Detection of cluster adverse drug events in the spontaneous reporting system of China using a disproportionality filter algorithm.

WHAT IS KNOWN AND OBJECTIVE: Cluster adverse drug events (CADEs) are multiple ADEs with similar clinical manifestations involving the same drug, manufactured by the same company, that occur within a short time period. The disproportionality filter algorithm (DFA) is a promising tool for the identification of historical clusters related to ADEs. The Chinese spontaneous adverse drug reaction reporting system (SRS) may serve as an important database for the detection of CADEs. The objective of this study was to evaluate the usefulness of DFA as an approach to identify CADEs using SRS. METHODS: Suspected adverse drug reaction (ADR) reports collected by the Chinese SRS in 2014-2015 were examined to identify potential CADEs. The reports were divided into 48 15-day subsets. Disproportionate excess reporting of ADEs for drugs from specific companies may be a signal for CADEs. The clusters were categorized as 'confirmed', 'potential', 'unlikely', 'indecisive' or 'information-loss' ADEs when evaluated by report units. Furthermore, early warning information in 2014-2015 from the Chinese early warning system (EWS) classified as 'concern', 'monitoring', 'ignorance' or 'rest' was compared with DFA to explore the applicability of the novel algorithm in Chinese SRS. RESULTS AND DISCUSSION: In total, 2294 CADEs, comprising of 380 confirmed, 1753 potential, 15 unlikely and 59 indecisive clusters, were generated; 87 clusters were missing additional information. There were 263 'significant' clusters with DFA, but only 26 'significant' clusters in EWS. The sensitivity of DFA was 88.5%, but the specificity and positive predictive value were low. WHAT IS NEW AND CONCLUSION: Spontaneous adverse drug reaction reporting system in China may be a potential database for the identification of CADEs engaging the DFA. This could supplement the EWS of CADEs in China. The DFA may be of value in detecting CADEs with high sensitivity, although expert screening is required given the low specificity and positive predictive value.

Enhancing effects of activated carbon supported nano zero-valent iron on anaerobic digestion of phenol-containing organic wastewater.

Activated carbon supported nano zero-valent iron material (NZVI/AC) was prepared and added to an anaerobic digestion tank to reduce the toxicity inhibition of phenols and increase the methane yield of phenol-containing organic wastewater (POW). The anaerobic digestion (AD) characteristics, including conversion rate of organic substances, removal rate of phenol, and methane yield of POW with different concentrations of phenol were studied, and moreover, the enhancing effects of NZVI/AC on the AD of POW were focused. When the concentration of phenol was below 500 mg/L, the methane yield from AD of POW was 387.5 mL, which was 10.71% higher than that from control organic water without phenol, however, phenol concentrations greater than 1000 mg/L severely inhibited AD, and methane yield was only 50% of the control sample. Indicating that anaerobic microorganisms had a certain degree of tolerance to phenol, and low concentration of phenol could promote AD of organic water although the phenol with high concentration showed severe inhibition. The methane yield increased due to the probable conversion of phenol to methane by microbial actions. In the AD of POW with 500 mg/L phenol, the conversion rate of organic substances increased from 37.49% (control group without any accelerant) to 66.56% after adding NZVI/AC. The removal rate of phenol also increased from 39.03% to 81.32%. Cumulative methane yield increased by 145.5%-810 mL compared with the control group. The AC carrier in NZVI/AC exerted a good adsorption effect on phenols, reducing the concentration of phenols in the solution and thus minimizing their toxic effects on microbial activity. The NZVI loaded on AC particles strengthened the electron transfer between methanogens by its good electrical conductivity, and then promoted the AD performance of organic matter. Furthermore, NZVI exerted a micro-electrolytic effect on phenolic substances, which could increase the removal rate of phenol. Therefore, NZVI/AC could be used as an efficient accelerant for the AD of POW to enhance the AD process.

Hydrogen Desorption Properties of LiBH4/xLiAlH4 (x = 0.5, 1, 2) Composites.

A detailed analysis of the dehydrogenation mechanism of LiBH4/xLiAlH4 (x = 0.5, 1, 2) composites was performed by thermogravimetry (TG), differential scanning calorimetry (DSC), mass spectral analysis (MS), powder X-ray diffraction (XRD) and scanning electronic microscopy (SEM), along with kinetic investigations using a Sievert-type apparatus. The results show that the dehydrogenation pathway of LiBH4/xLiAlH4 had a four-step character. The experimental dehydrogenation amount did not reach the theoretical expectations, because the products such as AlB2 and LiAl formed a passivation layer on the surface of Al and the dehydrogenation reactions associated with Al could not be sufficiently carried out. Kinetic investigations discovered a nonlinear relationship between the activation energy (Ea) of dehydrogenation reactions associated with Al and the ratio x, indicating that the Ea was determined both by the concentration of Al produced by the decomposition of LiAlH4 and the amount of free surface of it. Therefore, the amount of effective contact surface of Al is the rate-determining factor for the overall dehydrogenation of the LiBH4/xLiAlH4 composites.

