Blockade of a novel MAP4K4-LATS2-SASH1-YAP1 cascade inhibits tumorigenesis and metastasis in luminal breast cancer.

Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that expression of SAM and SH3 domain-containing protein 1 (SASH1) is negatively correlated with expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) in a subpopulation of patients with luminal-subtype BC. Downregulated SASH1 and upregulated MAP4K4 synergistically regulated the proliferation, migration, and invasion of luminal-subtype BC cells. The expression of LATS2, SASH1, and YAP1 and the phosphorylation of YAP1 were negatively regulated by MAP4K4, and LATS2 then phosphorylated SASH1 to form a novel MAP4K4-LATS2-SASH1-YAP1 cascade. Dephosphorylation of Yes1 associated transcriptional regulator (YAP1), YAP1/TAZ nuclear translocation, and downstream transcriptional regulation of YAP1 were promoted by the combined effects of ectopic MAP4K4 expression and SASH1 silencing. Targeted inhibition of MAP4K4 blocked proliferation, cell migration, and ER signaling both in vitro and in vivo. Our findings reveal a novel MAP4K4-LATS2-SASH1-YAP1 phosphorylation cascade, a noncanonical Hippo pathway that mediates ER signaling, tumorigenesis, and metastasis in breast cancer. Targeted intervention with this noncanonical Hippo pathway may constitute a novel alternative therapeutic approach for endocrine-resistant BC.

Donafenib inhibits PARP1 expression and induces DNA damage, in combination with PARP1 inhibitors promotes apoptosis in liver cancer cells.

Liver cancer is a prevalent malignant tumor globally. The newly approved first-line drug, donafenib, is a novel oral small molecule multi-tyrosine kinase inhibitor that has significant antitumor effects on liver cancer. This study aims to investigate the antitumor effects of donafenib on liver cancer and to explore its potential mechanisms. Donafenib significantly inhibited the viability of Huh-7 and HCCLM3 cells, inhibited malignant cell proliferation, and promoted cell apoptosis, as demonstrated by CCK-8, EdU, and Calcein/PI (propidium iodide) staining experiments. The results of DNA damage detection experiments and western blot analysis indicate that donafenib caused considerable DNA damage in liver cancer cells. The analysis of poly (ADP-ribose) polymerase 1 (PARP1) in liver cancer patients using online bioinformatics data websites such as TIMER2.0, GEPIA, UALCAN, cBioPortal, Kaplan-Meier Plotter, and HPA revealed a high expression of PARP1, which is associated with poor prognosis. Molecular docking and western blot analysis demonstrated that donafenib can directly target and downregulate the protein expression of PARP1, a DNA damage repair protein, thereby promoting DNA damage in liver cancer cells. Western blot and immunofluorescence detection showed that the group treated with donafenib combined with PARP1 inhibitor had significantly higher expression of γ-H2AX and 8-OHdG compared to the groups treated with donafenib or PARP1 inhibitors alone, the combined treatment suppresses the expression of the antiapoptotic protein Bcl2 and enhances the protein expression level of the proapoptotic protein Bcl-2-associated X protein (BAX). These data suggest that the combination of donafenib and a PARP1 inhibitor results in more significant DNA damage in cells and promotes cell apoptosis. Thus, the combination of donafenib and PARP1 inhibitors has the potential to be a treatment option for liver cancer.

The role of NLRP3 inflammasome in aging and age-related diseases.

The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.

Retyping and molecular pathology diagnosis of dyschromatosis universalis hereditaria.

Dyschromatosis universalis hereditaria (DUH) is characterized by diffuse symmetrically distributed hypopigmented macules mixed with hyperpigmentation. DUH is divided into three types by Online Mendelian inheritance in man (OMIM) that is, DUH1 (OMIM 127500), DUH2 (OMIM 612715) and DUH3 (OMIM 615402) according to the different linkage regions. Although each condition possesses corresponding phenotypic characteristics and the prognosis for each is somewhat different, these disorders are highly overlapped and difficult to differentiate in the clinical setting. Our latest study reveals a novel DUH subtype that presents a mild phenotype of pigmentation anomalies and is named PER3rs772027021 SNP related DUH or DUH4 by us, which make the DUH subtype can be further retyped. Heterozygous distribution or mosaic-like distribution of melanin is a newly discovered pathological features that is uniquely demonstrated in the affected layers of DUH1 and DUH4 patients. In this review, DUH is further divided into four subtypes according the causative genes and their mutational sites, and the mutation regions described in the previous reports. To make an accurate diagnosis, we suggest that Sanger sequencing or the target region sequencing (TRS) to the candidate causative genes related melanogenesis may be the most effective and convenient method of clinical diagnosis or/and prenatal diagnosis for DUH and DUH-like patients. More importantly, heterozygous distribution or mosaic-like distribution of melanin can be utilized for differential diagnosis of DUH. We also investigate the underlying molecular mechanism to form mosaic-like melanin in the affected layers of hyper- and/or hypo-pigmented macules from DUH1 and DUH4 patients. This review provides a molecular and pathological delineation of four types of DUH and aims to establish a concise diagnostic strategy to allow clinical dermatologists to make an accurate diagnosis.

Jumping of flea beetles onto inclined platforms.

The flea beetle, Altica cirsicola, escapes predators by jumping and landing in a dense maze of leaves. How do they land on such varied surfaces? In this experimental study, we filmed the take-off, flight, and landing of flea beetles on a configurable angled platform. We report three in-flight behaviors: winged, wingless, and an intermediate winged mode. These modes significantly affected take-off speed, acceleration, and the duration that wings were deployed. When wings were closed, flea beetles rolled or pitched up to five times in the air. This work may help to understand how insects can jump and right themselves onto variable surfaces.

Food-derived peptides as novel therapeutic strategies for NLRP3 inflammasome-related diseases: a systematic review.

NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3), a member of the nucleotide-binding domain (NOD) and leucine-rich repeat sequence (LRR) protein (NLR) family, plays an essential role in the inflammation initiation and inflammatory mediator secretion, and thus is also associated with many disease progressions. Food-derived bioactive peptides (FDBP) exhibit excellent anti-inflammatory activity in both in vivo and in vitro models. They are encrypted in plant, meat, and milk proteins and can be released under enzymatic hydrolysis or fermentation conditions, thereby hindering the progression of hyperuricemia, inflammatory bowel disease, chronic liver disease, neurological disorders, lung injury and periodontitis by inactivating the NLRP3. However, there is a lack of systematic review around FDBP, NLRP3, and NLRP3-related diseases. Therefore, this review summarized FDBP that exert inhibiting effects on NLRP3 inflammasome from different protein sources and detailed their preparation and purification methods. Additionally, this paper also compiled the possible inhibitory mechanisms of FDBP on NLRP3 inflammasomes and its regulatory role in NLRP3 inflammasome-related diseases. Finally, the progress of cutting-edge technologies, including nanoparticle, computer-aided screening strategy and recombinant DNA technology, in the acquisition or encapsulation of NLRP3 inhibitory FDBP was discussed. This review provides a scientific basis for understanding the anti-inflammatory mechanism of FDBP through the regulation of the NLRP3 inflammasome and also provides guidance for the development of therapeutic adjuvants or functional foods enriched with these FDBP.

Effect of PCSK9 Monoclonal Antibody Versus Placebo/Ezetimibe on Atrial Fibrillation in Patients at High Cardiovascular Risk: A Meta-Analysis of 26 Randomized Controlled Trials.

BACKGROUND: Patients at high cardiovascular risk are closely associated with an increased risk of atrial fibrillation (AF). Whether proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) can attenuate AF progression remains unknown. METHODS: To compare PCSK9 mAbs with placebo or ezetimibe to explore the effect of PCSK9 mAbs therapy on the end-point of incidence of AF, we searched PubMed, Embase, and ClinicalTrials.gov for articles. We used Mantel-Haenszel risk ratio (RR) with corresponding 95% CI for the categorical data, including the incidence of AF and predefined other outcomes of interest. RESULTS: We included 21 articles consisting of 26 randomized controlled trials with a total of 95,635 participants. Quantitative synthesis revealed that PCSK9 mAbs significantly reduce the incidence of AF events (RR 0.84; 95% CI 0.72-0.98; p = 0.03), whereas no obvious differences were seen between the PCSK9 mAbs group and the ezetimibe group (RR 0.90; 95% CI 0.29-2.76; p = 0.85). PCSK9 mAbs also markedly decreased the incidence of cerebrovascular events (RR 0.75; 95% CI 0.66-0.85; p < 0.0001) and new-onset hypertension (RR 0.92; 95% CI 0.87-0.97; p = 0.003), but not the risk of cardiovascular death (RR 0.95; 95% CI 0.85-1.07; p = 0.40) and new-onset diabetes mellitus (RR 1.01; 95% CI 0.95-1.08; p = 0.67). CONCLUSIONS: Overall, the PCSK9 mAbs therapy reduced AF and presented certain cardiovascular benefits in patients at high cardiovascular risk. Further big-scale and long follow-up duration randomized controlled trials that compare PCSK9 mAbs with ezetimibe are required to evaluate the effect of PCSK9 mAbs versus ezetimibe on AF.

