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1.
Artigo em Inglês | MEDLINE | ID: mdl-33465322

RESUMO

RATIONALE: Posttranscriptional modifications are implicated in vascular remodeling of pulmonary hypertension (PH). N6-methyladenosine (m6A) is an abundant RNA modification that is involved in various biological processes. Whether m6A RNA modification and m6A effector proteins play a role in pulmonary vascular remodeling and PH have not been demonstrated. OBJECTIVES: To determine whether m6A modification and m6A effectors contribute to the pathogenesis of PH. METHODS: m6A modification and YTHDF1 expression were measured in human and experimental PH samples. RIP analysis and m6A-sequencing were employed to screen m6A-marked transcripts. Genetic approaches were employed to assess the respective roles of YTHDF1 and MAGED1 in PH. Primary cells isolation and cultivation were utilized for function analysis of pulmonary artery smooth muscle cells (PASMCs). MEASUREMENTS AND MAIN RESULTS: Elevated m6A levels and increased YTHDF1 protein expression were found in human and rodent PH samples as well as in hypoxic PASMCs. Deletion of YTHDF1 ameliorated PASMCs proliferation, phenotype switch and PH development both in vivo and in vitro. m6A RIP analysis identified MAGED1 as an m6A-regulated gene in PH and genetic ablation of MAGED1 improved vascular remodeling and hemodynamic parameters in SU5416/Hypoxia mice. YTHDF1 recognized and promoted translation of MAGED1 in an m6A dependent manner which was absent in METTL3 deficient PASMCs. In addition, MAGED1 silencing inhibited hypoxia-induced proliferation of PASMCs through downregulating PCNA. CONCLUSIONS: YTHDF1 promotes PASMCs proliferation and PH by enhancing MAGED1 translation. This study identifies the m6A RNA modification as a novel mediator of pathological changes in PASMCs and PH.

2.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 35(1): 124-129, 2021 Jan 15.
Artigo em Chinês | MEDLINE | ID: mdl-33448210

RESUMO

Objective: To summarize research progress of change in bone mineral density (BMD) after knee arthroplasty and its diagnostic methods, influencing factors, and drug prevention and treatment. Methods: The relevant literature at home and abroad was reviewed and summarized from research status of the advantages and disadvantages of BMD assessment methods, the trend of changes in BMD after knee arthroplasty and its influencing factors, and the differences in effectiveness of drugs. Results: The central BMD and mean BMD around the prosthesis decrease after knee arthroplasty, which is closely associated with body position, age, weight, daily activities, and the fixation methods, design, and material of prosthesis. Denosumab, bisphosphonates, and teriparatide et al. can decrease BMD loss after knee arthroplasty. Conclusion: BMD after knee arthroplasty decreases, which is related to various factors, but the mechanism is unclear. At present, some inhibitors of bone resorption can decrease BMD loss after knee arthroplasty. However, its long-term efficacy remains to be further explored.


Assuntos
Artroplastia do Joelho , Conservadores da Densidade Óssea , Reabsorção Óssea , Artroplastia do Joelho/efeitos adversos , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/etiologia , Reabsorção Óssea/prevenção & controle , Humanos , Tíbia/cirurgia
3.
Cancer Gene Ther ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33323961

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive cancer, and rapidly progresses following relapse in advanced stage. This cancer is usually associated with worse overall survival, so the carcinogenesis of TNBC needs to be further explored to find more effective therapies. In this study, we intended to identify the roles of YY1-mediated long non-coding RNA Kcnq1ot1 in TNBC. First, the paired samples of tumor tissues and adjacent tissues were collected to determine YY1, lncRNA Kcnq1ot1, and PTEN expression using RT-qPCR and Western blot analysis followed by analysis of the relationship between them and patient survival. The results revealed that YY1 and lncRNA Kcnq1ot1 were upregulated in TNBC tissues, and high expression of YY1 and lncRNA Kcnq1ot1 was associated with poor patient survival. Then, ChIP and MSP assays were employed to explore interactions between YY1, lncRNA Kcnq1ot1, and PTEN gene. We obtained that YY1 upregulated lncRNA Kcnq1ot1, which mediated PTEN methylation via DNMT1, thus decreasing PTEN expression. Afterward, TNBC cells were examined for their viability using functional assays with the results displaying that overexpression of YY1 facilitated TNBC cell proliferation, invasion, and migration. Mechanistically, upregulated YY1 repressed tumor growth by inhibiting PTEN via upregulation of lncRNA Kcnq1ot1. Mouse models were also constructed, and the above effects of YY1, lncRNA Kcnq1ot1, and PTEN on TNBC were also established in vivo. Taken together, this study demonstrates that the silencing of YY1 exerted tumor-suppressive effects on TNBC by modulating lncRNA Kcnq1ot1/DNMT1/PTEN pathway, in support of further investigation into anti-tumor therapy for TNBC.