In Situ Coupling of CoP Polyhedrons and Carbon Nanotubes as Highly Efficient Hydrogen Evolution Reaction Electrocatalyst.

Hydrogen evolution reaction (HER) from water electrolysis is an attractive technique developed in recent years for cost-effective clean energy. Although considerable efforts have been paid to create efficient catalysts for HER, the development of an affordable HER catalyst with superior performance under mild conditions is still highly desired. In this work, metal-organic frameworks (MOFs)-templated strategy is proposed for in situ coupling of cobalt phosphide (CoP) polyhedrons nanoparticles and carbon nanotubes (CNTs). Due to the synergistic catalytic effect between CoP polyhedrons and CNTs, the as-prepared CoP-CNTs hybrids show excellent HER performance. The resultant CoP-CNTs demonstrate excellent HER activity in 0.5 m H2 SO4 with Tafel slope of 52 mV dec-1 , small onset overpotential of ≈64 mV, and a low overpotential of ≈139 mV at 10 mA cm-2 . Additionally, the catalyst also manifests superior durability in acid media. Considering the structure diversity of MOFs, the strategy presented here can be extended for synthesizing other well-defined metal phosphides-CNTs hybrids, which may be used in the fields of catalysis, energy conversion and storage.

Single-Molecule Analysis of Human Telomere Sequence Interactions with G-quadruplex Ligand.

Ligands that selectively promote the formation of G-quadruplexes in human telomeres have great potential for cancer treatment by inhibiting the telomere extension by telomerase. Thus, understanding the interactions of the G-quadruplex ligands with the telomere sequence at the single-molecule level is of significant importance. Here, human telomere sequence interactions with a small molecule ligand pyridostatin (PDS) were analyzed via α-hemolysin protein nanopore, and a nanopore thermodynamic analytical method was proposed. The prolonged unraveling time of the telomeric DNA G-quadruplex after PDS binding demonstrated the potent stabilization effect of ligand on G-quadruplex structure. The signature two-level electronic blocks generated by K(+)-PDS-G-quadruplex complexes suggested a two-state unraveling process, including the dissociation of the interquartet cation and the unraveling of the cation-free ligand-bound G-quadruplex. The translocation studies and the analysis of free-energy changes demonstrated a ligand-binding mode in which PDS molecule and K(+) were simultaneously bound to one G-quadruplex structure with the coordinated effect on G-quadruplex stabilization. The single-molecular nanopore platform permits the efficient and accurate determination of ligand affinity constants without the requirement for labeling, amplification, or ligand/receptor titration, which provides a general analytical tool for effectively monitoring and quantifying the G-quadruplex/ligand interactions, possessing important implications for the design and screen of anticancer drugs.

Emerging Pt-based intermetallic nanoparticles for the oxygen reduction reaction.

The advancement of highly efficient and enduring platinum (Pt)-based electrocatalysts for the oxygen reduction reaction (ORR) is a critical determinant to enable broad utilization of clean energy conversion technologies. Pt-based intermetallic electrocatalysts offer durability and superior ORR activity over their traditional analogues due to their definite stoichiometry, ordered and extended structures, and favourable enthalpy of formation. With the advent in new synthetic methods, Pt-based intermetallic nanoparticles as a new class of advanced electrocatalysts have been studied extensively in recent years. This review discusses the preparation principles, representative preparation methods of Pt-based intermetallics and their applications in the ORR. Our review is focused on L10 Pt-based intermetallics which have gained tremendous interest recently due to their larger surface strain and enhanced M(3d)-Pt(5d) orbital coupling, particularly in the crystallographic c-axis direction. Additionally, we discuss future research directions to further improve the efficiency of Pt-based intermetallic electrocatalysts with the intention of stimulating increased research ventures in this domain.

Study on Rock-Electric Characteristics of Cracked Porous Rocks by the Novel Multifactor Conductivity Model.

