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1.
Lab Chip ; 2020 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-32459276

RESUMO

The advent of intelligent image-activated cell sorting (iIACS) has enabled high-throughput intelligent image-based sorting of single live cells from heterogeneous populations. iIACS is an on-chip microfluidic technology that builds on a seamless integration of a high-throughput fluorescence microscope, cell focuser, cell sorter, and deep neural network on a hybrid software-hardware data management architecture, thereby providing the combined merits of optical microscopy, fluorescence-activated cell sorting (FACS), and deep learning. Here we report an iIACS machine that far surpasses the state-of-the-art iIACS machine in system performance in order to expand the range of applications and discoveries enabled by the technology. Specifically, it provides a high throughput of ∼2000 events per second and a high sensitivity of ∼50 molecules of equivalent soluble fluorophores (MESFs), both of which are 20 times superior to those achieved in previous reports. This is made possible by employing (i) an image-sensor-based optomechanical flow imaging method known as virtual-freezing fluorescence imaging and (ii) a real-time intelligent image processor on an 8-PC server equipped with 8 multi-core CPUs and GPUs for intelligent decision-making, in order to significantly boost the imaging performance and computational power of the iIACS machine. We characterize the iIACS machine with fluorescent particles and various cell types and show that the performance of the iIACS machine is close to its achievable design specification. Equipped with the improved capabilities, this new generation of the iIACS technology holds promise for diverse applications in immunology, microbiology, stem cell biology, cancer biology, pathology, and synthetic biology.

2.
Elife ; 92020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32393438

RESUMO

Platelets are anucleate cells in blood whose principal function is to stop bleeding by forming aggregates for hemostatic reactions. In addition to their participation in physiological hemostasis, platelet aggregates are also involved in pathological thrombosis and play an important role in inflammation, atherosclerosis, and cancer metastasis. The aggregation of platelets is elicited by various agonists, but these platelet aggregates have long been considered indistinguishable and impossible to classify. Here we present an intelligent method for classifying them by agonist type. It is based on a convolutional neural network trained by high-throughput imaging flow cytometry of blood cells to identify and differentiate subtle yet appreciable morphological features of platelet aggregates activated by different types of agonists. The method is a powerful tool for studying the underlying mechanism of platelet aggregation and is expected to open a window on an entirely new class of clinical diagnostics, pharmacometrics, and therapeutics.


Assuntos
Redes Neurais de Computação , Agregação Plaquetária , Citometria de Fluxo , Humanos , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas , Ativação Plaquetária , Trombose/classificação
3.
Analyst ; 145(12): 4204-4211, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32459250

RESUMO

An impedimetric aptasensor for the detection of endotoxin in a microfluidic chip was proposed, in which the Apt/AuNPs/SPCE sensing surface was fabricated in a screen-printed electrode with good biological activity and stability. The quantitative detection of endotoxin was accomplished by electrochemical impedance spectroscopy (EIS) measurement before and after exposing to samples. The impedance biosensor offers an ultrasensitive and selective detection of endotoxin down to 500 pg mL-1 with a wide linear range from 500 pg mL-1 to 200 ng mL-1. According to the Langmuir isotherm model, the interactions between the target molecules and the sensing surface had been analyzed and strong binding was concluded. Compared to the traditional static incubation methods, the microfluidic biosensor realizes the enrichment of endotoxin owing to the confined space and continuous flow nature, so that the lowest detection concentration is reduced from 5 ng mL-1 to 500 pg mL-1, which is much lower than the existing technology, and the total assay time is shortened from 1.0 h to 0.5 h. The proposed microfluidic impedance biosensor provides a new strategy for the design of an aptasensor to realize the rapid detection of target biomolecules with high sensitivity and it can be integrated into wearable medical devices due to its flexible properties.

