Chiyuan Ma

Heterotopic ossification (HO) is a pathological process characterized by ectopic bone formation in non‐osseous tissues, with an incidence reaching 80% following surgical procedures. Current treatments exhibit limited efficacy, significant rebound effects, and substantial trauma, highlighting the need for safer and more effective therapeutic strategies. This study aimed to explore the therapeutic potential of apoptotic bodies derived from hard palate mesenchymal stromal/stem cells in regulating bone remodeling, and to elucidate the underlying mechanisms, focusing on Caveolin‐1 (CAV1). Transcriptomic analysis of clinical HO samples revealed activation of osteogenesis‐ and calcification‐related pathways. Mechanistically, PMSC‐ABs inhibited osteogenic differentiation while promoting osteoclastogenesis in vitro. Proteomic analysis identified CAV1 as a key functional mediator, which was further validated through functional assays. In a mouse model of HO, systemic administration of PMSC‐ABs reduced ectopic bone formation and suppressed disease progression. These results demonstrate that PMSC‐ABs deliver CAV1 to modulate bone homeostasis, thereby suppressing HO. Our findings suggest that PMSC‐ABs represent a promising, minimally invasive, and effective prophylactic and therapeutic intervention for pathological ossification and related skeletal disorders.

Background: Periprosthetic joint infection (PJI) remains a devastating complication of joint arthroplasty. Although intraoperative frozen section histology (> 5 neutrophils/HPF) is incorporated into the 2018 MSIS diagnostic criteria, its prognostic value for predicting postoperative PJI remains controversial. Methods: Primary or revision THA/TKA procedures in our hospital between January 1, 2015 and December 31, 2021 with intraoperative frozen section histologic results were eligible for inclusion. Association between intraoperative frozen section histology and postoperative PJI was investigated based on the medical records, and a similar analysis of C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was also performed. Results: A total of 14,969 knee/hip procedures were identified. After case selection, 797 cases comprising 529 (66.4%) primary and 268 (33.6%) revision were included. According to our data, frozen section positivity showed no PJI association, both in primary (OR, 1.206 [95% CI, 0.133–10.914], P > 0.999) and revision procedures (OR, 1.287 [95% CI, 0.331–5.007], p = 0.717). Conversely, elevated CRP (OR, 15.196 [95% CI, 1.916–120.523], p = 0.001) and ESR (OR, 5.794 [95% CI, 1.4979–22.4129], p = 0.008) predicted PJI exclusively in revisions. Conclusions: Therefore, isolated positive frozen section results should not be the sole basis for surgical strategy. Elevated CRP / ESR levels during revision surgery warrant heightened vigilance and consideration of extended anti‐infective treatment. Level of Evidence: III.

Arthroscopic treatments of hip synovial osteochondromatosis are mostly performed under traction, resulting in neurovascular injury or iatrogenic damage to the labrum or cartilage. This study aimed to assess the effectiveness of outside‐in hip arthroscopy without traction in treating hip synovial osteochondromatosis. This retrospective study was conducted on a series of patients with hip synovial osteochondromatosis treated using outside‐in hip arthroscopy without traction in our hospital between 2018 and 2020. Plain radiography and magnetic resonance imaging (MRI) scans were obtained. The Harris hip score (HHS), hip range of motion (ROM), and visual analog scale (VAS) scores were analyzed. The preoperative scores and last follow‐up scores were compared with a paired‐sample t test. The complications and recurrence postsurgery were recorded. This study included five patients (three male and two female) with an average age of 41 years (range 28–54 years). The mean follow‐up time was 25.2 months (range 18–36 months). All patients experienced groin pain relief and improved ROM. The mean VAS score was significantly lower postoperatively (0.4 ± 0.5) than preoperatively (3.2 ± 0.8) (p < 0.001). The mean HHS improved from 58.6 ± 12.7 (range 43–73) to 89.8 ± 5.26 (range 81–95) (p < 0.001). No major complications, including infection, perineal numbness and swelling, neurotrosis, thromboembolism, or severe persistent pain, were reported. Synovial osteochondromatosis recurred in one patient after 2 years of follow‐up without any obvious symptoms such as hip pain or joint locking. Therefore, no further treatment was necessary. This study showed that outside‐in hip arthroscopy without traction might be a viable option for treating hip synovial osteochondromatosis, effectively and safely relieving symptoms with minimal complications, especially in patients without lesions in the central compartment.