4.
Acta Biomater ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33340734

RESUMO

Porous Fe-Mn biodegradable scaffolds fabricated by 3D printing are considered as a promising alternative biomaterial for repairing load-bearing bone defects. However, the mechanical adaptability, the thoughtful in vitro biocompatibility and especially the long-term in vivo osseointegration and biodegradation performances have not been investigated to date. Herein, the porous Fe-30Mn biodegradable scaffolds fabricated by selective laser melting (SLM) had the adjustable elastic modulus ranging from 10.04 GPa to 14.88 GPa by regulating the porosity from 37.89% to 47.17%. In vitro indirect and direct cytotoxicity as well as cell adhesion experiments demonstrated biocompatibility and a large number of cells with stretched filopodia adhered to the scaffolds. 48 weeks in vivo experiments showed that the scaffolds had no harm to liver and kidney, and exhibited long-term in vivo osseointegration performance. Volumes of the scaffolds decreased by 10.1-20.9%, and the retrieved scaffolds showed decreased elastic modulus (decreased by 34.1-42.3%) and yield strength (decreased by 15.8-23.3%) after the 48 weeks in vivo degradation. The Fe-30Mn-femoral condyle complex maintained the same level of stiffness as intact controls during 48 weeks. In summary, the porous Fe-30Mn biodegradable scaffolds fabricated by SLM could be a reliable and practical alternative for repairing load-bearing bone defects.

5.
Zhongguo Gu Shang ; 33(11): 1032-6, 2020 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-33269853

RESUMO

OBJECTIVE: To study the distribution and drug resistance of pathogens causing periprosthetic infections after hip and knee arthroplasty, and to formulate prevention and treatment strategies for drug-resistant bacteria. METHODS: The data of 146 cases of periprosthetic infection after primary hip and knee arthroplasty from 2010 to 2015 were collected, including 111 cases of periprosthetic infection after hip arthroplasty and 35 cases of periprosthetic infection after knee arthroplasty. The culture positive rate, pathogenic bacteria composition and drug resistance rate were counted over the years, and the change trend of pathogen distribution and drug resistance was analyzed. RESULTS: One hundredand eight strains of pathogenic bacteria were detected in 146 cases, and the positive rate of culture was 73.97%. Gram positive bacteria accounted for 55.48%, Staphylococcus epidermidis and Staphylococcus aureus accounted for 25.34% and 15.07% respectively. Gram negative bacteria accounted for 13.01%, including Enterobacter cloacae, Pseudomonas aeruginosa and Escherichia coli. There were 4 cases of Mycobacterium tuberculosis infection and mixed infection. The results of culture over the years showed that the constituent ratio of Gram positive bacteria had an increasing trend, fluctuating from 39.13% to 76.47%. The results of drug sensitivity showed that the pathogens were highly resistant to ß-lactams, quinolones, clindamycin and gentamicin, and the drug resistance rate was increasing, but it was still sensitive to rifampicin, nitrofurantoin, tigecycline, linezolid and vancomycin. CONCLUSION: Gram positive bacteria are the main pathogens of periprosthetic infection, and the proportion is increasing gradually.The pathogens have high resistance to many kinds of antibiotics, and the resistance rate is still increasing. To strengthen the monitoring of the distribution and drug resistance of pathogenic bacteria is helpful to grasp its change trend and formulate targeted prevention and control strategies.

