Rapid nanomolar detection of Δ9-tetrahydrocannabinol in biofluids via electrochemical aptamer-based biosensor.

BACKGROUND: The fabrication of sensors capable of achieving rapid, sensitive, and highly selective detection of target molecules in complex fluids is key to realizing their real-world applications. For example, there is an urgent need in drugged driving roadside screening scenarios to develop a method that can be used for rapid drug detection and that avoids interference from the matrix in the sample. How to minimize the interference of complex matrices in biofluids at the electrode interface is the key to improve the sensitivity of the sensor. RESULTS: This work develops a facile and green method to prepare rough electrodes with a porous structure for constructing electrochemical aptamer-based (EAB) sensors for rapid, sensitive and accurate detection of Δ9-tetrahydrocannabinol (THC) in biofluids. The electroactive area of the rough electrode was 21 times of smooth electrode. And the antifouling performance of the rough electrode was much better than that of smooth electrode. Based on the unique advantages of the rough electrode, the developed EAB sensor achieves rapid nanomolar detection of THC in undiluted serum, undiluted urine and 50 % saliva with the detection limit of 5.0 nM, 10 nM and 10 nM, respectively. Moreover, our method possesses good reproducibility, accuracy and specificity. SIGNIFICANCE: The porous structure can effectively reduce the non-specific adsorption and enhance the stability of the signal, while the larger active area can modify more aptamers, thus improving the sensitivity. The detection limits of the EAB sensor were lower than the cutoff concentration of THC in drugged driving and the measuring process was completed within 60 s after target addition, which makes the present sensors capable for real-world applications.

Heating promoted super sensitive electrochemical detection of p53 gene based on alkaline phosphatase and nicking endonuclease Nt.BstNBI-assisted target recycling amplification strategy at heated gold disk electrode.

An ultrasensitive electrochemical biosensor for detecting p53 gene was fabricated based on heated gold disk electrode coupling with endonuclease Nt.BstNBI-assisted target recycle amplification and alkaline phosphatase (ALP)-based electrocatalytic signal amplification. For biosensor assembling, biotinylated ssDNA capture probes were first immobilized on heated Au disk electrode (HAuDE), then combined with streptavidin-alkaline phosphatase (SA-ALP) by biotin-SA interaction. ALP could catalyze the hydrolysis of ascorbic acid 2-phosphate (AAP) to produce ascorbic acid (AA). While AA could induce the redox cycling to generate electrocatalytic oxidation current in the presence of ferrocene methanol (FcM). When capture probes hybridized with p53, Nt.BstNBI would recognize and cleave the duplexes and p53 was released for recycling. Meanwhile, the biotin group dropt from the electrode surface and subsequently SA-ALP could not adhere to the electrode. The signal difference before and after cleavage was proportional to the p53 gene concentration. Furthermore, with electrode temperature elevated, the Nt.BstNBI and ALP activities could be increased, greatly improving the sensitivity and efficiency for p53 detection. A detection limit of 9.5 × 10-17 M could be obtained (S/N = 3) with an electrode temperature of 40 °C, ca. four magnitudes lower than that at 25 °C.

Cadmium ions mediated turn-on electrogenerated chemiluminescence of ZnS nanoparticles for highly selective cadmium detection in seafood.

Cd2+ is one of the most toxic heavy metal ions that can be easily accumulated in human body via food chain. Thus, the onsite detection of Cd2+ in food is very important. However, present methods for Cd2+ detection either require the use of large equipment, or suffer from the severe interference from other analogical metal ions. This work establishes a facile Cd2+ mediated turn-on ECL method for highly selective detection of Cd2+ via cation exchanging with the nontoxic ZnS nanoparticles, owing to the unique surface-state ECL properties of CdS nanomaterials. The linear range of the calibration curve is from 7.0 × 10-8 to 1.0 × 10-6 M, while other analogical metal ions do not interfere, facilitating the selective detection of Cd2+ in oyster samples. The result agrees well with that obtained using atomic emission spectroscopy, indicating the potential for wider application of this approach.

