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ObjectiveTo develop a guideline for selecting biomarkers in the diagnosis and assessment in patients with axial spondyloarthritis (axSpA).MethodA joint effort was carried out by the core team, the literature review team and the multidisciplinary voting panel to formulate recommendations regarding biomarkers in axSpA, using an evidence-based and consensus-based strategy. Certainty of evidence and strength of recommendation were determined, and levels of agreement within the voting panel were calculated.ResultsA total of 20 recommendations were formulated in this guideline, with levels of agreement ranging from 6.48 to 9.71. The two strong recommendations, HLA-B27 testing in patients suspected of axSpA and regular-interval monitoring of CRP/ESR represent the status quo of axSpA evaluation, while the 13 conditional recommendations represent the promising biomarkers with clinical utility in diagnosis, disease activity assessment, prediction of radiographic progression and therapeutic responses. This guideline does not dictate clinical choices of tests on axSpA, and decisions should be made based on comprehensive consideration of costs, accessibility, patients’ values and willingness as well as the objective of testing in the local context.ConclusionThis guideline addresses the interpretation of the clinical significance of biomarkers in axSpA, and the biomarkers endorsed in this guideline composed a clinical toolkit for healthcare professionals to choose from.

A precise dynamic model and exact statistical information are required in a standard Kalman filter to ensure optimal performance. Without these, degraded performance may be obtained. In this paper, an improved adaptive estimation approach for uncertain models is proposed, and the fading matrix is adaptively estimated according to the observability of the system state. Meanwhile, a sequential way to calculate the covariance matrix of the measurement noises is performed, thereby strengthening its ability to resist disturbances further. The proposed algorithm was implemented in practical data processing of GNSS (Global Navigation Satellite System) and INS (Inertial Navigation System) integrated systems. The measurement sensors were equipped on aircraft and land vehicles to test their stability and robustness. Comparisons with existing fading filters and conventional nonlinear Kalman filters show that the proposed algorithm controls model errors, weakens influences of constantly changing and abrupt outliers, achieves relatively high precision, and restrains filter divergence effectively.

Abstract Background Diabetes increases the risk of hypertension morbidity, but whether this association is varied with glycemic control remains unknown. We aimed to examine the association of glycemic control with hypertension among individuals with diabetes. Methods Data was from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. Participants were categorized as having adequate glycemic control (HbA1c

The standard Kalman filter and most of its enhancements are typically designed based on the criterion that minimizes the mean squared error, with little discussion of multiple criteria in the positioning and navigation fields. Therefore, a novel data fusion method that takes into account weighted multiple criteria is proposed in this paper, implementing a filtering algorithm based on integrated criteria with different weights determined by a weight adjustment factor. The proposed algorithm and conventional filtering algorithms were utilized for data fusion in GNSS/INS integration. Experiments were conducted using actual data collected from an urban environment. Comparative analysis revealed that, when utilizing the proposed algorithm, the precision of the position, velocity, and attitude of the tested land vehicle could be improved by approximately 24%, 48%, and 35%, respectively. Furthermore, a series of filtering algorithms with different weight adjustment factors was performed to test their influence on the filtering. The application of the proposed algorithm should be accompanied by an appropriate weight adjustment factor.

Background. Colitis is a refractory intestinal inflammatory disease significantly affecting the quality of a patient’s life and increasing the risk of exacerbation. The primary factors leading to colitis encompass infections, insufficient blood flow, and the buildup of collagen as well as white blood cells. Among various available therapeutics, 5-methoxytryptophan (5-MTP) has emerged as one of the protectants by inhibiting inflammatory damage. Nonetheless, there is no report on the role of 5-MTP in the treatment of colitis. Materials and Methods. To verify the anti-inflammatory effect of 5-MTP in vivo, we first constructed mouse model with dextran sulfate sodium-induced colitis. Furthermore, the macrophage infiltration and release of inflammatory factors through western blot (WB) and hematoxylin–eosin staining analyses were examined. Intestinal epithelial cell tight junction damage and apoptosis were investigated by WB analysis, immunofluorescence, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Finally, we examined the generation of cellular inflammation and analyzed the influence of 5-MTP on M1 polarization at the cellular level. Results. This study initially confirmed that 5-MTP possessed an excellent therapeutic effect on colitis. 5-MTP inhibits macrophage infiltration and the generation of inflammatory factors. In addition to its effects on immune cells, 5-MTP significantly inhibits intestinal epithelial cell tight junction damage and apoptosis in vivo. Moreover, it inhibits inflammation and M1 polarization response in vitro. Conclusion. 5-MTP counteracts excessive inflammation, thereby preventing intestinal epithelial tight junction damage. In addition, inhibition of apoptosis suggests that 5-MTP may be a potential therapeutic agent for colitis.