4.
ACS Nano ; 14(4): 4890-4904, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32286784

RESUMO

The dense fibrotic stroma in pancreatic ductal adenocarcinoma (PDA) resists drug diffusion into the tumor and leads to an unsatisfactory prognosis. To address this problem, we demonstrate a dendrimer-camptothecin (CPT) conjugate that actively penetrates deep into PDA tumors through γ-glutamyl transpeptidase (GGT)-triggered cell endocytosis and transcytosis. The dendrimer-drug conjugate was synthesized by covalent attachment of CPT to polyamidoamine (PAMAM) dendrimers through a reactive oxygen species (ROS)-sensitive linker followed with surface modification with glutathione. Once the conjugate was delivered to the PDA tumor periphery, the overexpressed GGT on the vascular endothelial cell or tumor cell triggers the γ-glutamyl transfer reactions of glutathione to produce primary amines. The positively charged conjugate was rapidly internalized via caveolae-mediated endocytosis and followed by vesicle-mediated transcytosis, augmenting its deep penetration within the tumor parenchyma and releasing active CPT throughout the tumor after cleavage by intracellular ROS. The dendrimer-drug conjugate exhibited high antitumor activity in multiple mice tumor models, including patient-derived PDA xenograft and orthotopic PDA cell xenograft, compared to the standard first-line chemotherapeutic drug (gemcitabine) for advanced pancreatic cancer. This study demonstrates the high efficiency of an active tumor-penetrating dendrimer-drug conjugate via transcytotic transport with ROS-responsive drug release for PDA therapy.

5.
Aging (Albany NY) ; 12(6): 5411-5422, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32221047

RESUMO

OBJECTIVE: This study was aimed at investigating the regulation of mitochondrial function by histone deacetylase 6 (HDAC6) and the role of HDAC6 in the development and progression of sepsis. RESULTS: HDAC6 downregulated PHB1 and subsequently promoted the development of CLP-induced sepsis. Inhibition of HDAC6 significantly attenuated CLP-induced sepsis through inhibition of mitochondrial dysfunction and reduced oxidant production, thus protecting the rats from oxidative injury. CONCLUSIONS: In this sepsis model, HDAC6 inhibits the expression and function of PHB1 and alters the function of the mitochondrial respiratory chain mediated by PHB1, thus enhancing the production of oxidants and increasing oxidative stress and thereby leading to severe oxidative injury in multiple organs. METHODS: The expression of HDAC6 and prohibitin 1 (PHB1) in humans and in a rat model of sepsis was measured by quantitative reverse-transcription PCR and western blotting. Sepsis induction by cecal ligation and puncture (CLP) was confirmed by histological analysis. Concentrations of different sepsis markers were measured by an enzyme-linked immunosorbent assay, and mitochondrial function was assessed via the mitochondrial respiratory control rate.

6.
Am J Gastroenterol ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32221162

RESUMO

OBJECTIVES: Chronic hepatitis C virus (HCV) infection is associated with nonhepatocellular carcinoma malignancies. We aimed to evaluate whether achieving a sustained virological response (SVR, defined as HCV RNA seronegativity throughout posttreatment 24-week follow-up) could reduce the risk of non-hepatocellular carcinoma malignancy in a real-world nationwide Taiwanese Chronic Hepatitis C Cohort (T-COACH). METHODS: A total of 10,714 patients with chronic hepatitis C who had received interferon-based therapy (8,186 SVR and 2,528 non-SVR) enrolled in T-COACH and were linked to the National Cancer Registry database for the development of 12 extrahepatic malignancies, including those with potential associations with HCV and with the top-ranking incidence in Taiwan, over a median follow-up period was 3.79 years (range, 0-16.44 years). RESULTS: During the 44,354 person-years of follow-up, 324 (3.02%) patients developed extrahepatic malignancies, without a difference between patients with and without SVR (annual incidence: 0.69% vs 0.87%, respectively). Compared with patients with SVR, patients without SVR had a significantly higher risk of gastric cancer (0.10% vs 0.03% per person-year, P = 0.004) and non-Hodgkin lymphoma (NHL) (0.08% vs 0.03% per person-year, respectively, P = 0.03). When considering death as a competing risk, non-SVR was independently associated with gastric cancer (hazard ratio [HR]/95% confidence intervals [CIs]: 3.29/1.37-7.93, P = 0.008). When patients were stratified by age, the effect of SVR in reducing gastric cancer (HR/CI: 0.30/0.11-0.83) and NHL (HR/CI: 0.28/0.09-0.85) was noted only in patients aged <65 years but not those aged >65 years. DISCUSSION: HCV eradication reduced the risk of gastric cancer and NHL, in particular among younger patients, indicating that patients with chronic hepatitis C should be treated as early as possible.