Plasmonic Au nanocube enhanced SERS biosensor based on heated electrode and strand displacement amplification for highly sensitive detection of Dam methyltransferase activity.

In this work, a novel "turn-on" mode Au nanocubes (AuNCs) enhanced surface-enhanced Raman scattering (SERS) biosensing platform coupled with heated Au electrode (HAuE) and strand displacement amplification (SDA) strategy was proposed for highly sensitive detection of DNA adenine methylation (Dam) Methyltransferase (MTase) activity. The Dam MTase and DpnI enzyme activities were significantly increased by elevating the HAuE surface temperature, resulting in the rapid production of template DNA for later SDA. During the SDA process, the released single-stranded DNA (ssDNA) could be amplified exponentially, and its concentration was positively related to the Dam MTase activity. The plasmonic AuNCs in SERS tags could provide significant SERS enhancement due to their "lightning rod" effect resulting from the sharp feature of the edges and corners of AuNCs. Because of these factors, the proposed biosensors exhibited high sensitivity in detecting the Dam MTase activity. The limit of detection was estimated to be 8.65 × 10-5 U mL-1, which was lower than that in most of the sensors for detection of Dam MTase activity in the literature. This SERS biosensor could also be used to screen inhibitors of Dam MTase and had the potential for detecting Dam MTase activity in real biological samples.

Real-Time Tunable Dynamic Range for Calibration-Free Biomolecular Measurements with a Temperature-Modulated Electrochemical Aptamer-Based Sensor in an Unprocessed Actual Sample.

The sensing technologies for monitoring molecular analytes in biological fluids with high frequency and in real time could enable a broad range of applications in personalized healthcare and clinical diagnosis. However, due to the limited dynamic range (less than 81-fold), real-time analysis of biomolecular concentration varying over multiple orders of magnitude is a severe challenge faced by this class of analytical platforms. For the first time, we describe here that temperature-modulated electrochemical aptamer-based sensors with a dynamically adjustable calibration-free detection window could enable continuous, real-time, and accurate response for the several-hundredfold target concentration changes in unprocessed actual samples. Specifically, we could regulate the electrode surface temperature of sensors to obtain the corresponding dynamic range because of the temperature-dependent affinity variations. This temperature modulation method relies on an alternate hot and cold electrode reported by our group, whose surface could actively be heated and cooled without the need for altering ambient temperature, thus likewise applying for the flowing system. We then performed dual-frequency calibration-free measurements at different interface temperatures, thus achieving an extended detection window from 25 to 2500 µM for procaine in undiluted urine, 1-500 µM for adenosine triphosphate, and 5-2000 µM for adenosine in undiluted serum. The resulting sensor architecture could drastically expand the real-time response range accessible to these continuous, reagent-less biosensors.

Temperature-Alternated Electrochemical Aptamer-Based Biosensor for Calibration-Free and Sensitive Molecular Measurements in an Unprocessed Actual Sample.

Frequently calibrating electrochemical biosensors (ECBs) to obtain acceptable accuracy can be cumbersome for the users. Thus, the achievement of calibration-free operation would effectively lead to commercial applications for ECBs in the real world. Herein, we fabricated a temperature-alternated electrochemical aptamer-based (TAEAB) sensor, producing a cycle of "enhanced-responsive and ∼nonresponsive" state at rapidly alternated interface temperatures (5 and 30 °C, respectively). The ratio of peak currents collected at two temperatures overcomes sensor-to-sensor fabrication variations, obviating sensor calibration prior to use due to its good reproducibility. We then demonstrated the capability of TAEAB sensors for improved, sensitive, and calibration-free measurement of different targets within 7 min, which respectively achieved a detection limit of 0.5 µM procaine in undiluted urine and 1.0 µM adenosine triphosphate in undiluted serum. This generalizable approach ameliorates sensitivity without the complicated amplification step, thus simplifying the operation procedure and reducing the detection time, which will effectively improve the clinical utility of biosensors.

Monitoring colorless electroactive chemicals in complex background based on electrochemical difference absorption spectroscopy with twin flow cells.