BackgroundSeveral observational studies have suggested a potential relationship between gut microbiome and psoriatic arthritis (PsA). However, the causality of this relationship still remains unclear. We aim to explore if the specific gut microbiome is causally associated with PsA at the genetic level and offer valuable insights into the etiology of PsA.MethodsIn this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal effects of the gut microbiome on PsA. Publicly accessible genome-wide association study summary data of gut microbiome were obtained from the MiBioGen consortium (n = 14,306), while the summary statistics of psoriatic arthropathies were sourced from the FinnGen consortium R8 release data (2,776 cases and 221,323 controls). The primary analytical method employed was inverse variance weighted (IVW), complemented by supplementary methods including MR-Egger, weighted median, weighted mode, maximum likelihood, MR-PRESSO, and cML-MA. Reverse MR analysis was performed on the bacteria that were found to be causally associated with PsA in forward MR analysis. Cochran’s IVW Q statistic was utilized to assess the heterogeneity of instrumental variables among the selected single nucleotide polymorphisms.ResultsIVW estimates revealed that Ruminococcaceae_UCG-002 (odds ratio (OR) = 0.792, 95% confidence interval (CI), 0.643–0.977, p = 0.029) exhibited a protective effect on PsA. Conversely, Blautia (OR = 1.362, 95% CI, 1.008–1.842, p = 0.044), Eubacterium_fissicatena_group (OR = 1.28, 95% CI, 1.075–1.524, p = 0.006), and Methanobrevibacter (OR = 1.31, 95% CI, 1.059–1.621, p = 0.013) showed a positive correlation with the risk of PsA. No significant heterogeneity, horizontal pleiotropy, or outliers were observed, and the results of the MR analysis remained unaffected by any single nucleotide polymorphisms. According to the results of reverse MR analysis, no significant causal effect of PsA was found on gut microbiome.ConclusionThis study establishes for the first time a causal relationship between the gut microbiome and PsA, providing potential valuable strategies for the prevention and treatment of PsA. Further randomized controlled trials are urgently warranted to support the targeted protective mechanisms of probiotics on PsA.

Abstract Objectives The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. Methods We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than − 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. Results In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were − 4.6% and the lower limit of one-sided 97.5% confidence interval was − 14.29%, not less than the lower limit of the non-inferiority margin (− 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference − 4.6%, 95% CI − 14.29% to 5.12%) and PPS (difference – 3.3%, 95% CI – 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. Conclusions Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. Trial registration number NCT03478111.

Abstract. Background:. Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control. Methods:. The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months. Results:. Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of