6.
Chemosphere ; : 128648, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33268100

RESUMO

Advanced oxidation processes (AOPs) have been widely accepted as an efficient and promising strategy for treating organic pollutants, is mainly dominated by hydroxyl radicals (•OH); however, its further practical application has been hindered by its low decomposition rate of H2O2. Hence, for the first time, we propose an eco-friendly and facile synthesis methodology synthesize water-soluble Co9S8 quantum dots (QDs) derived from commercial cobalt disulfide (CoS2), which can serve as excellent co-catalysts to dramatically enhance the decomposition rate of H2O2. It is demonstrated that the conversion rate of H2O2 into •OH is ca. 80.02% promoted by Co9S8 QDs, whereas the conventional Fenton process is ca. 34.9%. The result shows that unsaturated edged S atoms on the surface of Co9S8 play a pivotal role in this enhancement, where the number of protons will react with sulfur atoms to form H2S and expose reductive metallic active sites to accelerate the Fe3+/Fe2+ conversion. In addition, to tackle the issue for difficult recovery of liquid quantum dots, the magnetic Co9S8 QDs/Fe3O4 nanoparticles are particularly synthesized, which show excellent performance for degradation of 20 mg/L Rhodamine B (RhB). Moreover, the TOC degradation rate can remain stable at 80% even after five cycles. It is expected that this work will provide a new pathway of thinking in the Fenton process and impulse the usage of liquid quantum dots in practical AOPs application.

7.
J Cell Mol Med ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135363

RESUMO

OBJECTIVES: Degenerative disc disease is characterized by an enhanced breakdown of its existing nucleus pulposus (NP) matrix due to the dysregulation of matrix enzymes and factors. Ubiquitin-specific protease 15 (USP15) is reported to be abnormal in certain human diseases. However, its role in NP degeneration remains unclear. Therefore, we aimed to explore the function of USP15 in degenerative NP cell specimens. METHODS: We induced gene silencing and overexpression of USP15 in degenerative NP cells using RNA interference (RNAi) and a lentiviral vector, respectively. qRT-PCR and Western blotting were used to determine gene and protein expression levels. Cell apoptosis was analysed via flow cytometry. Protein interaction was examined by performing a co-immunoprecipitation assay. Furthermore, the PI3K inhibitor LY294002 and agonist IGF-1 were used to investigate the link between USP15 and AKT in NP degeneration. RESULTS: We found that USP15 was up-regulated in degenerative NP cells and that its overexpression accelerated the process of apoptosis. Moreover, USP15 expression levels negatively correlated with AKT phosphorylation in degenerative NP cells. Furthermore, targeting and silencing USP15 with miR-338-3p and studying its interaction with FK506-binding protein 5 (FKBP5) revealed enhancement of FKBP5 ubiquitination, indicating that USP15 is a component of the FKBP5/AKT signalling pathway in degenerative NP cells. CONCLUSIONS: Our results show that USP15 exacerbates NP degradation by deubiquitinating and stabilizing FKBP5. This in turn results in the suppression of AKT phosphorylation in degenerative NP cells. Therefore, our study provides insights into the understanding of USP15 function as a potential molecule in the network of NP degeneration.

8.
Int J Exp Pathol ; 101(6): 215-222, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33146930

RESUMO

Tumour-associated macrophage (TAM) polarization is associated with hepatocellular carcinoma but the molecular mechanism of this polarization is still unknown. Peripheral blood mononuclear cells were induced to differentiate into M0, M1 and M2 macrophages and TAMs. TAMs were transfected with pcDNA3.1-GAS5, pcDNA3.1-NC, si-GAS5, si-PTEN or si-Ctrl. A human liver cancer cell line (SMCC-7721) was incubated with the modified TAM supernatant. Quantitative real-time PCR and Western blot were performed to detect gene and protein expression. The cell proliferation and invasion properties of the SMCC-7721 cells were detected by MTT and Transwell assays. GAS5 is up-regulated in M1 macrophages and down-regulated in M2 macrophages and TAMs. GAS5 overexpression promoted M1-like polarization of TAMs and inhibited M2-like polarization of TAMs. Moreover, GAS5 promoted the expression of PTEN in TAMs. PTEN-silenced TAM supernatant treatment promoted cell proliferative and invasive properties of the SMCC-7721 cells and diminished the effect of GAS5-overexpressed TAM supernatant on the cell proliferation and invasion by SMCC-7721 cells. Our results demostrared that GAS5 overexpression inhibited M2-like polarization of TAMs by enhancing PTEN expression, thereby inhibiting cell proliferation and invasion by SMCC-7721 cells. Thus, our results suggest that GAS5 may be a new therapeutic target for HCC treatment.

