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Lithium‐ion batteries with fast-charging/discharging properties are urgently needed for the mass adoption of electric vehicles. Here, we show that fast charging/discharging, long-term stable and high energy charge-storage properties can be realized in an artificial electrode made from a mixed electronic/ionic conductor material (Fe/LixM, where M = O, F, S, N) enabled by a space charge principle. Particularly, the Fe/Li2O electrode is able to be charged/discharged to 126 mAh g−1 in 6 s at a high current density of up to 50 A g−1, and it also shows stable cycling performance for 30,000 cycles at a current density of 10 A g−1, with a mass-loading of ~2.5 mg cm−2 of the electrode materials. This study demonstrates the critical role of the space charge storage mechanism in advancing electrochemical energy storage and provides an unconventional perspective for designing high-performance anode materials for lithium-ion batteries. Lithium-ion batteries with fast-charging properties are urgently needed for wide adoption of electric vehicles. Here, the authors show a fast charging/discharging and long-term stable electrode made from a mixed electronic/ionic conductor material enabled by a space charge mechanism. [ABSTRACT FROM AUTHOR]

Background: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial. Aim: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System. Method: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19. Results: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83–2.18) and renal disorder (ROR 2.35, 95% CI: 2.17–2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91–2.45) and ROR of renal disorder was 1.69 (95% CI 1.06–2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time. Conclusion: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic. [ABSTRACT FROM AUTHOR]

Background and objectives: miRNAs play a crucial role in regulating immune responses. However, the effect of miR-124-3p on type 2 inflammation in allergic rhinitis (AR) is unclear. We aimed to study the immune regulation of miR-124-3p in AR and the mechanisms involved. Methods: The direct interaction between miR-124-3p and IL-4Rα was confirmed through a dual-luciferase reporter assay. In vitro splenic lymphocytes from mice and peripheral blood mononuclear cells (PBMCs) from healthy individuals were cultured and treated with miR-124-3p mimic/inhibitor. Twenty-four female C57BL/C mice were divided into four groups: control, AR model, miR-124-3p agomir, and miR-124-3p antagomir groups (n = 6 per group). The allergic responses were evaluated based on the number of sneezing and nasal scratching, the serum HDM-specific IgE (sIgE) levels, and the degree of nasal mucosa eosinophil infiltration. The expression of IL-4Rα, p-STAT6, and type 2 inflammatory cytokines (IL-4, IL-5 and IL-13) in lymphocytes or nasal mucosa was determined by qPCR, western blotting, flow cytometry, immunohistochemistry and immunofluorescence. Results: miR-124-3p directly targets the 3'UTR of IL-4Rα. The miR-124-3p mimic lowered the IL-4Rα, p-STAT6, IL-4, IL-5, and IL-13 expression levels in both mouse splenic lymphocytes and human PBMCs in vitro, and the miR-124-3p inhibitor rescued these changes. Furthermore, the miR-124-3p agomir decreased the levels of IL-4Rα and IL-4 in nasal mucosa, Th2 differentiation in spleen, and allergic response in AR mice. Moreover, the miR-124-3p antagonist increased the IL-4Rα and IL-4 levels and further aggravated the allergic responses. Conclusions: miR-124-3p might attenuate type 2 inflammation in AR by regulating IL-4Rα signaling, and miR-124-3p may be a promising new target in AR treatment. [ABSTRACT FROM AUTHOR]

The microstructure and properties of bainitic multiphase steels with bainitic ferrite as the main phase are the focus of the current research. In the work, multiphase microstructures of pre-formed martensite (PM), bainitic ferrite (BF), and retained austenite (RA) was obtained via austempering processes in medium carbon bainitic steel. The relationship between the multiphase characteristics and mechanical properties was analyzed quantitatively. The results show that the thickness of bainitic ferrite laths and the size of blocky retained austenite of the PM-BF-RA samples are smaller than those of the BF-RA samples. The dislocation density of bainitic ferrite and carbon content in retained austenite of the PM-BF-RA samples are higher. The PM-BF-RA samples obtain higher strength. The yield strength that was calculated by measured microstructural parameters is similar to the tested value. The dominant strengthening phases of PM-BF-RA samples are pre-formed martensite and bainitic ferrite dual phases, while those of the BF-RA samples are the bainitic ferrite. The main of the strengthening mechanism of bainitic ferrite is grain boundary strengthening, while it is solid solution strengthening for martensite and retained austenite. Small and stable retained austenite with high carbon content effectively ensures the high plasticity of PM-BF-RA samples. Moreover, the high toughness of PM-BF-RA samples can be attributed to fine bainitic ferrite and small blocky retained austenite. This study demonstrates that medium carbon bainitic multiphase steel with PM-BF-RA microstructure exhibits excellent combination of strength, plasticity, and toughness. [ABSTRACT FROM AUTHOR]