ObjectiveOur previous studies revealed that normal synovial exosomes promoted chondrogenesis, and microRNA (miR)-19b-3p independently related to osteoarthritis (OA) risk. Subsequently, this study intended to further explore the effect of OA fibroblast-like synoviocyte (OA-FLS) exosomal miR-19b-3p on OA ferroptosis and its potential mechanisms.MethodsInterleukin (IL)-1β-stimulated chondrocytes and medial meniscus surgery were used to construct the OA cellular model and the OA rat model, respectively. OA-FLS exosomes with/without miR-19b-3p modification were added to the IL-1β-stimulated chondrocytes and OA rat models, followed by direct miR-19b-3p mimic/inhibitor transfection with/without SLC7A11 overexpression plasmids. miR-19b-3p, ferroptosis-related markers (malondialdehyde (MDA), glutathione (GSH)/oxidized glutathione (GSSG), ferrous ion (Fe2+), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4)), mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels were detected.ResultsEnhanced ferroptosis reflected by dysregulated ferroptosis-related markers, a reduced MMP, and an increased ROS was observed in cartilage tissues from OA patients vs. controls, IL-1β-stimulated chondrocytes vs. normal ones, and OA rat models vs. sham, so did miR-19b-3p. OA-FLS exosomes promoted MDA, Fe2+, ACSL4, and ROS but reduced cell viability, GSH/GSSG, GPX4, SLC7A11, and MMP in IL-1β-stimulated chondrocytes, whose effect was enhanced by miR-19b-3p mimics and attenuated by miR-19b-3p inhibitors. miR-19b-3p negatively regulated SLC7A11 and directly bound to SLC7A11 via luciferase reporter gene assay. Furthermore, SLC7A11 overexpression weakened miR-19b-3p mimics’ effect on ferroptosis-related markers, MMP, or ROS in IL-1β-stimulated chondrocytes. OA-FLS exosomes also induced cartilage damage and ferroptosis in OA rats whose influence was tempered by miR-19b-3p inhibitors.ConclusionOA-FLS exosomal miR-19b-3p enhances cartilage ferroptosis and damage by sponging SLC7A11 in OA, indicating a potential linkage among synovium, cartilage, and ferroptosis during the OA process.

IntroductionTo promote patients’ referral across healthcare institutions and integrated care delivery, we identified predictors of physicians’ behaviour and intention to refer patients in a county medical consortium in China on the basis of the theory of planned behaviour (TPB).MethodsThis census-based cross-sectional study was conducted in Yangxi Hospital Group (YHG). All physicians in county hospitals and township health centres were invited to participate. Structural equation modelling was employed to analyse the relationships between referral intention and behaviour and other TPB variables in the group of whole participants and in sub-groups.ResultsIn total, 330 physicians participated in this study. One-third of participants were general practitioners, and half of them were from county hospitals. Referral behaviour of females (χ2 = 20.372, p

Abstract With the popularity of various portable mobile devices with positioning functions, a large amount of spatial‐temporal trajectory data has emerged. To effectively compress large‐scale vehicle trajectory data and serve intelligent transportation system, we propose a spatial‐temporal trajectory data compression algorithm based on vehicle motion pattern recognition. The algorithm recognizes vehicles' turning behaviour and variable speed behaviour during the driving process through the analysis of vehicle motion patterns, and extracts the trajectory's turning feature points and variable speed feature points, so as to achieve online compression of the vehicle trajectory. By means of large‐scale experimental datasets, the authors compare this algorithm with representative trajectory compression algorithms in various performance metrics. The experimental results indicate that as an online vehicle trajectory compression algorithm, the proposed algorithm is superior to representative compression algorithms in compression accuracy and computational efficiency, and the compression results can reflect semantic motion information such as turning patterns and variable speed patterns in the trajectory. Therefore, this algorithm has comprehensive advantages, which is foundational for trajectory data mining in intelligent transportation systems.

Objective This study was performed to explore the function and mechanism of Dvl3 in RA-FLS by exosome intervention. Methods The expression pattern of Dvl3 was examined by IHC, WB, and qPCR. Modified exosomes obtained from culturing supernatant of RA-FLS infected with Dvl3 over expression (OE) lentivirus were administrated to the target RA-FLS. The ability of survival, migration, and the production of inflammatory factor influenced by exosomal Dvl3 were detected by CKK8 kits, Tunel, migration test, qPCR, and enzyme-linked immunosorbent assay (ELISA) respectively; Flow cytometry analysis was conducted to explorer the inflammatory moderate role of exosomes on CD4+ T cells. The possible downstream pathways of Dvl3 were screened by qPCR and WB and verified by double luciferase reporter experiment. Results The expression level of Dvl3 was significantly increased in RA and CIA. Exosomes from the OE group could significantly promote cell proliferation activity, migration/invasion ability. The augment of TNF-α, IL-1β, IL-17, and IL-21 was observed in exosomal Dvl3-OE group. Th1 and Th17 cells polarisation and cytokines related were both enhanced by Exosomal Dvl3. Over expression of Dvl3 was accompanied by the significant increase of β-catenin and RhoA activities. Conclusion This study discovered the high expression of Dvl3 of exosomes derived from RA patients which may possessed the ability to promote phenotypic transformation of RA-FLS through Wnt pathway.

