Immunomodulatory roles of metalloproteinases in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, autoimmune pathology characterized by persistent synovial inflammation and gradually advancing bone destruction. Matrix metalloproteinases (MMPs), as a family of zinc-containing enzymes, have been found to play an important role in degradation and remodeling of extracellular matrix (ECM). MMPs participate in processes of cell proliferation, migration, inflammation, and cell metabolism. A growing number of persons have paid attention to their function in inflammatory and immune diseases. In this review, the details of regulation of MMPs expression and its expression in RA are summarized. The role of MMPs in ECM remodeling, angiogenesis, oxidative and nitrosative stress, cell migration and invasion, cytokine and chemokine production, PANoptosis and bone destruction in RA disease are discussed. Additionally, the review summarizes clinical trials targeting MMPs in inflammatory disease and discusses the potential of MMP inhibition in the therapeutic context of RA. MMPs may serve as biomarkers for drug response, pathology stratification, and precision medicine to improve clinical management of rheumatoid arthritis

Microbiome-derived bile acids contribute to elevated antigenic response and bone erosion in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, disabling and incurable autoimmune disease. It has been widely recognized that gut microbial dysbiosis is an important contributor to the pathogenesis of RA, although distinct alterations in microbiota have been associated with this disease. Yet, the metabolites that mediate the impacts of the gut microbiome on RA are less well understood. Here, with microbial profiling and non-targeted metabolomics, we revealed profound yet diverse perturbation of the gut microbiome and metabolome in RA patients in a discovery set. In the Bacteroides-dominated RA patients, differentiation of gut microbiome resulted in distinct bile acid profiles compared to healthy subjects. Predominated Bacteroides species expressing BSH and 7a-HSDH increased, leading to elevated secondary bile acid production in this subgroup of RA patients. Reduced serum fibroblast growth factor-19 and dysregulated bile acids were evidence of impaired farnesoid X receptor-mediated signaling in the patients. This gut microbiota-bile acid axis was correlated to ACPA. The patients from the validation sets demonstrated that ACPA-positive patients have more abundant bacteria expressing BSH and 7a-HSDH but less Clostridium scindens expressing 7a-dehydroxylation enzymes, together with dysregulated microbial bile acid metabolism and more severe bone erosion than ACPA-negative ones. Mediation analyses revealed putative causal relationships between the gut microbiome, bile acids, and ACPA-positive RA, supporting a potential causal effect of Bacteroides species in increasing levels of ACPA and bone erosion mediated via disturbing bile acid metabolism. These results provide insights into the role of gut dysbiosis in RA in a manifestation-specific manner, as well as the functions of bile acids in this gut-joint axis, which may be a potential intervention target for precisely controlling RA conditions.Comment: 38 pages, 6 figure

Detection of microRNA Expression in Human Peripheral Blood Microvesicles

MicroRNAs (miRNA) are small non-coding RNAs that regulate translation of mRNA and protein. Loss or enhanced expression of miRNAs is associated with several diseases, including cancer. However, the identification of circulating miRNA in healthy donors is not well characterized. Microvesicles, also known as exosomes or microparticles, circulate in the peripheral blood and can stimulate cellular signaling. In this study, we hypothesized that under normal healthy conditions, microvesicles contain miRNAs, contributing to biological homeostasis.Microvesicles were isolated from the plasma of normal healthy individuals. RNA was isolated from both the microvesicles and matched mononuclear cells and profiled for 420 known mature miRNAs by real-time PCR. Hierarchical clustering of the data sets indicated significant differences in miRNA expression between peripheral blood mononuclear cells (PBMC) and plasma microvesicles. We observed 71 miRNAs co-expressed between microvesicles and PBMC. Notably, we found 33 and 4 significantly differentially expressed miRNAs in the plasma microvesicles and mononuclear cells, respectively. Prediction of the gene targets and associated biological pathways regulated by the detected miRNAs was performed. The majority of the miRNAs expressed in the microvesicles from the blood were predicted to regulate cellular differentiation of blood cells and metabolic pathways. Interestingly, a select few miRNAs were also predicted to be important modulators of immune function.This study is the first to identify and define miRNA expression in circulating plasma microvesicles of normal subjects. The data generated from this study provides a basis for future studies to determine the predictive role of peripheral blood miRNA signatures in human disease and will enable the definition of the biological processes regulated by these miRNA

Optimal Coordinated Strategy Analysis for the Procurement Logistics of a Steel Group

This paper focuses on the optimization of an internal coordinated procurement logistics system in a steel group and the decision on the coordinated procurement strategy by minimizing the logistics costs. Considering the coordinated procurement strategy and the procurement logistics costs, the aim of the optimization model was to maximize the degree of quality satisfaction and to minimize the procurement logistics costs. The model was transformed into a single-objective model and solved using a simulated annealing algorithm. In the algorithm, the supplier of each subsidiary was selected according to the evaluation result for independent procurement. Finally, the effect of different parameters on the coordinated procurement strategy was analysed. The results showed that the coordinated strategy can clearly save procurement costs; that the strategy appears to be more cooperative when the quality requirement is not stricter; and that the coordinated costs have a strong effect on the coordinated procurement strategy

The incidence and risk factors for femoral head necrosis after femoral neck fracture in pediatric patients: a systematic review and meta-analysis

