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OBJECTIVES: We sought to investigate the clinicopathologic features and differential diagnosis of plexiform fibrohistiocytic tumor (PFHT) and its pathogenesis. METHODS: Ten cases of PFHT were collected from Xi Jing Hospital, Fourth Military Medical University, from September 2008 to December 2022 for clinical data as well as microscopic and immunohistochemical observation. CCND1 gene amplification and break were assayed by fluorescence in situ hybridization (FISH). RESULTS: We report 10 cases of PFHT according to histologic classification. Seven cases were of histiocytoid type, and 3 had mucous degeneration in the nodules. One case was of fibroblastic type, which was mainly composed of fibroblast-like cells. Two cases were of mixed type. Immunohistochemically, the osteoclast-like multinucleated giant cells, histiocyte-like cells, and occasional spindle cells in the adjacent fascicles were reactive for CD68 (10/10), CD163 (5/8), CD10 (8/8), cyclin D1 (8/8), CDK4 (5/8), ß-catenin (4/6), MITF (2/6), and PGP9.5 (4/5). Vimentin (9/9) was strongly positive in tumor cells and peripheral fibroblast-like cells. The positive index of Ki-67 was 5% to 40%, with an average of 20%. The FISH analysis showed neither amplification nor break of the CCND1 gene. All cases underwent surgical resection, and patients were followed up for 9 months to 11 years. Only 2 cases recurred. CONCLUSIONS: Plexiform fibrohistiocytic tumor is a low-grade malignant soft tissue neoplasm. The diagnosis mainly depends on histopathologic and immunohistochemical markers. Cyclin D1 and CD10 expression has diagnostic value for the diagnosis and differential diagnosis of PFHT combined with its plexiform morphology. The overexpression of cyclin D1 suggests an involvement of cell cycle regulatory genes in the pathogenesis of PFHT.
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We conducted a phase I, randomized, double-blind, placebo-controlled trial including healthy adults in Sui County, Henan Province, China. Ninety-six adults were randomly assigned to one of three groups (high-dose, medium-dose, and low-dose) at a 3:1 ratio to receive one vaccine dose or placebo. Adverse events up to 28 days after each dose and serious adverse events up to 6 months after all doses were reported. Geometric mean titers and seroconversion rates were measured for anti-rotavirus neutralizing antibodies using microneutralization tests. The rates of total adverse events in the placebo group, low-dose group, medium-dose group, and high-dose group were 29.17 % (12.62 %-51.09 %), 12.50 % (2.66 %-32.36 %), 50.00 % (29.12 %-70.88 %), and 41.67 % (22.11 %-63.36 %), respectively, with no significant difference in the experimental groups compared with the placebo group. The results of the neutralizing antibody assay showed that in the adult group, the neutralizing antibody geometric mean titer at 28 days after full immunization in the low-dose group was 583.01 (95 % confidence interval [CI]: 447.12-760.20), that in the medium-dose group was 899.34 (95 % CI: 601.73-1344.14), and that in the high-dose group was 1055.24 (95 % CI: 876.28-1270.75). The GMT of serum-specific IgG at 28 days after full immunization in the low-dose group was 3444.26 (95 % CI: 2292.35-5175.02), that in the medium-dose group was 6888.55 (95 % CI: 4426.67-10719.6), and that in the high-dose group was 7511.99 (95 % CI: 3988.27-14149.0). The GMT of serum-specific IgA at 28 days after full immunization in the low-dose group was 2332.14 (95 % CI: 1538.82-3534.45), that in the medium-dose group was 4800.98 (95 % CI: 2986.64-7717.50), and that in the high-dose group was 3204.30 (95 % CI: 2175.66-4719.27). In terms of safety, adverse events were mainly Grades 1 and 2, indicating that the safety of the vaccine is within the acceptable range in the healthy adult population. Considering the GMT and positive transfer rate of neutralizing antibodies for the main immunogenicity endpoints in the experimental groups, it was initially observed that the high-dose group had higher levels of neutralizing antibodies than the medium- and low-dose groups in adults aged 18-49 years. This novel inactivated rotavirus vaccine was generally well-tolerated in adults, and the vaccine was immunogenic in adults (ClinicalTrials.gov number, NCT04626856).
