Dual-Ligand Strategy to Construct Metal Organic Gel Catalyst with the Optimized Electronic Structure for High-Efficiency Overall Water Splitting and Flexible Metal-Air Battery.

Non-noble metal catalysts are known for their efficient catalytic performance for oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER). Metal organic gels (MOGs) can be considered as a promising electrocatalyst owing to the diverse physicochemical properties but usually suffer from its poor electrical conductivity and catalytic stability. Here, a FeCo-MOG is constructed with considerable trifunctional activity. The optimal P-CoFe-H3 prepared by using phytic acid (PA) and 2,4,6-Tris[(p-carboxyphenyl)amino]-1,3,5-triazine benzoic acid (H3TATAB) as dual ligands), exhibits outstanding ORR, OER, and HER activities as well as stability, exceeding most of state-of-the-art catalysts. As expected, the flexible Zn-air battery applied with P-CoFe-H3 as air cathode displays considerable power density, discharge voltage plateau, and cycling stability. Impressively, it is also capable of driving the overall water-splitting device by applying the P-CoFe-H3 as anode and cathode. Furthermore, theoretical calculations reveal that dual ligands can optimize the coordination environment and charge density of active sites, thereby reducing the absorption energy of intermediate species and boosting the catalytic performance. This work endows the dual-ligands coordination strategy with great potentiality for MOGs-based electrocatalysts in energy conversion devices.

Exploring the oncogenic potential of circSOD2 in clear cell renal cell carcinoma: a novel positive feedback loop.

BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.

Enhanced Photocatalytic Hydrogen Evolution of In2S3 by Decorating In2O3 with Rich Oxygen Vacancies.

The hydrogen (H2) evolution rates of photocatalysts suffer from weak oxidation and reduction ability and low photogenerated charge carrier separation efficiency. Herein, by combining band-gap structure optimization and vacancy modulation through a one-step hydrothermal method, In2O3 containing oxygen vacancy (Ov/In2O3) is simply introduced into In2S3 to promote photocatalytic hydrogen evolution. Specifically, the change in the sulfur source ratio can induce the coexistence of Ov/In2O3 and In2S3 in a high-temperature hydrothermal process. Under light irradiation, In2S3@Ov/In2O3-0.1 nanosheets hold a remarkable average H2 evolution rate up to 4.04 mmol g-1 h-1, which is 32.14, 11.91, and 2.25-fold better than those of pristine In2S3, In2S3@Ov/In2O3-0.02, and In2S3@Ov/In2O3-0.25 nanosheets, respectively. The ultraviolet-visible (UV-vis) diffuse reflectance and photoluminescence (PL) spectra reveal that the formation of Ov/In2O3 in In2S3 optimizes the band-gap structure and accelerates the migration of the photogenerated charge carrier of In2S3@Ov/In2O3-x nanosheets, respectively. Both the enhancement of oxidation and reduction ability and photogenerated charge carrier separation ability are responsible for the remarkable improvement in photocatalytic H2 evolution performance. This work provides a new strategy to prepare a composite of metal sulfide and metal oxide through a one-step hydrothermal method.

Direct Growth of Polymeric Carbon Nitride Nanosheet Photoanode for Greatly Efficient Photoelectrochemical Water-Splitting.

A general method for the direct synthesis of highly homogeneous and dense polymerized carbon nitride (PCN) nanosheet films on F: SnO2 (FTO) is developed. Detailed photoelectrochemical (PEC) water-splitting studies reveal that the as-synthesized PCN films exhibit outstanding performance as photoanode for PEC water-splitting. The optimal PCN photoanode exhibits excellent photocurrent density of 650 µA cm-2 , and monochromatic incident photon-to-electron conversion efficiency (IPCE) value up to 30.55% (λ = 400 nm) and 25.97% (λ = 420 nm) at 1.23 VRHE in 0.1 m KOH electrolyte. More importantly, the PCN photoanode has an excellent hole extraction efficiency of up to 70 ± 3% due to the abundance of active sites provided by the PCN photoanode nanosheet, which promotes the transport rates of OER-relevant species. These PCN films provide a new benchmark for PCN photoanode materials.

Highly hydrophilic and dispersed TiO2 nano-system with enhanced photocatalytic antibacterial activities and accelerated tissue regeneration under visible light.

