Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 633
Filtrar
1.
Lung Cancer ; 156: 82-90, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33933895

RESUMO

OBJECTIVES: To explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT-CHT) with intensity modulated radiotherapy (IMRT) technique in non-small cell lung cancer (NSCLC) patients with postoperative locoregional recurrence (LRR). MATERIALS AND METHODS: NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT-CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a break. Patients with no disease progression and no persistent Grade ≥2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS). RESULTS: Fifty-eight patients were enrolled and analyzed. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7 % and 46.4 %, the 2-year and 3-year OS rate was 72.5 % and 52.2 %, respectively, and a favorable objective response rate of 95.9 % was obtained after the whole courses protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4 %) and 7 (12.1 %) patients, and fatal pneumonitis was reported in one case (1.7 %). Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1 % vs. 46.9 %,P = 0.001; 2-year OS, 100 % vs. 59.4 %, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8 % vs. 47.4 %, P = 0.008; 2-year OS, 100 % vs. 63.0 %, P = 0.001), and gross tumor volume (GTV) (<50cm3 vs. ≥ 50cm3: 2-year PFS, 70.6 % vs. 46.2 %, P = 0.024; 2-year OS, 85.6 % vs. 57.4 %, P = 0.034) were significantly associated with PFS and OS. CONCLUSION: Split-course HFRT-CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR of NSCLC. Good PS, a single recurrence site and GTV<50cm3 tended to have prolonged PFS and OS. Early detection of LRR may improve the efficacy of HFRT-CHT.

2.
Postgrad Med J ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879552

RESUMO

PURPOSE OF THE STUDY: Chronic kidney disease-associated pruritus (CKD-aP) is common among patients on maintenance haemodialysis (HD). We performed a study to explore the clinical features of patients with CKD-aP and evaluate the impact of CKD-aP on the quality of life of HD patients. STUDY DESIGN: Patients who were receiving regular HD over 3 months were recruited. Quality of life was quantified by the Short Form-12 (SF-12) questionnaire. Pruritus was evaluated by the 5D-Itch Scale. Demographic characteristics and biochemical indicators were obtained from the medical record system. Multiple linear regression was used to assess the association between pruritus and targeting factors. The relationship between the scores on the 5D-Itch Scale and SF-12 was analysed using multiple linear regression, adjusted for other factors, to demonstrate the impact of CKD-aP on the quality of life of HD patients. RESULTS: In total, 269 out of 301 (89.4%) patients accomplished all investigations. The prevalence of CKD-aP in our cohort was 40.9%. Age (B=0.339, p=0.042), treatment with haemoperfusion (B=1.853, p=0.018), and serum level of calcium (B=3.566, p=0.008) and phosphorus (B=1.543, p=0.002) were independently associated with pruritus. Score on the 5D-Itch Scale negatively impacted on physical component summary (B=-0.778, p<0.001) and mental component summary (B=-0.675, p<0.001). CONCLUSIONS: Pruritus significantly aggravates the quality of life of HD patients. Irregularity in the metabolism of calcium and phosphorus may partially explain the mechanism of CKD-aP. More effective treatment of CKD-MBD may help to prevent pruritus and improve patients' mental and physical health conditions.

3.
Eur J Pharm Sci ; 162: 105833, 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33826935

RESUMO

Hepatic and intestinal CYP3A and P-gp in diabetic rats exhibit opposite expression patterns. However, the underlying mechanisms remain unclear. In this study, CYP3A1 and P-gp protein and mRNA expression levels in liver and different intestinal segments (duodenum, jejunum, ileum and colon) were compared between diabetic and normal rats. The microbiota in the ileum and colon contents was analyzed via 16S rRNA high-throughput sequencing technology. Caco-2 cells were incubated with serum or culture supernatant of colon contents from diabetic and normal rats, and CYP3A4 and ABCB1 mRNA levels were measured. Compared with that in normal rats, hepatic CYP3A1 and P-gp protein expression in diabetic rats was increased. CYP3A1 and P-gp protein was not changed in the duodenum and jejunum but significantly decreased by 29-41% in the ileum and colon of diabetic rats. Cyp3a1 and Abcb1a mRNA expression results were similar to the protein expression results. The composition of some bacteria changed significantly in the ileum and colon of diabetic rats compared with normal rats. CYP3A1 and P-gp protein expression was positively correlated with Lachnoclostridium and unclassified_f_Ruminococcaceae but negatively correlated with Clostridium_sensu_stricto_1, Turicibacter, Ruminococcaceae_UCG-005 and several genera belonging to the family Prevotellaceae. In addition, in vitro cell culture experiments showed that serum from diabetic rats significantly induced CYP3A4 and ABCB1 mRNA expression, while the supernatant of colon contents of diabetic rats significantly reduced CYP3A4 and ABCB1 mRNA expression by 45% and 86% respectively in Caco-2 cells. In conclusion, diabetes exhibited synchronous and regional effects on CYP3A and P-gp expression in the intestinal tract, in which gut microbiota dysbiosis might play an important role.

