthiolated arylethanones were obtained in moderate to good yields. A possible mechanism was proposed based on the reaction results and control experiments.
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BACKGROUND: To retrospectively analyse postoperative adverse events in oldest-old patients (aged 90 years and older) with intertrochanteric fractures treated under various anaesthetic techniques. METHODS: A total of 153 consecutive patients participated in this study, of which 127 patients who underwent surgery with neuraxial anaesthesia or general anaesthesia for intertrochanteric fractures between October 2019 and October 2022 were eligible and evaluated. They were divided into the neuraxial anaesthesia and general anaesthesia groups. The demographic characteristics and postoperative adverse events were compared between the two groups. RESULTS: A total of 13 patients (10.24%), including 6 in the neuraxial anaesthesia group (8.22%) and 7 in the general anaesthesia group (12.96%), died within 30 days after surgery. No significant differences between the two groups were observed. Postoperative delirium occurred in 40 patients (31.49%), including 17 (23.29%) in the neuraxial anaesthesia group and 23 (42.59%) in the general anaesthesia group; there was a significant difference between the two groups [P = 0.02, odds ratio (OR) = 0.41]. The other postoperative adverse events, including heart failure, acute stroke, acute myocardial infarction, pulmonary disease, anaemia, deep vein thrombosis, hypoproteinaemia, and electrolyte disorders, were not significantly different between the two groups. CONCLUSION: Our data suggest that different anaesthesia methods do not affect the incidence of adverse events, such as death within 30 days after surgery in oldest-old patients with intertrochanteric fractures. However, more patients developed delirium after surgery in the general anaesthesia group (23, 42.59%) than in the neuraxial anaesthesia group (17, 23.29%); this may indicate that spinal anaesthesia reduces the incidence of postoperative delirium (P = 0.02, OR = 0.41). TRIAL REGISTRATION: Retrospectively registered.
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Delírio do Despertar , Fraturas do Quadril , Humanos , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Delírio do Despertar/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Anestesia Geral/efeitos adversos , Fraturas do Quadril/cirurgia , Fraturas do Quadril/etiologiaRESUMO
Installing a fluoroalkyl group onto the nitrogen atom of azoles represents a potential strategy for lead optimization in medicinal chemistry. Herein, we describe a method for the N-trifluoropropylation of azoles. This process is accomplished using a combination of regioselective N-vinylation and sequential hydrogenation. The two-step sequence is applicable to a diverse set of azoles and tolerates a wide range of functionalities. In addition, we showcase its practicability and utility through the gram-scale synthesis and the late-stage modification of a complex molecule.
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Azóis , Nitrogênio , Azóis/química , Hidrogenação , CatáliseRESUMO
BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.
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Pneumotórax , Síndrome do Desconforto Respiratório do Recém-Nascido , Pressão Positiva Contínua nas Vias Aéreas/efeitos adversos , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Pneumotórax/etiologia , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/complicações , Síndrome do Desconforto Respiratório do Recém-Nascido/epidemiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Admission hypothermia (AH, < 36.5â) remains a major challenge for global neonatal survival, especially in developing countries. Baseline research shows nearly 89.3% of very low birth weight (VLBW, < 1500 g) infants suffer from AH in China. Therefore, a prospective multicentric quality improvement (QI) initiative to reduce regional AH and improve outcomes among VLBW neonates was implemented. METHODS: The study used a sequential Plan-Do-Study-Act (PDSA) approach. Clinical data were collected prospectively from 5 NICUs within the Sino-Northern Neonatal Network (SNN) in China. The hypothermia prevention bundle came into practice on January 1, 2019. The clinical characteristics and outcomes data in the pre-QI phase (January 1, 2018- December 31, 2018) were compared with that from the post-QI phase (January 1, 2019-December 31, 2020). Clinical characteristics and outcomes data were analyzed. RESULTS: A total of 750 in-born VLBW infants were enrolled in the study, 270 in the pre-QI period and 480 in the post- QI period, respectively. There were no significant differences in clinical characteristics of infants between these two phases. Compared with pre-QI period, the incidence of AH was decreased significantly after the QI initiative implementation in the post-QI period (95.9% vs. 71.3%, P < 0.01). Incidence of admission moderate-to-severe hypothermia (AMSH, < 36â) also decreased significantly, manifesting a reduction to 38.5% in the post-QI (68.5% vs 30%, P < 0.01). Average admission temperature improved from after QI (35.5 [Formula: see text] 0.7â vs. 36.0 [Formula: see text] 0.6â, P < 0.01). There was no increase in proportion the number of infants with a temperature of > 37.5 °C or thermal burns between the two groups. The risk ratio of mortality in infants during the post-QI period was significantly lower in the post-QI period as compared to the pre-QI period [adjusted risk ratio (aRR): 0.26, 95% confidence interval (CI): 0.13-0.50]. The risk ratio of late-onset neonatal sepsis (LOS) also significantly lowered in the post-QI period (aRR: 0.66, 95% CI: 0.50-0.87). CONCLUSION: Implementation of multicentric thermoregulatory QI resulted in a significant reduction in AH and AMSH in VLBW neonates with associated reduction in mortality. We gained a lot from the QI, and successfully aroused the attention of perinatal medical staff to neonatal AH. This provided a premise for continuous quality improvement of AH in the future, and might provide a reference for implementation of similar interventions in developing countries. TRIAL REGISTRATION: Trial registration number: ChiCTR1900020861 . Date of registration: 21 January 2019(21/01/2019). Prospectively registered.