Conventional UV/Vis absorption spectroscopy is an economical and user-friendly technique for online monitoring, however, by which some electroactive chemicals are hardly determined in the presence of fluctuating background due to the formation of colored chemicals. Here, we propose an electrochemical difference absorption spectroscopy (EDAS) to accurately quantify colorless chemicals based on visible color change via electrolysis with strong variation in the background. EDAS is realized by twin spectroelectrochemical flow cells system, replacing the two cuvette cells of a dual beam spectrophotometer. Each cell consists of a three-electrode system, quartz windows and a thin flow channel. Flowing of analyte from one cell (reference cell) to the other (sample cell) can eliminate the influence of colored interferents even while their concentrations are changing. When different potentials are applied on the sample and reference cells respectively, electrolysis occurs and colored products flowing through quartz windows can absorb the incident light, resulting in difference absorption spectra induced from potential difference. We find that steady-state difference absorbance (ΔA) at characteristic wavelength is linearly changed with sample concentrations. EDAS is firstly verified by Fe(CN)64- at different potentials and flow rates, in good agreements with a simplified theory that describes linear relationship between ΔA and analyte concentration. Then EDAS is used to determine Cu(I) in Cu(I)-Cu(II) mixed solutions and tetramethylbenzidine in its partially oxidized solutions to illustrate the powerful ability to detect colorless chemicals with varied background, implying its promising potential applications in the chemical industry.

Ligand-Free Fabrication of Ag Nanoassemblies for Highly Sensitive and Reproducible Surface-Enhanced Raman Scattering Sensing of Antibiotics.

The assemblies of plasmonic nanoparticles (NPs) are the universal methods for enhancing their surface-enhanced Raman scattering (SERS) activities. However, the present methods suffer from the problems of poor reproducibility, complicated fabrication, or the adsorption of ligands on the surface, which limit their practical applications. In this work, by using a facile freeze-thaw method, we are able to fabricate the assemblies of Ag NPs with highly reproducible SERS activity without the use of ligands. Moreover, the Ag NPs can be well kept in a frozen state for a long time with few influences on the reproducibility (relative standard deviation, RSD ca. 7%), while those kept in colloid (4 °C) suffer from gradual surface oxidation and aggregation. Such a simple freeze-thaw method does not require the introduction of any ligands (or linkers) with long-term stability and reproducibility, implying its wide applications in practical SERS sensing.

Efficacy and Safety of Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Liver Disease: a Meta-Analysis and Systematic Review.

BACKGROUND: Liver disease is associated with increased bleeding risk. The efficacy and safety of direct oral anticoagulants (DOACs) is a subject of contention in atrial fibrillation (AF) patients with liver disease. METHODS: Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus warfarin in AF patients with liver disease from January 1980 to April 2020. A meta-analysis was conducted using a random-effects model. RESULTS: Six studies involving 41,859 patients were included. Compared with warfarin, DOACs demonstrated significant reduction in ischemic stroke (HR, 0.68; 95% CI (0.54-0.86)), major bleeding (0.74 (0.59-0.92)), and intracranial hemorrhage (ICH) (0.48 (0.40-0.58)), with no significant effect on gastrointestinal bleeding (P = 0.893) in AF patients with liver disease. Similar results were observed in regular-dose, reduced-dose, and active liver disease subgroups, albeit Asian patients had a slight reduction in major bleeding (P = 0.055). Furthermore, the pooled estimates of individual DOAC subgroups indicated that dabigatran and apixaban led to greater safety in major bleeding (P < 0.001), ICH (P < 0.001), and gastrointestinal bleeding (P < 0.005) in these patients. The same trends were observed in AF patients with cirrhosis. CONCLUSIONS: Our findings suggest that DOACs significantly reduce the risk of ischemic stroke, major bleeding, and ICH, with no significant effect on the risk of gastrointestinal bleeding in AF patients with liver disease compared with warfarin.

Clinical features and treatment outcomes of human immunodeficiency virus-associated cryptococcal meningitis: a 2-year retrospective analysis.