Introduction: TRIpartite motif (TRIM) proteins are important members of the Really Interesting New Gene‐finger‐containing E3 ubiquitin‐conjugating enzyme and are involved in the progression of hepatocellular carcinoma (HCC). However, the diverse expression patterns of TRIMs and their roles in prognosis and immune infiltrates in HCC have yet to be analyzed.Materials: Combined with previous research, we used an Oncomine database and the Human Protein Atlas to compare TRIM family genes' transcriptional levels between tumor samples and normal liver tissues, as verified by the Gene Expression Profiling Interactive Analysis database. We investigated the patient survival data of TRIMs from the Kaplan–Meier plotter database. Clinicopathologic characteristics associations and potential diagnostic and prognostic values were validated with clinical and expressional data collected from the cancer genome atlas.Results: We identified TRIM28, TRIM37, TRIM45, and TRIM59 as high‐priority members of the TRIMs family that modulates HCC. Low expression of TRIM28 was associated with shorter overall survival (OS) than high expression (log‐rank p = 0.009). The same trend was identified for TRIM37 (p = 0.001), TRIM45 (p = 0.013), and TRIM59 (p = 0.011). Multivariate analysis indicated that the level of TRIM37 was a significant independent prognostic factor for both OS (p = 0.043) and progression‐free interval (p = 0.044). We performed expression and mutation analysis and functional pathways and tumor immune infiltration analysis of the changes in TRIM factors.Conclusion: These data suggested that TRIM28, TRIM37, TRIM45, and TRIM59 could serve as efficient prognostic biomarkers and therapeutic targets in HCC.

Despite improvements reported in diagnosis and treatments in recent decades, pancreatic cancer is still characterized by poor prognosis and low survival rate among solid tumors. Intensive interests have grown in exploring novel predictive biomarkers, aiming to enhance the efficiency in early detection and treatment prognosis. In this study, we identified the differentially expressed genes (DEGs) in pancreatic cancer by analyzing five gene expression profiles and established the functional modules according to the functional interaction (FI) network between the DEGs. A significant upregulation of the selected DEG, interferon (IFN)-induced transmembrane protein 1 (IFITM1), was evaluated in several bioinformatics online tools and verified with immunohistochemistry staining from samples of 90 patients with pancreatic cancer. Prognostic data showed that high expression of IFITM1 associated with poor survival, and multivariate Cox regression analysis showed IFITM1 was one of the independent prognostic factors for overall survival. Meanwhile, significant correlations of the expression of IFITM1 and the infiltration of immune cells were found by TIMER. Furthermore, a higher level of IFITM1 was assessed in pancreatic cancer cell lines compared to normal human pancreatic duct epithelial cells, and silencing IFITM1 in tumor cells remarkedly inhibited cancer tumorigenicity. Collectively, our findings suggested that IFITM1 might have promising utility for pancreatic cancer.