Titanium dioxide (TiO2)-based photodynamic antibacterial (PDA) agents present a novel approach for addressing drug-resistant bacterial infections and the associated tissue damage. However, the suboptimal dispersibility, negative charge, and weak photocatalytic activity under visible light of TiO2 hinder its practical applications. This study aimed to address these limitations by developing a highly hydrophilic and dispersed Zn-TiO2/reduced graphene oxide (rGO) (HTGZ) nano-system with exceptional visible light catalytic activity and tissue repair ability. HTGZ produced an antibacterial ratio over 98% within a short time, likely due to the enhanced production of reactive oxygen species under visible light. After being co-cultured for 4 days, L929 cells and BMSCs maintained over 90% activity, indicating that HTGZ had no significant cytotoxicity. Furthermore, the transcriptomic and metabolic analyses revealed that the antibacterial mechanism mainly came from the destruction of cell membranes and the disruption of various metabolic processes, such as purine metabolism and fatty acid biosynthesis. Critically, results of in vivo experiments had authenticated that HTGZ significantly promoted infected tissue regeneration by slaughtering bacteria and release Zn2+. After 14 days, the wound area was only one-third that of the control group. Overall, the enhanced antibacterial efficacy and wound-healing potential position HTGZ as a promising nano-antibacterial medication for the clinical treatment of infectious bacterial diseases.

Design, Synthesis, and Biological Evaluation of Benzimidazole Derivatives as Potential Lassa Virus Inhibitors.

The Lassa virus (LASV) causes Lassa fever, a highly infectious and lethal agent of acute viral hemorrhagic fever. At present, there are still no effective treatments available, creating an urgent need to develop novel therapeutics. Some benzimidazole compounds targeting the arenavirus envelope glycoprotein complex (GPC) are promising inhibitors of LASV. In this study, we synthesized two series of LASV inhibitors based on the benzimidazole structure. Lentiviral pseudotypes bearing the LASV GPC were established to identify virus entry inhibitors. Surface plasmon resonance (SPR) was further used to verify the binding activities of the potential compounds. Compounds 7d-Z, 7h-Z, 13c, 13d, and 13f showed relatively excellent antiviral activities with IC50 values ranging from 7.58 to 15.46 nM and their SI values above 1251. These five representative compounds exhibited stronger binding affinity with low equilibrium dissociation constants (KD < 8.25 × 10-7 M) in SPR study. The compound 7h-Z displayed the most potent antiviral activity (IC50 = 7.58 nM) with a relatively high SI value (2496), which could be further studied as a lead compound. The structure-activity relationship indicated that the compounds with lipophilic and spatially larger substituents might possess higher antiviral activity and a much larger safety margin. This study will provide some good guidance for the development of highly active compounds with a novel skeleton against LASV.

Anti-BVDV Activity of Traditional Chinese Medicine Monomers Targeting NS5B (RNA-Dependent RNA Polymerase) In Vitro and In Vivo.

Natural products have emerged as "rising stars" for treating viral diseases and useful chemical scaffolds for developing effective therapeutic agents. The nonstructural protein NS5B (RNA-dependent RNA polymerase) of NADL strain BVDV was used as the action target based on a molecular docking technique to screen herbal monomers for anti-BVDV viral activity. The in vivo and in vitro anti-BVDV virus activity studies screened the Chinese herbal monomers with significant anti-BVDV virus effects, and their antiviral mechanisms were initially explored. The molecular docking screening showed that daidzein, curcumin, artemisinine, and apigenin could interact with BVDV-NADL-NS5B with the best binding energy fraction. In vitro and in vivo tests demonstrated that none of the four herbal monomers significantly affected MDBK cell activity. Daidzein and apigenin affected BVDV virus replication mainly in the attachment and internalization phases, artemisinine mainly in the replication phase, and curcumin was active in the attachment, internalization, replication, and release phases. In vivo tests demonstrated that daidzein was the most effective in preventing and protecting BALB/C mice from BVDV infection, and artemisinine was the most effective in treating BVDV infection. This study lays the foundation for developing targeted Chinese pharmaceutical formulations against the BVDV virus.

Electronic Structure Regulation of Iron Phthalocyanine Induced by Anchoring on Heteroatom-Doping Carbon Sphere for Efficient Oxygen Reduction Reaction and Al-Air Battery.

