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The biofilm-induced "relatively immune-compromised zone" creates an immunosuppressive microenvironment that is a significant contributor to refractory infections in orthopedic endophytes. Consequently, the manipulation of immune cells to co-inhibit or co-activate signaling represents a crucial strategy for the management of biofilm. This study reports the incorporation of Mn2+ into mesoporous dopamine nanoparticles (Mnp) containing the stimulator of interferon genes (STING) pathway activator cGAMP (Mncp), and outer wrapping by M1-like macrophage cell membrane (m-Mncp). The cell membrane enhances the material's targeting ability for biofilm, allowing it to accumulate locally at the infectious focus. Furthermore, m-Mncp mechanically disrupts the biofilm through photothermal therapy and induces antigen exposure through photodynamic therapy-generated reactive oxygen species (ROS). Importantly, the modulation of immunosuppression and immune activation results in the augmentation of antigen-presenting cells (APCs) and the commencement of antigen presentation, thereby inducing biofilm-specific humoral immunity and memory responses. Additionally, this approach effectively suppresses the activation of myeloid-derived suppressor cells (MDSCs) while simultaneously boosting the activity of T cells. Our study showcases the efficacy of utilizing m-Mncp immunotherapy in conjunction with photothermal and photodynamic therapy to effectively mitigate residual and recurrent infections following the extraction of infected implants. As such, this research presents a viable alternative to traditional antibiotic treatments for biofilm that are challenging to manage.
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Respiratory tract infections are the most common triggers for heart failure in elderly people. The healthy respiratory commensal microbiota can prevent invasion by infectious pathogens and decrease the risk of respiratory tract infections. However, upper respiratory tract (URT) microbiome in the elderly is not well understood. To comprehend the profiles of URT microbiota in the elderly, and the link between the microbiome and heart failure, we investigated the oropharyngeal (OP) microbiome of these populations in Heilongjiang Province, located in the North-East of China, a high-latitude and cold area with a high prevalence of respiratory tract infection and heart failure. Taxonomy-based analysis showed that six dominant phyla were represented in the OP microbial profiles. Compared with young adults, the OP in the elderly exhibited a significantly different microbial community, mainly characterized by highly prevalent Streptococcus, unidentified_Saccharibacteria, Veillonella, unidentified_Pre votellaceae, and Neisseria. While unidentified_Prevotellaceae dominated in the young OP microbiome. There was competition for niche dominance between Streptococcus and member of Prevotellaceae in the OP. Correlation analysis revealed that the abundance of unidentified_Saccharibacteria was positive, while Streptococcus was negatively correlated to age among healthy elderly. The bacterial structure and abundance in the elderly with heart failure were much like healthy controls. Certain changes in microbial diversity indicated the potential OP microbial disorder in heart failure patients. These results presented here identify the respiratory tract core microbiota in high latitude and cold regions, and reveal the robustness of OP microbiome in the aged, supplying the basis for microbiome-targeted interventions.IMPORTANCETo date, we still lack available data on the oropharyngeal (OP) microbial communities in healthy populations, especially the elderly, in high latitude and cold regions. A better understanding of the significantly changed respiratory tract microbiota in aging can provide greater insight into characteristics of longevity and age-related diseases. In addition, determining the relationship between heart failure and OP microbiome may provide novel prevention and therapeutic strategies. Here, we compared OP microbiome in different age groups and elderly people with or without heart failure in northeastern China. We found that OP microbial communities are strongly linked to healthy aging. And the disease status of heart failure was not a powerful factor affecting OP microbiome. The findings may provide basic data to reveal respiratory bacterial signatures of individuals in a cold geographic region.
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Regenerating bone defects in diabetic rats presents a significant challenge due to the detrimental effects of reactive oxygen species and impaired autophagy on bone healing. To address these issues, a metformin-modified biomimetic silicified collagen scaffold is developed utilizing the principles of biomimetic silicification. In vitro and in vivo experiments demonstrated that the scaffold enhanced bone tissue regeneration within the diabetic microenvironment through the release of dual bio-factors. Further analysis reveals a potential therapeutic mechanism whereby these dual bio-factors synergistically promoted osteogenesis in areas of diabetic bone defects by improving mitochondrial autophagy and maintaining redox balance. The present study provides critical insights into the advancement of tissue engineering strategies aimed at bone regeneration in diabetic patients. The study also sheds light on the underlying biological mechanisms.
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INTRODUCTION: Hyperglycemia-induced endothelial cell injury is one of the main causes of diabetic vasculopathy. Fat mass and obesity-associated protein (FTO) was the first RNA N6-methyladenosine (m6A) demethylase identified; it participates in the pathogenesis of diabetes. However, the role of FTO in hyperglycemia-induced vascular endothelial cell injury remains unclear. MATERIALS AND METHODS: The effects of FTO on cellular m6A, autophagy, oxidative stress, proliferation, and cytotoxicity were explored in human umbilical vein endothelial cells (HUVECs) treated with high glucose (33.3 mmol/mL) after overexpression or pharmacological inhibition of FTO. MeRIP-qPCR and RNA stability assays were used to explore the molecular mechanisms by which FTO regulates autophagy. RESULTS: High glucose treatment increased m6A levels and reduced FTO protein expression in HUVECs. Wild-type overexpression of FTO markedly inhibited reactive oxygen species generation by promoting autophagy, increasing endothelial cell proliferation, and decreasing the cytotoxicity of high glucose concentrations. The pharmacological inhibition of FTO showed the opposite results. Mechanistically, we identified Unc-51-like kinase 1 (ULK1), a gene responsible for autophagosome formation, as a downstream target of FTO-mediated m6A modification. FTO overexpression demethylated ULK1 mRNA and inhibited its degradation in an m6A-YTHDF2-dependent manner, leading to autophagy activation. CONCLUSIONS: Our study demonstrates the functional importance of FTO-mediated m6A modification in alleviating endothelial cell injury under high glucose conditions and indicates that FTO may be a novel therapeutic target for diabetic vascular complications.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Homólogo de la Proteína 1 Relacionada con la Autofagia , Autofagia , Hiperglucemia , Especies Reactivas de Oxígeno , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Autofagia/efectos de los fármacos , Autofagia/fisiología , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Angiopatías Diabéticas/metabolismo , Angiopatías Diabéticas/genética , Angiopatías Diabéticas/patología , Glucosa/farmacología , Glucosa/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Hiperglucemia/metabolismo , Péptidos y Proteínas de Señalización Intracelular , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Reducing hypertensive myocardial fibrosis is the fundamental approach to preventing hypertensive ventricular remodelling. C1q/TNF-related protein-3 (CTRP3) is closely associated with hypertension. However, the role and mechanism of CTRP3 in hypertensive myocardial fibrosis are unclear. In this study, we aimed to explore the effect of CTRP3 on hypertensive myocardial fibrosis and the potential mechanism. METHODS AND RESULTS: WKY and SHR rats were employed, blood pressure, body weight, heart weight, H/BW were measured, and fibrotic-related proteins, CTRP3 and Collagen I were tested in myocardium at 12 and 20âweeks by immunohistochemical staining and Western blotting, respectively. The results showed that compared with the WKY, SBP, DBP, mean arterial pressure and heart rate (HR) were all significantly increased in SHR at 12 and 20âweeks, while heart weight and H/BW were only increased at 20âweeks. Meanwhile, CTRP3 decreased, while Collagen I increased significantly in the SHR rat myocardium at 20âweeks, which compared to the WKY. Moreover, the expression of α-SMA increased from 12âweeks, Collagen I/III and MMP2/9 increased and TIMP-2 decreased until 20âweeks. In order to explore the function and mechanism of CTRP3 in hypertensive fibrosis, Angiotensin II (Ang II) was used to induce hypertension in primary neonatal rat cardiac fibroblasts in vitro . CTRP3 significantly inhibited the Ang II induced activation of fibrotic proteins, purinergic 2X7 receptor (P2X7R)-NLRP3 inflammasome pathway. The P2X7R agonist BzATP significantly exacerbated Ang II-induced NLRP3 inflammasome activation, which was decreased by the P2X7R antagonists A43079, CTRP3 and MCC950. CONCLUSION: CTRP3 expression was decreased in the myocardium of SHR rats, and exogenous CTRP3 inhibited Ang II-induced fibrosis in cardiac fibroblasts by regulating the P2X7R-NLRP3 inflammasome pathway, suggesting that CTRP3 is a potential drug for alleviating myocardial fibrosis in hypertensive conditions.