Competitive endogenous RNAs (ceRNAs), as a newly identified regulating mechanism, have been demonstrated to play a crucial role in various human diseases. An increasing number of recent studies have revealed that circular RNAs (circRNAs) can function as ceRNAs. However, little is known about the role of circFAM160A2 in the pathological process of osteoarthritis (OA). This study is the first to examine the crucial role of the circFAM160A2‐miR‐505‐3p‐SIRT3 axis in osteoarthritis progression. miR‐505‐3p was selected from the interaction of a microRNA (miRNA) microarray comparing chondrocytes in OA and normal conditions and prediction results from TargetScan. RT‐qPCR was performed to assess the expression of circFAM160A2, miR‐505‐3p, and SIRT3. A dual luciferase assay was used to validate the binding of circFAM160A2, miR‐505‐3p, and SIRT3. We used lentivirus and adeno‐associated virus to establish in vitro and in vivo overexpression models. Western blotting, apoptosis assay, ROS detection assay, Safranin O staining, and CCK‐8 assay were employed to assess the role of circFAM160A2, miR‐505‐3p, and SIRT3. We found that miR‐505‐3p was upregulated and circFAM160A2 was downregulated in OA. While overexpression of circFAM160A2 decreased the production of extracellular matrix (ECM) degrading enzymes and ameliorated chondrocyte apoptosis and mitochondrial dysfunction, inhibition of miR‐505‐3p could reverse the protective effect of circFAM160A2 on the OA phenotype both in vitro and in vivo. In conclusion, circFAM160A2 can promote mitochondrial stabilization and apoptosis reduction in OA chondrocytes by targeting miR‐505‐3p and SIRT3, which might be a potential therapeutic target for OA therapy.

Tendinopathy is a disabling musculoskeletal disease, the pathological process of which is tightly associated with inflammation. Spironolactone (SP) has been widely used as a diuretic in clinical practice. Recently, SP has shown anti‐inflammatory features in several diseases. Tendon‐derived stem cells (TDSCs), a subset cell type from tendon tissue possessing clonogenic capacity, play a vital role in the pathological process of tendinopathy. In the present study, the protective effect of SP on TDSCs was demonstrated under simulated tendinopathy conditions both in vitro and in vivo. SP contributed to the maintenance of TDSC‐specific genes or proteins, while suppressing the interleukin‐ (IL‐) 1β‐induced overexpression of inflammation‐mediated factors. Additionally, IL‐1β‐induced cellular senescence in TDSCs was inhibited, while autophagy was enhanced, as determined via β‐galactosidase activity, western blot (WB), and quantitative real‐time polymerase chain reaction analysis. With the aid of several emerging bioinformatics tools, the mitogen‐activated protein kinase (MAPK) pathway likely participated in the effect of SP, which was further validated through WB analysis and the use of MAPK agonist. Immunofluorescence analysis and an NF‐κB agonist were used to confirm the inhibitory effect of SP on IL‐1β‐induced activation of the NF‐κB pathway. X‐ray, immunofluorescence, immunohistochemistry, hematoxylin and eosin staining, histological grades, and Masson staining showed that SP ameliorated tendinopathy in an Achilles tenotomy (AT) rat model in vivo. This work elucidates the protective role of SP on the pathological process of tendinopathy both in vitro and in vivo, indicating a potential therapeutic strategy for tendinopathy treatment.

Several studies have investigated strategies to improve the clinical efficacy of radiotherapy (RT) against hepatocellular carcinoma (HCC), yet the prognosis remains poor. Human adipose tissue-derived mesenchymal stem cells (AT-MSCs), easily accessible and abundant in quantity, have represented as an attractive therapeutic tool for the stem cell-based treatment for cancer diseases. Through direct co-culture and indirect separate culture experiments, we showed that AT-MSCs could enhance inhibitory effect of RT on reducing HCC cell growth, migration and invasion in both in vitro and in vivo experiments. RNA-sequencing analysis revealed a noticeable interferon-induced transmembrane 1 (IFITM1)-induced tumor gene signature. Gain and loss of mechanistic studies indicated that mechanism was attributed to downregulated expression of signal transducer and activator of transcription 3 (STAT3) and matrix metallopeptidases (MMPs) and upregulated expression of P53 and caspases. Collectively, our findings suggest that AT-MSCs might enhance the therapeutic effects of RT on HCC, providing a rationale for AT-MSCs and RT combination therapy as a new remedy for HCC.