PSME2 offers value as a biomarker of M1 macrophage infiltration in pan-cancer and inhibits osteosarcoma malignant phenotypes.

A growing number of studies have revealed an association between proteasome activator complex subunit 2 (PSME2) and the progression of various forms of cancer. However, the effect of PSME2 on osteosarcoma progression is unknown. Pan-cancer analyses focused on the immunological activity and prognostic relevance of PSME2 have yet to be conducted. The Cancer Genome Atlas and Genome-Tissue Expression databases were leveraged to evaluate PSME2 expression and activity across 33 cancer types. Significant PSME2 dysregulation was noted in a wide range of cancer types and this gene was found to offer significant diagnostic and prognostic utility in most analyzed cancers. From a mechanistic perspective, PSME2 expression levels were correlated with DNA methylation, DNA repair, genomic instability, and TME scores in multiple cancer types. PSME2 was subsequently established as a pan-cancer biomarker of M1 macrophage infiltration based on a combination of bulk, single-cell, and spatial transcriptomic data and confirmatory fluorescent staining results. In osteosarcoma cells, overexpressing PSME2 significantly suppressed tumor proliferative, migratory, and invasive activity. Screening efforts also successfully identified the PSME2-activating drug irinotecan, which can synergistically promote the death of osteosarcoma cells when combined with the chemotherapeutic drug paclitaxel. As a biomarker of M1 macrophage infiltration, PSME2 expression levels may offer insight into tumor development and progression for a wide range of cancers including osteosarcoma, emphasizing its potential utility as a prognostic and therapeutic target worthy of further study.

The prevalence of hip osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: To estimate the global prevalence of hip osteoarthritis (HOA) through a systematic review and meta-analysis, and to determine by regression analysis the respective relationships between age and sex, and sex and prevalence. METHODS: EMBASE, PubMed, Web of science, CINAHL, and SCOPUS were searched from inception until August 2022. Two authors independently extracted data and assessed the quality of the retrieved literature. Random-effects meta-analysis was performed to derive the pooled prevalence. Variations in the prevalence estimate in different subgroups, including diagnostic methods, region, and patient sex, were examined by subgroup meta-analysis. Meta-regression was used to construct the age-specific prevalence of HOA. RESULTS: A total of 31 studies were included in our analysis, involving 326,463 participants. Quality evaluation showed that all studies included in the analysis had a Quality Score of at least 4. The most frequently used method for diagnosing HOA was the Kellgren-Lawrence (K-L) grade classification, accounting for 19/31 (61.3%) studies. The pooled prevalence of HOA diagnosed based on the K-L grade ≥ 2 criterion was 8.55% (95% CI 4.85-13.18) worldwide. The prevalence of HOA was lowest in Africa at 1.20% (95% CI: 0.40-2.38), followed by Asia at 4.26% (95% CI 0.02-14.93) and North America at 7.95% (95% CI 1.98-17.36), and highest in Europe at 12.59% (95% CI 7.17-19.25). There was no statistically significant difference in HOA prevalence between men (9.42%, 95% CI:4.81-15.34) and women at (7.94%, 95% CI: 3.57-13.81). The regression model showed a correlation between age and the prevalence of HOA. CONCLUSION: HOA has high prevalence worldwide and increases with age. The prevalence varies significantly by region but not by patient sex. High-quality epidemiological studies are warranted to more accurately estimate the prevalence of HOA.

Failure modes after anterior cruciate ligament reconstruction: a systematic review and meta-analysis.

PURPOSE: The reason for graft failure after anterior cruciate ligament reconstruction (ACLR) is multifactorial. Controversies remain regarding the predominant factor and incidence of failure aetiology in the literature. This review aimed to provide a meta-analysis of the literature to evaluate the relative proportion of various failure modes among patients with ACLR failure. METHODS: The PubMed, Embase, Cochrane Library, Web of Science, and EBSCO databases were searched for literature on ACLR failure or revision from 1975 to 2021. Data related to causes for ACLR surgical failure were extracted, and a random effects model was used to pool the results, which incorporates potential heterogeneity. Failure modes were compared between different populations, research methods, graft types, femoral portal techniques, and fixation methods by subgroup analysis or linear regression. Funnel plots were used to identify publication bias and small-study effects. RESULTS: A total of 39 studies were analyzed, including 33 cohort studies and six registry-based studies reporting 6578 failures. The results showed that among patients with ACLR failure or revision, traumatic reinjury was the most common failure mode with a rate of 40% (95% CI: 35-44%), followed by technical error (34%, 95% CI: 28-42%) and biological failure (11%, 95% CI: 7-15%). Femoral tunnel malposition was the most common cause of the technical error (29%, 95% CI: 18-41%), with more than two times higher occurrence than tibial tunnel malposition (11%, 95% CI: 6-16%). Traumatic reinjury was the most common factor for ACLR failure in European populations and in recent studies, while technical errors were more common in Asian populations, earlier studies, and surgery performed using the transtibial (TT) portal technique. Biological factors were more likely to result in ACLR failure in hamstring (HT) autografts compared to bone-patellar tendon-bone (BPTB) autografts. CONCLUSION: Trauma is the most important factor leading to surgical failure or revision following ACLR. Technical error is also an important contributing factor, with femoral tunnel malposition being the leading cause of error resulting in failure.