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra Rotavirus , Vacinas de Produtos Inativados , Humanos , Adulto , Método Duplo-Cego , Masculino , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas contra Rotavirus/imunologia , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/efeitos adversos , China , Imunogenicidade da Vacina , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/imunologia , Rotavirus/imunologia , Voluntários Saudáveis , Testes de NeutralizaçãoRESUMO
Microplastic pollution in the soil environment has received extensive attention, but the effects of different land use patterns on the sub-watershed scale on soil microplastic pollution are poorly understood. The Luoshijiang sub-watershed in the north of Erhai Lake was selected as the research object, and the characteristics of microplastic pollution in farmland, riparian zone, grassland, and woodland soils were analyzed. The pollution risks of microplastics in the four types of soil were assessed using the polymer risk index method, and the effects of land use patterns on the distribution and risk of microplastic pollution were further explored. The results showed that:â The abundance of microplastics in the soil of the Luoshijiang sub-watershed ranged from 220 to 1 900 n·kg-1, and the average abundance was (711 ± 55) n·kg-1. The main polymer types were polyester (PES, 32.52%) and polyethylene terephthalate (PET, 21.95%). The particle size of microplastics was concentrated in the range of 0.5-2 mm (61.89%). Fiber was the main shape of microplastics (>75%), and the dominant color was transparent (58.50%). â¡ Land use patterns determined the abundance and pollution characteristics of soil microplastics in the Luoshijiang sub-watershed. A significantly higher abundance of microplastics was found in the soil of farmland[(885 ± 95) n·kg-1] and riparian zone[(837 ± 155) n·kg-1], which had stronger intensities of human activity, than that in woodland soil[(491 ± 53) n·kg-1] (P<0.05). Film and fragment microplastics mainly occurred in farmland soil, which also had the largest number of polymer types and the most abundant colors. ⢠The risk index level of microplastics (Level â ¢) in the soil of farmland was higher than that of the other three land use patterns (Level â ). This research indicated that the higher the intensity of human activities of a sub-watershed was, the more complex the occurrence characteristics of soil microplastics, the richer the types of polymers, and the higher the potential pollution risks would be. Therefore, it is necessary to strengthen the control of soil microplastic pollution in farmland.
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HuR (Human antigen R) is an RNA binding protein (RBP) that specifically binds to certain RNA sequences, influencing post-transcriptional regulation. HuR is primarily involved in tumor regulation, as well as cell growth, proliferation, inflammation, and angiogenesis. HuR is implicated in endothelial activation, smooth muscle proliferation, inflammatory response, macrophage apoptosis, lipid regulation, and autophagy, playing a crucial regulatory role in atherosclerosis. Accumulating evidence suggests that HuR has dual roles in AS. On the one hand, HuR expedites the development of AS by facilitating endothelial activation, smooth muscle proliferation, and inflammation. On the contrary, it exerts beneficial effects by reducing macrophage apoptosis, regulating lipid efflux, and increasing autophagy. In this review, we aim to provide a comprehensive summary of the role of HuR in the development of AS by examining its involvement in cellular mechanisms, inflammation, autophagy, and apoptosis. Additionally, we discuss the mechanisms of drugs that target HuR, with the goal of offering new perspectives for the treatment of AS.