4.
Anticancer Res ; 41(4): 1831-1840, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33813388

RESUMO

BACKGROUND/AIM: Peroxiredoxin V (Prx V) plays crucial roles in cellular apoptosis and proliferation in various cancer cells by regulating the cellular reactive oxygen species (ROS) levels. MATERIALS AND METHODS: Here, we examined the possible regulatory effects of Prx V on doxorubicin (DOX)-induced cellular apoptosis and its mechanisms in the human gastric adenocarcinoma cell line (AGS cells). RESULTS: Our findings suggest that Prx V knockdown may significantly increase the DOX-induced apoptosis by aggravating intracellular ROS accumulation. We also found that DOX-induced mitochondrial ROS levels and membrane permeability were significantly higher in short hairpin Prx V cells than in mock cells, and these phenomena were dramatically reversed by ROS scavenger treatment. Prx V knockdown also significantly upregulated the cleaved caspase 9, 3, and B-cell lymphoma 2 (Bcl2)-associated agonist of cell death/Bcl2 protein expression levels, suggesting that Prx V knockdown activates mitochondria-dependent apoptotic signaling pathways. CONCLUSION: Taken together, this study suggests that Prx V may be a strong molecular target for gastric cancer (GC) chemotherapy, and further elucidates the role of Prx V in oxidative stress-induced cell apoptosis.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacologia , Inativação Gênica , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peroxirredoxinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Proteínas Reguladoras de Apoptose/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Peroxirredoxinas/genética , Transdução de Sinais , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
5.
Pestic Biochem Physiol ; 174: 104809, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33838710

RESUMO

Energy metabolism is important for the proliferation of microsporidia in infected host cells, but there is limited information on the host response. The energy metabolism response of silkworm (Bombyx mori) to microsporidia may help manage Nosema bombycis infections. We analyzed differentially expressed genes in the B.mori midgut transcriptome at two significant time points of microsporidia infection. A total of 1448 genes were up-regulated, while 315 genes were down-regulated. A high proportion of genes were involved in the phosphatidylinositol signaling system, protein processing in the endoplasmic reticulum, and glycerolipid metabolism at 48 h post infection (h p.i.), and a large number of genes were involved in the TCA cycle and protein processing at 120 h p.i. These results showed that the early stages of microsporidia infection affected the basic metabolism and biosynthesis processes of the silkworm. Knockout of Bm_nscaf2860_46 (Bombyx mori isocitrate dehydrogenase, BmIDH) and Bm_nscaf3027_062 (Bombyx mori hexokinase, BmHXK) reduced the production of ATP and inhibited microsporidia proliferation. Host fatty acid degradation, glycerol metabolism, glycolysis pathway, and TCA cycle response to microsporidia infection were also analyzed, and their importance to microsporidia proliferation was verified. These results increase our understanding of the molecular mechanisms involved in N. bombycis infection and provide new insights for research on microsporidia control. IMPORTANCE: Nosema bombycis can be vertically transmitted in silkworm eggs. The traditional prevention and control strategies for microsporidia are difficult and time-consuming, and this is a problem in silkworm culture. Research has mainly focused on host gene functions related to microsporidia infection and host immune responses after microsporidia infection. Little is known about the metabolic changes occurring in the host after infection. Understanding the metabolic changes in the silkworm host could aid in the recognition of host genes important for microsporidia infection and growth. We analyzed host metabolic changes and the main participating pathways at two time points after microsporidia infection and screened the microsporidia-dependent host energy metabolism genes BmIDH and BmHXK. The results revealed genes that are important for the proliferation of Nosema bombycis. These results illustrate how microsporidia hijack the host genome for their growth and reproduction.


