RESUMO
Glycosyltransferases (GTs) are enzymes that transfer sugars to various targets. They play important roles in diverse biological processes, including photosynthesis, cell motility, exopolysaccharide biosynthesis, and lipid metabolism; however, their involvement in regulating carbon metabolism in Synechocystis sp. PCC 6803 has not been reported. We identified a novel GT protein, Slr1064, involved in carbon metabolism. The effect of slr1064 deletion on the growth of Synechocystis cells and functional mechanisms of Slr1064 on carbon metabolism were thoroughly investigated through physiological, biochemistry, proteomic, and metabolic analyses. We found that this GT, which is mainly distributed in the membrane compartment, is essential for the growth of Synechocystis under heterotrophic and mixotrophic conditions, but not under autotrophic conditions. The deletion of slr1064 hampers the turnover rate of Gap2 under mixotrophic conditions and disrupts the assembly of the PRK/GAPDH/CP12 complex under dark culture conditions. Additionally, UDP-GlcNAc, the pivotal metabolite responsible for the O-GlcNAc modification of GAPDH, is downregulated in the Δslr1064. Our work provides new insights into the role of GTs in carbon metabolism in Synechocystis and elucidate the mechanism by which carbon metabolism is regulated in this important model organism.
Assuntos
Proteínas de Bactérias , Carbono , Glicosiltransferases , Synechocystis , Uridina Difosfato N-Acetilglicosamina , Synechocystis/metabolismo , Synechocystis/genética , Synechocystis/crescimento & desenvolvimento , Carbono/metabolismo , Glicosiltransferases/metabolismo , Glicosiltransferases/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Uridina Difosfato N-Acetilglicosamina/metabolismo , Regulação Bacteriana da Expressão Gênica , Deleção de GenesRESUMO
PURPOSE: Nearly all patients with hip fractures undergo surgical treatment. The use of different anesthesia techniques during surgery may influence the clinical outcomes. The optimal anesthetic technique for patients undergoing hip fracture surgery is still controversial. We performed this updated systematic review and meta-analysis to compare clinical outcomes of patients undergoing hip fracture surgery with different anesthesia techniques. SOURCE: Articles published from 2000 to May 2023 were included from MEDLINE, Embase, Web of Science, and the Cochrane Library. We included randomized controlled trials and observational studies comparing general anesthesia (GA) with regional anesthesia (RA) for the outcomes of 30-day mortality, 90-day mortality, in-hospital mortality, perioperative complications, length of hospital stay, and length of surgery in patients undergoing hip fracture surgery. Subgroup analyses were performed for the outcomes based on study design (randomized controlled trials or observational studies). We used a random-effects model for all analyses. PRINCIPAL FINDINGS: In this meta-analysis, we included 12 randomized controlled trials. There was no difference in postoperative 30-day mortality between the two groups (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.44 to 1.74; I2 = 0%). The incidence of intraoperative hypotension was lower in patients who received RA vs GA (OR, 0.52; 95% CI, 0.38 to 0.72; I2 = 0%). No significant differences were observed in 90-day mortality, in-hospital mortality, postoperative delirium, pneumonia, myocardial infarction, venous thromboembolism, length of surgery, and length of hospital stay. CONCLUSION: In this updated systematic review and meta-analysis, RA did not reduce postoperative 30-day mortality in hip fracture surgery patients compared to GA. Fewer patients receiving RA had intraoperative hypotension than those receiving GA did. Apart from intraoperative hypotension, the data showed no differences in complications between the two anesthetic techniques. STUDY REGISTRATION: PROSPERO (CRD42023411854); registered 7 April 2023.