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Thiram is a toxic fungicide extensively used for the management of pathogens in fruits. Although it is known that thiram degrades in plant tissues, the key enzymes involved in this process remain unexplored. In this study, we report that a tau class glutathione S-transferase (GST) from Carica papaya can degrade thiram. This enzyme was easily obtained by heterologous expression in Escherichia coli, showed low promiscuity toward other thiuram disulfides, and catalyzed thiram degradation under physiological reaction conditions. Site-directed mutagenesis indicated that G-site residue S67 shows a key influence for the enzymatic activity toward thiram, while mutation of residue S13, which reduced the GSH oxidase activity, did not significantly affect the thiram-degrading activity. The formation of dimethyl dithiocarbamate, which was subsequently converted into carbon disulfide, and dimethyl dithiocarbamoylsulfenic acid as the thiram degradation products suggested that thiram undergoes an alkaline hydrolysis that involves the rupture of the disulfide bond. Application of the GST selective inhibitor 4-chloro-7-nitro-2,1,3-benzoxadiazole reduced papaya peel thiram-degrading activity by 95%, indicating that this is the main degradation route of thiram in papaya. GST from Carica papaya also catalyzed the degradation of the fungicides chlorothalonil and thiabendazole, with residue S67 showing again a key influence for the enzymatic activity. These results fill an important knowledge gap in understanding the catalytic promiscuity of plant GSTs and reveal new insights into the fate and degradation products of thiram in fruits.
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Carica , Glutationa Transferase , Tiram , Carica/enzimologia , Carica/genética , Fungicidas Industriais/metabolismo , Glutationa Transferase/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/química , Mutagênese Sítio-Dirigida , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tiram/metabolismo , Escherichia coli/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Radiotherapy is one of the standard therapeutic regimens for medulloblastoma (MB). Tumor cells utilize DNA damage repair (DDR) mechanisms to survive and develop resistance during radiotherapy. It has been found that targeting DDR sensitizes tumor cells to radiotherapy in several types of cancer, but whether and how DDR pathways are involved in the MB radiotherapy response remain to be determined. Single-cell RNA sequencing was carried out on 38 MB tissues, followed by expression enrichment assays. Fanconi anemia group D2 gene (FANCD2) expression was evaluated in MB samples and public MB databases. The function of FANCD2 in MB cells was examined using cell counting assays (CCK-8), clone formation, lactate dehydrogenase activity, and in mouse orthotopic models. The FANCD2-related signaling pathway was investigated using assays of peroxidation, a malondialdehyde assay, a reduced glutathione assay, and using FerroOrange to assess intracellular iron ions (Fe2+ ). Here, we report that FANCD2 was highly expressed in the malignant sonic hedgehog (SHH) MB subtype (SHH-MB). FANCD2 played an oncogenic role and predicted worse prognosis in SHH-MB patients. Moreover, FANCD2 knockdown markedly suppressed viability, mobility, and growth of SHH-MB cells and sensitized SHH-MB cells to irradiation. Mechanistically, FANCD2 deficiency led to an accumulation of Fe2+ due to increased divalent metal transporter 1 expression and impaired glutathione peroxidase 4 activity, which further activated ferroptosis and reduced proliferation of SHH-MB cells. Using an orthotopic mouse model, we observed that radiotherapy combined with silencing FANCD2 significantly inhibited the growth of SHH-MB cell-derived tumors in vivo. Our study revealed FANCD2 as a potential therapeutic target in SHH-MB and silencing FANCD2 could sensitize SHH-MB cells to radiotherapy via inducing ferroptosis. © 2024 The Pathological Society of Great Britain and Ireland.