Visceral leishmaniasis (VL) is a chronic infectious disease transmitted by sandflies. The primary clinical manifestations are remittent fever, pancytopenia, and splenomegaly. As VL is rare with atypical symptoms, its diagnosis is often incorrect, missed, or delayed. Without appropriate treatment, the case fatality rate of symptomatic disease is more than 95%, but the prognosis is good if diagnosed and treated timeously. We report a case of VL that was diagnosed using metagenomic next-generation sequencing (mNGS) of a peripheral blood sample. By using mNGS and a bone marrow smear, we were able to make a timely diagnosis. The patient was treated with antimony, rapidly recovered, and was discharged from the hospital. This case illustrates the value of mNGS for making a timely diagnosis of VL.

ObjectiveThe aim of this review is to provide guidance on the selection of approaches to the screening and assessment of enthesitis in patients with spondyloarthritis (SpA).MethodsTwenty-four questions regarding the approaches to the screening and assessment of enthesitis and the implementation details were devised, followed by a systemic literature review. The Grading of Recommendations Assessment, Development, and Evaluation methodology was employed in the development of this guideline, with modifications to evaluate non-interventional approaches under comprehensive consideration of costs, accessibility, and evidence strength. A consensus from the voting panel was required for the inclusion of the final recommendations and the strength of each recommendation.ResultsSeventeen recommendations (including five strong recommendations) were included in this guideline. The voting panel expressed unequivocal support for the necessity of screening and assessment of enthesitis in patients with SpA. It was agreed unanimously that symptom evaluation and physical examination should serve as the initial steps to the recognition of enthesitis, whereas Maastricht Ankylosing Spondylitis Enthesitis Score is a reliable tool in both clinical trials and daily medical practice. Ultrasound examination is another reliable tool, with power Doppler ultrasound as an informative addition. Notwithstanding its high resolution, MRI is limited by the costs and relatively low accessibility, whereas radiographs had low sensitivity and therefore should be rendered obsolete in the assessment of enthesitis. PET/CT was strongly opposed in the detection of enthesitis.ConclusionThis guideline provides clinicians with information regarding the screening and assessment of enthesitis in patients with SpA. However, this guideline does not intend on dictating choices, and the ultimate decisions should be made in light of the actual circumstances of the facilities.

As a typical application of geodesy, the GNSS/INS (Global Navigation Satellite System and Inertial Navigation System) integrated navigation technique was developed and has been applied for decades. For the integrated systems with multiple sensors, data fusion is one of the key problems. As a well-known data fusion algorithm, the Kalman filter can provide optimal estimates with known parameters of the models and noises. In the literature, however, the data fusion algorithm of the GNSS/INS integrated navigation and positioning systems is performed under a certain norm, and performance of the conventional filtering algorithms are improved only under this fixed and limited frame. The mixed norm-based data fusion algorithm is rarely discussed. In this paper, a mixed norm-based data fusion algorithm is proposed, and the hypothesis test statistics are constructed and adopted based on the chi-square distribution. Using the land vehicle data collected through the multi-GNSS and the IMU (Inertial Measurement Unit), the proposed algorithm is tested and compared with the conventional filtering algorithms. Results show that the influences of the outlying measurements and the uncertain noises are weakened with the proposed data fusion algorithm, and the precision of the estimates is further improved. Meanwhile, the proposed algorithm provides an open issue for geodetic applications with mixed norms.