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Cardiomiopatías , Hipertensión , Ratas , Animales , Ratas Endogámicas SHR , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Complemento C1q/metabolismo , Ratas Endogámicas WKY , Cardiomiopatías/complicaciones , Miocardio/patología , Hipertensión/complicaciones , Angiotensina II/farmacología , Colágeno/metabolismo , FibrosisRESUMEN
BACKGROUND: Cardiomyocyte apoptosis plays an important role in alcoholic cardiac injury. However, the association between calcium-sensing receptor (CaSR) and alcohol-induced cardiomyocyte apoptosis remain unclear. Therefore, we investigated the role and its moleculer mechanism of CaSR in rat cardiomyocyte apoptosis induced by alcohol. METHODS: Alcohol-induced cardiomyocyte apoptosis in vivo and in vitro model of rats were applied in this study. The expression of CaSR, endoplasmic reticulum stress markers and apoptosis were tested by immunohistological staining, western blot, TUNEL and flow cytometry, respectively. [Ca2+]i were detected by confocal laser scanning microscopy. RESULTS: Compared with the control group, alcohol intake (AI) led to abnormal arrangements of cardiomyocytes and obvious increase of myocardial apoptosis. Moreover, AI also significantly upregulated protein expression of CaSR, GRP94, caspase-12 and CHOP. Alcohol induced apoptosis of cultured cardiomyocytes of rats in a dose-dependent way. Activation of CaSR markedly enhanced cardiomyocyte apoptosis and ERS induced by alcohol, ERS inducer also significantly increased cardiomyocyte apoptosis without activating CaSR. Furthermore, GdCl3 augmented alcohol-induced increase of [Ca2+]i in cardiomyocytes, which was attenuated by NPS2390 but not 4-PBA pre-treatment. CONCLUSIONS: Alcohol could induce cardiomyocyte apoptosis in rats in vivo and in vitro, which was mediated probably via activating CaSR, and then ERS and the increase of the cytosolic [Ca2+]i. This provides a potential target for preventing cardiomyocyte apoptosis and cardiomyopathy induced by alochol.
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Miocitos Cardíacos , Receptores Sensibles al Calcio , Ratas , Animales , Receptores Sensibles al Calcio/metabolismo , Calcio/metabolismo , Apoptosis , Consumo de Bebidas Alcohólicas/efectos adversos , Estrés del Retículo EndoplásmicoRESUMEN
Substituting mineral fertilizers (MFs) with manure nitrogen (N) can not only reduce environmental pollution, but also improve soil quality. However, the effects of various manure N substitution ratios (SRs, the ratio of manure N over total N applied) on soil properties and vegetable yields in China are poorly studied. Here, through a meta-analysis of 667 observations, we assessed the effects of three manure N SRs (low (SR ≤ 35%), medium (35% < SR ≤ 70%), and high (SR > 70%)) on vegetable yields and soil properties (soil organic carbon, SOC; soil total nitrogen, STN; microbial biomass carbon (C) and nitrogen (N), MBC/N; and available phosphorus and potassium, (AP/AK)) in the 0-20 cm soil under different climatic conditions, initial soil properties, and management practices. The results show that the SOC and STN contents increased by 28.5% and 21.9%, respectively, under the medium SRs compared to the MF, which were the highest among the three SRs. Both soil MBC and MBN increased with the increase in the SRs, and the increased ratios in the high SRs reached 203.4% and 119.3%, respectively. In addition, the AP also increased with the increase in the SR, but the AK was not significantly changed with the low and medium SRs compared with the MF. Overall, the medium SR produced the highest vegetable yield among the three SRs with an increase of 18.6%. Additionally, a random forest analysis indicated that the N application rate, planting years, and mean annual precipitation were the most important factors influencing vegetable yield. In conclusion, the SR of 35-70% is more conducive to increasing soil nutrient contents significantly and improves vegetable yields in Chinese vegetable fields.
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Marsdenia tenacissima is a medicinal plant widely distributed in the calcium-rich karst regions of southwest China. However, the lack of a reference genome has hampered the implementation of molecular techniques in its breeding, pharmacology and domestication. We generated the chromosome-level genome assembly in Apocynaceae using combined SMRT sequencing and Hi-C. The genome length was 381.76 Mb, with 98.9% of it found on 11 chromosomes. The genome contained 222.63 Mb of repetitive sequences and 21 899 predicted gene models, with a contig N50 of 6.57 Mb. Phylogenetic analysis revealed that M. tenacissima diverged from Calotropis gigantea at least 13.43 million years ago. Comparative genomics showed that M. tenacissima underwent ancient shared whole-genome duplication. This event, together with tandem duplication, contributed to 70.71% of gene-family expansion. Both pseudogene analysis and selective pressure calculations suggested calcium-related adaptive evolution in the M. tenacissima genome. Calcium-induced differentially expressed genes (DEGs) were mainly enriched in cell-wall-related processes. Domains (e.g. Fasciclin and Amb_all) and cis-elements (e.g. MYB and MYC) frequently occurred in the coding and promoter regions of cell-wall DEGs, respectively, and the expression levels of these genes correlated significantly with those of calcium-signal-related transcription factors. Moreover, calcium addition increased tenacissoside I, G and H contents. The availability of this high-quality genome provides valuable genomic information for genetic breeding and molecular design, and lends insights into the calcium adaptation of M. tenacissima in karst areas.
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Marsdenia , Plantas Medicinales , Calcio , Marsdenia/genética , Filogenia , FitomejoramientoRESUMEN
BACKGROUND: lncRNA, a type of non-coding RNA, plays an important role in the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). In this study, lncRNA and mRNA microarrays were performed to study the change of gene expression during osteogenic differentiation of BM-MSCs. We focused on Hedgehog interacting protein (HHIP), because HHIP mRNA and lncRNA HHIP-AS1 were gradually down-regulated on days 0, 7, and 14 during osteogenic differentiation. In addition, the gene coding lncRNA HHIP-AS1 is located on the anti-sense of Hhip gene, implying the potential interaction between lncRNA HHIP-AS1 and HHIP mRNA. METHODS: BM-MSCs with over-expressed or silenced lncRNA HHIP-AS1 were constructed to explore the biological role of HHIP-AS1 in osteogenic differentiation. BM-MSCs were lysed to determine the alkaline phosphatase activity. Fluorescence in situ hybridization and immunofluorescence were performed to analyze HHIP-AS1, HHIP, RUNX2 and osteocalcin. RESULTS: Overexpression of lncRNA HHIP-AS1 increased HHIP expression, which suppressed Hedgehog signaling pathway, as indicated by the reduction of SMO, Gli1 and Gli2. The suppression of Hedgehog signal was associated with the inhibited osteogenesis. HHIP knockdown abolished the suppression of osteogenesis induced by lncRNA HHIP-AS1 overexpression. Through binding to HHIP mRNA, lncRNA HHIP-AS1 recruited ELAVL1 to HHIP mRNA, whereby increasing the mRNA stability and the protein level. CONCLUSIONS: This study revealed that down-regulation of HHIP due to lncRNA HHIP-AS1 reduction promoted the osteogenic differentiation of BM-MSCs though removing the suppression of Hedgehog signal.