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Neoplasias Cerebelares , Anemia de Fanconi , Ferroptose , Meduloblastoma , Camundongos , Animais , Humanos , Meduloblastoma/genética , Meduloblastoma/radioterapia , Ferroptose/genética , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/radioterapia , Linhagem Celular Tumoral , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/genéticaRESUMO
Clinical data indicates that SARS-CoV-2 infection-induced respiratory failure is a fatal condition for severe COVID-19 patients. However, the pathological alterations of different types of respiratory failure remained unknown for severe COVID-19 patients. This study aims to evaluate whether there are differences in the performance of various types of respiratory failure in severe COVID-19 patients and investigate the pathological basis for these differences. The lung tissue sections of severe COVID-19 patients were assessed for the degree of injury and immune responses. Transcriptome data were used to analyze the molecular basis in severe COVID-19 patients. Severe COVID-19 patients with combined oxygenation and ventilatory failure presented more severe pulmonary fibrosis, airway obstruction, and prolonged disease course. The number of M2 macrophages increased with the degree of fibrosis in patients, suggesting that it may be closely related to the development of pulmonary fibrosis. The co-existence of pro-inflammatory and anti-inflammatory cytokines in the pulmonary environment could also participate in the progression of pulmonary fibrosis. Furthermore, the increased apoptosis in the lungs of COVID-19 patients with severe pulmonary fibrosis may represent a critical factor linking sustained inflammatory responses to fibrosis. Our findings indicate that during the extended phase of COVID-19, antifibrotic and antiapoptotic treatments should be considered in conjunction with the progression of the disease.
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COVID-19 , Fibrose Pulmonar , Insuficiência Respiratória , Humanos , COVID-19/complicações , COVID-19/patologia , Fibrose Pulmonar/patologia , Autopsia , SARS-CoV-2 , Pulmão/patologia , Macrófagos/patologia , Insuficiência Respiratória/patologia , ApoptoseRESUMO
Aspergillus flavus not only reduces kiwifruit production but also synthesizes carcinogenic aflatoxins, resulting in a relevant threat to human health. p-Hydroxybenzoic acid (pHBA) is one of the most abundant phenolics in kiwifruit. In this study, pHBA was found to reduce A. flavus mycelial growth by blocking the fungal mitotic exit network (MEN) and cytokinesis and to inhibit the biosynthesis of aflatoxins B1 and B2. The application of pHBA promoted the accumulation of endogenous pHBA and induced oxidative stress in A. flavus-infected kiwifruit, resulting in an increase in H2O2 content and catalase (CAT) and superoxide dismutase (SOD) activities. Preventive and curative treatments with 5 mM pHBA reduced A. flavus advancement by 46.1% and 68.0%, respectively. Collectively, the antifungal and elicitor properties of pHBA were examined for the first time, revealing new insights into the role of pHBA in the defense response of kiwifruit against A. flavus infection.
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Aflatoxinas , Aspergillus flavus , Humanos , Antifúngicos/farmacologia , Peróxido de HidrogênioRESUMO
Covalent organic frameworks (COFs) have emerged as significant candidates for visible-light photocatalysis due to their ability to regulate performance which is achieved through the careful selection of building modules, framework conjugation, and post-modification. This report focused on the efficient transformation of an imine-linked I-COF into a π-conjugated quinoline-based Q-COF, which enhanced both the chemical stability and conjugation of the network. By methylating the pyridyl groups in the Q-COF, an N+-COF was obtained. Subsequently, the Ru(N^N)3-photosensitizer ([Ru(dcbpy)3]4-) was incorporated into the channels of the cationic N+-COF through electrostatic interactions, resulting in the formation of [Ru(dcbpy)3]4-âN+-COF. This composite exhibited exceptional photocatalytic activity, demonstrating high yields and selectivity in the oxidation of sulfides or amines to their respective products.
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Introduction: Previous studies have demonstrated the long-term effectiveness of behavioral interventions for attention-deficit hyperactivity disorder (ADHD) in preschool children. We continue to design a caseâcontrol study to further investigate the factors influencing the long-term effect of behavioral intervention. Methods: From May 2020 to August 2021, children who were newly diagnosed with ADHD and not receiving any treatment received a one-year behavioral intervention. A total of 86 children completed the behavioral intervention and assessment. Results: 50 children (58.140%) were in the effective group, and 36 children (41.860%) were in the ineffective group. Attention retention time (OR=0.559, 0.322-0.969), Swanson, Nolan, and Pelham total score (OR=1.186, 1.024-1.374) at baseline, performance score for parents (OR=0.631, 0.463-0.859), and teacher coordination (OR=0.032, 0.002-0.413) were the influencing factors of behavioral intervention effects. The area under the receiver operating curve was 0.979 (p<0.001). The comprehensive nomogram model showed that the discrimination and mean absolute error were 0.979 and 0.023, respectively. Discussion: During behavioral intervention, the implementation skills of parents should be evaluated in a timely manner. The behavioral intervention effect can be predicted based on a child's attention retention time at baseline, teacher involvement, behavioral scale score, and performance score for parents, which can guide clinicians in adjusting personalized treatment plans and provide a basis for clinical decision-making. The treatment of ADHD in preschool children requires a systematic framework that integrates family, school, and society.
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OBJECTIVES: To investigate the effect of moderate-intensity continuous training (MICT) on the improvement of cardiopulmonary function for patients undergoing transcatheter aortic valve replacement (TAVR). DESIGN: Randomized controlled study. SETTING AND PARTICIPANTS: Between August 20, 2021, and February 28, 2022, a total of 66 patients after TAVR were screened for inclusion and randomly divided into the MICT and control groups at a ratio of 1:1. MICT was scheduled 3 times per week for 3 months in the intervention group. Patients in the control group received one-time advice on physical activity according to the current guideline. METHODS: The primary endpoint was the 3-month change in peak oxygen consumption (peak VO2) assessed by cardiopulmonary exercise testing. The secondary endpoints included the 3-month change in 6-minute walk test (6MWT), the 12-Item Short Form Health Survey (SF-12), New York Heart Association (NYHA) class, echocardiographic parameters, and laboratory parameters. RESULTS: After 3 months, the change in peak VO2 was higher in the MICT group than that in the control group (1.63 mL/kg/min, 95% CI 0.58-2.67, P = .003). Change in 6MWT (21.55 m, 95% CI 0.38-42.71, P = .046) was higher in the MICT group compared with the control group. A significant change in favor of MICT was also observed for low-density lipoprotein cholesterol (-0.62 mmol/L, 95% CI -1.00 to -0.23, P = .002). However, there were no significant changes in other echocardiographic indices, laboratory parameters, and SF-12 between the 2 groups (all P > .05). CONCLUSIONS AND IMPLICATIONS: MICT had a positive effect on the cardiopulmonary function and physical capacity of patients after TAVR.
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Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Humanos , Exercício Físico , Terapia por Exercício , Caminhada , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Resultado do TratamentoRESUMO
Microplastics (MPs) are ubiquitous emerging pollutants that have been found in the marine, freshwater, air, and soil environments. Wastewater treatment plants (WWTPs) play an important role in releasing MPs to the environment. Therefore, understanding the occurrence, fate, and removal mechanism of MPs in WWTPs is of great importance towards microplastic control. In this review, the occurrence characteristics and removal rates of MPs in 78 WWTPs from 57 studies were discussed based on Meta-analysis. Specifically, the key aspects regarding MPs removal in WWTPs, such as wastewater treatment processes and MPs shapes, sizes, and polymer compositions were analyzed and compared. The results showed that:â the abundances of MPs in the influent and effluent were 1.56×10-2-3.14×104 n·L-1 and 1.70×10-3-3.09×102 n·L-1, respectively. The abundance of MPs in the sludge ranged from 1.80×10-1 to 9.38×103 n·g-1. â¡ The total removal rate (>90%) of MPs by WWTPs using oxidation ditch, biofilm, and conventional activated sludge treatment processes was higher than that using sequencing batch activated sludge, anaerobic-anoxic-aerobic, and anoxic-aerobic processes. ⢠The removal rate of MPs in primary, secondary, and tertiary treatment process were 62.87%, 55.78%, and 58.45%, respectively. The combination process of "grid+ sedimentation tank+primary sedimentation tank" had the highest removal rate towards MPs in primary treatment processes, and the membrane bioreactor had the highest one beyond other secondary treatment processes. Filtration was the best process in tertiary treatment. ⣠The film, foam, and fragment MPs were easier to remove (>90%) than fiber and spherical (<90%) MPs by WWTPs. The MPs with particle size larger than 0.5 mm were easier to remove than those with particle size smaller than 0.5 mm. The removal efficiencies of polyethylene (PE), polyethylene terephthalate (PET), and polypropylene (PP) MPs were higher than 80%.
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Microplásticos , Plásticos , Esgotos , Biofilmes , Reatores BiológicosRESUMO
BACKGROUND: Kiwifruit is highly susceptible to fungal pathogens, such as Botrytis cinerea, which reduce crop production and quality. In this study, dipicolinic acid (DPA), which is one of the main components of Bacillus spores, was evaluated as a new elicitor to enhance kiwifruit resistance to B. cinerea. RESULTS: DPA enhances antioxidant capacity and induces the accumulation of phenolics in B. cinerea-infected 'Xuxiang' kiwifruit. The contents of the main antifungal phenolics in kiwifruit, including caffeic acid, chlorogenic acid and isoferulic acid, increased after DPA treatment. DPA enhanced H2 O2 levels after 0 and 1 days, which promoted catalase (CAT) and superoxide dismutase (SOD) activities, reducing long-term H2 O2 levels. DPA promoted the up-regulation of several kiwifruit defense genes, including CERK1, MPK3, PR1-1, PR1-2, PR5-1 and PR5-2. Furthermore, DPA at 5 mM inhibited B. cinerea symptoms in kiwifruit (95.1% lesion length inhibition) more effectively than the commercial fungicides carbendazim, difenoconazole, prochloraz and thiram. CONCLUSIONS: The antioxidant properties of DPA and the main antifungal phenolics of kiwifruit were examined for the first time. This study uncovers new insights regarding the potential mechanisms used by Bacillus species to induce disease resistance. © 2023 Society of Chemical Industry.
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Antifúngicos , Antioxidantes , Antifúngicos/farmacologia , Botrytis , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologiaRESUMO
CREB-regulated transcription coactivator2 (CRTC2 or TORC2) is a transcriptional coactivator of CREB(cAMP response element binding protein), which affects human energy metabolism through cyclic adenosine phosphate pathway, Mammalian target of rapamycin (mTOR) pathway, Sterol regulatory element binding protein 1(SREBP1), Sterol regulatory element binding protein 2 (SREBP2) and other substances Current studies on CRTC2 mainly focus on glucose and lipid metabolism, relevant studies show that CRTC2 can participate in the occurrence and development of related diseases by affecting metabolic homeostasis. It has been found that Crtc2 acts as a signaling regulator for cAMP and Ca2 + signaling pathways in many cell types, and phosphorylation at ser171 and ser275 can regulate downstream biological functions by controlling CRTC2 shuttling between cytoplasm and nucleus.
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Statins have been proven to be effective in minimizing the risk of cardiovascular adverse events, however, their effect on BP variability is debatable with respect to their significance and their use as a potential anti-hypertensive. Using a meta-analysis approach, the aim of this study was to explore whether certain statins have the potential to lower blood pressure (BP). For the period 2002-2022, Scopus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials databases were searched for the studies that examined the effect of statins on blood pressure in normotensive or hypertensive individuals. Randomized controlled clinical trials that investigated this effect were included based on our inclusion criteria. Our primary outcomes were changes in systolic and diastolic blood pressure (DBP). The final analysis of the study included 49 RCTs involving 45 173 participants randomized to receive either statins or placebo. Among the two groups, the total weighted mean difference (WMD) for systolic blood pressure (ΔSBP) was -1.42 (95% CI: -2.38, -0.46; p = .004) and diastolic blood pressure (ΔDBP) was 0.82 (95% CI: -1.28, -0.36; p = .0005). Despite various studies suggesting the efficacy of statins in blood pressure lowering to be significant and non-significant both, we observed a decrease in SBP and DBP both, although the change was not as large and could be considered significant. A large multicenter, multi-ethnic, large sample pool size, and a long period follow-up study is still required to assert these claims.
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Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Humanos , Pressão Sanguínea , Hipertensão/tratamento farmacológico , Hipertensão/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anti-Hipertensivos/efeitos adversos , Estudos Multicêntricos como AssuntoRESUMO
Generating precise in vivo arterial endothelial hemodynamic microenvironments using microfluidics is essential for exploring endothelial mechanobiology. However, a hemodynamic principle guiding the fabrication of microfluidic systems is still lacking. We propose a hemodynamic similarity principle for quickly obtaining the input impedance of the microfluidic system in vitro derived from that of the arterial system in vivo to precisely generate the desired endothelial hemodynamic microenvironments. First, based on the equivalent of blood pressure (BP) and wall shear stress (WSS) waveforms, we establish a hemodynamic similarity principle to efficiently map the input impedance in vivo to that in vitro, after which the multi-component microfluidic system is designed and fabricated using a lumped parameter hemodynamic model. Second, numerical simulation and experimental studies are carried out to validate the performance of the designed microfluidic system. Finally, the intracellular Ca2+ responses after exposure to different intensities of exercise-induced BP and WSS waveforms are measured to improve the reliability of EC mechanobiological studies using the designed microfluidic system. Overall, the proposed hemodynamic similarity principle can guide the fabrication of a multi-component microfluidic system for endothelial cell mechanobiology.
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Células Endoteliais , Microfluídica , Reprodutibilidade dos TestesRESUMO
Normal-functioning endothelium is crucial to maintaining vascular homeostasis and inhibiting the development and progression of cardiovascular diseases such as atherosclerosis. Exercise training has been proven effective in regulating arterial endothelial function, and the effect of this regulation is closely related to exercise intensity and the status of arterial endothelial function. With this review, we investigated the effects of the exercise of different intensity on the function of arterial endothelium and the underlying molecular biological mechanisms. Existing studies indicate that low-intensity exercise improves arterial endothelial function in individuals who manifest endothelial dysfunction relative to those with normal endothelial function. Most moderate-intensity exercise promotes endothelial function in individuals with both normal and impaired arterial endothelial function. Continuous high-intensity exercise can lead to impaired endothelial function, and high-intensity interval exercise can enhance both normal and impaired endothelial function. In addition, it was demonstrated that the production of vasomotor factors, oxidative stress, and inflammatory response is involved in the regulation of arterial endothelial function under different-intensity exercise interventions. We posit that this synthesis will then provide a theoretical basis for choosing the appropriate exercise intensity and optimize the prescription of clinical exercise for persons with normal and impaired endothelium.
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Objectives: To explore the association between left atrial (LA) strain and the GRACE score in patients with acute coronary syndrome (ACS) and to investigate the utility of LA function in predicting short-term adverse cardiovascular events post ACS. Methods: This retrospective study included ACS patients who underwent coronary angiography (CAG) in two independent cohorts from October 2020 to July 2022. The patients were classified into low-intermediate risk group and high-risk group based on the GRACE score. All participants underwent a transthoracic echocardiogram, with LA strain analysis before CAG. Correlation analysis was used to determine the relationship between LA strain and the GRACE score. The predictive value of LA strain was examined utilizing the area under the curve (AUC). Participants were followed for 10.5 ± 2.9 months for the primary endpoint of major adverse cardiovascular events (MACE). Results: A total of 229 patients were included in this study, including 196 in the primary group and 33 in the validation group. Spearman's correlation analysis showed there was a moderate negative correlation between the GRACE and left atrial reservoir strain (LASr) in both the primary (r = -0.63, P < 0.001) and validation (r = -0.73, P < 0.001) cohorts. Receiver operator characteristic (ROC) curve analysis showed that the AUC of LASr for prediction of the high-risk group was 0.86. Taking LASr 19.6% as the cut-off value, the sensitivity and specificity were 0.71 and 0.92, respectively. The cut-off value of 19.6% remains good at identifying high-risk group in the validation group (AUC = 0.87, sensitivity: 77.8%, specificity: 95.8%). Furthermore, 49 patients reached the endpoint in the primary cohort during the follow-up. On multivariable regression analysis, LASr (P = 0.03) was the independent echocardiographic predictor for the primary endpoint, rather than left atrial volume index (LAVI). Conclusions: LASr can identify high-risk patients with ACS as defined by the GRACE score and may be superior to Max LAVI in predicting incidents of MACE in the short-term following ACS.