BACKGROUND: Cryptococcal meningitis (CM) is one of the most common opportunistic infections caused by Cryptococcus neoformans in human immunodeficiency virus (HIV)-infected patients, and is complicated with significant morbidity and mortality. This study retrospectively analyzed the clinical features, characteristics, treatment, and outcomes of first-diagnosed HIV-associated CM after 2-years of follow-up. METHODS: Data from all patients (n = 101) of HIV-associated CM hospitalized in Shanghai Public Health Clinical Center from September 2013 to December 2016 were collected and analyzed using logistic regression to identify clinical and microbiological factors associated with mortality. RESULTS: Of the 101 patients, 86/99 (86.9%) of patients had CD4 count <50 cells/mm, 57/101 (56.4%) were diagnosed at ≥14 days from the onset to diagnosis, 42/99 (42.4%) had normal cerebrospinal fluid (CSF) cell counts and biochemical examination, 30/101 (29.7%) had concomitant Pneumocystis (carinii) jiroveci pneumonia (PCP) on admission and 37/92 (40.2%) were complicated with cryptococcal pneumonia, 50/74 (67.6%) had abnormalities shown on intracranial imaging, amongst whom 24/50 (48.0%) had more than one lesion. The median time to negative CSF Indian ink staining was 8.50 months (interquartile range, 3.25-12.00 months). Patients who initiated antiretroviral therapy (ART) before admission had a shorter time to negative CSF Indian ink compared with ART-naïve patients (7 vs. 12 months, χ = 15.53, P < 0.001). All-cause mortality at 2 weeks, 8 weeks, and 2 years was 10.1% (10/99), 18.9% (18/95), and 20.7% (19/92), respectively. Coinfection with PCP on admission (adjusted odds ratio [AOR], 3.933; 95% confidence interval [CI], 1.166-13.269, P = 0.027) and altered mental status (AOR, 9.574; 95% CI, 2.548-35.974, P = 0.001) were associated with higher mortality at 8 weeks. CONCLUSION: This study described the clinical features and outcomes of first diagnosed HIV-associated CM with 2-year follow-up data. Altered mental status and coinfection with PCP predicted mortality in HIV-associated CM.

Clinical outcomes of people living with human immunodeficiency virus (HIV) with diffuse large B-cell lymphoma (DLBCL) in Shanghai, China.

BACKGROUND: Numerous studies have focused on lymphoma among patients infected with human immunodeficiency virus (HIV). However, little is known about the treatment options and survival rate of lymphoma in the Chinese people living with HIV (PLHIV). Our study aimed to investigate the prognosis and compare outcome of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab(R-CHOP) as front line therapy for PLHIV with diffuse large B-cell lymphoma (DLBCL) receiving modern combined antiretroviral therapy (cART). METHODS: A retrospective analysis evaluating PLHIV with DLBCL was performed in Shanghai Public Health Clinical Center from July 2012 to September 2019. The demographic and clinical data were collected, and overall survival (OS) and progression-free survival (PFS) analyses of patients receiving R-CHOP or DA-EPOCH-R therapy were performed by Kaplan-Meier analysis. Additionally, a Cox multiple regression model was constructed to identify related factors for OS. RESULTS: A total of 54 eligible patients were included in the final analysis with a median follow-up of 14 months (interquartile range [IQR]: 8-29 months). The proportion of high international prognostic index (IPI) patients was much larger in the DA-EPOCH-R group (n = 29) than that in the R-CHOP group (n = 25). The CD4 cell counts and HIV RNA levels were not significantly different between the two groups. The 2-year OS for all patients was 73%. However, OS was not significantly different between the two groups, with a 2-year OS rate of 78% for the DA-EPOCH-R group and 66% for the R-CHOP group. Only an IPI greater than 3 was associated with a decrease in OS, with a hazard ratio of 5.0. The occurrence of grade 3 and 4 adverse events of chemotherapy was not significantly different between the two groups. CONCLUSIONS: Outcomes of R-CHOP therapy do not differ from those of DA-EPOCH-R therapy. No HIV-related factors were found to be associated with the OS of PLHIV in the modern cART era.