Abstract Background Genetic background affects serum urate concentration and gout risk, especially regarding these variants in the urate-transporter gene ABCG2. However, the role of epistasis between PKD2 and ABCG2 on the pathogenesis of gout is poorly understood. Here we assess this epistatic interaction in the progression from elevated serum urate to gout. Results We identified two epistatic interaction pairs (rs2728121: rs1481012 and rs2728121: rs2231137) were associated with urate levels in 4914 Chinese individuals (P int = 0.018 and 0.004, respectively). Using subgroup analysis for gender and BMI, we found the degree of associations was varied by gender and BMI. The SNP pair rs2728121:rs1481012 influenced urate levels in females and overweight subjects (P int = 0.006 and 0.022, respectively), but rs2728121:rs2231137 did in males, overweight and normal-weight subjects (P int = 0.017, 0.047 and 0.013, respectively). Consistent results were also observed in associations between these epistatic interactions with hyperuricemia. Next, the SNP pair rs2728121:rs2231137 was identified to influence the development of gout from both hyperuricemia and healthy (P int = 0.035 and 0.001, respectively), especially in males (P int = 0.030 and 0.001, respectively). Furthermore, we demonstrated that interacting regions were enriched by regulatory elements. Finally, we observed a strong gene co-expression pattern between PKD2 and ABCG2 (r = 0.743, P = 5.83E-06). Conclusion Our findings indicate epistasis between PKD2 and ABCG2 influence serum urate concentrations, hyperuricemia and gout risk, thus providing insight into the pathogenesis of gout.

Abstract Introduction This 24-week randomized, double-blind, non-inferiority study compared the efficacy and safety of febuxostat, a xanthine oxidase inhibitor, with allopurinol using an up-titration method in hyperuricemic Chinese subjects with or without gout. Methods Eligible adults (serum uric acid [SUA] > 7.0 mg/dl with a history of gout, SUA ≥ 8.0 mg/dl with complications or SUA ≥ 9.0 mg/dl without complications) were randomized (1:1:1) to febuxostat 40 mg/day, 80 mg/day, or allopurinol 300 mg/day. Starting doses of febuxostat 20 mg/day and allopurinol 100 mg/day were up-titrated, up to 16 weeks, to the randomized doses and maintained to week 24. Primary endpoint was non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day based on the percentage of subjects with SUA ≤ 6.0 mg/dl at week 24. The same comparison was made between febuxostat 60 mg/day or 80 mg/day versus allopurinol 300 mg/day. Safety assessments included measurement of treatment-emergent adverse events (TEAEs). Results The per-protocol population comprised 472 subjects. Non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not demonstrated based on the protocol-defined margin of − 10% (44.7 vs. 50.0%; − 5.3% difference; 95% confidence interval [CI]: − 16.4%, 5.8%); however, superiority over allopurinol 300 mg/day was demonstrated for febuxostat 60 mg/day at week 16 (66.3 vs. 51.2%; a 15.0% difference; 95% CI: 4.2%, 25.9%) and febuxostat 80 mg/day at week 24 (70.0 vs. 50.0%; a 20.0% difference; 95% CI: 9.3%, 30.7%). The frequency of TEAEs was similar across groups, with gout flares occurring frequently. Conclusions Using a novel dose-titration method, although the primary endpoint of non-inferiority of febuxostat 40 mg/day versus allopurinol 300 mg/day was not reached, non-inferiority and superiority of febuxostat 60 mg/day and 80 mg/day versus allopurinol 300 mg/day was demonstrated at weeks 16 and 24, respectively. Febuxostat demonstrated an acceptable tolerability profile in the treatment of hyperuricemia in Chinese subjects with or without gout. Trial Registration JapicCTI-132106. Funding Astellas Pharma Global Development, Inc.

