Background: Recently, the association between inflammatory bowel disease (including ulcerative colitis and Crohn’s disease) and BMD has attracted great interest in the research community. However, the results of the published epidemiological observational studies on the relationship between inflammatory bowel disease and BMD are still inconclusive. Here, we performed a two-sample Mendelian randomization analysis to investigate the causal link between inflammatory bowel disease and level of BMD using publically available GWAS summary statistics.Methods: A series of quality control steps were taken in our analysis to select eligible instrumental SNPs which were strongly associated with exposure. To make the conclusions more robust and reliable, we utilized several robust analytical methods (inverse-variance weighting, MR-PRESSO method, mode-based estimate method, weighted median, MR-Egger regression, and MR.RAPS method) that are based on different assumptions of two-sample MR analysis. The MR-Egger intercept test, Cochran’sQtest, and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on BMD. Outlier variants identified by the MR-PRESSO outlier test were removed step-by-step to reduce heterogeneity and the effect of horizontal pleiotropy.Results: Our two-sample Mendelian randomization analysis with two groups of exposure GWAS summary statistics and four groups of outcome GWAS summary statistics suggested a definitively causal effect of genetically predicted ulcerative colitis on TB-BMD and FA-BMD but not on FN-BMD or LS-BMD (after Bonferroni correction), and we merely determined a causal effect of Crohn’s disease on FN-BMD but not on the others, which was somewhat inconsistent with many published observational researches. The causal effect of inflammatory bowel disease on TB-BMD was significant and robust but not on FA-BMD, FN-BMD, and LS-BMD, which might result from the cumulative effect of ulcerative colitis and Crohn’s disease on BMDs.Conclusions: Our Mendelian randomization analysis supported the causal effect of ulcerative colitis on TB-BMD and FA-BMD. As to Crohn’s disease, only the definitively causal effect of it on decreased FN-BMD was observed. Updated MR analysis is warranted to confirm our findings when a more advanced method to get less biased estimates and better precision or GWAS summary data with more ulcerative colitis and Crohn’s disease patients was available.

An increasing number of studies have demonstrated that long non-coding RNAs (lncRNAs) play pivotal roles in cancer onset and development. LncRNA AFAP1-AS1 has been validated to be abnormally upregulated and play oncogenic roles in various malignant tumors. The biological role and mechanism of AFAP1-AS1 in OS (osteosarcoma) remains unclear. Quantitative reverse transcription PCR (qRT-PCR) is applied to examine AFAP1-AS1 expression in OS tissues and OS cell lines. The function of AFAP1-AS1 in OS cells is investigated via in-vitro and in-vivo assays. Western bolt and rescue experiments are applied to detect the expression changes of key molecules including epithelial-mesenchymal transition markers and identify the underlying molecular mechanism. RNA immunoprecipitation is performed to reveal the interaction between AFAP1-AS1 and RhoC. AFAP1-AS1 expression is upregulated in human OS tissues and cell lines. AFAP1-AS1 knockdown induces OS cell apoptosis and cell cycle G0/G1 arrest, suppresses OS cells growth, migration, invasion, vasculogenic mimicry formation and epithelial-mesenchymal transition (EMT), and affects actin filament integrity. AFAP1-AS1 knockdown suppresses OS tumor formation and growth in nude mice. AFAP1-AS1 knockdown elicits a signaling inhibition including decreased levels of RhoC, ROCK1, p38MAPK and Twist1. Moreover, AFAP1-AS1 interacts with RhoC. Overexpression of RhoC can partly reverse AFAP1-AS1 downregulation-induced cell EMT inhibition. AFAP1-AS1 is overexpressed in osteosarcoma and plays an oncogenic role in osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway, in which RhoC acts as the interaction target of AFAP1-AS1. Our findings indicated a novel molecular mechanism underlying the tumorigenesis and progression of osteosarcoma. AFAP1-AS1 could serve as a promising therapeutic target in OS treatment.

Poly(N-isopropylacrylamide) (PNIPAM) based electrically conductive hydrogels (PNIPAM-ECHs) have been extensively studied in recent decades due to their thermal-responsive (leading to the volume change of hydrogels) and electrically conductive performance. The incorporation of conductive components into the PNIPAM hydrogel network makes it become conductive hydrogel, and as a result, the PNIPAM hydrogel could become sensitive to an electrical signal, greatly expanding its application. In addition, conductive components usually bring new stimuli-responsive properties of PNIPAM-based hydrogels, such as near-infrared light and stress/strain responsive properties. PNIPAM-ECHs display a wide range of applications in human motion detection, actuators, controlled drug release, wound dressings, etc. To summarize recent research advances and achievements related to PNIPAM-ECHs, this manuscript first reviews the design and structure of representative PNIPAM-ECHs according to their conductive components. Then, the applications of PNIPAM-ECHs have been classified and discussed. Finally, the remaining problems related to PNIPAM-ECHs have been summarized and a future research direction is proposed which is to fabricate PNIPAM-ECHs with integrated multifunctionality.