RéSUMé: OBJECTIF: Presque toutes les personnes ayant subi une fracture de la hanche se font opérer. L'utilisation de différentes techniques d'anesthésie pendant la chirurgie peut influencer les issues cliniques. La technique d'anesthésie optimale pour la patientèle bénéficiant de chirurgie de fracture de la hanche est encore controversée. Nous avons réalisé cette mise à jour par revue systématique et méta-analyse pour comparer les issues cliniques des personnes bénéficiant d'une chirurgie de fracture de la hanche avec différentes techniques d'anesthésie. SOURCES: Les articles publiés de 2000 à mai 2023 ont été inclus à partir des bases de données MEDLINE, Embase, Web of Science et Cochrane Library. Nous avons inclus des études randomisées contrôlées et des études observationnelles comparant l'anesthésie générale (AG) à l'anesthésie régionale (AR) pour les issues de mortalité à 30 jours, de mortalité à 90 jours, de mortalité intrahospitalière, de complications périopératoires, de durée de séjour à l'hôpital et de durée de la chirurgie pour les personnes bénéficiant d'une chirurgie de fracture de la hanche. Des analyses de sous-groupes ont été réalisées pour les issues en fonction de la méthodologie utilisée (étude randomisée contrôlée ou étude observationnelle). Un modèle à effets aléatoires a été utilisé pour toutes les analyses. CONSTATATIONS PRINCIPALES: Dans cette méta-analyse, nous avons inclus 12 études randomisées contrôlées. Il n'y avait pas de différence dans la mortalité postopératoire à 30 jours entre les deux groupes (rapport de cotes [RC], 0,88; intervalle de confiance à 95 % [IC], 0,44 à 1,74; I2 = 0 %). L'incidence d'hypotension peropératoire était plus faible chez les patient·es ayant reçu une AR vs une AG (RC, 0,52; IC 95 %, 0,38 à 0,72; I2 = 0 %). Aucune différence significative n'a été observée dans les issues de mortalité à 90 jours, de mortalité intrahospitalière, de delirium postopératoire, de pneumonie, d'infarctus du myocarde, de thromboembolie veineuse, de durée de la chirurgie, et de durée du séjour à l'hôpital. CONCLUSION: Dans cette revue systématique avec méta-analyse, l'anesthésie régionale n'a pas réduit la mortalité postopératoire à 30 jours chez les personnes ayant bénéficié d'une chirurgie de fracture de la hanche par rapport à l'anesthésie générale. Une proportion moindre de patient·es ayant reçu une AR présentaient une hypotension peropératoire par rapport aux personnes ayant reçu une AG. En dehors de l'hypotension peropératoire, les données n'ont montré aucune différence dans les complications entre les deux techniques anesthésiques. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42023411854); enregistrée le 7 avril 2023.
Assuntos
Anestesia por Condução , Anestesia Geral , Fraturas do Quadril , Mortalidade Hospitalar , Tempo de Internação , Complicações Pós-Operatórias , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Fraturas do Quadril/cirurgia , Anestesia Geral/métodos , Anestesia por Condução/métodos , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologiaRESUMO
During a vertical vortex-induced vibration (VVIV), an undulating bridge deck will affect drivers' sightlines, causing the phenomenon of drifting and changes in the far blind area, thus presenting a potential threat to driving safety. Consequently, to ensure the safety of driving on a suspension bridge deck under VVIV, it is necessary to perceive the far blind spot caused by the occlusion of the driving sightlines under this condition, and to establish an online perception and evaluation mechanism for driving safety. With a long-span suspension bridge experiencing VVIV as the engineering background, this paper utilizes the acceleration integration algorithm and the sine function fitting method to achieve the online perception of real-time dynamic configurations of the main girder. Then, based on the configurations, the maximum height of the driver's far blind area and effective sight distance are calculated accordingly, and the impact of different driving conditions on them is discussed. The proposed technical framework for driving safety perception in far blind spots is feasible, as it can achieve real-time estimation of the maximum height and effective distance of the far blind area, thereby providing technical support for bridge-vehicle-human collaborative perception and traffic control during vortex-induced vibration.
RESUMO
It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein, a Mendelian randomization study conducted in East Asian population enhances the current clinical cognition that T2DM is not associated with reduction in BMD. PURPOSE: A Mendelian randomization (MR) approach was utilized to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in East Asian populations. METHODS: Genome-wide association study summary data from BioBank Japan were used to identify genetic variants strongly related to T2DM risk (36,614 cases and 155,150 controls) and osteoporosis (7788 cases and 204,665 controls). Heel BMD GWAS data of 1260 East Asian people from ieu open gwas project was considered as a second outcome. Inverse variance-weighted (IVW) analysis was mainly applied; MR-Egger and the weighted median were also used to obtain robust estimates. A series of sensitivity analyses including Cochran's Q test, MR-Egger regression, and leave-one-out analysis were used to detect pleiotropy or heterogeneity. RESULTS: In the main analysis, IVW estimates indicated that T2DM significantly associated with the risk of osteoporosis (odds ratio = 0.92, 95% CI: 0.86-0.99, p = 0.016) and with higher BMD (OR: 1.25, 95% CI: 1.06-1.46, p = 6.49 × 10-3). Results of comprehensive sensitivity analysis were consistent with the main causality estimate. Horizontal pleiotropy and heterogeneity were absent in our MR study. CONCLUSIONS: T2DM is not associated with reduction in BMD in terms of genetic polymorphism in East Asian populations.