Clinical features analysis of Kawasaki disease with abdominal symptoms as the first manifestation.

To investigate the clinical characteristics of Kawasaki disease (KD) presenting with abdominal manifestation as the first manifestation. Our findings may help improve the cognition of KD with abdominal complications, and avoid misdiagnosis and missed diagnosis. A retrospective analysis was conducted of 1490 KD patients admitted to Shengjing Hospital between January 2019 and March 2022. Clinical characteristics, related factors, and prognosis of KD with abdominal manifestation as first manifestation were analyzed. Based on the presenting symptoms, patients were divided into gastrointestinal symptom group (n = 141), liver dysfunction group (n = 55), and control group (n = 1294). In the gastrointestinal group, diarrhea [100 cases (70.9%)], vomiting [55 cases (39.0%)], and abdominal pain [34 cases (24.1%)] were the most common symptoms at onset. 8 cases (5.7%) were complicated with pseudo-intestinal obstruction, 6 cases (4.3%) with ischemic colitis, 5 cases (3.5%) with pancreatitis, 2 cases (1.4%) with appendicitis, and 1 case (0.7%) with cholecystitis. Comparied to ordinary gastroenteritis caused by infection, gastroenteritis with KD has longer fever duration before treatment, higher WBC, PLT, CRP, AST levels and lower albumin levels. All patients in the liver dysfunction group had elevated transaminases, and 19 patients (34.5%) presented with jaundice. In the gastrointestinal group, the average hospital stay was 10.3 days, and the incidence of IVIG unresponsiveness and coronary artery lesion were 18.4% and 19.9%, respectively, which were significantly higher than that in the control group. In the liver dysfunction group, the average hospital stay (11.18 days), incidence of IVIG unresponsiveness (25.5%), and incidence of coronary artery lesion (29.1%) were significantly higher than that in the control group. On multivariate logistic regression analysis, gastrointestinal involvement, fever duration, ALT, PLT, and CRP were identified as risk factors for CAL, younger age, gastrointestinal involvement and fever duration were risk factors for IVIG unresponsiveness.  Conclusion: KD with gastrointestinal involvement is associated with a higher risk of IVIG unresponsiveness and coronary artery lesion. KD should be considered in the differential diagnosis of children with acute fever, especially those with gastrointestinal involvement and liver dysfunction. What is Known: • Fever duration, PLT, and CRP were identified as risk factors for CAL. Timely diagnosis and application of IVIG treatment can avoid exploratory laparotomy for ileus, appendectomy for misdiagnosed appendicitis, colonoscopy for misdiagnosed inflammatory bowel disease, and reduce the complications of CAL and IVIG unresponsiveness. What is New: • Abdominal symptoms as the first manifestation can be an independent risk factor for CAL and IVIG unresponsiveness. KD should be considered in the differential diagnosis of children with acute fever, especially those with gastrointestinal symptoms or liver dysfunction. • Gastroenteritis in KD group had longer fever duration before treatment, accompanied with higher WBC, PLT, CRP, AST levels and lower albumin levels than those gastroenteritis caused by infection. Therefore, high attention should be paid to the possibility of KD when gastroenteritis accompanied by along fever duration, high WBC, PLT, CRP, AST level or lowalbumin level.