Some epidemiological studies and animal studies have reported a relationship between leukocyte telomere length (LTL) and bone mineral density (BMD). However, the causality underlying the purported relationship has not been determined. Here we performed a two-sample MR analysis to test the causal link between telomere length and BMD. Our research suggested no causal link of LTL and BMD using IVW method. The weighted median, MR-Egger regression and MR.RAPS method yielded a similar pattern of effects. MR-Egger intercept test demonstrated our results were not influenced by pleiotropy. Heterogeneities among the genetic variants on heel estimated BMD and TB-BMD vanished after excluding rs6028466. "Leave-one-out" sensitivity analysis confirmed the stability of our results. Our MR analysis did not support causal effect of telomere length on BMD. We utilized 5 independent SNPs robustly associated with LTL as instrument variables. The outcome results were obtained from GWAS summary data of BMD. The two-sample MR analysis was conducted using IVW, weighted median, MR-Egger regression and MR.RAPS method. MR-Egger intercept test, Cochran's Q test and I2 statistics and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities and stability of these genetic variants on BMD.

Meniscal injury is a prevalent orthopedic practice that causes articular cartilage wear and degeneration due to tissue damage or loss, and may eventually result in the occurrence of knee osteoarthritis (KOA). Hence, investigating the structural regeneration and mechanical function restoration of the meniscus after injury is pivotal research topic for preventing KOA. Animal models are essential for investigating therapeutic strategies for meniscal injuries and their clinical translation, yet no current model can fully recapitulate the complexity of human meniscal injuries. This review aims to categorize the prevalent animal models of meniscal injury by their establishment methods, elucidate their principles and procedures, and discuss the suitability and limitations of each model. We delineate the pros and cons of different models in simulating the pathology and biomechanics of human meniscal injury. We also analyze different animal species regarding their meniscal structure, function, and repair potential, and their implications for model selection. We conclude that selecting an appropriate animal model requires a comprehensive consideration of various factors, such as research aims, anticipated outcomes, and feasibility. Furthermore, to translate novel therapeutic approaches to clinical applications more safely and effectively, future model development should emphasize aspects such as choosing animals of suitable age.

Purpose: There have been many attempts to preoperatively evaluate the chemotherapy response of osteosarcoma patients using ^99mTc-MIBI scintigraphy. However, the evaluations were lacking in consistency. We performed this systematic review and meta-analysis to systematically evaluate the ability of ^99mTc-MIBI scintigraphy in preoperatively assessing the response of osteosarcoma patients to neoadjuvant chemotherapy. Methods: For this systematic review and meta-analysis, PubMed, Web of Science, OVID, the Cochrane Library, and CNKI were searched. Eligible studies were included based on the defined criteria. The index test was ^99mTc-MIBI scintigraphy, the reference standard was tumor necrosis rate. Quality Assessment of Diagnostic Accuracy Studies-2 was adopted for quality assessment of included studies. The statistical pooling analysis, meta-regression analysis, subgroup analysis, sensitivity analysis, and publication bias of our research were performed using STATA 15. Results: Eight articles with 189 osteosarcoma patients were included in this systematic review and meta-analysis. Our results demonstrated that the threshold effect of our meta-analysis was significant. The uptake change ratio of ^99mTc-MIBI scintigraphy had a pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and the area under curve of 0.98 (0.58–1.00), 0.68 (0.47–0.84), 3.1 (1.7–5.5), 0.03 (0.00–0.90), 103 (4–3,003), and 0.91 (0.88–0.93) in preoperative assessment of response of osteosarcoma patients to neoadjuvant chemotherapy. Meta-regression analysis and subgroup analysis indicated the factors of method and cut off value may introduce the heterogeneity. The pooled sensitivity, specificity, positive and negative likelihood ratio, diagnostic odds ratio, and the area under curve of washout rate of ^99mTc-MIBI were 0.87 (0.69–0.95), 0.91 (0.75–0.97), 9.3 (3.2–27.0), 0.15 (0.06–0.37), 64 (14–301), and 0.89 (0.86–0.92), respectively. Sensitivity analysis and publication bias demonstrated our meta-analysis was reliable. Conclusion: Both the ΔUR and WR derived from ^99mTc-MIBI scintigraphy were valuable in preoperatively assessing the response of osteosarcoma patients to neoadjuvant chemotherapy, and ΔUR may possess a more outstanding diagnostic accuracy than WR.