Abstract Background The incidence of avascular necrosis (AVN) after pediatric femoral neck fracture (PFNF) in the literature varies widely, and the risk factors associated with AVN after PFNF are controversial. Therefore, this study aimed to accurately investigate the incidence of AVN after PFNF and systematically evaluate and meta-classify their risk factors. Methods A comprehensive search was performed of PubMed, Web of Science, and Embase. The pooled rate and 95% confidence interval (CI) were used to assess the incidence of AVN after PFNF, and pooled odds ratio (OR) were calculated to measure the effect sizes. In addition, we performed subgroup, stratified, and publication bias analyses. Results A total of 30 articles were included in our meta-analysis, with 303 AVN cases among 1185 patients. The pooled incidence of AVN after PFNF was 22% (95% CI 18%, 27%). Subgroup analyses indicated Delbet type I–IV fracture incidences with AVN of 45%, 32%, 17%, and 12%, respectively. The incidence of AVN after PFNF in Asia was 19%, lower than in Africa at 36%, Europe at 26%, and North America at 23%. In addition, the larger sample size group and the earlier published literature group showed a higher incidence of necrosis. Stratified analyses showed that patient age and Delbet fracture classification were both important factors affecting AVN after PFNF (OR = 1.61, p = 0.02 and OR = 3.02, p < 0.001, respectively), while the time to treatment was not (OR = 0.9, p = 0.71). Conclusion The pooled incidence of AVN after PFNF was ~ 22%; furthermore, the available evidence demonstrates that patient age and Delbet type of fracture were important influencing factors of AVN after PFNF

Evaluation on the effectiveness of natural fractures in Changxing Fm reef-flat facies reservoirs, Yuanba area, Sichuan Basin

Study on the effectiveness of fractures is of great significance for understanding reservoir types and properties, identifying reservoir seepage mechanisms and delineating the reasonable development technologies and policies. In this paper, the Changxing reef-flat facies reservoirs in the Yuanba area, Sichuan Basin, was taken as an example. After the characteristics of natural fractures were evaluated, the effectiveness of different types of fractures was investigated by using core, thin section, imaging logging and production performance data. Then, the main geological factors that influence fracture effectiveness were analyzed, and the development significance of effective fractures was illustrated. The following results are obtained. (1) Structural fractures and diagenetic fractures are mainly developed in Changxing Fm carbonate reservoirs in Yuanba area. Structural fractures include shear fractures and extensional fractures, and diagenetic fractures include dissolution fractures, structural-dissolution fractures and pressure-solution fractures. (2) High-angle structural fractures are the most effective, followed by horizontal fractures and then oblique fractures, and pressure-solution fractures are the least effective. (3) Among structural fractures, those of NW–SE and nearly E–W oriented are more effective than those of the NE–SW oriented. (4) The earlier the fractures are formed, the more likely they are to be filled with calcite or dolomite and become invalid. (5) The fractures which are formed before or during the oil and gas charging tend to be filled with organic matters and become invalid. The late fractures which are formed after oil and gas charging are mostly effective and their contribution to the reservoir is the greatest. (6) The fractures nearly parallel to the maximum principal stress direction of current ground stress present good effectiveness with large opening. It is concluded that the opening and filling features of natural fractures help determine if fractures are effective or not, and the development degree, distribution and combination features of effective fractures and the matching relationship between fractures and pores further dominate the development significance of effective fractures; that when the effective fractures are more developed and are connected with each other to form a large-scale fracture network, separated and isolated pores and dissolved fractures and cavities can be connected, as a result, the physical properties of reservoirs are improved and high production rates of gas wells are realized

Early Spatiotemporal Patterns and Knee Kinematics during Level Walking in Individuals following Total Knee Arthroplasty

Purpose. With the aim of investigating the spatiotemporal features of early gait pattern and knee kinematics after total knee arthroplasty and analyzing the association between outcomes of gait analyses and knee kinematic parameters, the relationship between walking and dynamic knee deformity at the early period after total knee arthroplasty was assessed in this study. Methods. Eighteen patients including 14 women and 4 men who underwent total knee arthroplasty were analyzed using three-dimensional gait analysis system to observe gait parameters and values of maximum knee flexion angle (MKFA) during swing phase and knee flexion angle (KFA) and knee valgus angle (KVA) at midstance phase. Results. 3D gait analysis showed that operated side exhibited significantly less total support time and single support time as well as significantly longer swing phase compared with the other side. During walking, the operated side had significantly smaller MKFA and greater KFA and KVA than the nonoperated side. There was moderate to significant correlation between gait pattern and the dynamic knee kinematics. Conclusion. The gait abnormality of patients after TKA was associated with inadequate flexion of knees at swing phase and insufficient extension at stance phase as well as increased range of valgus

Opposing and Operated Side Electroacupuncture Generates Similar Analgesic Effects on Pain after Knee Surgery

The purpose of this study was to investigate whether opposing electroacupuncture (EA) could produce similar analgesic effects as operated side EA after knee surgery in rats. Sprague Dawley rats were randomly divided into the sham surgery group, and three surgery groups: opposing EA, operated side EA, and model. After surgery, compared with the sham surgery group, three kinds of pain behavior test methods (mechanical withdrawal threshold (MWT), cumulative pain score [CPS], and mechanical hypersensitivity of knee) were used to assess the pain behavior of the rats in the surgery groups. After knee surgery, the three surgery groups were intervened for three consecutive days: EA on the nonoperated side in the opposing EA group, EA on the operated side in the operated side EA group, and no intervention in the model group. It was shown that MWT was higher and CPS was lower in the two EA groups than in the model group on the first and second days after surgery. On the third day after surgery, MWT in the two EA groups was the highest among the 3 days, CPS was the lowest among the 3 days, and the number of nonvocalizations in rats also increased compared with the model group. Moreover, the MWT of the nonoperated side increased more in the opposing EA group than in the model and operated side EA groups. This indicated that both opposing EA and operated side EA methods can be used to relieve pain after knee joint surgery