Aluminum-air batteries (AABs) are deemed as a potential clean energy storage device. However, exploiting high-efficiency and stable oxygen reduction reaction (ORR) electrocatalysts in AABs is still a challenge. Iron phthalocyanine (FePc) shows a great prospect in ORR but still far from Pt-based catalysts. Here, the hybrid electrocatalysts of monolayer FePc and hollow N,S-doped carbon spheres (HNSCs) are innovatively constructed through π-π stacking to achieve high dispersion. The resulting FePc@HNSC catalyst exhibits an outstanding ORR activity, outperforming that of pristine FePc and even most Fe-based catalysts reported to date. Moreover, the AAB using FePc@HNSC catalyst not only demonstrates a superior power density than the battery with Pt/C, but also displays stable discharge voltages and excellent durability. Furthermore, the theoretical calculations confirm that the charge distribution and d-band center of the Fe atom in FePc are efficiently optimized by hybrid configuration via the introduction of N,S-doped carbon substrate. The design leads to an enriched electron density around Fe active sites and significant reduction of energy barrier for OH* formation, which are favorable for the improvement of electrocatalytic ORR performance. This work provides a chance to expand the application of metallic macrocyclic compound electrocatalysts in various energy technologies.

Iguratimod inhibits skin fibrosis by regulating TGF-ß1/Smad signalling pathway in systemic sclerosis.

BACKGROUND: Iguratimod (T-614), exerting a powerful anti-inflammatory ability, has therapeutic efficacy in multiple autoimmune diseases. However, the effect of T-614 on systemic sclerosis (SSc) is unclear. Here, we investigate the effect and molecular mechanism of T-614 in experimental SSc models. METHODS: In vitro, cultured dermal fibroblasts from four SSc patients were subjected to different doses of T-614 in the presence or absence of TGF-ß1 stimulation. Cell proliferation, apoptosis and migration were determined by CCK-8, flow cytometry and transwell assay, respectively. Fibrosis markers and smad signalling pathway-related proteins were detected by immunoblotting and immunofluorescence. In vivo, a bleomycin-induced SSc mouse model was used to evaluate the effect of T-614 on skin fibrosis. Pathological changes in skin tissues were evaluated by HE, Masson staining and immunohistochemistry. RESULTS: In the study, we found T-614 inhibited TGF-ß1-induced cell proliferation, migration and promoted apoptosis in a dose-dependent manner (all p < 0.01). T-614 partially reversed TGF-ß1-induced upregulation of fibrosis markers and phosphorylation of smad2 and smad3 and blocked p-Smad3 nuclear translocation (all p < 0.05), suggesting T-614 may inhibit dermal fibroblasts activation by regulating TGF-ß1/smad pathway. In vivo experiments, T-614 alleviated skin thickness in bleomycin-induced SSc mice (all p < 0.05). The expression of fibrosis markers and the infiltration of macrophages in skin tissue were significantly decreased after T-614 treatment (all p < 0.05). CONCLUSION: Our preliminary data indicated T-614 inhibited dermal fibroblasts activation and skin fibrosis at least partly by regulating TGF-ß1/smad pathway in experimental SSc models and may be a promising therapeutic agent for SSc.

Anchoring Highly Dispersed Pt Electrocatalysts on TiOx with Strong Metal-Support Interactions via an Oxygen Vacancy-Assisted Strategy as Durable Catalysts for the Oxygen Reduction Reaction.

Pt electrocatalysts with high activity and durability have still crucial issues for the oxygen reduction reaction (ORR) in proton exchange membrane fuel cells (PEMFCs). In this study, a novel catalyst consisting of Pt nanoparticles (NPs) on TiOx/C composites (TiOx-Vo-H/C) with abundant oxygen vacancies (Vo) is proposed, which is abbreviated as PTO-Vo-H/C. The introduction of Vo helps anchor highly dispersed Pt NPs with low loading and strengthen the strong metal-support interaction (SMSI), which benefits to the enhanced ORR catalytic activity. Moreover, the accelerated durability test (ADT) demonstrates the higher retention of ORR activity for PTO-Vo-H/C. Experimental and theoretical analyses reveal that electronic interactions between Pt NPs and TiOx/C composite support give rise to an electron-rich Pt NPs and strong SMSI effect, which is favorable for the electron transfer and stabilization of Pt NPs. More importantly, the assembled PEMFC with PTO-Vo-H/C shows only 6.9% of decay on maximum power density after 3000 ADT cycles while the performance of Pt/C sharply decreased. This work provides a new insight into the unique vacancy regulation of dispersive Pt on metal oxides for superior ORR performance.