Nanoparticles in the New Era of Cardiovascular Therapeutics: Challenges and Opportunities.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Although a cadre of therapeutic strategies have been made available for CVDs in the clinical setting, predominantly through medication and surgery, these do not fully address the clinical needs of patients with CVD. As a new technique for CVD treatment, nanocarriers are employed to modify and package medications to ease the targeting of tissues, cells and molecules within the cardiovascular system. Nanocarriers are made of biomaterials, metals, or a combination of these materials, with sizes similar to bioactive molecules such as proteins and DNA. Cardiovascular nanomedicine (CVN) has only surfaced in recent years and is still in its infancy. Ample studies have displayed promise for the clinical utility of nanomedicine techniques, courtesy of continued perfection in nanocarrier design to optimize drug delivery and treatment outcomes. Here in this review, we will summarize the research advances in the literature on nanoparticles in the management of CVDs, including ischemic and coronary heart disease (e.g., atherosclerosis, angina pectoris and myocardial infarction), myocardial ischemia-reperfusion injury, aortic aneurysm, myocarditis, hypertension, and pulmonary artery hypertension and thrombosis.

Electrochemical Behavior of ß-Cyclodextrin-Ni-MOF-74/Reduced Graphene Oxide Sensors for the Ultrasensitive Detection of Rutin.

Rutin, as a biological flavonoid glycoside, has very important medicinal value. The accurate and rapid detection of rutin is of great significance. Herein, an ultrasensitive electrochemical rutin sensor based on ß-cyclodextrin metal-organic framework/reduced graphene oxide (ß-CD-Ni-MOF-74/rGO) was constructed. The obtained ß-CD-Ni-MOF-74 was characterized by X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and nitrogen adsorption and desorption. The ß-CD-Ni-MOF-74/rGO presented good electrochemical properties benefiting from the large specific surface area and good adsorption enrichment effect of ß-CD-Ni-MOF-74 and the good conductivity of rGO. Under optimal conditions for the detection of rutin, the ß-CD-Ni-MOF-74/rGO/GCE showed a wider linear range (0.06-1.0 µM) and lower detection limit (LOD, 0.68 nM, (S/N = 3)). Furthermore, the sensor shows good accuracy and stability for the detection of rutin in actual samples.

Pt2CeO2 Heterojunction Supported on Multiwalled Carbon Nanotubes for Robust Electrocatalytic Oxidation of Methanol.

Herein, we prepared Pt2CeO2 heterojunction nanocluster (HJNS) on multiwalled carbon nanotubes (MWCNTs) in deep eutectic solvents (DESs) which is a special class of ionic liquids. The catalyst was then heat-treated at 400 °C in N2 (refer to Pt2CeO2/CNTs-400). The Pt2CeO2/CNTs-400 catalyst showed remarkably improved electrocatalytic performance towards methanol oxidation reaction (MOR) (839.1 mA mgPt-1) compared to Pt2CeO2/CNTs-500 (620.3 mA mgPt-1), Pt2CeO2/CNTs-300 (459.2 mA mgPt-1), Pt2CeO2/CNTs (641.6 mAmg-1) (the catalyst which has not been heat-treated) and commercial Pt/C (229.9 mAmg-1). Additionally, the Pt2CeO2/CNTs-400 catalyst also showed better CO poisoning resistance (onset potential: 0.47 V) compared to Pt2CeO2/CNTs (0.56 V) and commercial Pt/C (0.58 V). The improved performance of Pt2CeO2/CNTs-400 catalyst is attributed to the addition of appropriate CeO2, which changed the electronic state around the Pt atoms, lowered the d-band of Pt atoms, formed more Ce-O-Pt bonds acting as new active sites, affected the adsorption of toxic intermediates and weakened the dissolution of Pt; on the other hand, with the assistance of thermal treatment at 400 °C, the obtained Pt2CeO2 HJNS expose more new active sites at the interface between Pt and CeO2 to enhance the electrochemical active surface area (ECSA) and the dehydrogenation process of MOR. Thirdly, DES is beneficial to the increase of the effective component Pt(0) in the carbonization process. The study shows a new way to construct high-performance Pt-CeO2 catalyst for the direct methanol fuel cell (DMFC).

Efficacy and Safety of Cilostazol for Atherosclerosis: A Meta-analysis of Randomized Controlled Trials.