Due to the influence of multiple factors on the conductive properties of rocks, the Archie's formula, considering only a single factor, makes it difficult to reasonably explain rock-electric characteristics of cracked porous rocks. In order to better describe the conductive mechanism of cracked porous rocks, a generalized multifactor conductivity model was proposed by considering and introducing multiple influencing factors such as the series-parallel structure, conductive matrix, cracks, and fluids, which is conducive to more accurate research on the conductive mechanism of rocks. It should be noted that the developed model is not only applicable to cracked porous rocks but also useful for porous rocks. Through the study and analysis of various influencing factors, it is demonstrated by the simulation results that both the conductive matrix and cracks improve the conductive ability, which are crucial factors resulting in the non-Archie behavior and low-resistivity pay zone, and rock conductivity is more sensitive to the conductive matrix and cracks in tight reservoirs with porosity below 10%. Furthermore, experimental data are available to validate the novel multifactor conductivity model, and the comparison results show its advantages in predicting and explaining the conductive properties of cracked porous rocks.

FUNDC1 Induces Apoptosis and Autophagy Under Oxidative Stress via PI3K/Akt/mTOR Pathway in Cataract Lens Cells.

PURPOSE: The purpose of the study is to explore the mRNA and protein expression of FUNDC1 in cataract cells and tissues, and clarify the function and mechanism of FUNDC1 in cataract cells under oxidative stress. METHODS: We used bioinformatic analysis to screen differentially expressed genes in cataract cells from GSE153933. The expression of FUNDC1 in cataract specimens and cells was measured by reverse transcription quantitative polymerase chain reaction and western blotting. MethPrimer was used to predict CpG island of FUNDC1 promoter. The methylation of FUNDC1 in cataract specimens and cells was determined by methylation-specific polymerase chain reaction assay. Flow cytometry assay was used to measure cell apoptosis in FUNDC1-knockdown and -overexpression SRA01/04 cells. The expression of LC3 was analyzed by immunofluorescence assay. The expression of apoptosis-related proteins, autophagy, and PI3K/Akt/mTOR-related proteins was determined by western blotting. RESULTS: The results of bioinformatic analysis revealed that FUNDC1 was upregulated in cataract. FUNDC1 was high expression in SRA01/04 cells with H2O2 treatment, whereas hypomethylation of FUNDC1 in cataract lens cells under oxidative stress. The knockdown of FUNDC1 decreased cell apoptosis and autophagy in comparison with the negative control of SRA01/04 cells. While the overexpression of FUNDC1 elevated cell apoptosis and autophagy compared to the empty vector group in SRA01/04 cells. Mechanically, FUNDC1 reduced the phosphorylation of PI3K/Akt/mTOR pathway under oxidative stress in SRA01/04 cells. CONCLUSION: Our study suggested that FUNDC1 deficiency restrains cell apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signal pathway.

A Study on COMP and CTX-II as Molecular Markers for the Diagnosis of Intervertebral Disc Degeneration.

BACKGROUND: Diagnosis of intervertebral disc degeneration (IVDD) is challenging at the early stage. The cartilage oligomeric matrix protein (COMP) and extracellular matrix degradation products of C-telopeptide of type II collagen (CTX-II) serve as markers for the serological diagnosis of IVDD. Oxidative stress might cause IVDD and matrix degeneration. METHODS: A total of 128 male adult Sprague-Dawley (SD) rats were randomly and equally assigned to the experimental and control groups. The experimental group was used to construct IVDD models by acupuncture, while the control group underwent sham operation. The animals were executed every week for 8 weeks after intervertebral disc acupuncture, and serum samples were collected for the estimation of CTX-II and COMP concentrations by enzyme-linked immunosorbent assay (ELISA). Also, the histological changes and caudal magnetic resonance imaging (MRI) changes were examined in the intervertebral disc. RESULTS: IVDD in rats worsened with prolonged follow-up after acupuncture. At all the time points, the experimental group showed altered histological and caudal vertebra MRI signals, and serum CTX-II and COMP concentrations were significantly greater than those of the control group. These levels increase with the process of IVDD. CONCLUSION: Serum CTX-II and COMP estimation is a reliable method to diagnose IVDD, and their concentrations show a positive correlation with the process of IVDD.

High performance aqueous supercapacitor based on nitrogen-doped coal-based activated carbon electrode materials.