Main conclusion: The zqdm1identified from a rice mutant is a novel allele of BRD2 and is responsible for regulating rice plant height, grain size and appearance, which has possibilities on improving rice quality. Plant height is an important agronomic trait related to rice yield, and grain size directly determines grain yield in rice (Oryza sativa L.). With the development of molecular biotechnology and genome sequencing technology, more and more key genes associated with plant height and grain size have been cloned and identified in recent years. This study identified the zqdm1 gene from a mutant with reduced plant height and grain size. The zqdm1 gene was revealed to be a new allele of BRASSINOSTEROID DEFICIENT DWARF 2 (BRD2), encoding a FAD-linked oxidoreductase protein involved in the brassinosteroid (BR) biosynthesis pathway, and regulates plant height by reducing cell number of longitudinal sections of the internode and regulates grain size by altering cell expansion. A 369-bp DNA fragment was found inserted at the first exon, resulting in protein-coding termination. This mutation has not been discovered in previous studies. Complementation tests have confirmed that 369-bp insertion in BRD2 was responsible for the plant height and grain size changing in the zqdm1 mutant. Over-expression of BRD2 driven by different promoters into indica rice variety Jiafuzhan (JFZ) results in slender grains, suggesting its function on regulating grain shape. In summary, the current study has identified a new BRD2 allele, which facilitated the further research on the molecular mechanism of this gene on regulating growth and development. [ABSTRACT FROM AUTHOR]

Background: The use of hydroxychloroquine or chloroquine (HCQ/CQ) as monotherapy or combined with azithromycin for the treatment of coronavirus disease 2019 (COVID-19) may increase the risk of serious cardiovascular adverse events (SCAEs). Objective: Our objective was to describe and evaluate the risk of SCAEs with HCQ/CQ as monotherapy or combined with azithromycin compared with that for therapeutic alternatives. Methods: We performed a disproportionality analysis and descriptive case series using the US FDA Adverse Event Reporting System. Results: Compared with remdesivir, HCQ/CQ was associated with increased reporting of SCAEs (reporting odds ratio [ROR] 2.1; 95% confidence interval [CI] 1.8–2.5), torsade de pointes (TdP)/QTc prolongation (ROR 35.4; 95% CI 19.4–64.5), and ventricular arrhythmia (ROR 2.5; 95% CI 1.6–3.9); similar results were found in comparison with other therapeutic alternatives. Compared with lopinavir/ritonavir, HCQ/CQ was associated with increased reporting of ventricular arrhythmia (ROR 10.5; 95% CI 3.3–33.4); RORs were larger when HCQ/CQ was used in combination with azithromycin. In 2020, 312 of the 575 reports of SCAEs listed concomitant use of HCQ/CQ and azithromycin, including QTc prolongation (61.4%), ventricular arrhythmia (12.0%), atrial fibrillation (8.2%), TdP (4.9%), and cardiac arrest (4.4%); 88 (15.3%) cases resulted in hospitalization and 79 (13.7%) resulted in death. In total, 122 fatal QTc prolongation-related cardiovascular reports were associated with 1.4 times higher odds of reported death than those induced by SCAEs; 87 patients received more than one QTc-prolonging agent. Conclusions: Patients treated with HCQ/CQ monotherapy or HCQ/CQ + azithromycin may be at increased risk of SCAEs, TdP/QTc prolongation, and ventricular arrhythmia. Cardiovascular risks need to be considered when evaluating the benefit/harm balance of treatment with HCQ/CQ, especially with the concurrent use of QTc-prolonging agents and cytochrome P450 3A4 inhibitors when treating COVID-19. [ABSTRACT FROM AUTHOR]