Assuntos
Diabetes Mellitus Tipo 2 , Osteoporose , Humanos , Densidade Óssea/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , População do Leste Asiático , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Osteoporose/epidemiologia , Osteoporose/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial. METHODS: Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18-59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18-59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.
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COVID-19 , Vacinas Virais , Adolescente , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Chile , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina , Imunoglobulina G , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinas de Produtos Inativados/efeitos adversos , Adulto JovemRESUMO
Establishing an online perception mechanism for a driver's front blind area on a full bridge under vertical vortex-induced vibration (VVIV) is essential for ensuring road safety and traffic control on bridge decks under specific conditions. Based on accelerations of vibration monitoring of the main girders, this paper uses a real-time acceleration integration algorithm to obtain real-time displacements of measurement points; realizes the real-time estimation of the dynamic configurations of a main girder through parametric function fitting; and then can perceive the front blind area for vehicles driving on bridges experiencing VVIV in real time. On this basis, taking a long-span suspension bridge suffering from VVIV as an engineering example, the influence of different driving conditions on the front blind area is examined. Then, the applicability of the intelligent perception technology framework of the front blind area is verified. The results indicate that, during VVIV, the driver's front blind area changes periodically and the vehicle model has the most significant impact on the front blind area; in contrast, the vehicle's speed and the times of the vehicle entering the bridge have minimal impact on it. Meanwhile, it is shown that the framework can accurately perceive front blind areas of vehicles driving on the bridge, and identify different vehicle models, speeds and times of vehicle bridge entries in real time.
Assuntos
Condução de Veículo , Aceleração , Acidentes de Trânsito , Percepção , VibraçãoRESUMO
The ability of an off-road robot to traverse obstacles determines whether the robot can complete complex environmental tasks. In order to improve the off-road ability of off-road robots, this paper proposes a new design idea, in which four hub motors are the power system of the robot, the steering system of the robot is composed of a steering machine and a stepping motor, and a five degree of freedom robot model is established. The body structure is designed according to the characteristics of arthropods. The body structure is divided into three modules, and the connecting rod is used as the joint system of the robot to connect the three parts. The body can deform when facing complex obstacles, so as to adapt to different terrains. Then the body structure is simplified, and a mathematical model is established to describe the mathematical relationship between body joint changes. In order to verify the ability of the adaptive all-terrain cross-country robot to traverse obstacles, the load-bearing experiment and obstacle-crossing simulation experiment were carried out through Adams software, and the continuous traversing performance at low obstacles and the ability to break through high obstacles were tested, respectively. The experimental results prove that the designed adaptive all-terrain off-road robot is feasible, has good carrying capacity, and has good passability in the face of low obstacles and high obstacles. Using Ansys software to perform finite element analysis on the wheel connection, the experimental results show that the strength meets the material strength requirements. Finally, a real vehicle test is carried out to verify the correctness of the simulation results.
Assuntos
Robótica , Simulação por Computador , Robótica/métodos , SoftwareRESUMO
BACKGROUND AND AIMS: The Wnt/ß-catenin signaling pathway has a well-described role in liver pathobiology. Its suppression was recently shown to decrease bile acid (BA) synthesis, thus preventing the development of cholestatic liver injury and fibrosis after bile duct ligation (BDL). APPROACH AND RESULTS: To generalize these observations, we suppressed ß-catenin in Mdr2 knockout (KO) mice, which develop sclerosing cholangitis due to regurgitation of BA from leaky ducts. When ß-catenin was knocked down (KD) in KO for 2 weeks, hepatic and biliary injury were exacerbated in comparison to KO given placebo, as shown by serum biochemistry, ductular reaction, inflammation, and fibrosis. Simultaneously, KO/KD livers displayed increased oxidative stress and senescence and an impaired regenerative response. Although the total liver BA levels were similar between KO/KD and KO, there was significant dysregulation of BA transporters and BA detoxification/synthesis enzymes in KO/KD compared with KO alone. Multiphoton intravital microscopy revealed a mixing of blood and bile in the sinusoids, and validated the presence of increased serum BA in KO/KD mice. Although hepatocyte junctions were intact, KO/KD livers had significant canalicular defects, which resulted from loss of hepatocyte polarity. Thus, in contrast to the protective effect of ß-catenin KD in BDL model, ß-catenin KD in Mdr2 KO aggravated rather than alleviated injury by interfering with expression of BA transporters, hepatocyte polarity, canalicular structure, and the regenerative response. CONCLUSIONS: The resulting imbalance between ongoing injury and restitution led to worsening of the Mdr2 KO phenotype, suggesting caution in targeting ß-catenin globally for all cholestatic conditions.