The performance of a supercapacitor (SCs) fabricated from coal-based activated carbon was studied in terms of its specific capacitance (C), life cycle and rate performance. In this work, a low cost modified nitrogen-doped coal-based activated carbon (MACN) was prepared by KOH/H2O co-activation from lignite. Experimental results and density functional theory (DFT) calculations showed that introducing nitrogen atoms into the coal-based activated carbon leads to a rearrangement of the carbon skeleton structure and changes the surface chemical environment. Leading to the MACN internal disorder increases (ID/IG is up to 0.99), structural stability improves (TGA curves shift right), and various nitrogen functional groups (N-5, N-6, N-Q) are formed on the carbon surface. In addition, the MACN possesses high specific surface area (SBET: 2129 m2/g), abundant micropores (Vmic: 0.62 cm3/g), appropriate mesopores (Vmes: 0.39 cm3/g, Vmes ratio: 38.6%), low impurity content, and highly N-doping (9.59 wt%). These characteristics of the MACN provide for a high C of 323 F/g at a current density of 0.5 A/g. The enhanced MACN is 64.8% higher than the undoped MAC. Furthermore, a high energy density of 10 Wh/kg can be achieved with a MACN-assembled symmetrical cell when the power density of 250 W/kg in 6 M KOH.

Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study.

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61-3.18), coagulation disorders (aOR 1.81, 95% CI 1.43-2.30), and decreased PLT (aOR 1.46, 95% CI 1.25-1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79-1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11-2.10), coagulation disorders (aOR 1.53, 95% CI 1.21-1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81-1.07) or bleeding (aOR 1.11, 95% CI 0.87-1.42), compared with those receiving cefoperazone-tazobactam.Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.

Numerical study of an alternative to a deuterium-tritium source in gas saturation logging based on the inelastic gamma spectrum.

In this study, we investigated the feasibility of using a D-Li7 neutron generator to replace a deuterium-tritium (D-T) neutron generator in gas saturation logging. The logging response and gas sensitivity of gas saturation logging based on the inelastic gamma spectrum were simulated with the Monte Carlo method, and the factors that influenced the gas sensitivity and inelastic gamma counts were analyzed based on the spatial response distribution. The results showed that the logging response based on the D-Li7 source was similar to that based on the D-T neutron generator after calibration, which validated the feasibility of this method. Using the D-Li7 neutron generator, the sensitivity of gas saturation was higher when the scattering cross section of formation was not high.

SP1-induced upregulation of lncRNA PANDAR predicts adverse phenotypes in retinoblastoma and regulates cell growth and apoptosis in vitro and in vivo.

Retinoblastoma (RB) is an intraocular malignancy for children and has a high mortality rate. Long non-coding RNAs (lncRNAs) are emerging as gene regulators and biomarkers in various malignancies. PANDAR is a novel cancer-related lncRNA that dysregulated in several types of cancers. However, its clinical value and potential effects on RB remains unclear. RT-qPCR was used to assess the relative expression of PANDAR in RB tissues and cells. Additionally, chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to investigate whether SP1 could bind to the promoter region of PANDAR and activate its transcription. Furthermore, in vitro and in vivo studies were induced to elucidate the biological functions of PANDAR. The results indicated that PANDAR was increased in RB tissues and cells, and this upregulation was associated with advanced IIRC stage, positive optic nerve invasion, and lower differentiation grade in RB patients. In addition, SP1 could bind directly to the PANDAR promoter region and activate its transcription. Furthermore, PANDAR silencing yielded tumor suppressive effects both in vitro and in vivo. Importantly, PANDAR protects against apoptosis partly by affecting Bcl-2/caspase-3 pathway. Ultimately, our work first illustrate that PANDAR plays an oncogenic role in RB and may offer a potential therapeutic target for treating this devastating disease.

The diagnostic accuracy of B-mode ultrasound in detecting meniscal tears: a systematic review and pooled meta-analysis.

AIM: To evaluate the diagnostic accuracy of meniscal tears using B-mode ultrasound and high-frequency linear probe by conducting a systematic review and pooled meta-analysis. MATERIAL AND METHODS: The Cochrane library, Embase, and Pubmed were searched for relevant studies up to 29 July 2017. The arthroscopy was used as the reference standard. The results were estimated by pooled sensitivity, specificity, diagnostic odds ratio, likelihood ratio, and the area under the summary receiver operating characteristic (SROC). RESULTS: Seven prospective studies met the selection criteria, comprising 321meniscal tears from 472 patients. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the SROC curve were 88.80% (95%CI: 82.83-92.87), 84.66% (95%CI: 75.89-90.64), 5.79(95%CI: 3.66-9.15), 0.13 (95%CI: 0.09-0.20), and 43.74 (95%CI: 24.01-79.68), respectively. The area under the SROC curve was 93% (95%CI: 91-95). CONCLUSIONS: This meta-analysis indicates that 2-dimensional ultrasound is useful, and could be routinely used for estimating meniscal injuries in the human knee joint.

The role of ultrasonography in the diagnosis of anterior cruciate ligament injury: A systematic review and meta-analysis.