Assuntos
Bombyx , Nosema , Animais , Bombyx/genética , Metabolismo Energético/genética , Perfilação da Expressão Gênica , Nosema/genética
6.
Clin Appl Thromb Hemost ; 27: 1076029621996810, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33783251

RESUMO

Peripheral artery disease (PAD) is a common disease affecting over 200 million people worldwide. PAD is associated with significant limb and cardiovascular morbidity and mortality which is reduced by antiplatelet and antithrombotic therapy. However, the optimal type, dose, and time of antithrombotic therapy is still uncertain.We searched 4 electronic databases from January 1, 1990, to June 1, 2020, for randomized controlled trials of patients who received oral anticoagulant and antiplatelet therapy for PAD. The primary outcome was a composite of acute limb ischemia, major amputation, myocardial infarction, ischemic stroke, death from cardiovascular events, or death from any cause. Secondary outcomes included major bleeding, fatal bleeding, and intracranial hemorrhage events.We identified 3 studies that satisfied inclusion and exclusion criteria. Compared with antiplatelet alone, oral anticoagulant plus antiplatelet therapy improved acute limb ischemia (p < 0.00001), stroke (p = 0.005), and major amputation events (p = 0.11). However, oral anticoagulant plus antiplatelet therapy was not effective for prevention of myocardial infarction (p = 0.23), death from cardiovascular events (p = 0.65), or death from any cause (p = 0.66). Additionally, a significant increase in major bleeding events was demonstrated (p < 0.00001). There was no significant difference in fatal bleeding (p = 0.16) or intracranial hemorrhage events (p = 0.43). This meta-analysis showed that oral anticoagulant plus antiplatelet therapy for PAD may improve acute limb ischemia and major amputation or stroke risk compared with antiplatelet therapy alone, but could increase the risk of major bleeding events. On the other hand, measuring myocardial infarction, death, fatal bleeding, or intracranial hemorrhage risk remains controversial.

7.
Hum Mol Genet ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33729517

RESUMO

Keratoconus is a common corneal defect with a complex genetic basis. By whole exome sequencing of affected members from 11 multiplex families of European ancestry, we identified 23 rare, heterozygous, potentially pathogenic variants in 8 genes. These include nonsynonymous single amino acid substitutions in HSPG2, EML6 and CENPF in two families each, and, in NBEAL2, LRP1B, PIK3CG and MRGPRD in three families each; ITGAX had nonsynonymous single amino acid substitutions in two families and an indel with a base substitution producing a nonsense allele in the third family. Only HSPG2, EML6 and CENPF have been associated with ocular phenotypes previously. With the exception of MRGPRD and ITGAX, we detected the transcript and encoded protein of the remaining genes in the cornea and corneal cell cultures. Cultured stromal cells showed cytoplasmic punctate staining of NBEAL2, staining of the fibrillar cytoskeletal network by EML6, while CENPF localized to the basal body of primary cilia. We inhibited the expression of HSPG2, EML6, NBEAL2, and CENPF in stromal cell cultures and assayed for the expression of COL1A1 as a readout of corneal matrix production. An upregulation in COL1A1 after siRNA inhibition indicated their functional link to stromal cell biology. For ITGAX, encoding a leukocyte integrin, we assayed its level in the sera of 3 affected families compared to 10 unrelated controls to detect an increase in all affecteds. Our study identified genes that regulate the cytoskeleton, protein trafficking and secretion, barrier tissue function and response to injury and inflammation, as being relevant to keratoconus.