AuNanostar@4-MBA@Au Core-Shell Nanostructure Coupled with Exonuclease III-Assisted Cycling Amplification for Ultrasensitive SERS Detection of Ochratoxin A.

The "turn-on" mode surface-enhanced Raman scattering (SERS) aptasensor for ultrasensitive ochratoxin A (OTA) detection was developed based on the SERS "hot spots" of AuNanostar@4-MBA@Au core-shell nanostructures (AuNS@4-MBA@Au) and exonuclease III (Exo III)-assisted target cycle amplification strategy. Compared with conventional gold nanoparticles, AuNS@4-MBA@Au provides a much higher SERS enhancement factor because AuNS exhibits a larger surface roughness and the lightning rod effect, as well as an excellent electromagnetic field between the AuNS core and the Au shell, which contribute to the superstrong SERS signal. Meanwhile, Exo III-assisted target cycle amplification can be used as an effective method for the further amplified detection of OTA. Additionally, the utilization of streptavidin magnesphere paramagnetic particles offers a green, economical, and facile technology for the accumulation and separation of the signal probe AuNS@4-MBA@Au from solution. All these factors lead to a significant enhancement of detectable signals and superhigh sensitivity. As a result, the limit of detection as low as 0.25 fg mL-1 could be achieved, which was lower than that in the other reported literatures on SERS methods for OTA detection as we know. The developed SERS aptasensor also provides a promising tool for foodstuff detection.

[Study on protective effect of vanillic acid from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology screen].

To identify and verify the active ingredients from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology and heart RNA-sequencing data. The monomers of A. membranaceus and their intervention target database were established by using network pharmacology. The genes associated to cardiac remodeling were then screened by analyzing cardiac RNA-sequencing data. An overlap between genes related to cardiac remodeling and targets of ingredients form A. membranaceus was collected to obtain monomers with protective effect on hypertensive cardiac remodeling. Angiotensin Ⅱ(AngⅡ)-induced mouse cardiac remodeling model was used to validate the protective effect of active ingredients from A. membranaceus on hypertensive cardiac remodeling. Finally, a total of 81 monomers and 1 197 targets were enrolled in our database. Mouse RNA-sequencing data showed that 983 genes were significantly up-regulated and 465 genes were down-regulation in myocardial tissues of the cardiac remodeling mice as compared with blank group mice, respectively. Ninety-two genes were found via overlapping between genes related to cardiac remodeling and targets, involving 59 monomers from A. membranaceus. Further research found that vanillic acid(VA) could intervene 27 genes associated with hypertensive cardiac remodeling, ranking top 1. Meanwhile, VA could significantly inhibit AngⅡ-induced increase in ratio of heart weight to body weight and heart weight to tibial length, ANP and BNP mRNA levels in myocardial tissues, myocardial tissue damage, cardiac fibrosis level and cardiac hypertrophy level in vivo. Those results showed that network pharmacology screen-based VA has protective effect on AngⅡ-induced cardiac remodeling.

Unveiling the size effect of Pt-on-Au nanostructures on CO and methanol electrooxidation by in situ electrochemical SERS.

In situ monitoring of electrocatalytic processes at solid-liquid interfaces is essential for the fundamental understanding of reaction mechanisms, yet quite challenging. Herein, Pt-on-Au nanocatalysts with a Au-core Pt-satellite superstructure have been fabricated. In such Pt-on-Au nanocatalysts, the Au cores can greatly amplify the Raman signals of the species adsorbed on Pt, allowing the in situ surface-enhanced Raman spectroscopy (SERS) study of the electrocatalytic reactions on Pt. Using the combination of an electrochemical method and in situ SERS, size effects of Pt on the catalytic performance of the core-satellite nanocomposites towards CO and methanol electrooxidation are revealed. It is found that such Pt-on-Au nanocomposites show improved activity and long-term stability for the electrooxidation of CO and methanol with a decrease in the Pt size. This work demonstrates an effective strategy to achieve the in situ monitoring of electrocatalytic processes and to simultaneously boost their catalytic performance towards electrooxidation.