A specific surface-enhanced Raman scattering (SERS) assay for dopamine (DA) based on an azo derivatization reaction is proposed for the first time by preparation of p-aminothiophenol (PATP)-modified composite SERS substrate, composed of metal–organic framework (MIL-101) decorated with Au and Ag nanoparticles. As the result, the SERS method for detection of the azo reaction between PATP and DA exhibits superior sensitivity, selectivity, and stability. A reasonable linearity in the range 10−6 to 10−10 mol∙L−1 is achieved, and the limit of detection is 1.2 × 10−12 mol∙L−1. The reactive SERS assay is free from interference in complex physiological fluid. The feasibility of the proposed SERS method for the detection of DA levels in fetal bovine serum (FBS) samples and human serum samples is validated by HPLC–MS methods, displaying promising application potential in early disease diagnosis. [ABSTRACT FROM AUTHOR]

Background Rivaroxaban, apixaban and dabigatran are non-vitamin K antagonist oral anticoagulants (NOACs) that are widely used for treatment or prevention of venous thromboembolism and stroke in patients with atrial fibrillation. Objective To estimate and compare hemorrhagic events report of rivaroxaban, apixaban and dabigatran. Setting FDA Adverse Event Reporting System (FAERS) database. Methods The reporting odds ratio (ROR) was used to assess the signal of hemorrhagic events of different NOACs. Main outcome measure The overall hemorrhagic events and hemorrhagic events in different physiological systems. Results From January 1, 2014 to December 31, 2019, the total number of reports of hemorrhage related to rivaroxaban was 53,085, and the numbers of apixaban and dabigatran were 13,151 and 14,100 respectively. The overall ROR (95% CI) of hemorrhagic events reporting for rivaroxaban versus dabigatran and apixaban versus dabigatran were 1.58 (1.54–1.62) and 0.47 (0.46–0.48) respectively. The ROR (95% CI) for rivaroxaban versus dabigatran in gastrointestinal system, nervous system, renal and urinary system, skin and subcutaneous tissue, and eye system was 1.38 (1.34–1.42), 0.94 (0.90–0.98), 1.07 (1.01–1.13), 0.80 (0.70–0.90), and 1.38 (1.19–1.60) respectively. The RORs (95% CI) for apixaban versus dabigatran in gastrointestinal system, nervous system, renal and urinary system, skin and subcutaneous tissue, and eye system were 0.28 (0.27–0.29), 0.69 (0.66–0.73), 0.31 (0.29–0.34), 0.98 (0.86–1.12), and 1.18 (1.00–1.39), respectively. Conclusions Overall, we found a moderate signal of higher frequency of reporting hemorrhage in rivaroxban compared with dabigatran and decreased hemorrhagic event reporting in apixaban compared with dabigatran. While this potential signal has not been confirmed in clinical trials or observational studies, in clinical practice, attention should be paid to the risk of potential hemorrhage when the patients switch from apixaban to dabigatran or rivaroxban. [ABSTRACT FROM AUTHOR]

The carbide precipitation, microstructure evolution, and tensile properties of Fe-30Mn-0.14C-7Cr-0.26Ni (in wt pct) steel after cold rolling to 95 pct reduction followed by annealing at temperatures ranging from 600 °C to 900 °C for 1 hour were investigated. The results show that, when the annealing temperature is increased from 600 °C to 900 °C, the grain size increases from 0.65 ± 0.30 to 5.75 ± 3.87 μm. When the annealing temperature is 600 °C, Cr23C6 carbides begin to precipitate. When the annealing temperature is increased from 600 °C to 800 °C, the average size of carbides increases from 39 to 69 nm. When the annealing temperature is increased to 900 °C, no carbides are produced due to the increased solubility of C in the austenite matrix. Ultrafine grains (~ 0.8 ± 0.58 μm) with a large amount of nanoscale carbides (~ 53 ± 21.8 nm) were obtained after annealing at 700 °C, resulting in a good combination of yield strength (679 MPa) and total elongation (38.4 pct). The fraction of deformation twins within the samples under different tensile strains was calculated, and it was revealed that grain refinement can seriously inhibit the generation of deformation twins. In addition, it has been found that grain refinement strengthening, precipitation strengthening, and dislocation strengthening have significant effects on yield strength, while the effects of solution strengthening and lattice friction are relatively weaker. [ABSTRACT FROM AUTHOR]