To evaluate the value of ultrasonography in the diagnosis of anterior cruciate ligament injury (ACL injury) by conducting a systematic review and meta-analysis. A literature search was carried out in the Cochrane Library, Embase, Pubmed databases and included studies prior to April 2017. Based on inclusion and exclusion criteria, studies evaluating ultrasound to diagnose ACL injury were selected. MRI, arthroscopy and clinical-follow were considered the reference standards. The diagnostic accuracy of ultrasound was assessed using a combination of sensitivity, specificity, likelihood ratio (LR), post-test probability, diagnostic odds ratio (DOR) and by summarizing the area under the receiver operating characteristic (SROC) curve. A total of 4 studies involving 246 patients were eventually included in the analysis. In these four studies, the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, post-test probability and DOR were 90.0% (95% CI: 77-96), 97% (95% CI: 90-99), 31.08 (95% CI: 8.75-110.41), 0.11 (95% CI: 0.05-0.24), 89% (3%) and 288.81 (95% CI: 78.51-1062.48), respectively. The area under the SROC curve was 0.98 (95% CI: 0.97-0.99). Our meta-analysis showed that ultrasound can play an important role in the diagnosis of ACL injury. Because of its high sensitivity, high specificity and high diagnostic ability, ultrasound should be a part of the standard diagnostic work-up of an ACL injury.

Co9S8 nanoparticles anchored on nitrogen and sulfur dual-doped carbon nanosheets as highly efficient bifunctional electrocatalyst for oxygen evolution and reduction reactions.

To promote the practical application of electrochemical energy storage and conversion systems, nonprecious electrocatalysts of low cost and with highly efficient performance in oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are highly desired. In this work, a cubic sodium chloride (NaCl) crystal-templated strategy is proposed for coupling Co9S8 nanoparticles to nitrogen- and sulfur-doped carbon nanosheets (Co9S8/N,S-CNS) by facile pyrolysis. The nitrogen and sulfur dual-doped carbon nanosheets can effectively prevent the aggregation of Co9S8 nanoparticles and greatly improve the conductivity of the hybrid structure. The well-dispersed Co9S8 nanoparticles could provide more active sites. When evaluated as a bifunctional electrocatalyst, an overpotential of 350 mV could yield 10 mA cm-2 current density for OER and a high onset potential around 0.90 V vs. RHE was obtained with a four-electron pathway for ORR, which is comparable to that of a Pt/C catalyst. The remarkable electrochemical performance can be attributed to the synergistic catalytic effect of Co9S8 nanoparticles and the N,S-doped carbon nanosheets. Considering the simplicity, low cost and scalability of the approach, the strategy presented here can be extendable to the preparation of other nanoparticles/carbon hybrid nanosheets, which may potentially be applied in the fields of high-performance supercapacitors, lithium-ion batteries, catalysts, sensors, adsorbents and so on.

Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China.

Japanese encephalitis (JE) is the most severe form of viral encephalitis in Asia and no specific treatment is available. Vaccination provides an effective intervention to prevent JE. In this paper, surveillance data for adverse events following immunization (AEFI) related to SA-14-14-2 live-attenuated Japanese encephalitis vaccine (Chengdu Institute of Biological Products) was presented. This information has been routinely generated by the Chinese national surveillance system for the period 2009-2012. There were 6024 AEFI cases (estimated reported rate 96.55 per million doses). Most common symptoms of adverse events were fever, redness, induration and skin rash. There were 70 serious AEFI cases (1.12 per million doses), including 9 cases of meningoencephalitis and 4 cases of death. The post-marketing surveillance data add the evidence that the Chengdu institute live attenutated vaccine has a reasonable safety profile. The relationship between encephalitis and SA-14-14-2 vaccination should be further studied.

Effective visible light-active boron and europium co-doped BiVO4 synthesized by sol-gel method for photodegradion of methyl orange.

Eu-B co-doped BiVO4 visible-light-driven photocatalysts have been synthesized using the sol-gel method. The resulting materials were characterized by a series of joint techniques, including XPS, XRD, SEM, BET, and UV-vis DRS analyses. Compared with BiVO4 and B-BiVO4 photocatalysts, the Eu-B-BiVO4 photocatalysts exhibited much higher photocatalytic activity for methyl orange (MO) degradation under visible light irradiation. The optimal Eu doping content is 0.8 mol%. It was revealed that boron and europium were doped into the lattice of BiVO4 and this led to more surface oxygen vacancies, high specific surface areas, small crystallite size, a narrower band gap and intense light absorbance in the visible region. The doped Eu(III) cations can help in the separation of photogenerated electrons. The synergistic effects of boron and europium in doped BiVO4 were the main reason for improving visible light photocatalytic activity.