Evaluation of Sanders Type 2 Joint Depression Calcaneal Fractures in 197 Patients from a Single Center Using Three-Dimensional Mapping.

BACKGROUND This study aimed to evaluate Sanders type 2 calcaneal fractures in 197 patients from a single center using the 3D (three-dimensional) CT (computed tomography) mapping method. MATERIAL AND METHODS A consecutive series of 197 Sanders type 2 joint depression calcaneal fractures was used. The segment and split functions were used to create each calcaneal fragment using Mimics Research 20.0 software. The fracture fragments were reduced in 3-matic Research 12.0 software. In the E-3D Medical 18.01 software, after superimposing the fractured calcaneus entity with the calcaneus template, we drew the fracture line on the template. Finally, the heatmap was obtained by fracture statistical analysis function. Simultaneously, the distribution of the fracture lines in the anterior part of the calcaneus (APC) and middle talar joint was recorded. RESULTS There were 109 cases of Sanders type 2A, 46 cases of Sanders type 2B, and 42 cases of Sanders type 2C. Based on the data, we drew the characteristic fracture map of type 2A 2B and 2C. This study found that the most common types of Sanders type 2A in APC and middle talar articular surface are type AC and type AD. In Sanders type 2B, the most common type is type AC, and in Sanders type 2C it is type ACD. CONCLUSIONS The findings from this study showed that 3D CT imaging and reconstruction of the calcaneus was a useful diagnostic method to evaluate and classify joint depression calcaneal fractures. The calcaneal fracture map can be used to guide surgical planning and optimize the design of internal fixation.

Quality of life and treatment satisfaction with pharmacological interventions in Chinese adults with chronic pain due to osteoarthritis.

BACKGROUND: Aim of this multicenter, observational, cross-sectional study was to evaluate health-related quality of life (HRQoL) and treatment satisfaction of current medications in Chinese knee OA patients. METHODS: Brief Pain Inventory (BPI), Treatment Satisfaction Questionnaire (TSQM-1.4), and HRQoL (EQ-5D-5L) were assessed in total of 601 OA of knee patients. Impact on QoL (EQ-5D-5L) and treatment satisfaction (TSQM-1.4) by BPI-Severity score (< 4 and ≥ 4) were presented using mean standard deviations (SDs) and were compared using a t-test. For each of self-assessed health EQ-5D-5L and TSQM, a linear regression model was used to estimate the regression coefficient along with corresponding 95% confidence interval (CI) for BPI-Severity. RESULTS: Mean score of EQ-5D-5L of patients with BPI-Severity ≥4 was significantly lower than those with BPI-Severity < 4. All the scores of TSQM in 4 dimensions were lower in patients with BPI-Severity ≥4 than in those with BPI-Severity < 4. Both HRQoL scores and TSQM scores showed a statistically significant decreasing trend with increasing BPI-Severity pain score. CONCLUSION: Chronic knee OA pain has a significant impact on patients' HRQoL. More severe patients with OA were less satisfied with current treatments.

A comparison and review of three sets of classification criteria for systemic lupus erythematosus for distinguishing systemic lupus erythematosus from pure mucocutaneous manifestations in the lupus disease spectrum.

Although the original purpose of the systemic lupus erythematosus (SLE) classification criteria was to distinguish SLE from other mimic diseases, and to facilitate sample selection in scientific research, they have become widely used as diagnostic criteria in clinical situations. It is not known yet if regarding classification criteria as diagnostic criteria, what problems might be encountered? This is the first study comparing the three sets of classification criteria for SLE, the 1997 American College of Rheumatology (ACR'97), 2012 Systemic Lupus International Collaborating Clinics (SLICC'12) and 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR'19), for their ability to distinguish patients with SLE from patients with pure mucocutaneous manifestations (isolated cutaneous lupus erythematosus without internal disease, i-CLE) in the lupus disease spectrum. 1,865 patients with SLE and 232 patients with i-CLE were recruited from a multicenter study. We found that, due to low specificity, none of the three criteria are adept at distinguishing patients with SLE from patients with i-CLE. SLICC'12 performed best among the original three criteria, but if a positive ANA was removed as an entry criterion, EULAR/ACR'19 would performed better. A review of previous studies that compared the three sets of criteria was presented in this work.

Modulation of the plasticity of an all-metal oxide synaptic transistor via laser irradiation.

Artificial intelligence devices that can mimic human brains are the foundation for building future artificial neural networks. A key step in mimicking biological neural systems is the modulation of synaptic weight, which is mainly achieved by various engineering approaches using material design, or modification of the device structure. Here, we realize the modulation of the synaptic weight of a Ta2O5/ITO-based all-metal oxide synaptic transistor via laser irradiation. Prior to the deposition of the active layer and electrodes, a femtosecond laser was used to irradiate the surface of the insulator layer. Typical synaptic characteristics such as excitatory postsynaptic current, paired pulse facilitation and long-term potentiation were successfully simulated under different laser intensities and scanning rates. In particular, we demonstrate for the first time that laser irradiation could control the quantity of oxygen vacancies in the Ta2O5 thin film, leading to precise modulation of the synaptic weight. Our research provides an instantaneous (<1 s), convenient and low-temperature approach to improving synaptic behaviors, which could be promising for neuromorphic computing hardware design.

All-metal oxide synaptic transistor with modulatable plasticity.

The artificial neural system has attracted tremendous attention in the field of artificial intelligence due to operate mode of parallel computation which is superior to traditional Von Neumann computers in processing complex sensory data and real-time situations with extremely low power dissipation. Remarkable progress has been made in the hardware-based electric-double-layer synaptic transistors as its modulation by ion movement is similar to biological synapse for the past few years. Unfortunately, long-term potentiation (LTP) timescale is still a big challenge in hardware-based electric-double-layer synaptic transistors which is essential to processing capacity and memory formation. Meanwhile, the effect of ion concentration on the synaptic plasticity has rarely been reported. Here, a solid state electrolyte-gated transistor using Ta2O5 as dielectric layer with unique ionic composition was demonstrated and the regulation of synaptic weight was realized by changing ion concentration. Both the potentiation and depression of synaptic weight such as excitatory post-synaptic current, inhibitory response (IPSC), paired pulse facilitation as well as LTP were successfully simulated. More importantly, oxygen vacancy content was tuned for the first time to modulate synaptic plasticity by varying film thickness and gas ratio, through which the intensity and duration of memory were enhanced with appropriate vacancy concentration. It indicated that appropriate vacancy concentration avoided the effects of internal electric field induced by ion excess, leading to a long-term memory. These results reveal a promising path to improve memory capacity of artificial synapse via ion modulation.

[Correlations of Methylenetetrahydrofolate Reductase Gene Polymorphism and Genomic DNA Hypomethylation Level with Ankylosing Spondylitis].

Objective To investigate the relationship of both DNA methylation level and methylenetrahydrofolate reductase(MTHFR)gene polymorphism with ankylosing spondylitis(AS). Methods Totally 200 Chinese AS patients with HLA-B27(+)and 120 healthy controls were included from Hunan Province.All the cases were diagnosed according to the 1984 modified New York criteria for AS.The DNA methylation was examined by cytosine extension method,while the MTHFR gene C677T polymorphism was analyzed by the polymerase chain reaction(PCR)and restriction fragment length polymorphism(RFLP).The plasma homocysteine(Hcy)level was examined by enzyme-linked immunosorbent assay(ELISA),while the red blood folate level was analyzed by the specific immunoassays. Results The ratio of the T/T genotype mutation in the AS group was significantly higher than in the control group(17.0% vs. 5.0%;χ2=9.874, P=0.002).The plasma homocysteine concentration of AS group was(18.71 ± 2.42)µmol/L,which was significantly higher than that in normal control group [(10.97 ± 2.93)µmol/L](t=24.402, P<0.001).The plasma Hcy concentration of the T/T genotype [(21.70±1.80)µmol/L] was significantly higher than that of the C/C genotype[(18.31±1.94)µmol/L](q=12.088, P=0.01)and the C/T genotype [(17.80±2.18)µmol/L](q=6.496, P=0.01)in the AS group.The DNA methylation level of the T/T genotype in AS group was significantly lower than that in normal control group(t=5.655, P<0.001)and also significantly lower than those of the C/C genotype(t=11.514, P<0.001)and the C/T genotype in AS group(t=10.287, P<0.001). Conclusions In the Han population in Hunan Province,the C677T polymorphism of the MTHFR gene is associated with the onset of AS.The T/T mutation at position 677 of the MTHFR gene is an important influencing factor for hyperhcyemia in the AS patients.The T/T mutation at position 677 of the MTHFR gene is associated with genomic DNA hypomethylation.Thus,hypomethylation of DNA may be one of the pathogenic mechanisms of AS.

T cell receptor ß repertoires as novel diagnostic markers for systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: T cell receptor (TCR) diversity determines the autoimmune responses in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is closely associated with autoimmune diseases prognosis and prevention. However, the characteristics of variations in TCR diversity and their clinical significance is still unknown. Large series of patients must be studied in order to elucidate the effects of these variations. METHODS: Peripheral blood from 877 SLE patients, 206 RA patients and 439 healthy controls (HC) were amplified for the TCR repertoire and sequenced using a high-throughput sequencer. We have developed a statistical model to identify disease-associated TCR clones and diagnose autoimmune diseases. RESULTS: Significant differences were identified in variable (V), joining (J) and V-J pairing between the SLE or RA and HC groups. These differences can be utilised to discriminate the three groups with perfect accuracy (V: area under receiver operating curve > 0.99). One hundred ninety-eight SLE-associated and 53 RA-associated TCRs were identified and used for diseases classification by cross validation with high specificity and sensitivity. Disease-associated clones showed common features and high similarity between both autoimmune diseases. SLE displayed higher TCR heterogeneity than RA with several organ specific properties. Furthermore, the association between clonal expansion and the concentration of disease-associated clones with disease severity were identified, and pathogen-related TCRs were enriched in both diseases. CONCLUSIONS: These characteristics of the TCR repertoire, particularly the disease-associated clones, can potentially serve as biomarkers and provide novel insights for disease status and therapeutical targets in autoimmune diseases.

Maintenance of effect of duloxetine in Chinese patients with pain due to osteoarthritis: 13-week open-label extension data.

BACKGROUND: The objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data. METHODS: This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed. RESULTS: Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was - 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was - 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p < 0.001). Significant within-group improvements in all BPI items were observed for both PLA_DLX and DLX_DLX groups during the extension phase (all p < 0.01). No deaths or suicide-related events occurred. Seven (4.0%) PLA_DLX-treated patients and no DLX_DLX-treated patients discontinued due to an adverse event. CONCLUSION: The analgesic effect of duloxetine 60 mg QD among treatment responders was maintained for the entire duration of the extension phase. Duloxetine 60 mg QD was well tolerated during the extension phase. TRIAL REGISTRATION: ClinicalTrials.gov identification number NCT01931475 . Registered 29 August 2013.

Associations between the SLC22A12 gene and gout susceptibility: a meta-analysis.

OBJECTIVES: The aim of this study is to explore whether the polymorphisms of rs475688 and rs3825016 in the solute carrier family 22 member 12 (SLC22A12) gene are associated with the susceptibility to gout or hyperuricaemia. METHODS: Relevant studies were enrolled by searching databases systematically. The pooled odds ratios (ORs) with 95% confidence interval (CI) were used to evaluate the associations. Q-test and I2 statistics were used to evaluate the heterogeneity. Publication bias was evaluated using Begg's funnel plots and Egger regression test. RESULTS: A total of 7 articles involving 1216 patients and 1844 healthy controls were included in this meta-analysis. Significant association was detected between rs475688 polymorphism and gout susceptibility in three genetic models (C vs. T: OR=1.464, 95% CI 1.078-1.989, p=0.015; CC+CT vs. TT: OR=2.028, 95% CI 1.488-2.763, p=0.000; CC vs. CT+TT: OR=2.226, 95% CI 1.746-2.838, p=0.000). Significant association was observed between rs3825016 polymorphism and hyperuricaemia susceptibility only in allelic comparison (C vs. T: OR=1.274, 95% CI 1.101-1.474, p=0.001). CONCLUSIONS: The rs475688 polymorphism is associated with gout susceptibility. The correlation between rs3825016 polymorphism of SLC22A12 and hyperuricaemia susceptibility is possible.