Background Liver injury has been documented independently in novel coronavirus disease 2019 (COVID-19) patients and patients treated with lopinavir-ritonavir. Objective to investigate the drug-induced liver injury associated with lopinavir-ritonavir among the patients with COVID-19. Methods We conducted a disproportionality analysis of US Food and Drug Administration Adverse Event Reporting System (FAERS) between 2020Q1 and 2021Q1 to evaluate the association between lopinavir-ritonavir and risk of drug-induced liver injury (or severe drug-induced liver injury) and calculated their reporting odds ratios (RORs) with 95% confidence intervals (CIs). Results A total of 3,425 cases of drug-induced liver injury were reported in 19,782 patients with COVID-19. The ROR for drug-induced liver injury was 2.99 (2.59-3.46), 3.16 (2.68-3.73), and 5.39 (4.63-6.26) when comparing lopinavir-ritonavir with all other drugs, hydroxychloroquine/chloroquine only, and remdesivir, respectively. For severe drug-induced liver injury, RORs for lopinavir-ritonavir provided evidence of an association compared with all other drugs (3.98; 3.15-5.05), compared with hydroxychloroquine/chloroquine only (5.33; 4.09-6.94), and compared with remdesivir (3.85; 3.03-4.89). Conclusions In the FAERS, we observed a disproportional signal for drug-induced liver injury associated with lopinavir-ritonavir in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background: A recent study is raising concerns that dipeptidyl peptidase 4 inhibitors are associated with increased risk of venous thromboembolism. Objective: We aimed to assess the association between dipeptidyl peptidase-4 inhibitors and venous thromboembolism using the US Food and Drug Administration Adverse Event Reporting System database. Methods: We searched the venous thromboembolism cases related to dipeptidyl peptidase-4 inhibitors from 2004 first quarter to 2018 first quarter. We compared dipeptidyl peptidase-4 inhibitors versus three groups: (1) all other glucose-lowering drugs excluding insulins; (2) sulfonylureas and sodium–glucose-cotransporter-2 inhibitors; (3) sodium–glucose-cotransporter-2 inhibitors. In each comparison, we calculated proportional rate ratios and 95% confidence ratios by SAS 9.4. Results: We obtained 873 dipeptidyl peptidase-4 inhibitors-associated venous thromboembolism events. Compared to all other glucose lowering-drugs excluding insulins, the proportional reporting ratio for overall venous thromboembolism, deep vein thrombosis, pulmonary embolism were 0.92 (0.86, 0.99), 0.91 (0.82,1.01), and 0.82 (0.74,0.90), respectively; the proportional reporting ratio for portal vein thrombosis, splenic vein thrombosis, mesenteric vein thrombosis were 3.94 (2.96, 5.25), 10.80 (6.14, 18.99), and 4.98 (2.76,8.96), respectively. Conclusion: Our analysis found no association between dipeptidyl peptidase-4 inhibitors and venous thromboembolism risk, while moderate to strong signals of portal vein thrombosis, splenic vein thrombosis, mesenteric vein thrombosis risks were observed. [ABSTRACT FROM AUTHOR]

Background Few studies on the causes of drug-induced anaphylaxis (DIA) in the hospital setting are available. Objective We aimed to use the Beijing Pharmacovigilance Database (BPD) to identify the causes of DIA in Beijing, China. Setting Anaphylactic case reports from the BPD provided by the Beijing Center for Adverse Drug Reaction Monitoring. Method DIA cases collected by the BPD from January 2004 to December 2014 were adjudicated. Cases were analyzed for demographics, causative drugs and route of administration, and clinical signs and outcomes. Main outcome measure Drugs implicated in DIAs were identified and the signs and symptoms of the DIA cases were analyzed. Results A total of 1189 DIA cases were analyzed. The mean age was 47.6 years, and 732 (61.6%) were aged from 18 to 59 years. A total of 627 patients (52.7%) were females. There was a predominance of cardiovascular (83.8%) followed by respiratory (55.4%), central nervous (50.1%), mucocutaneous (47.4%), and gastrointestinal symptoms (31.3%). A total of 249 different drugs were involved. DIAs were mainly caused by antibiotics (39.3%), traditional Chinese medicines (TCM) (11.9%), radiocontrast agents (11.9%), and antineoplastic agents (10.3%). Cephalosporins accounted for majority (34.5%) of antibiotic-induced anaphylaxis, followed by fluoroquinolones (29.6%), beta-lactam/beta-lactamase inhibitors (15.4%) and penicillins (7.9%). Blood products and biological agents (3.1%), and plasma substitutes (2.1%) were also important contributors to DIAs. Conclusion A variety of drug classes were implicated in DIAs. Patients should be closely monitored for signs and symptoms of anaphylaxis when medications are administered especially with antibiotics, TCM, radiocontrast and antineoplastic agents. [ABSTRACT FROM AUTHOR]