ABSTRACT: To investigate the efficacy and safety of cilostazol for atherosclerosis. PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to May 29, 2021, were searched for randomized clinical trials (RCTs). Ten trials with 1577 patients were included. Treatment with cilostazol significantly reduced carotid intima-media thickness [mean difference (MD), -0.12 mm; 95% confidence interval (CI), -0.17 to -0.06]. According to the difference in intervening measures, the cilostazol group was superior to the control group in inhibiting the progression of carotid intima-media thickness: cilostazol versus placebo (MD, -0.04 mm; 95% CI, -0.06 to -0.02; P < 0.00001), cilostazol versus no antiplatelet drug (MD, -0.14 mm; 95% CI, -0.26 to -0.03; P = 0.02), cilostazol versus aspirin (MD, -0.17 mm; 95% CI, -0.32 to -0.02; P = 0.02), cilostazol + aspirin versus aspirin (MD, -0.08 mm; 95% CI, -0.14 to -0.02; P = 0.007), cilostazol + aspirin versus clopidogrel + aspirin (MD, -0.07 mm; 95% CI, -0.14 to -0.00; P = 0.04), and cilostazol + clopidogrel + aspirin versus clopidogrel + aspirin (MD, -0.16 mm; 95% CI, -0.30 to -0.02; P = 0.03). Cilostazol treatment considerably decreased triglyceride (MD, -20.18 mg/dL; 95% CI, -39.03 to -1.34) and improved high-density lipoprotein cholesterol (MD, 4.35 mg/dL; 95% CI, 2.61-6.10). Cilostazol therapy significantly increased the risk of adverse events of headache (odds ratio, 12.91; 95% CI 5.33-31.29). Our research has revealed that cilostazol has potent antiatherosclerotic effects and can reverse atherosclerosis progress even in high-risk patients, such as those with type 2 diabetes mellitus, and does not increase the risk of bleeding.

Start-up and synergistic nitrogen removal of partial nitrification and anoxic/aerobic denitrification in membrane aerated biofilm reactor.

To reduce energy consumption and improve operational stability of traditional biological nitrogen removal (BNR) system, partial nitrification and anoxic/aerobic denitrification were synergistically implemented in membrane aerated biofilm reactor (MABR) by regulating DO and pH. The results indicated that the optimal DO, pH and C/N ratio were 1-2 mg/L, 9.0 and 4-7, respectively. The corresponding average organic removal rate (ORR), total nitrogen removal rate (TNRR) and nitrite accumulation rate (NAR) reached 324 gCOD・m-3・d-1, 48 gN・m-3・d-1 and 77.70%, respectively. Extracellular polymeric substance (EPS) content in biofilm was more abundant than that in inoculated sludge. Multiple aerobic denitrifiers were detected in the biofilm with the relative abundance of 11.19%-22.71%. AQUASIM simulation implied that the distribution and proportion of substrates and bacteria were significantly affected by DO and pH regulation. Overall, this study provided some important insights in the start-up and operation of synergistic nitrogen removal process in BNR system.

An ultrasensitive high-performance baicalin sensor based on C3N4-SWCNTs/reduced graphene oxide/cyclodextrin metal-organic framework nanocomposite.

Baicalin (Bn) obtained from natural plants has been found to exhibit significant antiviral activity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Herein, a novel ultrasensitive Bn electrochemical sensor was proposed based on graphitized carbon-nitride - single-walled carbon nanotube nanocomposites (C3N4-SWCNTs), reduced graphene oxide (rGO) and electrodeposited cyclodextrin-metal organic framework (CD-MOF). The sensing nanomaterials were characterized by X-ray diffraction spectroscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, scanning electron microscopy, and transmission electron microscopy. Under optimal conditions, the sensor exhibited sensitive detection of Bn in a wide linear range of 1 × 10-9-5 × 10-7 M with an LOD of 4.6 × 10-10 M and a sensitivity of 220 A/M, and it showed satisfactory stability and accuracy for detecting Bn in real samples (human serum and bear bile scutellaria eye drops). In addition, the electrochemical reaction sites and redox mechanism of Bn were revealed through electrochemical behavior and density functional theory. This work provided an insightful solution for detecting Bn, and extensive potential applications could be further expected.

Efficacy and Safety of LCZ696 for Short-term Management of Essential Hypertension Compared With ARBs: A Meta-analysis of Randomized Controlled Trials.

ABSTRACT: Whether LCZ696 (neprilysin inhibitor + valsartan) has greater advantages of blood pressure (BP) lowering than angiotensin II type 1 receptor blockers (ARBs) is unclear. To provide more detailed information about the benefits of LCZ696, we conducted a meta-analysis to evaluate the efficacy and safety of LCZ696 for short-term management of hypertension compared with ARBs. We searched PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov, using relevant keywords. We used a random or fixed effects model to calculate the weighted mean difference (WMD) of changes in BP and the risk ratio (RR) for BP control rates and adverse events (AEs). In this meta-analysis, 9 studies were incorporated. Compared with ARBs, LCZ696 revealed a significant reduction in mean sitting systolic BP [msSBP; WMD -4.79 mm Hg; 95% confidence interval (CI): -5.46 to -4.11 mm Hg], mean sitting diastolic BP (msDBP; WMD -2.12 mm Hg; 95% CI: -2.53 to -1.71 mm Hg), mean sitting pulse pressure (msPP; WMD -2.79 mm Hg; 95% CI: -3.52 to -2.07 mm Hg), and mean ambulatory pulse pressure (maPP; WMD -2.96 mm Hg; 95% CI: -3.35 to -2.57 mm Hg). LCZ696 had a higher BP control rate than ARBs (OR = 1.55; 95% CI: 1.39 to 1.73). There was no significant difference between LCZ696 and ARBs in the incidence of AEs (RR = 1.10; 95% CI: 0.96 to 1.25) and discontinuations because of AEs (RR = 0.97; 95% CI: 0.54 to 1.32). Overall, in short-term treatment, LCZ696 has greater advantages of antihypertensive efficacy and the safety is not inferior to ARBs. Further long-term studies are required to rule out the potential risks of beta amyloid accumulation and the potential for Alzheimer's disease.

[A Real-time Reconstruction Method of CBCT Short Scan Based on Attenuation Compensation].

Aiming at the problem of timeliness of CBCT reconstruction, a CBCT fast short scan reconstruction method is proposed. At the same time, the image reconstruction process in which a new attenuation compensation algorithm is applied to improve image quality. When performing FDK three-dimensional reconstruction of a single-frame acquisition image, the Parker-weighted image is calculated in real time, and a new attenuation compensation algorithm is applied in the back projection process to complete the short scan Parker-weighted reconstruction. This method simulates the CBCT synchronous acquisition and reconstruction process by establishing collection and reconstruction threads. Under the premise of satisfying the reconstruction quality, the reconstruction can be completed within 1 to 2 seconds after the patient collection is completed, which achieves the purpose of real-time.

Efficacy and safety of oral anticoagulants in atrial fibrillation patients with cancer-a network meta-analysis.

There are no guideline recommendations for the use of anticoagulant therapy in atrial fibrillation (AF) patients with cancer, which creates uncertainty about the optimal antithrombotic treatment in these patients. We conducted a network meta-analysis for the first time to assess the efficacy and safety of anticoagulant drugs in patients with AF and concurrent cancer. The PubMed, EMBASE, and Cochrane databases were searched up to March 2019. A search was made for the main anticoagulant drugs (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). Outputs were presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities. We identified 414 relevant studies and included 5 trials involving 31,660 participants. In reducing the risk of stroke or systemic embolism, rivaroxaban and apixaban ranked the best and second best (SUCRA, 25.2% and 29.3%, respectively), followed by dabigatran, edoxaban, and warfarin. Apixaban and dabigatran were associated with lower probability of achieving at venous thromboembolism (VTE) (OR 0.12, 95% CI 0.05-0.52, SUCRA, 0.1%; and OR 0.24, 95% CI 0.07-1.00, SUCRA, 33.3%, respectively) than warfarin (SUCRA, 100.0%). For the prevention of all-cause death, apixaban was nonsignificantly less likely than warfarin. In addition, there were nonsignificant differences among all interventions in major bleeding, with the exception of apixaban vs. warfarin (OR 0.39, 95% CI 0.18-0.79; SUCRA 4.9%). In AF patients with cancer, nonvitamin K antagonist oral anticoagulants showed a lower incidence of stroke/systemic embolism, VTE, all-cause death, and major bleeding than warfarin, with apixaban being the best of those studied.

Interrupted or Uninterrupted Oral Anticoagulants in Patients Undergoing Atrial Fibrillation Ablation.