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Células Madre Mesenquimatosas , ARN Largo no Codificante , Proteínas Hedgehog/genética , Osteogénesis/genética , ARN Largo no Codificante/genética , Hibridación Fluorescente in Situ , Diferenciación Celular/genética , ARN Mensajero , Transducción de Señal/genética , Células CultivadasRESUMEN
In this study, we performed a meta-analysis to investigate the anesthesia effects of remifentanil plus dexmedetomidine versus remifentanil alone in cardiac surgery. Literature search was performed on PubMed, Web of Science, Embase, China Knowledge Infrastructure, Wanfang Data, and other databases for relevant literature published in English or Chinese before October 2021. A total of 17 studies, consisting of 1350 patients, were included in this study. Of these, 10 studies showed that remifentanil plus dexmedetomidine had a good anesthesia effect in cardiac surgery (OR = 3.61, 95% CI: 1.73, 7.52, P < 0.001), and 8 studies showed that the Ramsay score test of anesthesia (SMD = 0.88; 95% CI: -0.77, 2.53; P < 0.001) in the experimental group was better than that in the control group. In addition, changes in the hemodynamic heart rate (SMD = -0.74; 95% CI: -1.41, -0.07; P < 0.001) and mean arterial pressure (SMD = -0.18; 95% CI: -0.72, 0.36; P < 0.001) of the two groups of anesthesia were counted in 17 studies, which also showed that the anesthesia effect of remifentanil plus dexmedetomidine was good. Thus, remifentanil plus dexmedetomidine may be a more promising option for cardiac surgery anesthesia than remifentanil alone.
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Anestésicos , Procedimientos Quirúrgicos Cardíacos , Dexmedetomidina , Dexmedetomidina/farmacología , Humanos , Piperidinas/farmacología , RemifentaniloRESUMEN
The global coronavirus disease 2019 (COVID-19) pandemic has led to a health crisis. It remains unclear how anxiety affects blood pressure (BP) and cardiovascular risk among older patients with hypertension. In this study, we extracted longitudinal data on home BP monitored via a smartphone-based application in 3724 elderly patients with hypertension from a clinical trial (60-80 years; 240 in Wuhan and 3484 in non-Wuhan areas) to examine changes in morning BP during the COVID-19 outbreak in China. Anxiety was evaluated using Generalized Anxiety Disorder-7 item scores. Changes in morning systolic BP (SBP) were analyzed for five 30-day periods during the pandemic (October 21, 2019 to March 21, 2020), including the pre-epidemic, incubation, developing, outbreak, and plateau periods. Data on cardiovascular events were prospectively collected for one year. A total of 262 individuals (7.0%) reported an increased level of anxiety, and 3462 individuals (93.0%) did not. Patients with anxiety showed higher morning SBP than patients without anxiety, and the between-group differences in SBP change were +1.2 mmHg and +1.7 mmHg during the outbreak and plateau periods (P < 0.05), respectively. The seasonal BP variation in winter among patients with anxiety was suppressed during the pandemic. Anxious patients had higher rates of uncontrolled BP. During the 1-year follow-up period, patients with anxiety had an increased risk of cardiovascular events with a hazard ratio of 2.47 (95% confidence interval, 1.10-5.58; P = 0.03). In summary, COVID-19-related anxiety was associated with a short-term increase in morning SBP among older patients and led to a greater risk of cardiovascular events. (ClinicalTrials. gov number, NCT03015311).
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COVID-19 , Hipertensión , Anciano , Anciano de 80 o más Años , Ansiedad/epidemiología , Trastornos de Ansiedad/epidemiología , Presión Sanguínea/fisiología , Monitoreo Ambulatorio de la Presión Arterial , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Persona de Mediana Edad , PandemiasRESUMEN
ABSTRACT: MicroRNAs (miRNAs) are noncoding RNAs that play an important role in the mechanisms of diabetic cardiomyopathy (DCM); however, whether human recombinant relaxin-3 (H3 relaxin) inhibits myocardial injury in DCM rats and the underlying mechanisms involving miRNAs remain unknown. miRNA expression profiles were detected using miRNA microarray and bioinformatics analyses of myocardial tissues from control, DCM, and H3 relaxin-administered DCM groups, and the regulatory mechanisms of the miRNAs were investigated. A total of 5 miRNAs were downregulated in the myocardial tissues of DCM rats and upregulated in H3 relaxin-treated DCM rats, and 1 miRNA (miRNA let-7d-3p) was increased in the myocardial tissue of DCM rats and decreased in H3 relaxin-treated DCM rats as revealed by miRNA microarray and validated by real-time polymerase chain reaction. Important signaling pathways were found to be triggered by the differentially expressed miRNAs, including metabolism, cancer, Rap1, PI3K-Akt, and MAPK signaling pathways. The study revealed that H3 relaxin improved glucose uptake in DCM rats, potentially via the regulation of miRNA let-7d-3p.