Assuntos
Colangite Esclerosante/complicações , Colangite Esclerosante/genética , Colestase/etiologia , Colestase/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Animais , Ácidos e Sais Biliares/metabolismo , Ductos Biliares/patologia , Colestase/genética , Modelos Animais de Doenças , Hepatócitos/metabolismo , Hepatócitos/patologia , Junções Intercelulares/metabolismo , Junções Intercelulares/patologia , Camundongos Knockout , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATPRESUMO
BACKGROUND: The Sabin strain-based inactivated polio vaccine (sIPV) plays a vital role in eradicating poliomyelitis in developing countries. METHODS: The study was designed as a randomized, controlled, double-blinded, noninferiority trial. A total of 1200 healthy infants aged 60-90 days were enrolled and randomly assigned to receive 3 doses of either sIPV (the experimental arm) or IPV (the control arm) at days 0, 30, and 60. Immunogenicity and safety outcomes were assessed using the per-protocol and safety populations, respectively. RESULTS: A total of 553 and 562 participants in the sIPV and IPV groups, respectively, were included in the per-protocol population. Seroconversion rates in the sIPV and IPV groups were 98.0% and 94.1%, respectively, for type 1 poliovirus (P < .01); 94.8% and 84.0%, respectively, for type 2 (P < .01); and 98.9% and 97.7%, respectively, for type 3 (P = .11). A total of 599 and 600 participants in the sIPV and IPV groups, respectively, were included in the safety population. Fever was the most common adverse event, occurring in 61.6% and 49.8% of participants in the experimental and control arms, respectively (P < .01). CONCLUSIONS: The sIPV demonstrated an immunogenicity profile noninferior to that of the conventional IPV and had a good safety profile. CLINICAL TRIALS REGISTRATION: NCT03526978.
Assuntos
Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/imunologia , Poliovirus/imunologia , Anticorpos Antivirais/sangue , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Lactente , Masculino , Poliomielite/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/efeitos adversosRESUMO
BACKGROUND: This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of enterovirus 71 (EV71) vaccine (dose 1) with recombinant hepatitis B vaccine (HepB) on day 1 and EV71 vaccine (dose 2) with group A meningococcal polysaccharide vaccine (MenA) on day 30 is not inferior to separate administration of each vaccine. METHODS: The study was designed as a randomized, open-label, noninferiority trial. A total of 775 healthy infants aged 6 months were randomly assigned in a ratio of 1:1:1 to receive simultaneous administration of EV71 vaccine (dose 1) and HepB on day 1 and EV71 vaccine (dose 2) and MenA on day 30 (the SI group); administration of doses 1 and 2 of EV71 vaccine on days 1 and 30, respectively (the SE1 group); or administration of HepB and MenA on days 1 and 30, respectively (the SE2 group). RESULTS: According to the per protocol set, antibody responses against EV71, hepatitis B virus (HBV), and group A meningococcal polysaccharide were similar regardless of administration schedule. With the non-inferiority margin setting at 10%, the seroconversion rates of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) were not inferior to those in SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72], respectively). Frequencies of adverse reactions to each vaccination regimen were comparable (60.62% in the SI group vs 52.33% in the SE1 group and 56.98% in the SE2 group; P = .16). CONCLUSIONS: Simultaneous administration of combined EV71 vaccine with HepB and MenA has noninferior immunogenicity and safety, compared with separate administration of these vaccines. CLINICAL TRIALS REGISTRATION: NCT03274102.
Assuntos
Formação de Anticorpos/imunologia , Vacinas contra Hepatite B/imunologia , Vacinas Meningocócicas/imunologia , Polissacarídeos Bacterianos/imunologia , Vacinas Combinadas/imunologia , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Anticorpos Antivirais/imunologia , Enterovirus/imunologia , Infecções por Enterovirus/imunologia , Feminino , Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Humanos , Lactente , Masculino , Infecções Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Vacinação/efeitos adversosRESUMO
BACKGROUND: The therapeutic outcome of the local arthrodesis surgery for type 2 accessory navicula (AN) is rarely reported. This study aimed to compare the clinical outcomes between Kidner and arthrodesis procedures for type 2 AN. METHODS: Sixteen patients (20 feet) with symptomatic type 2 AN receiving surgical treatment in our hospital between November 2013 and December 2015 were retrospectively included. Ten patients (13 feet) underwent the Kidner surgery (Kidner group) and 6 patients received local arthrodesis procedure (arthrodesis group). Radiographic indices before/after surgery were compared between the two groups. Patient's satisfaction with surgery outcome was evaluated by patient self-assessment questionnaire. RESULTS: The calcaneal pitch angle was significantly increased after surgery in both groups (bothp<0.01), while the talocalcaneal coverage angle and lateral talo-first metatarsal angle were not significantly changed after surgery. There was no significant difference regarding the postoperative changes in the three radiographic indices between the two groups. In the arthrodesis group, 3 patients (4 feet) had an excellent outcome, 2 patients (2 feet) a good outcome, and 1 patient (1 foot) had a fair outcome. In the Kidner group, 6 patients (8 feet), 2 patients (3 feet), 1 patient (1 foot) and 1 patient (1 foot) had excellent, good, fair, and poor treatment outcomes, respectively. The rate of good-to-excellent outcomes was comparable between the arthrodesis group and Kidner group (83% vs. 80%, p=0.696). CONCLUSION: Our results suggested that both the Kidner surgery and arthrodesis surgery were an effective treatment for symptomatic type 2 AN.
Assuntos
Artrodese , Artroplastia , Doenças do Pé/cirurgia , Ossos do Tarso/anormalidades , Tendões/cirurgia , Adolescente , Adulto , Feminino , Doenças do Pé/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Estudos Retrospectivos , Ossos do Tarso/diagnóstico por imagem , Ossos do Tarso/cirurgia , Resultado do Tratamento , Adulto JovemRESUMO
Emerging evidence shows that rheumatoid arthritis (RA) progression can be induced by the activation of Toll-like receptor (TLR) signaling pathway. Regulator of G-protein signaling 1 (RGS1) is observed to be a candidate biomarker for arthritis. Accordingly, the present study aims to determine the potential effects of RGS1 mediating TLR on RA. A rat model of collagen-induced arthritis (CIA) was established to mimic the features of RA by injection of bovine type II collagen. The rats with CIA were treated with short hairpin RNA (shRNA) against RGS1 or TLR pathway activator Poly I:C to elucidate the role of RGS1 in RA progression. The inflammatory factors were measured, and the thoracic gland and spleen indexes as well as the vascular density were determined. The expression levels of RGS1, TLR3, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), MMP-9, and interleukin 1 receptor-associated kinase-4 (IRAK4) were determined. RGS1 was robustly increased in RA. The TLR signaling pathway was suppressed by RGS1 silencing. shRNA-mediated depletion of RGS1 was shown to significantly enhance thoracic gland index and inhibit the serum levels of TNF-α, IL-1ß, and IL-17, spleen index, vascular density, and the expression levels of TLR3, VEGF, MMP-2, MMP-9, and IRAK4. However, when the rats with CIA were treated with Poly I:C, the trend of effects was opposite. These findings highlight that functional suppression of RGS1 inhibits the inflammatory response and angiogenesis by inactivating the TLR signaling pathway in rats with CIA, thereby providing a novel therapeutic target for RA treatment.
Assuntos
Artrite Reumatoide/genética , Neovascularização Patológica/genética , Proteínas RGS/genética , Receptores Toll-Like/efeitos dos fármacos , Animais , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Células Cultivadas , Colágeno Tipo II/metabolismo , Fibroblastos/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Neovascularização Patológica/tratamento farmacológico , Ratos Wistar , Receptores Toll-Like/metabolismoRESUMO
Polyomavirus BK (BKV) is an important pathogen in kidney transplant patients. Regulation of BKV encoded microRNAs (miRNAs) is not well understood. Therefore, tubular epithelial cells infected with BKV were examined for changes in small RNA expression. The observed changes were further evaluated by real-time PCR and RNA-seq analysis of renal allograft biopsies. BKV-miR-B1-5p and BKV-miR-B1-3p showed a 1000-fold increase over 12 days but did not prevent cell lysis. Downregulation of host miR-10b and miR-30a could be confirmed on all three platforms evaluated. Whereas, the BKV genome expressed more 3p than 5p miRNA species, the reverse was true for the human genome. Decreased expression of TP53INP2, and increased expression of BCL2A1, IL-6, IL8 and other proinflammatory cytokines were shown in biopsies with BKV nephropathy. No change in expression was seen in miR-10a dependent expression of NKG2D ligands ULBP3, MICA, or MICB. In conclusion, BKV infection results in regulation of cellular genes regulated by and possibly amenable to therapies targeting miR-10 and miR-30.