BACKGROUND AND PURPOSE: The safety and efficacy of uninterrupted, minimally interrupted (one dose skipped) or completely interrupted (24 h skipped) oral anticoagulant therapy in patients with atrial fibrillation (AF) ablation are poorly defined. We conducted a network meta-analysis to explore the effect of interrupted or uninterrupted oral anticoagulants in patients with AF undergoing ablation. METHODS: The Cochrane Library, PubMed and Embase databases were systematically searched for studies comparing uninterrupted, minimally interrupted or completely interrupted non-vitamin K antagonist oral anticoagulants (NOACs) with continuous or interrupted warfarin in patients undergoing AF ablation. RESULTS: Twelve randomized clinical trials (RCTs) with a total of 5597 patients with AF undergoing catheter ablation were included. For thromboembolism, minimally interrupted NOACs (OR 0.03, 95% CI 0.01-0.35), uninterrupted NOACs (OR 0.04, 95% CI 0.01-0.23) and continuous VKAs (OR 0.05, 95% CI 0.01-0.21) were better than interrupted warfarin. The risk of total bleeding appeared higher in the completely interrupted NOAC group compared with the minimally interrupted NOACs (OR 2.74, 95% CI 1.18-6.37), uninterrupted NOACs (OR 2.15, 95% CI 1.05-4.38) and uninterrupted warfarin (OR 2.04, 95% CI 1.02-4.08). To reduce the risk of total bleeding, minimally interrupted NOACs (OR 0.15, 95% CI 0.08-0.27), uninterrupted NOACs (OR 0.19, 95% CI 0.14-0.42) and uninterrupted warfarin (OR 0.24, 95% CI 0.15-0.39) were better than interrupted warfarin. In the event of major bleeding, there was no significant difference in the interrupted NOAC, uninterrupted NOAC, interrupted VKA and uninterrupted VKA groups. CONCLUSIONS: These three NOAC strategies may have similar safety and efficacy in terms of thromboembolism and major bleeding complications. The total bleeding risk of completely interrupted oral anticoagulants is higher than that of uninterrupted and minimally interrupted NOACs. For thromboembolism, minimally interrupted NOACs, uninterrupted NOACs and continuous VKAs were better than interrupted warfarin.

Ultra-sensitive amperometric determination of quercetin by using a glassy carbon electrode modified with a nanocomposite prepared from aminated graphene quantum dots, thiolated ß-cyclodextrin and gold nanoparticles.

Thiolated ß-cyclodextrin functionalized gold nanoparticles (Au-ß-CDs) with layered wrinkled flower structure were prepared. Au-ß-CDs were electrostatically combined with protonated aminated graphene quantum dots (NH2-GQDs) to form a nanocomposite with better supramolecular recognition, conductivity, catalysis and dispersion properties. For constructing a quercetin (QU) sensor, the nanocomposites were one-step electrodeposited by a cyclic voltammetry (CV) method onto a glassy carbon electrode to form a stable film. Under optimized conditions, the sensor showed a wide linear response range of 1-210 nM, with a lower detection limit of 285 pM. At the same time, flavonoids with similar structures hardly interfere with the determination of QU. The sensor has been used to determine QU in honey, tea, honeysuckle and human serum with satisfactory results. Graphical abstractSchematic representation of the fabrication of an ultrasensitive quercetin electrochemical sensor based on aminated graphene quantum dots, thiolated ß-cyclodextrin and gold nanoparticles (NH2-GQDs/Au-ß-CD/GCE).

Combined microwave ablation and antiangiogenic therapy to increase local efficacy.

Purpose: We aim to evaluate the efficacy, safety and survival time of microwave ablation (MWA) with adjuvant antiangiogenic therapy-endostatin in animal models.Material and methods: A total of 40 rabbits successfully implanted with VX2 tumors were randomly assigned to four experimental groups: Group A underwent only microwave ablation of the tumors; Group B received only antiangiogenic drugs endostatin; Group C received endostatin immediately after MWA; Group D followed up without treatment.Results: Two months post-treatment, tumor sizes of Group A and Group C were reduced to 1.936 ± 0.373 cm3 and 1.592 ± 0.382 cm3, respectively. However, tumors grew to 15.091 ± 1.735 cm3 and 47.825 ± 7.664 cm3 in Group B and the control group. Three months post-treatment, tumor sizes in Group A and Group C maintained as 1.395 ± 0.394 cm3 and 1.482 ± 0.305 cm3, significantly smaller than Group B (35.277 ± 6.019 cm3). All animals in the control group died, while four (40%) survived in Group B (Endo Group). The numbers of survivals in Groups A and C were seven (70%) and eight (80%), respectively. The lowest metastasis rate (2/10, 20%) was observed in Group C (combination therapy).Conclusion: The combination of MWA and antiangiogenic therapy triggered a significant reduction in the growth rate and metastases of tumors and may potentially improve survivals.