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Diabetes Mellitus , Cardiomiopatías Diabéticas , MicroARNs , Relaxina , Animales , Biología Computacional , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/prevención & control , Perfilación de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , Fosfatidilinositol 3-Quinasas , Ratas , Relaxina/genéticaRESUMEN
Osteoporosis, a bone disease is caused by the deterioration of bone and shows an enhanced risk of bone fracture and decreasing bone mineral density. Unfortunately, the available radiological techniques are expensive, and have disadvantages such as radiation intake, need a specialist to handle the instrument, and so forth. This research is focused to develop a point-of-care system to identify osteocalcin on current-volt sensor, which helps to diagnose the bone metabolism and prognostics. Antiosteocalcin antibody was attached on the electrode through the silane-modified iron material. The antibody-immobilized sensing surface was utilized to identify the level of osteocalcin and the detection limit of 100 pg/ml reached on linear concentrations of 0.01-3000 ng/ml. Calculations were made by triplicates (n = 3; 3δ) on the determination coefficient of y = 0.2637x-0.6012; R2 = 0.9319. Further, control proteins failed to bind with immobilized antibody, confirmed by the specific osteocalcin detection. This research is to identify the osteoporosis biomarker and to help determine the conditions with osteoporosis.
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Osteoporosis , Humanos , Osteocalcina , Osteoporosis/diagnóstico , Osteoporosis/etiología , Osteoporosis/metabolismo , Densidad Ósea , Huesos/metabolismo , Minerales/metabolismo , Anticuerpos/metabolismoRESUMEN
Sodium and potassium intake in hypertensive patients in China is not clear. The authors aimed to investigate the distribution of sodium and potassium intake in hypertensive patients in China, and to analyze the relationship between sodium and potassium intake and blood pressure. The study was performed in 130 hospitals from 23 provinces across China from 2016 to 2019. Finally, 9501 hypertensive patients average aged 54 years were included. 24 h urinary sodium and potassium excretion were measured. Distribution of urinary electrolytes were described according to age, gender and region. The association between urinary electrolytes and blood pressure was analyzed by multivariate linear regression. Hypertensive patients exhibited an average 24 h urinary sodium and potassium excretion of 156.7 ± 81.5 mmol/d and 39.2 ± 20.2 mmol/d (equivalent to sodium chloride of 9.2 g/d, potassium chloride of 2.9 g/d), sodium/potassium ratio (median) of 4.14 (2.92,5.73). Urinary electrolytes were lower in women than men (sodium: 171.1 vs 138.7, p < .05; potassium: 40.3 vs 37.7, p < .05), in the elderly than in the younger (sodium: 168.7 vs 139.9, p < .05; potassium: 39.5 vs. 37.5, p < .05). For every 1 unit of Na/K ratio increase, blood pressure increased by 0.46/0.24 mmHg. Blood pressure was 2.75/1.27 mmHg higher in quartile 4 than quartile 1 of Na/K. It remains high sodium and low potassium for hypertensive patients in China. Decreased sodium, Na/K ratio and increased potassium may help for blood pressure management.
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Hipertensión , Sodio , Anciano , Presión Sanguínea , China/epidemiología , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Masculino , PotasioRESUMEN
BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).