8.
Health Phys ; 120(5): 541-551, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33760770

RESUMO

ABSTRACT: The impact of long-term low-dose radiation on human health has always been a concern. Long-term low-dose gamma radiation causes cells continuous injury and causes chromosomal mutations to greatly increase the chance of cancer. Because it is significant to identify biomarkers for long-term low-dose gamma radiation, we investigate the influence of low dose rate on the gene expressions in the AHH-1 lymphocytes cell line (AHH-1 cells) for long-term irradiation. Different dose rates (7, 14, 26, 34, and 43 µGy h-1) of irradiation from gamma radiation in uranium tailings powder were used to irradiate AHH-1 lymphocytes. We used flow cytometry to test the apoptosis of AHH-1 lymphocytes at different dose rates and irradiation times (7-84 d). It was found that 14 µGy h-1 is the most sensitive dose rate of AHH-1 lymphocyte irradiation. The 7-, 14-, and 21-d (2.4, 4.8, and 7.2 mGy) irradiation groups were sensitive, and the 84-d (28.8 mGy) irradiation group was insensitive to low dose gamma radiation. Microarray analysis was conducted on the significantly differentially expressed genes (p<0.05) in the 2.4, 4.8, 7.2, and 28.8 mGy irradiation groups. We found that TFRC1, SLC3A2, SLC39A8, FTH1, ACSL4, and GPX4 are significant genes with low-dose radiation and were constituents of the ferroptosis signaling pathway. In the range of 0-4.8 mGy radiation dose, the expressions of these genes were downregulated with increasing radiation dose, while in the range of 4.8-28.8 mGy, its expression increased with increasing radiation dose. RT-PCR and Western blot were used to detect the mRNA and protein expression of these genes. The results were consistent with those from microarray analysis. Our findings indicate that expression of the TFRC, SLC3A2, SLC39A, FTH1, ACSL4, and GPX4 genes is sensitive to low-dose radiation, and they are main members of the ferroptosis signaling pathway. Therefore, there is a very important connection between ferroptosis and low-dose radiation, which has become a hot topic in international research. These results can provide reference to the effect of ferroptosis on human health with low-dose radiation.

9.
Aging (Albany NY) ; 13(7): 9766-9779, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33744848

RESUMO

As biomolecules of great clinical value, lncRNAs play a crucial role as regulators in the processes of tumor origin, metastasis, and recurrence. Thus, lncRNAs are urgently needed for research in gastric cancer. We elucidated the specific function of OGFRP1, both in vitro and in vivo. OGFRP1 was expressed at abnormally high levels in gastric cancer samples (n = 408) compared to normal samples (n = 211). Similar results were obtained in 30 clinical case samples. Interference of OGFRP1 markedly blocked cell proliferation and migration, and it induced cell cycle arrest and the apoptosis of gastric cancer cells in vitro. Phosphorylation of AKT was inhibited in cells transfected with OGFRP1 siRNA, as compared to their control cells. The in vivo results further confirmed the antitumor effects of OGFRP1 knockdown on gastric cancer. Decreases in tumor volume (104.23±62.27 mm3) and weight (0.1006±0.0488 g) in nude mice were observed during the OGFRP1 interference, as compared with the control group (418.96±211.96 mm3 and 0.2741±0.0769 g). OGFRP1 promotes tumor progression through activating the AKT/mTOR pathway. Our findings provide a new potential target for the clinical treatment of human gastric cancer.

10.
Acta Biomater ; 126: 524-536, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33684537

RESUMO

Orthopedic and dental implants made of ß-type Ti alloys have low elastic modulus which can better relieve the stress shielding effects after surgical implantation. Nevertheless, clinical application of ß-type Ti alloys is hampered by the insufficient mechanical strength and gradual release of pro-inflammatory metallic ions under physiological conditions. In this study, the ß-type Ti-45Nb alloy is subjected to high-pressure torsion (HPT) processing to refine the grain size. After HPT processing, the tensile strength increases from 370 MPa to 658 MPa due to grain boundary strengthening and at the same time, the favorable elastic modulus is maintained at a low level of 61-72 GPa because the single ß-phase is preserved during grain refinement. More grain boundaries decrease the work function and facilitate the formation of thicker and less defective passive films leading to better corrosion resistance. In addition, more rapid repair of the passive layer mitigates release of metallic ions from the alloy and consequently, the inflammatory response is suppressed. The results reveal a strategy to simultaneously improve the mechanical and biological properties of metallic implant materials for orthopedics and dentistry. STATEMENT OF SIGNIFICANCE: The low modulus Ti-45Nb alloy is promising in addressing the complication of stress shielding induced by biomedical Ti-based materials with too-high elastic modulus. However, its insufficient strength hampers its clinical application, and traditional strengthening via heat treatments will compromise the low elastic modulus. In the current study, we enhanced the ultimate tensile strength of Ti-45Nb from 370 MPa to 658 MPa through grain-refinement strengthening, while the elastic modulus was maintained at a low value (61-72 GPa). Moreover, substrate grain-refinement has been proved to improve the corrosion resistance of Ti-45Nb with reduced inflammatory response both in vitro and in vivo. A relationship between the substrate microstructure and the surface passive layer has been established to explain the beneficial effects of substrate grain-refinement.