Abstract Objective Human adipose-derived mesenchymal progenitor cells (haMPCs) are stem cells with multiple differentiation potential and immunomodulatory function. Re-Join® comprises in vitro expanded haMPCs from adipose tissue of patients combined with cell suspension solution. This study was undertaken to evaluate the efficacy and safety of Re-Join® in patients with symptomatic knee osteoarthritis (OA). Methods Patients with Kellgren–Lawrence grade 1–3 knee OA were recruited from two centers and randomized to receive intra-articular injection of Re-Join® or HA. Pain and function were assessed by using WOMAC score, VAS, and SF-36. Magnetic resonance imaging (MRI) analysis was performed to measure cartilage repair. Adverse events (AEs) were collected. Results Fifty-three patients were randomized. Significant improvements in WOMAC, VAS, and SF-36 scores were observed in both groups at months 6 and 12 compared with baseline. Compared with the HA group, significantly more patients achieved 50% improvement of WOMAC and a trend of more patients achieved a 70% improvement rate in Re-Join® group after 12 months. Meanwhile, there was notably more increase in articular cartilage volume of both knees in the Re-Join® group than in the HA group after 12 months as measured by MRI. AEs were comparable between two groups. Most AEs were mild and moderate except one SAE of right knee joint infection in the HA group. Conclusions Significant improvements in joint function, pain, quality of life, and cartilage regeneration were observed in Re-Join®-treated knee OA patients with good tolerance in a period of 12 months. Trial registration ClinicalTrials.gov Identifier: NCT02162693. Registered 13 June 2014.

Abstract 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

Background: Osteonecrosis of the femoral head (ONFH) remains a major cause of disability in patients with systemic lupus erythematosus (SLE) and seriously impairs quality of life. This study aimed to investigate associations between glucocorticoids (GCs), antiphospholipid antibodies (aPLs), and ONFH in patients with SLE. Methods: We conducted a multicentre cohort study on patients with SLE and used a directed acyclic graph-based analysis strategy. Details of GC therapy, aPLs status, other drug administration and other SLE-related characteristics were collected. ONFH occurrence during follow-up was determined by magnetic resonance imaging. Multivariable logistic regression and generalized estimating equation models were performed to assess their effects on ONFH, and a simplified scoring system comprising these factors for short- and medium-term SLE-ONFH prediction was developed by receiver operating characteristic curve analysis. Results: Of 449 SLE patients with a median follow-up duration of 5.3 years, 41 (9.1%) developed ONFH. Independently risk factors of SLE-ONFH including: average daily GC dose with an adjusted odds ratio (aOR) of 1.1 and 95% confidence interval (CI) of 1.0–1.1; GC therapy duration (3–5 years: aOR 3.3, 95% CI 1.4–7.8; >5 years: aOR 8.0, 95% CI 3.3–19.4); initial intravenous GC (aOR 4.4, 95% CI 1.9–10.1); positive aPLs (aOR 2.8, 95% CI 1.4–5.8); and Arterial hypertension secondary to GC usage (aOR 5.2, 95% CI 1.4–19.1). And we successfully developed the simplified scoring system (SCORE model) with an area under the curve of 0.88 (95% CI 0.82–0.94). Conclusion: Based on the risk factors involved in the development of SLE-ONFH, a novel SCORE model was developed, which might be helpful for risk stratification of SLE-ONFH in clinical practice.

Objectives: A phase III, 24-weeks Chinese clinical trial demonstrated that efficacy and safety outcomes of treatments with 40 mg/0.8 ml HS016 (n = 416) or adalimumab (n = 232) for active ankylosing spondylitis (AS) patients was comparable. In the present study, a subanalysis of the clinical trial was conducted to determine whether also individual efficacy indicators were comparable between HS016 and adalimumab.Methods: The individual efficacy indicators total and nocturnal back pain, global assessment of disease activity, swollen joint count, Maastricht AS Enthesitis Score, Bath AS Disease Activity Index, Bath AS Functional Index, Bath AS Metrology Index and chest expansion, were assessed at baseline and every 2 weeks during the treatment period.Results: This subanalysis revealed no significant difference between the patient groups treated with HS016 or adalimumab for any individual efficacy indicator investigated at any time point (all p > 0.05) beside faster total back pain score improvements in the adalimumab group on week 10, 12 and 22, which became equal at week 24. Among these indicators, chest expansion showed a significant increase at each time point compared with baseline, whereas all other efficacy indicators showed significant decreases compared with baseline at each time point (all p < 0.05). All efficacy indicators had increased or decreased rapidly by week 2, and the values continued to increase/decrease up to week 12, with subsequent smaller changes thereafter up to week 24 of treatment.Conclusion: The response trajectory of most individual efficacy indicators was comparable between HS016 and adalimumab at each time point during the 24 weeks of the trial.Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=37910, identifier [ChiCTR1900022520]