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Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Femenino , Humanos , Hipertensión/complicaciones , Hipotensión/inducido químicamente , Incidencia , Masculino , Persona de Mediana Edad , Nivel de Atención , SístoleRESUMEN
ABSTRACT: There has been no ideal surgical approach for lumbar brucella spondylitis (LBS). This study aims to compare clinical efficacy and safety of posterior versus anterior approaches for the treatment of LBS.From April 2005 to January 2015, a total of 27 adult patients with lumbar brucella spondylitis were recruited in this study. The patients were divided into 2 groups according to surgical approaches. Thirteen cases in group A underwent 1-stage anterior debridement, fusion, and fixation, and 14 cases in group B underwent posterior debridement, bone graft, and fixation. The clinical and surgical outcomes were compared in terms of operative time, intraoperative blood loss, hospitalizations, bony fusion time, complications, visual analog scale score, recovery of neurological function, deformity correction.Lumbar brucella spondylitis was cured, and the grafted bones were fused within 11âmonths in all cases. It was obviously that the operative time and intraoperative blood loss of group A were more than those of group B (Pâ=â.045, Pâ=â.009, respectively). Kyphotic deformity was signifcantly corrected in both groups after surgery; however, the correction rate was higher in group B than in group A (Pâ=â.043). There were no significant differences between the two groups in hospitalizations, bony fusion time, and visual analog scale score in the last follow-up (Pâ=â.055, Pâ=â.364, Pâ=â.125, respectively).Our results suggested that both anterior and posterior approaches can effectively cure lumbar brucella spondylitis. Nevertheless, posterior approach gives better kyphotic deformity correction, less surgical invasiveness, and less complications.
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Trasplante Óseo/métodos , Brucelosis/cirugía , Vértebras Lumbares/cirugía , Dolor Postoperatorio/diagnóstico , Espondilitis/cirugía , Adulto , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Trasplante Óseo/efectos adversos , Brucella/aislamiento & purificación , Brucelosis/diagnóstico , Brucelosis/microbiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Dimensión del Dolor/estadística & datos numéricos , Dolor Postoperatorio/etiología , Espondilitis/diagnóstico , Espondilitis/microbiología , Resultado del TratamientoRESUMEN
Chemokines may promote the formation and instability of atherosclerotic plaque, which is the most common cause of acute coronary syndrome. The aim of this study was to clarify the function of monocyte chemotactic protein-3 (MCP-3) in the stability of atherosclerotic plaque, to determine the role of tissue factor pathway inhibitor (TFPI) on the development and stability of atherosclerotic plaques, and to further elucidate the anti-atherosclerotic mechanism of TFPI with the emphasis on chemokine MCP-3. We constructed an adenovirus-mediated shRNA against mouse MCP-3 (Ad-MCP-3-shRNA) and an adenovirus-containing TFPI (Ad-TFPI), and tranferred them in a model of vulnerable plaque in ApoE-/- mice respectively. Here, we reported that MCP-3-shRNA and TFPI could both reduce the plaque area and decrease the content of lipids and macrophages, on the contrary, the fibrous cap thickness and content of collagen and smooth muscle cells were increased. In addition, the expression of MCP-3 and CC chemokine receptor 2 (CCR2) was decreased by TFPI transfer. These data provide the first in vivo evidence that MCP-3 is a major contributor to the unstability of atherosclerotic plaque and TFPI may exert its anti-atherosclerotic effects and promote stabilisation of plaque at least partly through inhibiting MCP-3/CCR2 pathway, which may be a new therapeutic method for atherosclerosis.