Temperature controllable electrochemical sensors based on horseradish peroxidase as electrocatalyst at heated Au disk electrode and its preliminary application for H2O2 detection.

In this paper, horseradish peroxidase (HRP) was successfully immobilized on heated Au disk electrode (HAuDE) by biotin-streptavidin specific interaction through HS-ssDNA-biotin self-assembled on HAuDE for investigation the electrocatalytic activity of HRP. With elevated electrode temperature, the significant temperature effect of the electrocatalytic activity of HRP for H2O2 reduction was demonstrated by using this bio-sensing platform. With an electrode temperature of 40 °C, a detection limit of 1.5 × 10-6 mol L-1 for H2O2 reduction could be obtained, which was more than one magnitude lower than that with an electrode temperature of 0 °C. Because HRP can be widely used as an enzyme label for amplification detection, this sensing platform can be broadly applied to analytical chemistry such as nucleic acid detection, and aptamer-based biosensors.

Self-Reference Analysis Based on Temperature Difference Absorption Spectra.

The direct qualitative identification of pure liquids in laboratories and in security checks is generally performed by the detection of the refractive index or the permittivity. However, refractive indices are strongly influenced by temperature, while the permittivities of some organics are difficult to differentiate. On the other hand, the quantitative monitoring of samples with high concentration in plating baths and in chemical production lines are generally performed via a "Sampling-Dilution-Analysis" approach because of significant deviations from the linear range at high concentration, which makes the real-time monitoring of concentrated samples difficult. Here, we propose a self-reference analysis (SRA) method to directly analyze pure liquids and concentrated samples based on temperature difference absorption spectra (TDAS) without the need for dilution. This method was performed by simultaneously scanning the spectra of the reference and the sample, which are both obtained from the same analyte for detection but are at different temperatures. Compared to conventional absorption spectra with a blank reference, the red-shifted peak wavelengths of TDAS enable the detection of many far UV absorptive compounds in the near-ultraviolet region (λ > 190 nm). More importantly, organic compounds with similar structures can be easily distinguished. In addition, TDAS can also be used for the quantitative detection of concentrated analytes. The proposed SRA-TDAS method is a rapid and effective method; this approach does not require dilution and utilizes a self-reference, implying the wide potential applicability in security checks, and the real-time monitoring of concentrated compounds in chemical production lines.

Protective effect of RNA interference targeting Ikkß on hepatic fibrosis in rats.

Nuclear factor-κB (NF-κB) is an important regulatory factor in cells. NF-κB has a wide range of biological activities. After activation, it participates in the transcription and regulation of many genes and plays a role in infection, inflammatory response, oxidative stress, cell multiplication, and apoptosis. The activation of the NF-κB signal pathway is dependent on the degradation of the IκB kinase ß (IKKß) complex. IKK ß is the key kinase in the NF-κB activation pathway. After inhibition, it can block the activation of NF-κB. IKKß is a key regulator of NF-κB activation, also an early regulator of inflammation in all stages of the immune response. This study aimed to investigate the effect of IKKß-siRNA lentivirus vector treatment for hepatic fibrosis of rats. An IKKß-siRNA expression plasmid was constructed and injected in the tail vein of rats. Then, IKKß-siRNA distribution in the liver was observed by immunofluorescence, and the quantitative polymerase chain reaction was used to detect inflammation-related and fibrosis-related factors. IKKß-siRNA lentiviruses could be delivered to the liver and significantly decrease carbon tetrachloride-induced hepatic fibrosis. Furthermore, serum transaminase levels significantly decreased, and inflammation-related and fibrosis-related factors decreased. IKKß-siRNA can be an effective method of anti-fibrosis gene therapy for liver fibrosis.

Temperature-Controllable Electrodes with a One-Parameter Calibration.