11.
World Neurosurg ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33746099

RESUMO

BACKGROUND: Gliomas, particularly high-grade gliomas, are the most common primary brain tumors. From the Chinese Glioma Genome Atlas (CGGA) database, the relationships between the altered molecular pathways and gliomas could be easily observed. A close connection in the occurrence of the pathogenesis exists between the microenvironment, the glioma, and the associated genes. METHODS: Validation of the role of ZNF311 oncogene was confirmed by data from the CGGA dataset on glioblastoma and low-grade glioma. Furthermore, we used CIBERSORT to analyze the correlation between ZNF311 and cancer immune infiltrates. RESULTS: According to our analysis, ZNF311 was expressed higher in patients with grade-depended glioma with poor prognosis. In addition, we obtained valuable prognostic results between isocitrate dehydrogenase 1 (IDH1) and ZNF311 through the analysis of integrated correlations. Similarly, we simultaneously revealed the prognostic results between 1p/19q and ZNF311. In addition, we found that ZNF311 is correlated with a large number of tumor-infiltrating immune cells. CONCLUSIONS: Based on the study findings, we conclude that ZNF311 is potentially a novel biomarker for assessing prognosis and immune infiltration in glioblastoma and diffuse glioma cases.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33612440

RESUMO

OBJECTIVE: The objective of this study was to evaluate the effect of combined temporomandibular joint (TMJ) disk repositioning by suturing through open incision and orthodontic functional appliance (OFA) treatment for adolescents with mandibular asymmetry. STUDY DESIGN: Adolescent patients (12-20 years old) with mandibular asymmetry combined with unilateral TMJ disk displacement without reduction were treated with disk repositioning by suturing through open incision with and without postoperative OFA. Magnetic resonance imaging and posteroanterior cephalometric radiographs (PA) were used to measure and compare the changes in condylar height, joint space, and menton deviation pre- and postoperatively. RESULTS: Twenty-six patients were included in the study. Joint space was significantly increased postoperatively and new bone mostly formed at the superior or posterior superior part of the condyle after 6 to 18 months in all surgically treated joints. Fourteen patients with OFA had a significant increase in condylar height and menton deviation compared to 12 patients without OFA (2.29 ± 0.91 mm vs 1.22 ± 0.69 mm, P = .003; 4.56 ± 1.48 mm vs 2.01 ± 0.74 mm, P = .000). CONCLUSIONS: Combined treatment with TMJ disk repositioning by suturing through open incision and OFA can promote condylar growth and correct mandibular deviation in adolescent patients. Postoperative OFA can maintain the increased joint space created by disk repositioning and promote new bone formation at the superior and posterior parts of the condyle.


Assuntos
Luxações Articulares , Aparelhos Ortodônticos Funcionais , Adolescente , Adulto , Cefalometria , Criança , Humanos , Imagem por Ressonância Magnética , Côndilo Mandibular , Articulação Temporomandibular , Disco da Articulação Temporomandibular/diagnóstico por imagem , Disco da Articulação Temporomandibular/cirurgia , Adulto Jovem
14.
Toxicol Appl Pharmacol ; 414: 115426, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33524445

RESUMO

Activation of NLRP3 inflammasome is implicated in varieties of pathologies, the aim of the present study is to characterize the effect and mechanism of mitochondrial uncouplers on NLRP3 inflammasome activation by using three types of uncouplers, niclosamide, CCCP and BAM15. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increases of NLRP3 protein and IL-1ß mRNA levels in RAW264.7 macrophages and THP-1 derived macrophages. Niclosamide, CCCP and BAM15 inhibited LPS plus ATP-induced increase of NFκB (P65) phosphorylation, and inhibited NFκB (P65) nuclear translocation in RAW264.7 macrophages. Niclosamide and BAM15 inhibited LPS-induced increase of IκBα phosphorylation in RAW264.7 macrophages, and the inhibitory effect was dependent on increased intracellular [Ca2+]i; however, CCCP showed no significant effect on IκBα phosphorylation in RAW264.7 macrophages stimulated with LPS. In conclusion, chemical mitochondrial uncouplers niclosamide, CCCP and BAM15 share common inhibitory effect on NLRP3 inflammasome activation through inhibiting NFκB nuclear translocation.