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Hipotermia , Feminino , Humanos , Hipotermia/epidemiologia , Hipotermia/prevenção & controle , Lactente , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Gravidez , Estudos Prospectivos , Melhoria de QualidadeRESUMO
This study aims to investigate the compatibility mechanism of Trichosanthis Fructus-Allii Macrostemonis Bulbus combination against atherosclerosis(AS) in apolipoprotein E-deficient(ApoE~(-/-)) mice. To be specific, high-fat diet was used to induce AS in mice. The pathological morphology of mice aorta was evaluated based on hematoxylin-eosin(HE) staining and Masson staining. The metabolic profiling of mouse serum samples was performed with ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Multiple statistical analysis methods including partial least squares-discriminant analysis and orthogonal partial least squares-discriminant analysis were employed to screen potential biomarkers in mice. With the techniques in network pharmacology, the metabolites related to AS and the targets in the metabolic pathways were screened out. The results showed that Trichosanthis Fructus alone and the pair all reduced the plaque area of aortic sinus(P<0.05) and collagen area(P<0.05). Compared with the Trichosanthis Fructus alone and Allii Macrostemonis Bulbus alone, the combination significantly decreased the plaque area of aortic sinus(P<0.05) and collagen area(P<0.05). Metabolomics revealed 16 biomarkers in mice. Trichosanthis Fructus re-gulated the abnormal levels of 4 metabolites in glycerophosphatide metabolic pathway. Allii Macrostemonis Bulbus modulated the abnormal levels of 2 metabolites in arachidonic acid metabolic pathway and the combination recovered the levels of 8 metabolites in glycerophosphatide, linoleic acid, arachidonic acid, and pyrimidine metabolic pathways. Network pharmacology suggested that Trichosanthis Fructus regulated 24 targets which related to 2 AS-associated metabolites and involved glycerophosphatide metabolic pathway. Allii Macroste-monis Bulbus modulated 40 targets which related to 2 AS-associated metabolites and involved the arachidonic acid metabolic pathway. The combination regulated 57 targets which related to 6 AS-metabolites and involved linoleic acid metabolic pathway, glycerophosphatide metabolic pathway, and arachidonic acid metabolic pathway. These results indicate that the Trichosanthis Fructus-Allii Macrostemonis Bulbus combination enhances the regulation of linoleic acid metabolism, glycerophosphatide metabolism, and arachido-nic acid metabolism, thereby synergistically alleviating lipid disorder and inflammatory response in AS mice.
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Aterosclerose , Medicamentos de Ervas Chinesas , Camundongos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Ácido Araquidônico , Ácido Linoleico , Farmacologia em Rede , Metabolômica , Biomarcadores , Aterosclerose/tratamento farmacológico , Aterosclerose/genéticaRESUMO
According to the pharmacophore binding strategy and principle of bioelectronic isobaric, used the sulfonylurea bridge as the parent structure, a series of novel thiourea compounds containing aromatic-substituted pyrimidines were designed and synthesized. The preliminary herbicidal activity tests showed that some compounds had good herbicidal activity against Digitaria adscendens, Amaranthus retroflexus, especially for compound 4d and 4f. The results showed that compound 4d had an inhibition rate of 81.5% on the root growth of Brassica napus L. at the concentration of 100 mg L-1, and compound 4f had an inhibition rate of 81% on the root growth of Digitaria adscendens at the concentration of 100 mg L-1. Compounds 4d and 4f had higher comparative activity on Echinochloa crus-galli than the commercial herbicide bensulfuron-methyl. The preliminary structure-activity relationship (SAR) was also summarized. We also tested the in vivo AHAS enzyme activity inhibition experiment of 14 compounds at 100 mg L-1, and the results showed that they all have inhibitory activity on the enzyme, with the highest inhibition rate reaching 44.4% (compound 4d). Based on the results of molecular docking to yeast acetohydroxyacid synthase (AHAS), the possible herbicidal activity mechanism of these compounds was evaluated.