Assuntos
Vírus BK/genética , Expressão Gênica , Interações entre Hospedeiro e Microrganismos , MicroRNAs/genética , Infecções por Polyomavirus/genética , RNA Viral/genética , Adulto , Idoso , Biópsia , Células Cultivadas , Células Epiteliais/virologia , Feminino , Humanos , Rim/patologia , Nefropatias/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Análise de Sequência de RNA , Transplante Homólogo , Replicação Viral , Adulto JovemAssuntos
Leucemia Linfocítica Crônica de Células B , Linfoma de Célula do Manto , Humanos , Adulto , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , ImunofenotipagemRESUMO
Simultaneous mutations in CTNNB1 and activation of c-MET occur in 9%-12.5% of patients with hepatocellular carcinoma (HCC). Coexpression of c-MET-V5 and mutant ß-catenin-Myc in mouse liver by sleeping beauty transposon/transposase and hydrodynamic tail vein injection (SB-HTVI) led to the development of HCC with 70% molecular identity to the clinical subset. Using this model, we investigated the effect of EMD1214063, a highly selective c-MET inhibitor. Five weeks after SB-HTVI when tumors were established, EMD1214063 (10 mg/kg) was administered by gastric gavage as a single agent on 5-day-on/3-day-off schedule, compared to vehicle only control. Mice were harvested at 8 or 11 weeks posttreatment. Decreased p-MET, p-AKT, p-STAT3, and p-ERK proved in vivo efficacy of EMD1214063. We observed lower Ki-67, PCNA, V5-tag, and cyclin D1 after EMD1214063 treatment only at 8 weeks. Overall, no significant differences were observed in tumor burden between the groups, although EMD1214063 marginally but significantly improved overall survival by 1.5-2 weeks. Tumors remained α-fetoprotein+, did not show any differences in inflammation, and lacked fibrosis in either group. In conclusion, c-MET inhibition alone had a minor effect on Met-ß-catenin HCC at the early stages of HCC development. Thus, a single therapy with the c-MET inhibitor will be insufficient for sustained response in Met-ß-catenin HCC requiring assessment of additional combinations.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Piridazinas/uso terapêutico , Pirimidinas/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Neoplasias Hepáticas/genética , Masculino , Camundongos , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/metabolismo , Piridazinas/administração & dosagem , Piridazinas/farmacologia , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , beta Catenina/genéticaRESUMO
In the clinical practice, Professor Jiang Liangduo, a national senior Chinese medicine doctor, has created the theory of "sanjiao meridian stasis" from the theory of meridian dialectics and from the overall state. In this paper, the traditional Chinese medicine and Western medicine clinical characteristics of sanjiao meridian stasis theory which is often used by Professor Jiang Liangduo in the treatment of out-patient syndrome differentiation, were first studied and summarized to investigate its inherent regularity. First, the source of data and research methods were introduced, and then the Traditional Chinese Medicine Inheritance Support System was used with the method of data mining to retrospectively analyze the disease characteristics of Chinese and Western medicine in 279 patients with sanjiao meridian stasis diagnosed by Professor Jiang in 2014. Then the following main conclusions were made after research: sanjiao meridian stasis was more common in women as well as young and middle-aged population. Often manifested by prolonged treatment course, red tongue with yellowishfur, with good correlation between modern Western medicine diagnosis and TCM differentiation syndrome. The symptoms of sanjiao meridian stasis syndrome are mostly of heat syndromes, and middle-aged patients are the most common patients with stasis and stasis of sanjiao. Related information of Western medicine diagnosis can help to diagnose the "sanjiao meridian stasis".