7.
Sci Rep ; 10(1): 5372, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32214132

RESUMO

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

8.
Opt Express ; 28(1): 519-532, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-32118978

RESUMO

Optofluidic time-stretch quantitative phase imaging (OTS-QPI) is a powerful tool as it enables high-throughput (>10,000 cell/s) QPI of single live cells. OTS-QPI is based on decoding temporally stretched spectral interferograms that carry the spatial profiles of cells flowing on a microfluidic chip. However, the utility of OTS-QPI is troubled by difficulties in phase retrieval from the high-frequency region of the temporal interferograms, such as phase-unwrapping errors, high instrumentation cost, and large data volume. To overcome these difficulties, we propose and experimentally demonstrate frequency-shifted OTS-QPI by bringing the phase information to the baseband region. Furthermore, to show its boosted utility, we use it to demonstrate image-based classification of leukemia cells with high accuracy over 96% and evaluation of drug-treated leukemia cells via deep learning.

9.
Chem Commun (Camb) ; 56(24): 3488-3491, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32163089

RESUMO

A novel protocol for the construction of functionalized (Z)-3-(1(-arylamino)-2-oxoarylidene)indolin-2-ones (AOIDOs) from isatins 1 with nitro-substituted enamines 2via an unprecedented cascade reaction catalyzed by sulfamic acid is developed. The AOIDOs are prepared by simply refluxing a mixture of isatins with a wide variety of nitro-substituted enamines. Interestingly, the AOIDOs 3 were formed through the novel cascade reaction involving a unique cleavage of two C-N bonds of the nitro-substituted enamines. Overall, the novel reaction is accomplished by the formation of three new bonds and the cleavage of two C-N bonds in a single step. This protocol can be used in the synthesis of a wide variety of AOIDOs and is suitable for combinatorial and parallel syntheses of natural-like AOIDO products.

10.
PLoS One ; 15(3): e0230322, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32182277

RESUMO

First reported in March 2014, an Ebola epidemic impacted West Africa, most notably Liberia, Guinea and Sierra Leone. We demonstrate the value of social media for automated surveillance of infectious diseases such as the West Africa Ebola epidemic. We experiment with two variations of an existing surveillance architecture: the first aggregates tweets related to different symptoms together, while the second considers tweets about each symptom separately and then aggregates the set of alerts generated by the architecture. Using a dataset of tweets posted from the affected region from 2011 to 2014, we obtain alerts in December 2013, which is three months prior to the official announcement of the epidemic. Among the two variations, the second, which produces a restricted but useful set of alerts, can potentially be applied to other infectious disease surveillance and alert systems.


Assuntos
Mineração de Dados/métodos , Epidemias/prevenção & controle , Monitoramento Epidemiológico , Doença pelo Vírus Ebola/epidemiologia , Mídias Sociais/estatística & dados numéricos , Conjuntos de Dados como Assunto , Ebolavirus , Epidemias/estatística & dados numéricos , Guiné/epidemiologia , Doença pelo Vírus Ebola/diagnóstico , Doença pelo Vírus Ebola/virologia , Humanos , Libéria/epidemiologia , Serra Leoa/epidemiologia
11.
World J Gastroenterol ; 26(6): 686-695, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32103876

RESUMO

BACKGROUND: Neuroendocrine neoplasms are rarely located in the gallbladder (GB), and carcinoid syndrome is exceedingly rare in patients with GB neuroendocrine neoplasms. CASE SUMMARY: We report a case of GB neuroendocrine carcinoma (GB-NEC) in a 65-year-old man, who presented with flushing for 2 mo. Pathological specimens of the flushed skin revealed that mucin was deposited between the collagen bundles in the dermis. Computed tomography and magnetic resonance imaging indicated neoplasm in the GB with liver invasion and enlarged lymph nodes in the portacaval space. High fluorodeoxyglucose uptake was detected in lymph nodes in the portacaval space, but distant metastasis was not seen by positron emission tomography. Ultrasound-guided needle biopsy of the GB neoplasm was suggestive of high-grade NEC. Because of the functional characteristics of poorly differentiated NEC, en bloc cholecystectomy, resection of hepatic segments IVb and V, pancreaticoduodenectomy, and regional lymphadenectomy were performed. A diagnosis of poorly differentiated NEC was made by pathological findings and immunohistochemical staining data. Ki-67 index was > 80%. The patient refused adjuvant therapy and passed away in the 7th month. CONCLUSION: Distinctive manifestation combined with imaging helps make correct preoperative diagnosis. Radical surgery and adjuvant chemotherapy might improve prognosis.

12.
J Invest Surg ; : 1-9, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32093527

RESUMO

Background: There is no specific evidence regarding the benefits of external and internal pancreatic duct stents after pancreaticoduodenectomy since pancreatic fistula (grade A) have been redefined with no clinical treatment effect. We aimed to reevaluate the prognostic value of external and internal stents in clinically relevant postoperative pancreatic fistula over pancreaticoduodenectomy.Methods: PubMed, Web of Science, EMBASE and the Cochrane Database were specifically searched for pertinent and original articles published before May 2019. The project has been registered in PROSPERO (Registration number: CRD42019137579).Results: Four randomized controlled trials and six nonrandomized controlled trials with a total of 2101 patients were enrolled in this meta-analysis. The use of an external stent resulted in better performance than the use of an internal stent in terms of pancreatic fistula (grade C) (OR 0.58, P = 0.03) but did not reduce the rate of pancreatic fistula (grade B) (OR 0.99, P = 0.94) in all studies. The meta-analysis of randomized controlled trials found that the use of an external stent approached a level of significance for an increased rate of clinically relevant postoperative pancreatic fistula compared to the use of an internal stent (OR 1.40, P = 0.10) but had no significant effect on pancreatic fistula (grade B) (OR 1.34, P = 0.26) or pancreatic fistula (grade C) (OR 1.68, P = 0.62).Conclusion: Compared with internal stents, the use of external stent might be associated with a lower rate of pancreatic fistula (grade C). More randomized clinical trials are warranted to further explore safety and efficacy of pancreatic duct external stents.

13.
J Minim Access Surg ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31929223

RESUMO

Background: Haemorrhage during the splenic parenchyma transection is a major threat for laparoscopic partial splenectomy (LPS). We here aim to evaluate the feasibility and safety of pre-coagulation of a 915 MHz microwave (MW) device during LPS. Materials and Methods: Data of four patients admitted to our hospital between November 2016 and July 2018 were retrospectively analysed. The mean age was 24 years (range, 19-33); they all diagnosed with splenic unifocal lesion with a mean diameter of 4.6 cm (ranged from 3.7 to 6 cm) and underwent LPS with pre-coagulation of a 915 MHz MW. Results: The LPS with pre-coagulation was successfully resulted in complete resection without microscopic residual tumour (R0 resection). The mean operative time was 205 min, and the minimum blood loss was at the range of 30-50 ml. No complication was observed, and the length of stay in hospital was varied from 5 to 10 days. Conclusion: Based on our observation, pre-coagulation of a 915 MHz MW during LPS is a safe and efficient technique. More studies are required before applying extensively.

14.
Colloids Surf B Biointerfaces ; 188: 110769, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31918157

RESUMO

Polysulfone (PSf) membrane is widely employed in blood purification fields, but the blood compatibility of PSf membrane is not adequate. To improve the hemocompatibility of PSf membrane, 4-(chloromethyl)benzoic acid (CMBA) and sulfonated hydroxypropyl chitosan (SHPCS) were grafted onto PSf membrane surface. In our strategy, CMBA was firstly grafted on the PSf membrane surface through the Friedel-Crafts alkylation reaction, and the product was named BAPSf membrane. Then, SHPCS was grafted onto the BAPSf membrane surface by esterification, and the product was named SHPCS-BAPSf membrane. The effects of temperature and reaction time on the productivity of BAPSf and the grafting density of carboxyl and the effects of reaction time on the grafting density of SHPCS grafted onto the BAPSf membrane surface were studied. The SHPCS-BAPSf membranes are investigated by ATR-FTIR, XPS, contact angle measurements and evaluated by blood compatibility in vitro. The results reveal that the hydrophilicity of SHPCS-BAPSf membranes were grealy improved and the evaluation of protein adsorption, hemolysis test, platelet adhesion plasma recalcification time(PRT), activated partial thromboplastin time(APTT), prothrombin time(PT) and thrombin time(TT) confirmed that the SHPCS-BAPSf membranes have remarkable blood compatibility.

15.
Ann Vasc Surg ; 63: 34-44, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563653

RESUMO

BACKGROUND: Takayasu's arteritis (TA) is an uncommon chronic vasculitis, and there is a lack of long-term large cohort studies regarding the optimal revascularization outcomes of patients with TA. METHODS: One hundred and sixteen patients with TA who underwent surgery or endovascular repair over a 10-year period were studied retrospectively. One hundred and fifty-four vascular procedures were performed consisting of 69 open and 85 endovascular repairs. RESULTS: After a mean follow-up period of 48.5 ± 38.5 months, three cases each of cerebrovascular accident (CVA) and death occurred in the open repair group while two cases of CVA and 4 deaths were observed in the endovascular repair group. At 1, 3, 5, and 10 years of follow-up, the primary patency rates were 97.3%, 86.2%, 70.5%, and 48.8% in the open repair group and 93.3%, 73.1%, 57.5%, and 31.8% in the endovascular repair group, respectively. The primary assisted patency rates were 98.2%, 90.3%, 73.2%, and 47.2% in the open repair group and 95%, 81%, 64.4%, and 35% in the endovascular repair group, respectively. The secondary patency rates were 98.2%, 96.1%, 83.5%, and 56.2% in the open repair group and 98.7%, 86%, 71.2%, and 44.9% in the endovascular repair group, respectively. The cumulative survival rates were 96.9%, 96.9%, 96.9%, and 90% in the open repair group and 97.4%, 97.4%, 88%, and 79.2% in the endovascular repair group, respectively. CONCLUSIONS: Both surgical repair and endovascular management are safe and efficient modes of treatment of TA. Surgical repair showed long-term durability, and it is suitable for complex lesions and failed cases of endovascular management.

16.
Neuroendocrinology ; 110(3-4): 307-320, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31261148

RESUMO

BACKGROUND: Serine/threonine kinase 33 (STK33) has been reported to play an important role in cancer cell proliferation. We investigated the role of STK33 in pancreatic neuroendocrine tumour (PNET) and the underlying mechanisms. METHODS: PNET specimens and adjacent non-tumorous pancreatic tissues from 84 patients who underwent curative surgery for PNET were stained by immunochemistry for STK33. The relationships among STK33 expression, clinicopathological parameters and clinical prognosis were statistically analysed. MTT, scratching, Transwell and apoptosis assays were employed to detect the effects of STK33 knockdown (siSTK33) or STK33 overexpression (pSTK33) on major oncogenic properties of cells of 2 PNET cell lines (BON and QGP-1), and real-time PCR and western blot were used to examine the expression of relevant genes. RESULTS: Relative to its expression in normal pancreatic tissue, STK33 was overexpressed in PNET specimens. Furthermore, STK33 expression was significantly associated with World Health Organization classification (p < 0.001), American Joint Committee on Cancer stage (p < 0.001), lymph node metastasis (p < 0.001), tumour size (p = 0.022), sex (p = 0.003), perineural invasion (p < 0.001) and shorter disease-free survival of patients with PNET (p < 0.001). Enforced STK33 expression promoted PNET cell proliferation, migration and invasion and tumour growth and inhibited cell apoptosis, whereas STK33 depletion exerted the opposite effects. Mechanistic studies revealed that STK33 promoted growth and progression of PNET via activation of the phosphotidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. CONCLUSIONS: STK33 plays important roles in the tumour growth and progression of PNET via activation of the PI3K/AKT/mTOR pathway and has potential as a therapeutic target to improve PNET treatment.

17.
J Org Chem ; 85(2): 327-338, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31799851

RESUMO

A novel approach has been constructed for the synthesis of two types of 2-amino-4-coumarinyl-5-arylpyrroles (ACAPs, 5 and 6) through a cascade reaction and a metal-free catalyzed aerobic oxidation reaction of arylglyoxal monohydrates 1, 1,1-enediamines (EDAMs) 2 and 3, and 4-hydroxy-2H-chromen-2-ones 4 via multicomponent reactions to produce the target compounds with good to excellent yields. Specifically, hydroxyl-substituted 2-amino-4-coumarinyl-5-arylpyrroles, that is, 2-amino-4-coumarinyl-5-aryl-6-hydroxylpyrroles (ACAHPs) 6, were obtained by metal-free aerobic oxidation in 1,4-dioxane at simple reflux for approximately 10 h. As a result, ACAHPs 6 have been produced without metal catalysts or traditional oxidizing agents. This method represents a route to obtain the novel ACAPs in an environmentally friendly, concise, rapid, and practical manner with potential biological activity of the product.

18.
Heart Lung ; 49(1): 66-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31376922

RESUMO

BACKGROUND: Atrial fibrillation (AF) burden might link to increased risk of systemic embolism. Current scoring systems for evaluating stroke risks such as CHA2DS2-VASc do not incorporate AF burden partly because of the difficulty to assess these data. Patients with dual-chamber pacemakers implanted have opportunities to acquire incidence and duration of AF. OBJECTIVES: We aimed to evaluate the AF burden and its association with thromboembolism in patients with dual-chamber pacemakers. METHODS: This retrospective cohort study enrolled patients who underwent dual-chamber pacemaker implantation at our center between October 2003 and May 2017. We excluded patients with prior thromboembolism or receiving anticoagulants. The incidence and duration of pacemaker-detected AF were compared between patients with and without thromboembolic outcomes. Propensity score matching (1:1) was conducted based on clinical characteristics. Multivariate regressions were performed to determine the predictors of thromboembolic outcomes. Survival free from stroke and thromboembolism was assessed using Kaplan-Meier analysis in groups with different AF burden. RESULTS: Among the 152 patients enrolled (43.4% women; age 73.2 ±â€¯13.3 years), ten experienced thromboembolic events within a median follow-up of 67 months. Patients with thromboembolisms had higher CHA2DS2-VASc scores but not higher AF burden. Higher CHA2DS2-VASc score was associated with increased risk for systemic thromboembolism [hazard ratio (HR), 1.87; 95% confidence interval (CI), 1.07-3.24; P = 0.027). In the propensity score-matched cohort with comparable CHA2DS2-VASc score, patients with thromboembolism had higher AF burden. Pacemaker-detected AF was associated with increased risk for thromboembolism (propensity-adjusted HR, 9.33; 95% CI, 1.19-72.99; P = 0.033). Experiencing AF episodes lasting >6 min was a predictor of significantly higher risk of future stroke or thromboembolism (propensity-adjusted HR, 6.75; 95% CI, 1.30-35.11; P = 0.023). CONCLUSION: In patients with dual-chamber pacemakers and comparable CHA2DS2-VASc score, pacemaker-detected AF burden is associated with elevated risk for thromboembolism. Further research is needed to clarify how pacemaker-detected AF burden could incorporate with CHA2DS2-VASc score variables and help to guide anticoagulation.

19.
J Vet Med Sci ; 82(2): 115-124, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31852859

RESUMO

High-producing dairy cows are easily affected by left displacement of the abomasum (LDA) within 4 weeks postpartum. Although LDA is highly associated with metabolic disturbances, the related information on comprehensive metabolic changes, with the exception of some blood biochemical parameters, remains limited. In this study, the changes in plasma metabolites and in the metabolic profile of postpartum dairy cows with LDA were investigated through liquid chromatography coupled with quadrupole time of flight mass spectrometry (LC-Q/TOF-MS)-based metabolomics, and the metabolic networks related to LDA were constructed through metabolomics pathway analysis (MetPA). An obvious change in the metabolic profile was reflected by significant variations in 68 plasma metabolites in postpartum dairy cows with LDA, and these variations consequently altered 13 metabolic pathways (histidine metabolism, tyrosine metabolism, valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, arginine and proline metabolism, tryptophan metabolism, synthesis and degradation of ketone bodies, linoleic acid metabolism, arachidonic acid metabolism, citrate cycle, butanoate metabolism, vitamin B6 metabolism and pyrimidine metabolism). This study shows that the more detailed information obtained by LC-Q/TOF-MS-based metabolomics and MetPA might contribute to a better understanding of the disordered metabolic networks in postpartum dairy cows with LDA.

20.
Shanghai Kou Qiang Yi Xue ; 28(4): 412-416, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31792484

RESUMO

PURPOSE: To investigate the correlation between CD44v6 and cyclooxygenase-2(COX-2) expression and recurrence and deterioration of pleomorphic adenoma of parotid gland. METHODS: Immunohistochemistry was used to detect the expression of CD44v6 and COX-2 in 19 normal parotid tissues, 25 primary pleomorphic adenomas, 15 first recurrent pleomorphic adenoma, 15 second recurrent pleomorphic adenoma and 13 cancer in pleomorphic adenomas. The correlation between CD44v6 and COX-2 and the recurrence and deterioration of pleomorphic adenomas was evaluated using SPSS 15.0 software package. RESULTS: The positive expression rate of CD44v6 in normal parotid gland, primary pleomorphic adenoma, first recurrent pleomorphic adenoma, second recurrent pleomorphic adenoma and cancer was 5.26%, 44.00%, 60.00%, 93.37% and 100.00%, respectively;and the positive expression rate of COX-2 was 10.53%, 40.00%, 63.33%, 93.37% and 100.00%, respectively. There was significant difference in the positive expression intensity of CD44v6 and COX-2 among the groups (P<0.05). The positive expression rate and intensity of CD44v6 and COX-2 in normal parotid gland tissue were significantly lower than those in other groups (P<0.05). There was no significant difference in the positive expression rate and intensity of CD44v6 between primary pleomorphic adenoma and first recurrent pleomorphic adenoma (P>0.05). There was no significant difference in the expression intensity of COX-2 between the two groups (P>0.05), but the positive expression rate of COX-2 between the two groups was not significant(P>0.05). The positive expression rate and intensity of CD44v6 and COX-2 in the second recurrent pleomorphic adenoma were significantly higher than those in the first recurrent pleomorphic adenoma(P<0.05), but there was no significant difference between the two groups(P>0.05). CD44v6 in the second recurrent pleomorphic adenoma and cancer was significantly higher than that in the first recurrent pleomorphic adenoma(P<0.05). There was no significant difference in the expression rate and intensity of COX-2 (P>0.05). CONCLUSIONS: CD44v6 and COX-2 may play an important role in promoting occurrence, invasion, recurrence and deterioration of pleomorphic adenoma through synergistic action.


Assuntos
Adenoma Pleomorfo , Neoplasias Parotídeas , Ciclo-Oxigenase 2 , Humanos , Recidiva Local de Neoplasia , Glândula Parótida
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