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Acetolactato Sintase , Herbicidas , Acetolactato Sintase/metabolismo , Herbicidas/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Pirimidinas/farmacologia , Relação Estrutura-Atividade , Tioureia/farmacologiaRESUMO
To evaluate the efficacy and safety of Chinese patent medicine in the treatment of knee osteoarthritis(KOA) with network Meta-analysis, and provide evidence-based medicine evidences for clinical practice. PubMed, Cochrane Library, EMbase, CNKI, Wanfang, VIP and CBM were used to search for clinical randomized controlled trials(RCTs) on Chinese patent medicines for treatment of knee osteoarthritis, with a time limit from the establishment of each database to March 2020. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. The network Meta-analysis was performed by Stata 14.0 software. A total of 5 788 patients in 58 RCTs were included, involving 9 kinds of Chinese patent medicines. The results of the network Meta-analysis indicated that in terms of total effective rate, the top three optimal medication regimens were Jinwu Gutong Capsules + Amino Acid Glucose(AAG), Xianling Gubao + AAG and Biqi Capsules; the top three interventions to reduce the VAS score were Panlongqi Tablets > Xianling Gubao + AAG > Xianling Gubao + non steroidal anti-inflammatory drugs(NSAIDs); the top three interventions to reduce the total score of WOMAC were Jintiange Capsules+NSAIDs> Jinwu Gutong Capsules + AAG > Biqi Capsules + NSAIDs; the top three medication schemes with better curative effect to reduce Lequesnse index were Xianling Gubao + NSAIDs > Biqi Capsules + NSAIDs > Jintiange Capsules + NSAIDs; the top three interventions to reduce TNF-α level Xianling Gubao + AAG > Jintiange Capsules > Jintiange Capsules + AAG=Jinwu Gutong Capsules + AAG. In terms of safety, the top five interventions with the least adverse reactions were Biqi Capsules > Jinwu Gutong Capsules > Biqi Capsules + NSAIDs > Xianling Gubao + NSAIDs > Jintiange Capsules. The combined application of Chinese patent medicine and NSADIs or AAG can improve the clinical treatment effect and reduce adverse reactions in KOA patients.
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Medicamentos de Ervas Chinesas , Osteoartrite do Joelho , Produtos Biológicos , China , Humanos , Metanálise em Rede , Medicamentos sem Prescrição , Osteoartrite do Joelho/tratamento farmacológicoRESUMO
OBJECTIVES: To study the clinical features of obstructive sleep apnea (OSA) in children with obesity. METHODS: A retrospective analysis was performed on the medical data of 33 obese children aged 7-15 years, who were diagnosed with OSA and received polysomnography (PSG) in the Department of Respiratory Medicine in Shenzhen Children's Hospital. Fifty OSA children with normal body weight, matched for sex and age, were enrolled as the control group. RESULTS: Among the 33 obese children with OSA, the three most common daytime symptoms were inattention in 30 children (91%), somnolence in 22 children (67%), and morning fatigue in 21 children (64%), and the three most common nocturnal symptoms were snoring in 27 children (82%), mouth breathing in 20 children (61%), and sweating in 16 children (49%). Compared with the reference values of normal children, both the OSA + obesity group and the control group had prolonged light sleep, shortened deep sleep, and a significantly shortened rapid eye movement (REM) period, while there was no significant difference in these indices between the two groups (P>0.05). The apnea-hypopnea index, obstructive apnea/hypopnea index, and oxygen desaturation index in both REM and non-REM periods in the OSA +obesity group were significantly higher than those in the control group (P<0.05), while the lowest blood oxygen saturation during sleep was significantly lower in the OSA + obesity group (P<0.05). CONCLUSIONS: The children with obesity and OSA have the main daytime symptoms of inattention, somnolence, and morning fatigue and the main nocturnal symptoms of snoring, mouth breathing, and sweating. There is no significant difference in sleep structure between OSA children with obesity and those with normal body weight; however, respiratory events and blood oxygen saturation decline are more severe in OSA children with obesity. Citation.
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Obesidade Infantil , Apneia Obstrutiva do Sono , Criança , Humanos , Obesidade Infantil/complicações , Polissonografia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/complicações , RoncoRESUMO
Inflammation is considered to be critical in the pterygium progression and recurrence. However, the underlying molecular mechanism is not well understood. Herein, we investigated the potential role of RNA binding protein human antigen R (HuR) responsible for the impact of inflammation on pterygium development. The expression of HuR and matrix metallopeptidase-9 (MMP-9) in pterygium and normal conjunctiva was detected with immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The influence of interleukin-1ß (IL-1ß) on HuR expression and cellular distribution was determined with western blot and immunofluorescence. The pterygium fibroblast (PTF) migration was determined with scratch wound healing assay and Transwell migration assay. MMP-9 production was determined with qRT-PCR and gelatin zymography. The interaction between HuR and MMP-9 was investigated with RNP immunoprecipitation (IP) followed by RT-PCR and messenger RNA (mRNA) stability analysis. HuR and MMP-9 expression are elevated in pterygium, especially progressive pterygium compared with normal conjunctiva. IL-1ß could increase the expression and nucleus-cytoplasm shuttle of HuR in cultured PTFs. HuR mediated the stimulatory effect of IL-1ß on PTF migration and MMP-9 production. HuR bound to MMP-9 mRNA and in turn increased it stability. Our results suggest that posttranscriptional regulation of MMP-9 via stabilizing mRNA by HuR might contribute to the stimulatory effect of inflammatory factor IL-1ß on pterygium progression. These findings shed light on the pathogenesis of pterygium and provide a promising target for adjuvant treatment of pterygium.