Background Traditional Chinese medicine (TCM) is one of the major triggers for drug-induced anaphylaxis (DIA). Objective We aimed to use the Beijing pharmacovigilance database (BPD) to analyze TCM-induced DIAs in Beijing, China. Setting Drug allergy case reports from the BPD provided by the Beijing Center for Adverse Drug Reaction Monitoring. Method Drug allergy cases from January 2004 to December 2014 were adjudicated. DIA triggered by TCMs were analyzed and compared with those triggered by non-TCM drugs by calculating the reported risk ratio (RRR). We also calculated the RRRs based on severe DIA and death outcomes. Main outcome measure TCMs implicated in DIAs were identified and compared with non-TCM drugs. Results TCMs accounted for 1651 (18.2%) of the total 9074 allergic cases, in which 84.4% (1393/1651) were triggered by injections. Of the TCM allergic cases, 8.5% (141) were DIAs and 7.3% (120) were severe DIAs, and three patients died from injections. The RRR between TCMs and non-TCM-induced DIAs was 0.63. When anaphylactic cases were compared between TCMs to the top four non-TCM drug triggers, RRRs were 0.73 (95% CI 0.61-0.87) for antibiotics, 0.36 (95% CI 0.29-0.44) for radiocontrast agents, 0.55 (95% CI 0.43-0.68) for chemotherapeutics, and 0.29 (95% CI 0.23-0.37) for biologics. Compared to TCM oral or topic formulations, TCM injections had higher RRRs in each of the above comparisons. Conclusion TCM was associated with a decreased risk of DIA compared to non-TCM drugs in drug allergy cases, and the risk was higher for TCM injections. [ABSTRACT FROM AUTHOR]

Background Rational drug use and drug safety are becoming increasingly important concerns in China with the increasing public access to drugs and the health-care system, and this has led to the development of pharmacovigilance in China. Aim of the review To provide a brief introduction about pharmacovigilance in China in terms of system development, utilization and challenges. Method Relevant studies on pharmacovigilance related to the study aim was undertaken through literature search to synthesize the extracted data. Results The creation and evolvement of China's pharmacovigilance system spans across 30 years since 1989. The system consists of four progressing administrative layers: county, municipal, provincial and national levels. China has passed over 20 laws and regulations related to pharmacovigilance covering the processes of drug development, manufacture, distribution and use with the aim to guard drug safety. An online spontaneous self-reporting Adverse Drug Reaction (ADR) Monitoring System was established in 2003. ADRs are mainly reported by medical institutions, pharmaceutical manufacturers, and drug distributors. Currently there is no mandatory ADR reporting requirement for pharmaceutical manufacturers, and a proposed regulation under public comment will likely change this. China has started to build active pharmacovigilance surveillance programs in addition to the passive ADR reporting system. The China Food and Drug Administration has established the intensive Safety Monitoring Program and the National Adverse Drug Reaction Monitoring Sentinel Alliance Program based on electronic health records to further the efforts of ADR reporting, monitoring and analysis. Conclusion The practice of ADR monitoring and pharmacovigilance in China have made great progress. More efforts are needed both in system building, and creation of laws and regulations to strengthen the safe use of medicines. [ABSTRACT FROM AUTHOR]