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Medicina Tradicional Chinesa , Meridianos , Mineração de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Today's rapid growth of migrant populations has been a major contributor to the human immunodeficiency virus (HIV) epidemic. However, relatively few studies have focused on HIV/acquired immunodeficiency syndrome (AIDS)-related knowledge, attitudes, and practice among rural-to-urban migrants in China. This cross-sectional study was to assess HIV/AIDS-related knowledge and perceptions, including knowledge about reducing high-risk sex. METHODS: Two-phase stratified cluster sampling was applied and 2,753 rural migrants participated in this study. An anonymous self-administered questionnaire was conducted in Guangdong and Sichuan provinces in 2007. Descriptive analysis was used to present the essential characteristics of the respondents. Chi-square test and multiple logistic regression models were performed to examine the associations between identified demographic factors and high-risk sex, sexually transmitted disease (STD) symptoms, and access to HIV screening services among the seven types of workers. RESULTS: 58.6% of participants were knowledgeable about HIV/AIDS transmission, but approximately 90% had a negative attitude towards the AIDS patients, and that 6.2% had engaged in high-risk sex in the past 12 months. Logistic regression analysis revealed sex, marital status, income, migration and work experience to be associated with high-risk sex. Among the 13.9% of workers who reported having STD symptoms, risk factors that were identified included female gender, high monthly income, being married, daily laborer or entertainment worker, frequent migration, and length of work experience. Only 3% of migrant workers received voluntary free HIV screening, which was positively associated with monthly income and workplace. CONCLUSIONS: HIV/AIDS knowledge, attitudes, and practices among rural migrants in China remain a thorny health issue, and use of healthcare services needs to be improved. Low levels of education and knowledge regarding HIV/AIDS among housekeepers and migrant day laborers result in this population likely being engaged in high-risk sex. Government programs should pay more attention to public education, health promotion and intervention for the control of the HIV/AIDS epidemic in China.
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Síndrome da Imunodeficiência Adquirida/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Serviços de Saúde/estatística & dados numéricos , Migrantes , Sexo sem Proteção , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural , Inquéritos e Questionários , Sexo sem Proteção/estatística & dados numéricos , Adulto JovemRESUMO
The tensile properties of coal under dynamic loading are important mechanical characteristics of coal and are highly important for controlling coal rock stability under impact loading conditions, selecting blasting engineering parameters, and studying the mechanism of rockburst disasters. To investigate the dynamic tensile failure process of coal subjected to impact loading, this study used high-speed photography and digital image correlation technology to capture the dynamic tensile failure of coal under impact loading. The dynamic tensile evolution was quantitatively analyzed from the beginning of coal sample being loaded to failure. The captured images of the coal were processed, and the fractal dimension was used to quantitatively describe the evolution of the coal surface cracks under impact loading. The following conclusions were drawn from the experimental results: (1) An empirical formula was established to describe the dynamic tensile strength characteristics of coal under different loading rates. (2) Under impact loading, the maximum strain of a Brazilian disc coal sample first appeared at the contact end between the sample and the incident rod. (3) Under impact loading, a Brazilian disc coal sample cracked from the center of the sample outward, and the crack subsequently extended toward both ends. The fractal dimension of the crack exhibited a power function relationship with time, and the variation range of the fractal dimension of the crack was 1.05-1.39.
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Safe and effective vaccines against COVID-19 for children and adolescents are needed. This international multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial assessed the efficacy, immunogenicity, and safety of CoronaVac® in children and adolescents (NCT04992260). The study was carried out in Chile, South Africa, Malaysia, and the Philippines. The enrollment ran from September 10, 2021 to March 25, 2022. For efficacy assessment, the median follow-up duration from 14 days after the second dose was 169 days. A total of 11,349 subjects were enrolled. Two 3-µg injections of CoronaVac® or placebo were given 28 days apart. The primary endpoint was the efficacy of the CoronaVac®. The secondary endpoints were the immunogenicity and safety. The vaccine efficacy was 21.02% (95% CI: 1.65, 36.67). The level of neutralizing antibody in the vaccine group was significantly higher than that in the placebo group (GMT: 390.80 vs. 62.20, P <0.0001). Most adverse reactions were mild or moderate. All the severe adverse events were determined to be unrelated to the investigational products. In conclusion, in the Omicron-dominate period, a two-dose schedule of 3 µg CoronaVac® was found to be safe and immunogenic, and showed potential against symptomatic COVID-19 in healthy children and adolescents.