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Proteína Semelhante a ELAV 1/genética , Inflamação/genética , Interleucina-1beta/genética , Metaloproteinase 9 da Matriz/genética , Pterígio/genética , Idoso , Movimento Celular/genética , Túnica Conjuntiva/crescimento & desenvolvimento , Túnica Conjuntiva/patologia , Progressão da Doença , Feminino , Fibroblastos/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Processamento de Proteína Pós-Traducional/genética , Pterígio/metabolismo , Pterígio/patologia , Estabilidade de RNA/genéticaRESUMO
Group-IV phosphide monolayers (MP, M=C, Si, Ge and Sn) provide a versatile platform for photocatalysts, as well as optoelectronic and nanoelectronic devices. Herein, comprehensive first-principles calculations and ab initio molecular dynamics (AIMD) simulations were performed to explore their stabilities in the air. We identified that the MP monolayers have excellent mechanical properties and their carrier mobilities are higher than that of phosphorene. The MP monolayers were predicted to possess superior oxidation resistance than the boron phosphide (BP) monolayer based on the proposed donation-backdonation theory. It was observed that the dissociation and chemisorption of a water molecule on the monolayers are kinetically difficult both in the water and in oxygen-water environments involving energy barriers of 1.28-3.48â eV. We also performed AIMD simulations at 300, 1000, 1200 and 1500â K. It is noteworthy that only the carbon phosphide (CP) monolayer can retain an intact structure at 1500â K, while the other three monolayers can just sustain to 1200â K. These results provide a guidance for their practical application and experimental fabrication.
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Group-III phosphide (MP, M = B, Al, Ga and In) monolayers have promising applications in photocatalysis, nanoelectronics and optoelectronics. Their stabilities in oxygen and water environments are crucial to their practical applications. In order to investigate the stabilities of the MP monolayers, density functional theory calculations combined with ab initio molecular dynamics (AIMD) simulations were performed to illustrate their interactions with oxygen and water molecules. It was found that an oxygen molecule spontaneously dissociates on the AlP, GaP and InP monolayers. In the meantime, the corresponding monolayer structures are severely distorted after annealing. In contrast, BP monolayer is stable in the oxygen environment due to a high dissociative barrier of 0.89 eV. We found that a water molecule dissociates on AlP monolayer with a dissociative energy barrier of 0.42 eV, but it can be stably adsorbed on the BP, GaP and InP monolayers without the breakage of O-H bonds. Nevertheless, with the increase of the number of water molecules, the formed intermolecular H-bonding can promote interactions between water molecules and the monolayers, leading to structural distortion in the GaP and InP monolayers. When putting a water molecule near the oxygen molecule, the oxidation barrier of the BP monolayer is reduced to 0.75 eV, which is still high enough to maintain its stable state. This investigation theoretically provides environmental conditions for the experimental fabrication and practical application of semiconductor monolayers.
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BACKGROUND: There is an increasing public interest in the use of TM internationally, yet there is a paucity of research on the use of TM by the public in the dental setting. This study aimed to explore the views, use of and access to TM in dentistry among different ethnic groups residing in New Zealand. METHODS: Qualitative study and in-depth interviews were used. An individual semi-structured questionnaire was used to collect data. Interviews were recorded, transcribed, and analysed using an inductive approach to identify the main themes. RESULTS: Three main themes were extracted from interviews with 14 participants from diverse cultural backgrounds: [1] the perspectives of TM varied among different ethnic groups and included the involvement of spirituality, the environment, knowledge and usage of TM. [2] The TM that was used by different ethnic groups included plants, herbs, massage, and other forms of healing. Reasons for choosing traditional or western medicines generally included family tradition, access to TM, and finding a competent traditional healer. [3] The barriers in accessing TM included the paucity of traditional healers, difficulty accessing plants and cost, therefore most would look for a substitution or alternative treatment. CONCLUSION: Even though the access to these TM in New Zealand was a challenge for the majority of the participants, they are still considered the first-line treatment for the majority. This study provided dental practitioners an insight into the different sort of TM used by the population. By understanding and acknowledging the use of TM, dental practitioners could create a supportive environment for patients to disclose their use of TM and allow them to educate patients on the use of TM.