9.
Transp Res E Logist Transp Rev ; 143: 102095, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33013184

RESUMO

This special issue explores new practices and applications in logistics and supply chain management for luxury goods. This editorial note summarizes the discussions on different important topics, including sustainability, sourcing, advertising, behavioral consideration, product sharing, and channel management among other aspects.

10.
Chem Commun (Camb) ; 56(87): 13429-13432, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33043926

RESUMO

Utilizing the C4 reactive site of cyclopropyl ketones and a chiral N,N'-dioxide-scandium(iii) complex as a catalyst, a concise ring-opening/cyclization/thio-Michael cascade method was developed for the synthesis of chiral benzothiazole derivatives from a simple 2-aminothiophenol material. The kinetic resolution and the origin of stereoselectivity were elucidated via a possible catalytic model.

11.
Nat Commun ; 11(1): 5155, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33056995

RESUMO

The diverse physiological functions of tocotrienols have listed them as valuable supplementations to α-tocopherol-dominated Vitamin E products. To make tocotrienols more readily available, tocotrienols-producing S. cerevisiae has been constructed by combining the heterologous genes from photosynthetic organisms with the endogenous shikimate pathway and mevalonate pathway. After identification and elimination of metabolic bottlenecks and enhancement of precursors supply, the engineered yeast can produce tocotrienols at yield of up to 7.6 mg/g dry cell weight (DCW). In particular, proper truncation of the N-terminal transit peptide from the plant-sourced enzymes is crucial. To further solve the conflict between cell growth and tocotrienols accumulation so as to enable high-density fermentation, a cold-shock-triggered temperature control system is designed for efficient control of two-stage fermentation, leading to production of 320 mg/L tocotrienols. The success in high-density fermentation of tocotrienols by engineered yeast sheds light on the potential of fermentative production of vitamin E tocochromanols.


Assuntos
Fermentação/fisiologia , Microbiologia Industrial/métodos , Engenharia Metabólica , Saccharomyces cerevisiae/metabolismo , Tocotrienóis/metabolismo , Aclimatação/genética , Vias Biossintéticas/genética , Temperatura Baixa/efeitos adversos , Resposta ao Choque Frio/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Fúngica da Expressão Gênica , Mutação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
12.
J Pharm Sci ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049261

RESUMO

Dropping during shipping and handling of liquid biopharmaceutical formulations has long been known to cause protein degradation and aggregation. On the other hand, accidental dropping of freeze-dried protein formulations is generally considered not a major issue for biopharmaceutical quality. Reports of stability and especially the underling degradation mechanism(s) during shipping and handling of freeze-dried protein formulations were rarely seen in literature. In this manuscript, we report an interesting phenomenon in which repeated dropping of freeze-dried monoclonal antibody X (mAb-X) formulation powder resulted in significant protein sub-visible particles (SbVPs) in the reconstituted liquid as determined by the sensitive particle analyzing technique micro-flow imaging (MFI). Free radicals were observed after repeated dropping by electron paramagnetic resonance (EPR). Formation of SbVPs could be partially inhibited by the free radical scavengers methionine and 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidin-yloxy free radical (CTPO). The amount of free radicals and SbVPs was correlated to the sample temperature during dropping. Therefore we propose that the high temperature formed during dropping was probably the root cause for protein aggregation and free radical formation, which could further cause protein aggregation. Our observations suggest that similar to liquid protein formulations, dropping of freeze-dried protein formulations should also be avoided or mitigated.