15.
Biom J ; 63(4): 806-824, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33586212

RESUMO

Random coefficient regression (also known as random effects, mixed effects, growth curve, variance component, multilevel, or hierarchical linear modeling) can be a natural and useful approach for characterizing and testing hypotheses in data that are correlated within experimental units. Existing power and sample size software for such data are based on two variance component models or those using a two-stage formulation. These approaches may be markedly inaccurate in settings where more variance components (i.e., intercept, rate of change, and residual error) are warranted. We present variance, power, sample size formulae, and software (R Shiny app) for use with random coefficient regression models with possible missing data and variable follow-up. We illustrate sample size and study design planning using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We additionally examine the drivers of variability to better inform study design.

16.
Int Immunopharmacol ; 94: 107466, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33636561

RESUMO

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have increased mortality related to cardiovascular disease (CVD). This systematic review and meta-analysis identified the risk of CVD in SLE patients, CVD risk factors in SLE patients, and the risk of CVD in lupus nephritis (LN) patients. METHODS: On-line databases were used to search the eligible studies from January 2013 to August 2020. The relevant characteristics and the data of disease extracted from included publications. RESULTS: A total of 20 studies were included in this meta-analysis. Compared with the general or healthy population, the risk of CVD in SLE patients increased by 2 times (RR = 2.35, 95% CI: 1.95-2.84, P < 0.05). SLE patients had a significantly increased risk of atherosclerosis (RR = 2.31, 95% CI: 1.16-4.60), stroke (RR = 2.30, 95% CI: 1.52-3.50), myocardial infarction (RR = 2.66, 95% CI: 1.97-3.59), peripheral vascular disease (RR = 2.56, 95% CI: 1.07-6.09) and heart failure (RR = 2.89, 95% CI: 1.63-5.13), but no significant increased risk of coronary artery disease (RR = 1.93, 95% CI: 0.67-5.59). SLE patients were more susceptible to lead hypertension than general or healthy population (RR = 2.31, 95% CI: 1.62-3.29). Compared with the SLE patients, the risk of CVD in LN patients was increased by 2 times (RR = 1.75, 95% CI: 1.13-2.70). CONCLUSION: The results of this meta-analysis suggest that SLE patients have a higher risk of developing CVD compared with the general or healthy population, and the risk of CVD in LN patients is significantly higher than that in SLE patients.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33640348

RESUMO

OBJECTIVES: This study sought to evaluate atrial fibrillation (AF) ablation outcomes based on scar patterns and contiguous area available for AF wavefronts to propagate. BACKGROUND: The relevance of ablation scar pattern acting as a barrier for electrical propagation in recurrence after catheter ablation for persistent AF is unknown. METHODS: Three-month post-ablation atrial cardiac magnetic resonance was used to determine post-ablation scar. The left atrium (LA) was divided into 5 areas based on anatomical landmarks and scar patterns. The length of gaps in scar on the area boundaries was used to calculate fibrillatory areas (FAs) by adding the weighted contribution of adjacent areas. Cylindrical as well as patient-specific computational models were used to further confirm findings. RESULTS: A total of 75 patients that underwent an initial ablation for AF with 2 years of follow-up were included. The average maximum FA was 7,896 ± 1,988 mm2 in patients with recurrence (n = 40) and 6,559 ± 1,784 mm2 in patients without recurrence (n = 35) (p < 0.008). After redo ablation in 19 patients with recurrence, average maximum FA was 7,807 ± 1,392 mm2 in 9 patients with recurrence and 5,030 ± 1,765 mm2 in 10 without recurrence (p < 0.007). LA volume and total scar were not significant predictors of recurrence after the first ablation. In the cylindrical model, AF self-terminated after reducing the FAs. In the patient-specific models, simulation matched the clinical outcomes with larger FAs associated with post-ablation arrhythmia recurrences. CONCLUSIONS: This data provides mechanistic insights into AF recurrence, suggesting that post-ablation scar pattern dividing the atria into smaller regions is an important and better predictor than LA volume and total scar, with improved long-term outcomes in persistent AF.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33629409