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OBJECTIVE: To assess the efficacy of Da Chaihu decoction combined with metformin tablets on patients with type 2 diabetes compared with metformin alone. METHODS: This systematic review and meta-analysis is written based on 2020 PRISMA Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020) reporting guidelines. We reviewed all the relevant studies from a search of the following databases from inception to February 2022 without any language restriction: Excerpta Medica Database (EMBASE), Google Scholar, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database(CBM). Data were extracted and the quality was independently evaluated by two reviewers, based on the inclusion and exclusion criteria. Data were analyzed using the Cochrane software RevMan 5.3. RESULTS: Six randomized controlled trials comprising 516 participants were included. The meta-analysis revealed the Da Chaihu decoction combined with metformin tablets group was significantly superior to the metformin tablets group in terms of fasting blood glucose(FPG) (-0.66 mmol/L; 95 % CI (confidence intervals) [- 1.28, - 0.04]), plasma glucose 2 h after meal (2-h PG) (-1.18 mmol/L; 95 % CI [-1.94, -0.42]) in six RCTs, body mass index (BMI) (-3.07 mmol/L; 95 % CI [-6.89, 0.75]) in three RCTs, glycosylated hemoglobin (HbAlc) (-0.36 mmol/L; 95 % CI [-1.04, 0.31]) in three RCTs, and triglycerides (TG) (-0.76 mmol/L; 95 % CI [-1.37, -0.15]) in two RCTs. In two RCTs, there were significant differences in terms of total cholesterol (TC) (-0.97 mmol/L; 95 % CI [-1.18, -0.76]). CONCLUSIONS: Very low-quality research shows that Da Chaihu decoction combined with metformin tablets exert a certain level of efficacy on patients with type 2 diabetes compared with metformin alone. However, random sequence generation methodology was reported in five studies leading to the low quality of the included studies. None of the six studies depicted the blinding method, allocation concealment, selective reporting, and assessed the purity and potency of the product. This observation requires verification through high-quality, multi-center, double-blinded randomized controlled trials, and assesses the purity and potency of the product.
Assuntos
Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Metformina , Humanos , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Medicamentos de Ervas Chinesas/uso terapêutico , Índice de Massa Corporal , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Toxoptera aurantii Boyer de Fonscolombe (Hemiptera: Aphididae) can attack many plant hosts, including tea (Camellia sinensis L.), citrus (Citrus spp.), lychee (Litchi chinensis Sonn.), banana (Musa spp.), and pineapple (Ananas comasus L.) among others. It is a widely distributed hexapod and one of the most destructive pests in tea plantations, causing enormous economic losses in tea production each year. A high-quality reference genome is important to study the phylogenetics and evolution of T. aurantii because its genome is highly heterozygous and repetitive. We obtained a de novo genome assembly of T. aurantii at the chromosome level using a combination of long Nanopore reads from sequencing with high-throughput chromosome conformation capture technology. When finally assembled, the genome was 318.95 Mb on four chromosomes with a 15.19 Mb scaffold N50. A total of 12,162 genes encoded proteins, while there were 22.01% repetitive sequences that totaled 67.73 Mb. Phylogenetic analyses revealed that T. aurantii and Aphis gossypii parted ways approximately 7.6 million years ago (Mya). We used a combination of long-read single-molecule sequencing with Hi-C-based chromatin interaction maps that resulted in a reference chromosomal level reference genome of T. aurantii that was high quality. Our results will enable the exploration of the genetics behind the special biological features of T. aurantii and also provide a source of data that should be useful to compare the compare genome among the Hemiptera.