Objective Our objective was to explore the molecular pathogenesis of the onset of gout and the mechanism underlying the effect of interleukin (IL)-37 on PDZ domain-containing 1 (PDZK1) protein through the nuclear factor-κB signaling pathway. Methods Real-time PCR and western blotting were used to detect expression of PDZK1 mRNA and protein, respectively, in the HK-2 cell line. The inhibitors pyrrolidine dithiocarbamate (PDTC) and wortmannin were added to HK-2 cells stimulated by IL-37, and changes in PDZK1 protein were detected by western blotting. Results Based on our previous research, we used 10 µmol/L PDTC. We detected no significant change in PDZK1 at the mRNA level among the IL-37, PDTC+IL-37, and wortmannin+IL-37 groups. With increasing IL-37 concentration, the protein level of PDZK1 increased. After adding wortmannin, the protein level of PDZK1 increased with increasing concentration of IL-37, albeit not significantly, and the level of PDZK1 remained lower than that with IL-37 alone. After adding PDTC, the protein level of PDZK1 showed a trend to decrease with increasing concentrations of IL-37 up to 40 ng/mL. The immunofluorescence results supported the western blot results. Conclusions IL-37 can affect protein expression of PDZK1, but not at the translational level, in the pathogenesis of gout.

The popularization of smart phones and the large-scale application of location-based services (e.g., exercises, traveling and food delivery via cycling) have resulted in the emergence of massive amounts of personalized cycling trajectory data, spurring the demand for map navigation based on cycling trajectories. Therefore, in the current paper, we propose a cycling trajectory-based navigation algorithm without the need for road network data support. The proposed algorithm focuses on extracting navigation information from a given trajectory and then guiding others to the destination along the original trajectory. In particular, the algorithm analyzes the coordinate and azimuth angle data collected by the built-in positioning and direction sensors of mobile smart phones to identify several turning modes from the provider’s cycling trajectory. In addition, the interference of the traffic conditions during data collection is considered in order to improve the recognition accuracy of the turning modes. The turning modes in the trajectory are subsequently transformed into navigation information and shared with users, so as to realize the shared navigation of the cycling trajectory. Experimental results indicate that the algorithm can accurately extract the turning feature points from cycling trajectory data, recognize various turning modes and generate correct navigation messages, thereby guiding users to arrive at the destination safely and accurately along the original trajectory. The algorithm is independent of electronic map platforms and does not require road network data support.

Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009). In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A) decreased the risk of gout (OR = 0.77, P = 0.015), whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020). The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.