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Apolipoproteínas E/genética , Quimiocina CCL7/genética , Lipoproteínas/genética , Placa Aterosclerótica/patología , Adenoviridae/genética , Animales , Silenciador del Gen , Humanos , Metabolismo de los Lípidos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Noqueados , Miocitos del Músculo Liso/metabolismo , Placa Aterosclerótica/genéticaRESUMEN
To report the blood pressure (BP) data obtained in the May Measurement Month (MMM) 2019 in China. Study participants were recruited if ≥18 years of age and had ideally not had their BP measured for ≥1 year. BP was measured three times consecutively with a 1-min interval in the sitting position, using a validated electronic BP monitor. Trained volunteer investigators administered a questionnaire to collect information on lifestyle, medical history, and use of medications. The measurement was performed in 238 387 participants in 250 sites across 31 China provinces. The majority of screening took place in hospitals or clinics (78.7%), with 17.1% in outdoor public areas and 4.2% in other settings. The study participants included 127 853 women (53.6%) and had a mean (±SD) age of 48.9 ± 16.2 years. The mean (of readings two and three) systolic/diastolic BP was 121.8/73.8 mmHg. In all hypertensive patients (n = 66 181, 27.8%), the awareness, treatment, and control rates of hypertension were 51.5%, 48.4%, and 29.1%, respectively. Linear regression models showed differences in systolic and diastolic BP according to sex and age and several other major characteristics, such as previous stroke, myocardial infarction, and diabetes mellitus, antihypertensive medication use and known hypertension, previous hypertension in pregnancy and current pregnancy, alcohol intake and current smoking, and body mass index. The MMM 2019 campaign has been successful in measuring BP in a large member of participants in China.
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Patients with essential hypertension (EH) and hyperhomocysteinemia (HHCY) suffer from more increased thrombotic events than those in EH alone. However, the underlying mechanisms for this effect are not well understood. This study hypothesized that neutrophil extracellular trap (NET) releasing may be triggered by HHCY in patients in EH, thereby predisposing them to a more hypercoagulable state. Using a modified-capture enzyme-linked immunosorbent assay (ELISA) method, we observed that cell-free DNA (CF-DNA) and myeloperoxidase DNA (MPO-DNA) in patients With EH and HHCY were significantly higher. The NET formation was also positively correlated with homocysteine levels, neutrophil-lymphocyte ratio (NLR), and hypercoagulable markers (thrombin-antithrombin complex, D-dimers). Furthermore, neutrophils from patients in EH with HHCY were found to be predisposed to amplified NET release when compared to patients in EH without HHCY or CTR. Coagulation function assays showed that NETs in patients With EH and HHCY resulted in a significantly increased ability to generate thrombin and fibrin than in those in EH without HHCY or CTR. These procoagulant effects of NETs in patients With EH and HHCY were markedly inhibited (approximately 70%) by the cleavage of NETs with DNase I. Isolated NETs from patients With EH and HHCY neutrophils also exerted a strong cytotoxic effect on endothelial cells (ECs), converted them to apoptosis. This study revealed a previously unrecognized association between the hypercoagulable state and neutrophils in patients With EH and HHCY. Therefore, blocking NETs may represent a new therapeutic objective for preventing thrombosis in these patients.
Asunto(s)
Trampas Extracelulares , Hiperhomocisteinemia , Coagulación Sanguínea , Células Endoteliales , Hipertensión Esencial , Humanos , Hiperhomocisteinemia/complicaciones , NeutrófilosRESUMEN
The exact mechanism of the prothrombotic state of essential hypertension (EH) patients remains elusive. Our objective was to assess whether phosphatidylserine (PS) exposure on endothelial cells (ECs), platelets, and microparticles (MPs) can account for the hypercoagulability in EH patients. PS exposure on cells and MPs, mainly from platelets and ECs was analyzed with flow cytometry. Procoagulant activity (PCA) was evaluated by purified coagulation complex assays, clotting time, and fibrin turbidity. We found that EH patients exhibited elevated levels of PS+ platelets, serum-cultured ECs, MPs, endothelial-derived MPs and platelet-derived MPs compared to the controls (all P < 0.05). Moreover, platelets and MPs from the patients and their sera-cultured ECs showed markedly enhanced intrinsic/extrinsic FXa, thrombin, and fibrin generation, and greatly shortened coagulation time. This PCA could be blocked approximately 80%, by the addition of lactadherin. Furthermore, we detected elevated levels of IL-8, IL-6, and TNF-α in EH patients could activate platelets/ECs and induce elevated PS exposure on their membranes. Our results suggest that inflammatory cytokines could enhance procoagulant activity of platelets and endothelial cells via their PS exposure in EH patients. As such, a PS blockade may be a viable therapeutic strategy for treating such patients.