Background Pharmacovigilance databases are utilized to identify serious adverse drug events (ADEs). In China, very few studies have evaluated the validity of using pharmacovigilance databases to identify drug-induced anaphylaxis (DIA). Objective We aimed to develop and validate an algorithm to identify DIA using the Beijing Pharmacovigilance Database (BPD). Setting ADEs from the BPD mainly spontaneously reported from 94 hospitals in Beijing, China. Method Using the diagnoses, we developed an algorithm to identify potential DIAs from the BPD between January 2004 and December 2014. A sample of 500 patients was randomly selected for chart abstraction. Two physician adjudicators assessed whether DIA occurred using the published clinical criteria as the gold standard. Main outcome measure Positive predictive values (PPVs) and 95% confidence intervals of the algorithm and algorithm criteria components were calculated. Results 500 patients (53.2% female; the mean age 48.2 years) with potential DIA were selected using the algorithm. 444 were adjudicated as having anaphylaxis by physicians. The PPV of the overall algorithm was 88.8% (95% CI 86.0-91.6%). PPV for the algorithm only using specific diagnoses of "anaphylactic shock", "anaphylactic reaction", and "anaphylactoid reaction [severe]" was 89.6% (95% CI 86.6-92.4%); this partial algorithm identified 387 (87.2%) DIAs. The diagnosis that identified the most DIAs (83.8%) was "anaphylactic shock", with a PPV of 91.6% (95% CI 88.9-94.3%). Conclusion The overall algorithm identified a greater number of DIAs than the algorithm that only used specific diagnoses; however, its PPV was slightly lower. We were able to identify DIAs with the algorithm we developed. [ABSTRACT FROM AUTHOR]

We assessed the clinical features and treatment of pediatric patients with drug-induced anaphylaxis in clinical settings. Pediatric drug-induced anaphylaxis cases collected by the Beijing Pharmacovigilance Database from 2004 to 2014 were analyzed. A total of 91 cases were identified. Drug-induced anaphylaxis was primarily caused by antibiotics (53%). Children of 0-5 years were more likely to develop cyanosis symptoms than children of 13-17 years (OR = 5.14, 95%CI [1.74, 15.20], P = 0.002). Children of 13-17 years were more likely to develop hypotension than children of 6-12 years (OR = 11.79, 95%CI [2.28, 60.87], P = 0.002), and to manifest both neurological symptoms (OR = 3.56, 95%CI [1.26, 10.08], P = 0.015) and severe anaphylaxis than children of 0-5 years (OR = 15.46, 95%CI [1.85, 129.33], P = 0.002). Supratherapeutic doses of epinephrine were more likely with intravenous (IV) bolus (92%) in contrast to either intramuscular (IM) (36%, OR = 19.25, 95%CI [1.77, 209.55], P = 0.009) or subcutaneous (SC) injections (36%, OR = 19.80, 95% CI [1.94, 201.63], P = 0.005). Only 62 (68%) patients received epinephrine treatment as the first-line therapy.Conclusion: This study demonstrates that antibiotics were the most common cause of pediatric drug-induced anaphylaxis. Children may present with different anaphylactic signs/symptoms based on age groups. Epinephrine is under-utilized and provider education on the proper management of drug-induced anaphylaxis is warranted. What is Known: • The most common causes of anaphylaxis in children are allergies to foods. Drugs are the second most common cause of pediatric anaphylaxis. • IM epinephrine is the recommended initial treatment of anaphylaxis. What is New: • Drug-induced anaphylaxis in pediatric patients has age-related clinical features. • IV bolus epinephrine was overused and associated with supratherapeutic dosing. [ABSTRACT FROM AUTHOR]

Background: Genetic polymorphisms of cytochrome P450 enzymes, especially CYP2C19, could influence voriconazole pharmacokinetics. The association between CYP2C19 polymorphisms and voriconazole clinical outcomes is not well established. The aim of this meta-analysis was to evaluate the effect of CYP2C19 polymorphisms on clinical outcomes in patients treated with voriconazole. Methods: PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases were searched from their inception to January 2016 to identify eligible trials that reported voriconazole exposure and clinical outcomes of voriconazole according to CYP2C19 polymorphisms. Two reviewers independently reviewed the citations, extracted the data, and assessed the quality of the trials. The meta-analysis was performed using RevMan5.3. Results: A total of ten studies involving 598 patients were included. Compared with patients with extensive metabolizer (EM) phenotype, patients with poor metabolizer (PM) phenotype had significantly higher trough concentrations (MD, 1.22 mg/L; 95 % confidence interval (CI), 0.72-1.71; P < 0.0001). PM phenotype was also associated with a higher treatment success rate compared with EM phenotype (risk ratio (RR), 1.31; 95 % CI, 1.04-1.67; P = 0.02). However, there was no significant association between CYP2C19 polymorphisms and daily maintenance dose, overall adverse events, hepatotoxicity, and neurotoxicity. Conclusions: Patients with CYP2C19 PM phenotype were associated with increased treatment success rate and trough concentrations as compared with those with EM phenotype. There was no significant association between CYP2C19 polymorphisms and either daily maintenance dose or adverse outcomes of voriconazole. However, large-scale, high-quality trials are still needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction: Osteoporosis is an under-recognized problem threatening men. Bisphosphonates are the main treatment but their comparative efficacy is unclear for men with osteoporosis. Therefore, we performed this systematic review with network meta-analyses to summarize the evidence of comparative efficacy of bisphosphonates in men with osteoporosis. Methods: We completed network meta-analyses with a frequentist model to compare the efficacy of different bisphosphonates. Randomized controlled trials investigating bisphosphonates used in men with osteoporosis were included. The primary outcome was the rate of patients with a new vertebral fracture. The secondary outcome was the rate of patients with a non-vertebral fracture, which was defined as any fractures reported other than vertebral fractures. Pairwise meta-analyses were performed to compare bisphosphonates with placebo. We included open-label studies in the analyses as a sensitivity analysis. Results: Ten trials were included, using alendronate, ibandronate, risedronate, and zoledronic acid. No significant difference was found between any pairs of alendronate, ibandronate, risedronate, and zoledronic acid for both vertebral and non-vertebral fractures. Zoledronic acid ranked as the most effective in preventing vertebral fracture in primary osteoporosis. Risedronate ranked best in preventing non-vertebral fracture in both primary osteoporosis and corticosteroid-induced osteoporosis. In the sensitivity analyses with the open-label studies, the ranking order did not change. Conclusion: The current evidence for bisphosphonates used in men with osteoporosis is inadequate. On the basis of the current evidence, zoledronic acid is most effective at preventing vertebral fractures, while risedronate has the highest possibility to rank the first in preventing non-vertebral fracture in men with primary osteoporosis and corticosteroid-induced osteoporosis. More well-designed studies are needed to test our findings and to better know the comparative efficacy of bisphosphonate to prevent vertebral fracture in men with osteoporosis. [ABSTRACT FROM AUTHOR]

A number of new agents for the management of chronic obstructive pulmonary disease (COPD) are at different stages of development, including several inhaled long-acting antimuscarinics (LAMA). Long-acting bronchodilators are considered to be central to the management of COPD due to the evidence supporting their efficacy and safety. Umeclidinium, a LAMA, has recently been approved for the maintenance treatment of moderate to very severe COPD in a number of countries. This comprehensive review and pooled meta-analysis provides detailed information about the efficacy and safety of this agent. The pharmacokinetics and pharmacodynamics of umeclidinium observed in phase I and II studies support its once-daily administration. Umeclidinium is rapidly cleared from blood, and renal or hepatic impairment do not lead to significant changes in drug disposition. A pooled analysis of phase III and comparative studies of umeclidinium in patients with moderate to very severe COPD showed significant improvement in lung function measures, including trough forced expiratory volume in 1 s (FEV), as well as in acute exacerbations of COPD, dyspnea, and quality of life. Adverse effects, including known anticholinergic effects, were uncommon with umeclidinium. Limited data suggest the efficacy of umeclidinium is similar to that of tiotropium. Umeclidinium is administered as a dry powder inhaler, provides adequate lung delivery in patients with moderate to very severe airflow obstruction, and appears to be easily used by patients. Umeclidinium provides a safe and effective option as an inhaled LAMA for the management of COPD. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the influence of follicle-stimulating hormone receptor (FSHR) Asn680Ser polymorphism on the ovarian response to exogenous follicle-stimulating hormone (FSH) and clinical outcomes in women undergoing controlled ovarian hyperstimulation (COH). Methods: A database search was conducted to identify the eligible studies that investigated the effect of FSHR Asn680Ser polymorphism on ovarian response and clinical outcomes. A pooled analysis was performed with the odds ratio (OR) or weighted mean difference (WMD) and their respective 95 % confidence interval (CI) by the STATA software with random effects model. Results: Sixteen cohort studies comprising a total of 4287 subjects were included. The number of retrieved oocytes was significantly fewer in subjects with the SS genotype at position 680, compared to subjects with the NN or NS genotype (WMD = −1.36, 95 % CI = −1.85 to −0.87). Lack of association was detected between the genotypes (SS genotype vs. NN or NS genotype) and clinical outcomes such as exogenous FSH dose (WMD = 98.96 IU, 95 % CI = −22.33 to 220.24), poor response (OR = 1.08, 95 % CI = 0.71-1.64), ovarian hyperstimulation syndrome (OHSS) (OR = 1.58, 95 % CI = 0.41-6.07), and clinical pregnancy rate (OR = 1.10, 95 % CI = 0.86-1.40). However, poor ovarian response and number of retrieved oocytes were significantly influenced by the Asn680Ser polymorphism in the Asian subjects. In addition, no publication bias was detected. Conclusion: FSHR Asn680Ser polymorphism might be a significant biomarker for predicting the number of retrieved oocytes and poor response, especially in Asian subjects. Other outcomes such as exogenous FSH dose, OHSS, and pregnancy rate were not influenced by FSHR Asn680Ser polymorphism. [ABSTRACT FROM AUTHOR]