Cost Effectiveness of Pharmacological Management for Osteoarthritis: A Systematic Review.

BACKGROUND AND OBJECTIVE: Osteoarthritis (OA) is a highly prevalent, disabling disease requiring chronic management that is associated with an enormous individual and societal burden. This systematic review provides a global cost-effectiveness evaluation of pharmacological therapy for the management of OA. METHODS: Following Center for Reviews and Dissemination (CRD) guidance, a literature search strategy was undertaken using PubMed, EMBASE, Cochrane Library, Health Technology Assessment (HTA) database, and National Health Service Economic Evaluation database (NHS EED) to identify original articles containing cost-effectiveness evaluation of OA pharmacological treatment published before 4 November 2021. Risk of bias was assessed by two independent reviewers using the Joanna Briggs Institute (JBI) critical appraisal checklist for economic evaluations. The Quality of Health Economic Studies (QHES) instrument was used to assess the reporting quality of included articles. RESULTS: Database searches identified 43 cost-effectiveness analysis studies (CEAs) on pharmacological management of OA that were conducted in 18 countries and four continents, with one study containing multiple continents. A total of four classes of drugs were assessed, including non-steroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), and intra-articular (IA) injections. The methodological approaches of these studies showed substantial heterogeneity. The incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) were (in 2021 US dollars) US$44.40 to US$307,013.56 for NSAIDS, US$11,984.84 to US$128,028.74 for opioids, US$10,930.17 to US$27,799.73 for SYSADOAs, and US$258.36 to US$58,447.97 for IA injections in different continents. The key drivers of cost effectiveness included medical resources, productivity, relative risks, and selected comparators. CONCLUSION: This review showed substantial heterogeneity among studies, ranging from a finding of dominance to very high ICERs, but most studies found interventions to be cost effective based on specific ICER thresholds. Important challenges in the analysis were related to the standardization and methodological quality of studies, as well as the presentation of results.

Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway.

BACKGROUND: Oxidative stress is a main cause of piglet gut damage and diarrhea. Pyrroloquinoline quinone (PQQ), is a novel redox cofactor with antioxidant properties. However, the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood. Therefore, the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line (IPEC-J2) challenged with H2O2. RESULTS: Experiment 1, 144 Duroc × Landrace × Yorkshire pigs (weaned at 28 d) were allocated to four groups: received a basal diet (control) and diets supplemented with 0.15%, 0.30% and 0.45% PQQ, respectively. On d 28, growth performance, diarrhea incidence and redox factors were measured. Experiment 2, IPEC-J2 were treated with or without PQQ in the presence or absence of H2O2 for indicated time points. Experiment 3, IPEC-J2 were transfected with or without Nrf2 siRNA, then treated according to Experiment 2. The cell viability, redox factors, protein of tight junctions and Nrf2 pathway were determined. In vivo, PQQ supplementation demonstrated dose-related improvements in average daily gain, and gain to feed ratio (Linear P < 0.05). During d 0-28, compared to controls, 0.45% PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum, and increased concentration of SOD in liver; 0.3% PQQ supplementation decreased ileal and liver MDA concentration; and 0.15% PQQ supplementation decreased ileal MDA concentration (P < 0.05). In vitro, compared to cells cultured with H2O2, pre-treatment with PQQ increased cell viability, tight junction proteins expression including ZO-1, ZO-2, Occludin and Claudin-1; and decreased ROS concentration and level of Caspase-3 (P < 0.05); as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2, HO-1. Notably, Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H2O2-induced intracellular changes. CONCLUSIONS: PQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway.