[Retracted] NR4A1 promotes TNF­α­induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that fluorescence microscopy data shown in Fig. 2C were strikingly similar to data appearing in different form in Fig. 3G in a previously published paper by different authors at different research institutes [Jieensinue S, Zhu H, Li G, Dong K, Liang M and Li Y: Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK­Mff signaling pathways. BMC Cell Biology 19: 21, 2018]. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 45: 151­161, 2020; DOI: 10.3892/ijmm.2019.4398].

Pseudoprogression of thoracic tumor after radiotherapy in the era of immunotherapy: a case series.

Pseudoprogression is rarely mentioned after radiotherapy except for central nervous system tumors. With the widespread of immunotherapy, the incidence of pseudoprogression of thoracic tumor after radiotherapy is increasing. This study summarized the clinical features of pseudoprogression in 4 patients who had underwent thoracic radiotherapy after and/or followed by immunotherapy. All of them had received chemotherapy and immunotherapy before thoracic radiotherapy. After radiotherapy, pseudoprogression occurred within 3 months after initiation of immune consolidation/rechallenge therapy. At least a 20% increase in the sum of the longest diameter of target lesions were measured on their chest image. During this period, patients' ECOG PS scores remained stable, specific serum tumor markers did not increase significantly. Treatment strategies did not change after pseudoprogression. The causes of radiographic pseudoprogression in this case series may be attributed to disturbances such as pneumonitis, atelectasis, mucus blockages and infection. In the era of immunotherapy, pseudoprogression of thoracic tumors after chest radiotherapy might become a common phenomenon. It is important for us to identify pseudoprogression based on patient's general status, radiological changes, and laboratory tests.

The role of PET/CT in radiotherapy for nasopharyngeal carcinoma.

Radiotherapy has already been developed as the standard of care for patients with nasopharyngeal carcinoma (NPC), and precision staging, target volume delineation, prognosis prediction, and post-treatment surveillance are essential in the management of NPC. Positron emission tomography/computed tomography (PET/CT) is increasingly recognized as an imaging modality to guide precision radiotherapy in these areas. The feasibility and efficacy of 18F-FDG PET/CT have been confirmed in tumor diagnosis, treatment planning, prognosis, surveillance, and assessment. Coupled with the capability of revealing tumor metabolic information, 18F-FDG PET/CT is more accurate in identifying primary lesions and metastases of NPC than other conventional imaging methods including CT and MRI and shows the independently diagnostic and prognostic value for radiotherapy. However, 18F-FDG has limitations due to its physiological distribution in brain tissue and increasing uptake in post-radiation inflammation. Novel PET radiotracers including FAPI, NaF, CHO, and FLT are explored as alternatives with potential superiority for radiotherapy in NPC. In this review, we summarized the evolving role of PET/CT in the management of radiotherapy in NPC patients, aiming to facilitate precision radiotherapy from a molecular imaging aspect.

LncRNA THUMPD3-AS1 enhances the proliferation and inflammatory response of chondrocytes in osteoarthritis.

OBJECTIVE: Long noncoding RNAs (lncRNAs) regulate the occurrence and development of osteoarthritis (OA), whereas the biological roles and mechanisms of the lncRNA THUMPD3-AS1 (THUMPD3 antisense RNA 1) in OA remain still unclear. This study described the role and molecular mechanism of lncRNA THUMPD3-AS1 in regulating OA biology. METHOD: The knee normal and OA cartilage tissues from ten participants were sequenced to reveal the differentially expressed lncRNAs. The interleukin (IL)-1ß-stimulated C28/I2 cell served as OA cells. Flow cytometry assays, Western blot, enzyme-linked immunosorbent assays were used for our experiments. RESULTS: The results revealed that lncRNA THUMPD3-AS1 was downregulated in OA cartilage tissues and IL-1ß-stimulated chondrocyte cell line. Overexpression of lncRNA THUMPD3-AS1 alleviated cell apoptosis and facilitated inflammatory responses, whereas knockdown had opposite effects. LncRNA THUMPD3-AS1 markedly increased the cyclin E2, cyclin-dependent kinase 4, B-cell lymphoma 2, tumor necrosis factor-α, nitric oxide, and IL-6 levels, and decreased the caspase-3 level. Furthermore, the target proteins of phosphorylation were identified as nuclear factor-κB p65 and mitogen-activated protein kinase p38, which could be indirectly suppressed by lncRNA THUMPD3-AS1 knockdown. CONCLUSION: Our findings highlight the different effects of lncRNA THUMPD3-AS1 on cell apoptosis and inflammatory response, which extend the multiple functions of lncRNA epigenetics in OA biology.

Glomus tumors associated with the bone and joints: a review of 91 cases.

BACKGROUND: Glomus tumors (GTs) commonly affect the subungual soft tissue but rarely affect the bone and joints. Meanwhile, GTs associated with the bone and joints have been misdiagnosed for decades. METHODS: The PubMed, Embase, and Web of Science databases were searched, and primary data extracted from selected articles were quantitively analyzed. RESULTS: The number of male and female patients was 52 and 39, respectively, and the right side was more commonly affected than the left. The median age at onset of male and female patients was 43.61±19.20 and 33.16±14.87 years, respectively, and the median illness duration was 3.00 (1.00, 10.00) and 3.00 (0.50, 7.50) years, respectively. The median follow-up time was 12 months, and the median time to recurrence or metastasis was also 12 months. Of the 91 total cases, 3 had a malignant pathological type and 4 had an uncertain malignant potential. Moreover, five cases recurred postoperatively, including two malignant cases, two benign GTs, and one case of glomangiomatosis. Of the 54 patients with recorded data on trauma, 12 reported a definite history of trauma. CONCLUSIONS: Interestingly, the history of trauma is an important cause of GTs. The most common site of extra-subungual tissue is the knee, especially in young adults. Surgical removal was the most commonly used treatment method, and radiotherapy and chemotherapy can be combined if necessary. Furthermore, patients should be followed up for at least 2 years postoperatively to monitor for possible recurrence. Fortunately, most patients with GTs have a good prognosis.

Mst1 promotes mitochondrial dysfunction and apoptosis in oxidative stress-induced rheumatoid arthritis synoviocytes.

In this study, we investigated the role of macrophage stimulating 1 (Mst1) and the AMPK-Sirt1 signaling pathway in the oxidative stress-induced mitochondrial dysfunction and apoptosis seen in rheumatoid arthritis-related fibroblast-like synoviocytes (RA-FLSs). Mst1 mRNA and protein expression was significantly higher in hydrogen peroxide (H2O2)-treated RA-FLSs than untreated controls. H2O2 treatment induced the mitochondrial apoptotic pathway by activating caspase3/9 and Bax in the RA-FLSs. Moreover, H2O2 treatment significantly reduced mitochondrial membrane potential and mitochondrial state-3 and state-4 respiration, but increased reactive oxygen species (ROS). Mst1 silencing significantly reduced oxidative stress-induced mitochondrial dysfunction and apoptosis in RA-FLSs. Sirt1 expression was significantly reduced in the H2O2-treated RA-FLSs, but was higher in the H2O2-treated Mst1-silenced RA-FLSs. Pretreatment with selisistat (Sirt1-specific inhibitor) or compound C (AMPK antagonist) significantly reduced the viability and mitochondrial function in H2O2-treated Mst1-silenced RA-FLSs by inhibiting Sirt1 function or Sirt1 expression, respectively. These findings demonstrate that oxidative stress-related upregulation and activation of Mst1 promotes mitochondrial dysfunction and apoptosis in RA-FLSs by inhibiting the AMPK-Sirt1 signaling pathway. This suggests the Mst1-AMPK-Sirt1 axis is a potential target for RA therapy.

Artificial Intelligence-Assisted System in Postoperative Follow-up of Orthopedic Patients: Exploratory Quantitative and Qualitative Study.

BACKGROUND: Patient follow-up is an essential part of hospital ward management. With the development of deep learning algorithms, individual follow-up assignments might be completed by artificial intelligence (AI). We developed an AI-assisted follow-up conversational agent that can simulate the human voice and select an appropriate follow-up time for quantitative, automatic, and personalized patient follow-up. Patient feedback and voice information could be collected and converted into text data automatically. OBJECTIVE: The primary objective of this study was to compare the cost-effectiveness of AI-assisted follow-up to manual follow-up of patients after surgery. The secondary objective was to compare the feedback from AI-assisted follow-up to feedback from manual follow-up. METHODS: The AI-assisted follow-up system was adopted in the Orthopedic Department of Peking Union Medical College Hospital in April 2019. A total of 270 patients were followed up through this system. Prior to that, 2656 patients were followed up by phone calls manually. Patient characteristics, telephone connection rate, follow-up rate, feedback collection rate, time spent, and feedback composition were compared between the two groups of patients. RESULTS: There was no statistically significant difference in age, gender, or disease between the two groups. There was no significant difference in telephone connection rate (manual: 2478/2656, 93.3%; AI-assisted: 249/270, 92.2%; P=.50) or successful follow-up rate (manual: 2301/2478, 92.9%; AI-assisted: 231/249, 92.8%; P=.96) between the two groups. The time spent on 100 patients in the manual follow-up group was about 9.3 hours. In contrast, the time spent on the AI-assisted follow-up was close to 0 hours. The feedback rate in the AI-assisted follow-up group was higher than that in the manual follow-up group (manual: 68/2656, 2.5%; AI-assisted: 28/270, 10.3%; P<.001). The composition of feedback was different in the two groups. Feedback from the AI-assisted follow-up group mainly included nursing, health education, and hospital environment content, while feedback from the manual follow-up group mostly included medical consultation content. CONCLUSIONS: The effectiveness of AI-assisted follow-up was not inferior to that of manual follow-up. Human resource costs are saved by AI. AI can help obtain comprehensive feedback from patients, although its depth and pertinence of communication need to be improved.

NR4A1 promotes TNF­α­induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway.

Nuclear receptor subfamily 4 group A member 1 (NR4A1)­induced chondrocyte death plays a critical role in the development of osteoarthritis through poorly defined mechanisms. The present study aimed to investigate the role of NR4A1 in regulating chondrocyte death in response to tumor necrosis factor­α (TNF­α) and cycloheximide (CHX) treatment, with a focus on mitochondrial fission and the AMP­activated protein kinase (AMPK) signaling pathway. The results demonstrated that NR4A1 was significantly upregulated in TNF­α and CHX exposed chondrocytes. Increased NR4A1 triggered mitochondrial fission via the AMPK/dynamin­related protein 1 (Drp1) pathway, resulting in mitochondrial dysfunction, and mitochondrial permeability transition pore (mPTP) opening­related cell death. Furthermore, excessive mitochondrial fission impaired chondrocyte migration through imbalance of F­actin homeostasis. Inhibiting NR4A1 attenuated TNF­α and CHX­induced mitochondrial fission and, thus, reduced mitochondrial dysfunction in chondrocytes, mPTP opening­related cell death and migration injury. Altogether, the present data confirmed that mitochondrial fission was involved in NR4A1­mediated chondrocyte injury via regulation of mitochondrial dysfunction, mPTP opening­induced cell death and F­actin­related migratory inhibition.

Neuroma of the Infrapatellar branch of the saphenous nerve following Total knee Arthroplasty: a case report.

BACKGROUND: Injury to the infrapatellar branch of the saphenous nerve (IBSN) is common during total knee arthroplasty (TKA) with a standard midline skin incision. Occasionally, painful neuromas form at the transection of nerve and cause pain and limitation of the range of motion of the knee joint. CASE PRESENTATION: A 70-year-old woman experienced right knee pain and stiffness for 4 years after TKA. Physical assessment revealed medial tenderness; Tinel's sign was positive. Radiographs revealed that the prosthesis was well-placed and well-fixed. She was diagnosed with arthrofibrosis and possible neuroma after TKA. She underwent right knee exploration, neurectomy, adhesiolysis and spacer exchange. The neuroma-like tissue was sent for pathological examination. The patient recovered uneventfully and at 3-month follow-up reported no recurrence of pain or stiffness. The pathological report confirmed the diagnosis of neuroma. CONCLUSIONS: IBSN injury should be a concern if surgeons encounter a patient who has pain and stiffness after TKA. Tinel's sign, local anesthetic injection, MRI and ultrasound could help the diagnosis and identify the precise location of neuroma. Surgical intervention should be performed if necessary.