This study aims to investigate the prevalence of short-term and long-term adverse events associated with tumor necrosis factor-α (TNF-α) blocker treatment in Chinese Han patients suffering from ankylosing spondylitis (AS).The study included 402 Chinese Han AS patients treated with TNF-α blockers. Baseline data was collected. All patients were monitored for adverse events 2 hours following administration. Long-term treatment was evaluated at 8, 12, 52 and 104 weeks follow-up for 172 patients treated with TNF-α blockers.Short-term adverse events occurred in 20.15% (81/402), including rash (3.5%; 14/402), pruritus (1.2%; 5/402), nausea (2.2%; 9/402), headache (0.7%; 3/402), skin allergies (4.0%; 16/402), fever (0.5%; 2/402), palpitations (3.0%; 12/402), dyspnea (0.5%; 2/402), chest pain (0.2%; 1/402), [corrected] abdominal pain (1.0%; 4/402), hypertension (2.2%; 9/402), papilledema (0.5%; 2/402), laryngeal edema (0.2%; 1/402) and premature ventricular contraction (0.2%; 1/402). Long-term adverse events occurred in 59 (34.3%; 59/172) patients, including pneumonia (7.6%; 13/172), urinary tract infections (9.9%; 17/172), otitis media (4.7%; 8/172), tuberculosis are (3.5%; 6/172) [corrected], abscess (1.2%; 2/172), oral candidiasis (0.6%; 1/172), elevation of transaminase (1.7%; 3/172), anemia (1.2%; 2/172), hematuresis (0.6%; 1/172), constipation (2.3%; 4/172), weight loss (0.6%; 1/172), exfoliative dermatitis (0.6%; 1/172). CRP, ESR and disease duration were found to be associated with an increased risk of immediate and long-term adverse events (P

BACKGROUND: Recently, there have been a number of studies on the association between XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL) risk. However, the results of previous reports are inconsistent. Thus, we performed a meta-analysis to clarify the effects of XRCC1 variants on childhood ALL risk. METHODS: A meta-analysis was performed to examine the association between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and childhood ALL risk. We critically reviewed 7 studies with a total of 880 cases and 1311 controls for Arg399Gln polymorphism, 3 studies with a total of 345 cases and 554 controls for Arg280His polymorphism, and 6 studies with a total of 783 cases and 1180 controls for Arg194Trp polymorphism, respectively. Odds ratio (OR) and its 95% confidence interval (CI) were used. RESULTS: Significant association between XRCC1 Arg399Gln polymorphism and childhood ALL risk was observed in total population analyses (OR(additive model) = 1.501, 95% CI 1.112-2.026, P(OR) = 0.008; OR(dominant model) = 1.316, 95% CI = 1.104-1.569, P(OR) = 0.002) and Asian subgroup analyses (OR(additive model) = 2.338, 95%CI = 1.254-4.359, P(OR) = 0.008; OR(dominant model) = 2.108, 95%CI = 1.498-2.967, P(OR) = 0.000). No association was detected in Caucasians, Metizo and mixed populations. Ethnicity was considered as a significant source of heterogeneity in the meta-regression model. For the other two XRCC1 polymorphisms, no association with childhood ALL risk was found. CONCLUSIONS: The meta-analysis results suggested that XRCC1 Arg399Gln polymorphism might be associated with elevated childhood ALL risk among Asian population.

Topography plays a critical role in soil migration and redistribution, but few studies have been conducted to quantify its effects on sediment deposition. In this study, we established a physical simulation and analysis framework to investigate the erosional and depositional impacts of two-dimensional slope terrain, specifically applied to Xiannangou small watershed in the loess hilly region. The results showed that the slope gradient, slope length, and slope shape have significantly influence the distribution of soil erosion and deposition. The magnitude of the erosion/deposition rate (Yr) determines the relative intensity of slope erosion and deposition, where Yr < 0 indicates erosion and Yr > 0 signifies deposition. The erosion rate on straight slope exhibited a positive correlation with slope length, while the erosion/deposition rate on concave and convex slopes exhibited fluctuations with slope length. Soil erosion predominantly occurred along the main flow line and the middle slope, aligning with the observed distribution of gully and slope erosion in the field. The sediment deposition was primarily concentrated on the lower slope or the lowest outlet of the basin, notably in gullies and gentle slopes where the terrain slows, especially during transition from steep to gradual slopes. These results can effectively predict the relative erosion/sedimentation rate of two-dimensional slopes, significantly contributing to a comprehensive understanding of how topography influences soil erosion and deposition. This study thoroughly considers the role of sediment deposition in the soil erosion process, providing a more accurate reflection of soil erosion/deposition in small watersheds. It addresses the existing deficiency in sediment consideration within soil erosion evaluation and supports the enhancement of soil erosion model. [ABSTRACT FROM AUTHOR]