To modify the endoscopic frontal sinus surgery and improve the therapeutic effect of recurrent chronic frontal sinusitis (RCFS). Eighty-five patients with RCFS were divided into two groups. Endoscopic frontal sinus surgery through an approach of Frontomaxillary Process-Agger Nasi, a modified Draf IIb procedure, was carried out in 51 patients (Group A), and conservative medication was applied in 34 patients as control (Group B). The therapeutic effect was prospectively evaluated with statistically validated measures of sinusitis-specific quality of life, sino-nasal outcome test-20 questionnaire (SNOT-20). Compared with pre-treatment, the average total score of SNOT-20 in RCFS patients was significantly decreased at the time of 6, 12 months after modified endoscopic frontal sinus surgery and medical treatments ( p < 0.05). However, the total score of SNOT20 was significantly lower in group A than group B at the same period of the follow-up after treatments ( p < 0.05). The overall efficacy evaluated by patients' self showed that the rate of 'much improved' and 'improved' was respectively 68.6 and 17.6 % in group A, and significantly better than group B ( p < 0.001). Furthermore, the frontal sinus patency rate in group A was 85 %, and significantly higher than group B ( p < 0.001). Endoscopic frontal sinus surgery through an approach of Frontomaxillary Process-Agger Nasi, a modified Draf IIb procedure, is an effective procedure to treat the RCFS. [ABSTRACT FROM AUTHOR]

Residual microstresses in particle reinforced alumina/SiC and alumina/mullite composites were calculated. The results indicated that there existed a linear relation between matrix microstresses and the particle contents in the composites. The influence of stress state on crack propagating and grain boundary strengthening was analyzed. Ratios of grain boundary toughness to grain toughness of these composites were calculated in view of microstress analysis, and percentage of transgranular fracture (PTF) that increases with the microstress in the alumina matrix was then deduced. The relationship between microstructure, component, matrix microstresses, and PTF was established. Therefore, the fracture characteristic was predicted on basis of the particle content and distribution in addition to the microstructure of the composites. [ABSTRACT FROM AUTHOR]

A flip-chip-type gradiometer has been constructed with a 10 mm × 5 mm planar DCSQUID gradiometer fabricated on a SrTiO3 bicrystal substrate and a flux transformer made from a YBCO*/YBCO/CeO2/YSZ multilayer on ϕ50.8 mm Si wafer. The coupling coefficient between the flux transformer and the planar gradiometer is 0.18. The transformer increases effectively the resolution of the gradiometer. A magnetic field gradient resolution of 73 fT.cm−1Hz−1/2 in the white region and 596 fT.cm−1Hz−1/2 at 1 Hz has been obtained. High quality magnetocardiogram signals have been successfully measured by using this flip-chip-type gradiometer in an unshielded environment. [ABSTRACT FROM AUTHOR]

This report investigated dislocation-twin boundary (TB) interactions that cause the TB to disappear and turn into a high-angle grain boundary (GB). The evolution of the microstructural characteristics of Hadfield steel was shown as a function of severe plastic deformation processing time. Sessile Frank partial dislocations and/or sessile unit dislocations were formed on the TB through possible dislocation reactions. These reactions induced atomic steps on the TB and led to the accumulation of gliding dislocations at the TB, which resulted in the transition from coherent TB to incoherent GB. The factors that affect these interactions were described, and a physical model was established to explain in detail the feasible dislocation reactions at the TB. [ABSTRACT FROM AUTHOR]