13.
Pharm Res ; 37(11): 228, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33098017

RESUMO

PURPOSES: The main purposes of this article are to describe an unprecedented phenomenon in which significant amount of a shoulder peak impurity was observed during normal non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis of a recombinant fusion protein X, and to evaluate the root cause for this phenomenon. METHODS: A series of experiments were conducted to study the nature of this degradation. Effects of iodoacetamide (IAM), heating temperature, duration, and SDS on the formation of this specific impurity were evaluated using a variety of characterization techniques. RESULTS: The formation of the impurity as observed in CE-SDS was actually due to alkylation of lysine and serine residues with IAM, as confirmed by peptide mapping and LC-MS/MS, which increased the molecular weight and therefore decreased the electrophoretic mobility. The amount of impurity was also strongly dependent on sample preparation conditions including the presence or absence of SDS. CONCLUSIONS: Our study clearly suggested that even though IAM has been used extensively as an alkylation reagent in the traditional non-reducing CE-SDS analysis of monoclonal antibodies and other proteins, alkylation with IAM could potentially lead to additional impurity peak, and therefore complicating analysis. Therefore, before performing CE-SDS and other analyses, the effects of sample preparation procedures on analytical results must be evaluated. For protein X, IAM should be excluded for CE-SDS analysis.

14.
Beilstein J Nanotechnol ; 11: 1361-1370, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974114

RESUMO

We studied the structural and electronic properties of 2,3,9,10-tetrafluoropentacene (F4PEN) on Ag(111) via X-ray standing waves (XSW), low-energy electron diffraction (LEED) as well as ultraviolet and X-ray photoelectron spectroscopy (UPS and XPS). XSW revealed that the adsorption distances of F4PEN in (sub)monolayers on Ag(111) were 3.00 Å for carbon atoms and 3.05 Å for fluorine atoms. The F4PEN monolayer was essentially lying on Ag(111), and multilayers adopted π-stacking. Our study shed light not only on the F4PEN-Ag(111) interface but also on the fundamental adsorption behavior of fluorinated pentacene derivatives on metals in the context of interface energetics and growth mode.

15.
Transp Res E Logist Transp Rev ; 142: 102066, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32905037

RESUMO

We examine the value of blockchain for disclosing secondhand product quality in a supply chain in which contributors consign secondhand products to an online platform that resells them and competes with suppliers of new products. We find that the platform is more likely to provide a uniform (differential) pricing strategy with new products when the revenue sharing portion of the consignment contract is sufficiently low (high). Moreover, surprisingly, without blockchain, the platform prefers moderately perceived and true quality secondhand products, instead of extremely high or low quality. With blockchain, the platform prefers selling low-uniqueness and low-quality (or high-uniqueness and high-quality) secondhand products. Furthermore, we find that with blockchain, horizontal integration is more effective in improving the supply chain's total profit. A win-win-win outcome can be achieved for the platform, the supplier, and consumers in a supply chain that sells low-uniqueness products.

16.
World J Clin Cases ; 8(16): 3431-3439, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32913849

RESUMO

BACKGROUND: Conventional plain X-ray images of rats, the most common animals used as degeneration models, exhibit unclear vertebral structure and blurry intervertebral disc spaces due to their small size, slender vertebral bodies. AIM: To apply molybdenum target X-ray photography in the evaluation of caudal intervertebral disc (IVD) degeneration in rat models. METHODS: Two types of rat caudal IVD degeneration models (needle-punctured model and endplate-destructed model) were established, and their effectiveness was verified using nuclear magnetic resonance imaging. Molybdenum target inspection and routine plain X-ray were then performed on these models. Additionally, four observers were assigned to measure the intervertebral height of degenerated segments on molybdenum target plain X-ray images and routine plain X-ray images, respectively. The degeneration was evaluated and statistical analysis was subsequently conducted. RESULTS: Nine rats in the needle-punctured model and 10 rats in the endplate-destructed model were effective. Compared with routine plain X-ray images, molybdenum target plain X-ray images showed higher clarity, stronger contrast, as well as clearer and more accurate structural development. The McNemar test confirmed that the difference was statistically significant (P = 0.031). In the two models, the reliability of the intervertebral height measured by the four observers on routine plain X-ray images was poor (ICC < 0.4), while the data obtained from the molybdenum target plain X-ray images were more reliable. CONCLUSION: Molybdenum target inspection can obtain clearer images and display fine calcification in the imaging evaluation of caudal IVD degeneration in rats, thus ensuring a more accurate evaluation of degeneration.