Electrically heated electrodes have been applied for various chemical and biological sensors. However, previous electrically heated electrodes, including microwires and microdiscs, are usually small and often suffer from the requirement of frequent calibrations of the electrode surface temperature ( Ts) at different environment temperatures. Here, we fabricate a temperature-controllable disk electrode (TCDE) with a conventional size (3-5 mm in diameter). A one-parameter temperature calibration is proposed using a temperature transfer coefficient α and a structural model ( Ts = Te + α ( Th - Te)) to estimate Ts ( Th and Te are the temperature of the heating element and environment, respectively). The value of α is unique for a TCDE and mainly dependent on the structure and materials of the electrodes and the solution in nature. Once α is experimentally determined, Ts can be calibrated and found to be applicable to wide fluctuations in room temperature (15.0-33.0 °C) with errors below 1.5% for three types of disk electrodes (gold, glassy carbon, and platinum). The required Ts can be obtained by just setting Th without thermal characterization between the heating power and Ts. A simple relationship for exploring the dependence of α on the height ( H) and radius ( R) of the electrode materials and other constants ( a, b, c, and R0), α = 1 - c - aH - b ( R - R0)2, is revealed by numerical simulations (COMSOL). The impact of the radii of both the insulating materials of the electrode and the electrochemical cells on Ts is also considered. The effect of the solution thermal conductivity on α is studied. TCDEs are expected to be used as a sensor platform with enhanced performance.

Efficacy and safety of direct oral anticoagulants versus low-molecular-weight heparin in patients with cancer: a systematic review and meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOACs) versus low-molecular-weight heparin (LMWH) are still debated in the treatment of patients with cancer, and the optimal duration of therapy remains uncertain. Electronic databases (PubMed, Embase, and Cochrane Library) were searched to retrieve studies on the efficacy and safety of DOACs versus LMWH in treating patients with cancer from January 1980 to October 2018. The primary efficacy and safety endpoints were recurrent venous thromboembolism (VTE) and major bleeding. Our study included two randomized controlled trials (RCTs) and nine observational studies, together comprising 4509 patients with cancer. The pooled estimates indicated that DOACs led to a modest reduction recurrent VTE in the RCTs [RR: 0.63, 95% confidence interval (CI), 0.42-0.96, P = 0.03] and in the observational studies (RR: 0.74, 95% CI, 0.58-0.93, P = 0.011), without increasing the risk of major bleeding for observational studies (P = 0.805), but increased for RCTs (P = 0.017). The same trends were observed in the rivaroxaban subgroup. Moreover, subgroup analyses according to the treatment duration indicated that DOACs significantly reduced the incidence of recurrent VTE (P = 0.006 at 6 months; P < 0.001 at 12 months) without significant differences in major bleeding compared with LMWH at 6 or 12 months. Patients with cancer who received DOACs exhibited a significant reduction in recurrent VTE with no increased risk of major bleeding compared with LMWH. DOACs may be an alternative choice for long-term anticoagulant therapy in patients with cancer.

Triple versus dual oral antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of dual therapy (dual antiplatelet therapy [DAPT] and warfarin plus single antiplatelet [WS]) versus triple therapy (TT, DAPT plus warfarin) are still debated in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). The purpose of this study was to determine the optimal antithrombotic strategy. METHODS: Electronic databases (PubMed, Embase, Cochrane Library, CNKI and WanFang Data) were searched to retrieve studies on the efficacy and safety of TT vs. dual therapy in patients with AF undergoing PCI until August 2017. A meta-analysis was conducted using a random-effects model. The primary efficacy and safety endpoints were major adverse cardiac events (MACEs) and major bleeding events. RESULTS: Twenty-four studies involving 21,167 patients were included. The TT group had a significantly lower risk of MACEs (P=0.024) but a higher risk of major bleeding (P<0.001). In TT vs. DAPT subgroup, TT was associated with a lower risk of MI and stent thrombosis in Asian patients and a lower risk of stroke in non-Asian patients. Furthermore, TT did not decrease MACEs incidence (P=0.458) but increased the risk of major bleeding (P=0.008) relative to WS. The same trends were observed in Asian and non-Asian patients. CONCLUSION: Patients with AF undergoing PCI who received TT had significant reduction in MACEs but increased the risk of major bleeding compared with DAPT. However, WS had a similar efficacy but reduced the risk of major bleeding compared with TT. Current evidence suggests that TT might not be required and might be replaced by WS.