RESUMO

AIM: There is limited information on the health status of urban Australian Aboriginal children and young people attending community-based child health services. Such information is vital to plan appropriate services. The objective of the study is to describe the health status and service use of children and young people presenting to an urban Aboriginal Community Paediatric Service in Sydney, Australia. METHODS: Cross-sectional analysis of routinely collected data extracted from electronic medical records and the Australian Immunisation Register for urban Aboriginal children and young people aged 0-18 years who visited the service between January 2013 and December 2017. RESULTS: A total of 273 Aboriginal children and young people had 609 occasions of service. Almost all (97.35%) were fully immunised. Forty-six percent of occasions of service noted >3 diagnoses; 55% of the consultations were for mental health and behavioural disorders. The most frequent diagnoses were speech and language delay, attention deficit hyperactivity disorder and school difficulty. Psychosocial concerns were noted in 61.2% of occasions of service, and 19.4% of children had a history of prematurity. Eighty-five percent of consultations had an onward referral to additional services. The most common referrals were for audiology, ear-nose and throat specialists and speech therapy. There were low numbers of referrals to mental health services relative to the high number of mental health diagnoses. CONCLUSION: It is essential that we address the mental, developmental and psychosocial needs of Aboriginal children and young people who attend urban Community Child Health services. Integrated service models should be developed in partnership with Aboriginal community to do this.

19.
Molecules ; 26(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540725

RESUMO

The title alkaloids, often referred to collectively as crinines, are a prominent group of structurally distinct natural products with additional members being reported on a regular basis. As such, and because of their often notable biological properties, they have attracted attention as synthetic targets since the mid-1950s. Such efforts continue unabated and more recent studies on these alkaloids have focused on using them as vehicles for showcasing the utility of new synthetic methods. This review provides a comprehensive survey of the nearly seventy-year history of these synthetic endeavors.

20.
Clin Cancer Res ; 27(8): 2301-2313, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33419778

RESUMO

PURPOSE: On the basis of the recent discovery of mutations in Bruton tyrosine kinase (BTK) in follicular lymphoma, we studied their functional properties. EXPERIMENTAL DESIGN: We identified novel somatic BTK mutations in 7% of a combined total of 139 follicular lymphoma and 11 transformed follicular lymphoma cases, none of which had received prior treatment with B-cell receptor (BCR) targeted drugs. We reconstituted wild-type (WT) and mutant BTK into various engineered lymphoma cell lines. We measured BCR-induced signal transduction events in engineered cell lines and primary human follicular lymphoma B cells. RESULTS: We uncovered that all BTK mutants destabilized the BTK protein and some created BTK kinase-dead mutants. The phospholipase C gamma 2 (PLCγ2) is a substrate of BTK but the BTK mutants did not alter PLCγ2 phosphorylation. Instead, we discovered that BTK mutants induced an exaggerated AKT phosphorylation phenotype in anti-Ig-treated recombinant lymphoma cell lines. The short hairpin RNA-mediated knockdown of BTK expression in primary human nonmalignant lymph node-derived B cells resulted in strong anti-Ig-induced AKT activation, as did the degradation of BTK protein in cell lines using ibrutinib-based proteolysis targeting chimera. Finally, through analyses of primary human follicular lymphoma B cells carrying WT or mutant BTK, we detected elevated AKT phosphorylation following surface Ig crosslinking in all follicular lymphoma B cells, including all BTK-mutant follicular lymphoma. The augmented AKT phosphorylation following BCR crosslinking could be abrogated by pretreatment with a PI3Kδ inhibitor. CONCLUSIONS: Altogether, our data uncover novel unexpected properties of follicular lymphoma-associated BTK mutations with direct implications for targeted therapy development in follicular lymphoma.See related commentary by Afaghani and Taylor, p. 2123.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...