17.
Cell Chem Biol ; 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32888499

RESUMO

The interleukin-1 receptor-activated kinase 4 (IRAK4) belongs to the IRAK family of serine/threonine kinases and plays a central role in the innate immune response. However, the function of IRAK4 in tumor growth and progression remains elusive. Here we sought to determine the enzymatic and scaffolding functions of IRAK4 in activated B-cell-like diffuse large B cell lymphoma (ABC DLBCL). We chose a highly selective IRAK4 kinase inhibitor to probe the biological effects of kinase inhibition and developed a series of IRAK4 degraders to evaluate the effects of protein degradation in ABC DLBCL cells. Interestingly, the results demonstrated that neither IRAK4 kinase inhibition nor protein degradation led to cell death or growth inhibition, suggesting a redundant role for IRAK4 in ABC DLBCL cell survival. IRAK4 degraders characterized in this study provide useful tools for understanding IRAK4 protein scaffolding function, which was previously unachievable using pharmacological perturbation.

18.
Clin Epigenetics ; 12(1): 133, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883357

RESUMO

BACKGROUND: Atrial natriuretic peptide (ANP), one of the main members of the natriuretic peptides system, has been associated with hypertension and related complications, but the underlying molecular mechanisms are not very clear. Here, we aimed to examine whether DNA methylation, a molecular modification to the genome, of the natriuretic peptide A gene (NPPA), the coding gene of ANP, was associated with hypertension. METHODS: Peripheral blood DNA methylation of NPPA promoter was quantified by target bisulfite sequencing in 2498 community members (mean aged 53 years, 38% men) as a discovery sample and 1771 independent participants (mean aged 62 years, 54% men) as a replication sample. In both samples, we conducted a single CpG association analysis, followed by a gene-based association analysis, to examine the association between NPPA promoter methylation and hypertension, adjusting for age, sex, education level, cigarette smoking, alcohol consumption, obesity, fasting glucose, and lipids. Multiple testing was controlled by the false discovery rate approach. RESULTS: Of the 9 CpG loci assayed, hypermethylation at 5 CpGs (CpG1, CpG3, CpG6, CpG8, and CpG9) was significantly associated with a lower odds of prevalent hypertension in the discovery sample, and one CpG methylation (CpG1 located at Chr1:11908353) was successfully replicated in the replication sample (OR = 0.82, 95%CI 0.74-0.91, q = 0.002) after adjusting for covariates and multiple testing. The gene-based analysis found that DNA methylation of the 9 CpGs at NPPA promoter as a whole was significantly associated with blood pressure and prevalent hypertension in both samples (all P < 0.05). CONCLUSIONS: DNA methylation levels at NPPA promoter were decreased in Chinese adults with hypertension. Aberrant DNA methylation of the NPPA gene may participate in the mechanisms of hypertension.

19.
20.
Int J Surg ; 82: 182-191, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32877755

RESUMO

PURPOSE: Glucocorticoids are a mainstay to control postoperative pain, inflammation, nausea and vomiting (PONV) in total knee arthroplasty (TKA). Understanding the optimal dose and route of glucocorticoids administration in TKA is of great significance in speedy functional recovery. We aimed to summarize, evaluate and rank order the efficacy of glucocorticoids regimens in TKA. METHODS: Electronic databases (PubMed et al.) were systematically searched from inception up to April 30, 2020. The primary outcomes were visual analogue scale (VAS), range of motion (ROM) and knee society score (KSS). C-reactive Protein (CRP) and PONV were also evaluated. Multivariable Bayesian random effects models were used to synthesize and rank the comparative efficacy of glucocorticoids regimens. RESULTS: A total of 34 eligible randomized controlled trials with 11 different glucocorticoids regimens were assessed. Overall inconsistency and heterogeneity were acceptable. Multiple medium dose perioperative intravenous injection (IV) ranked first in the analgesia network and a single high doses of preoperative IV ranked first in the inflammation and PONV network. There was no statistically significant increase in ROM or KSS in all the glucocorticoid formulations and doses compared with controls on postoperative day 30. CONCLUSIONS: Glucocorticoid multiple intravenous injection was preferable to a single intravenous injection (preoperative and postoperative), periarticular injection and intra-articular injection in analgesia. Based on the available evidence, a medium dose of hydrocortisone of 2-4 mg/kg is optimal.

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