Osteoarthritis (OA) involves cartilage degeneration, thereby causing inflammation and pain. Cardiovascular diseases, such as dyslipidemia, are risk factors for OA; however, the mechanism is unclear. We investigated the effect of dyslipidemia on the development of OA. Treatment of cartilage cells with low-density lipoprotein (LDL) enhanced abnormal autophagy but suppressed normal autophagy and reduced the activity of transcription factor EB (TFEB), which is important for the function of lysosomes. Treatment of LDL-exposed chondrocytes with rapamycin, which activates TFEB, restored normal autophagy. Also, LDL enhanced the inflammatory death of chondrocytes, an effect reversed by rapamycin. In an animal model of hyperlipidemia-associated OA, dyslipidemia accelerated the development of OA, an effect reversed by treatment with a statin, an anti-dyslipidemia drug, or rapamycin, which activates TFEB. Dyslipidemia reduced the autophagic flux and induced necroptosis in the cartilage tissue of patients with OA. The levels of triglycerides, LDL, and total cholesterol were increased in patients with OA compared to those without OA. The C-reactive protein level of patients with dyslipidemia was higher than that of those without dyslipidemia after total knee replacement arthroplasty. In conclusion, oxidized LDL, an important risk factor of dyslipidemia, inhibited the activity of TFEB and reduced the autophagic flux, thereby inducing necroptosis in chondrocytes.

Objective: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI). Materials and Methods: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm 2 was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive.The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC). Results: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4–79.9), 90.8% (95% CI: 85.6–94.2), and 83.5% (95% CI: 78.6–87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8–97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9–89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1–79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52–0.63) before training and 0.68 (95% CI: 0.62–0.74) after training, with a difference of 0.11 (95% CI: 0.02–0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69–0.74) before training and 0.79 (95% CI: 0.76–0.80) after training (P = 0.002). Conclusion Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI.

Purpose: This study aimed to evaluate the cumulative recurrence rate and risk factors for recurrent abdominal wall endometriosis (AWE) after surgical treatment. Materials and Methods: A retrospective cohort study was conducted at a single gynecological surgery center between January 2004 and December 2020. Patients who were surgically treated and followed up for at least 6 months after surgery were selected. Results: Eighteen patients with pathologically diagnosed AWE were included in this study. The median follow-up duration was 22.5 months (range, 6–106). The median age was 37 years (range, 22–48), and 33.3% of the patients were nulliparous. Among the patients included in our study, 55.6% complained of a mass with cyclic pain, and 27.8% had a palpable mass. In addition, 22.2% of patients experienced recurrence with 17.5±9.7 months of mean time to recurrence. The cumulative recurrence rates at 24 and 60 months after surgical treatment of AWE were 23.8% and 39.1%, respectively. There were no statistically significant risk factors for the recurrence of AWE, including postoperative medical treatment. Conclusion The recurrence rate of AWE appears to be correlated with the follow-up duration. There was no statistically significant risk factor for the recurrence of AWE. Unlike ovarian endometriosis, postoperative hormonal treatment does not seem to lower the recurrence of AWE. The findings of the current study may help healthcare providers in counselling and managing patients with AWE.

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetateinduced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.

Osteoarthritis (OA) is the most common form of arthritis associated with ageing. Vitamin D has diverse biological effect on bone and cartilage, and observational studies have suggested it potential benefit in OA progression and inflammation process. However, the effect of vitamin D on OA is still contradictory. Here, we investigated the therapeutic potential of vitamin D in OA. Six-week-old male Wistar rats were injected with monosodium iodoacetate (MIA) to induce OA. Pain severity, cartilage destruction, and inflammation were measured in MIA-induced OA rats. Autophagy activity and mitochondrial function were also measured. Vitamin-D (1,25(OH) 2 D3) and celecoxib were used to treat MIAinduced OA rats and OA chondrocytes. Oral supplementation of vitamin D resulted in significant attenuations in OA pain, inflammation, and cartilage destruction. Interestingly, the expressions of MMP-13, IL-1β, and MCP-1 in synovial tissues were remarkably attenuated by vitamin D treatment, suggesting its potential to attenuate synovitis in OA.Vitamin D treatment in OA chondrocytes resulted in autophagy induction in human OA chondrocytes and increased expression of TFEB, but not LC3B, caspase-1 and -3, in inflamed synovium. Vitamin D and celecoxib showed a synergistic effect on antinociceptive and chondroprotective properties in vivo. Vitamin D showed the chondroprotective and antinociceptive property in OA rats. Autophagy induction by vitamin D treatment may be a promising treatment strategy in OA patients especially presenting vitamin D deficiency.Autophagy promoting strategy may attenuate OA progression through protecting cells from damage and inflammatory cell death.

Aim To investigate the effeets of prolifera¬tion and autophagy of BV2 eells in OGD/R models when the 18 ku transloeator protein( TSPO) was inhibi¬ted.Methods BV2 microglia were eultured in vitro and the model established by oxygen-glueose depriva- tion/reperfusion( OGD/R) , the eells were divided into eontrol group and OGD/R group, OGD/R + small hair¬pin RNA negative eontrol group ( OGD/R + NCshR- NA) , OGD/R + TSPO small hairpin RNA group (OGD/R + TSPOshRNA ).The expression of TSPO mRNA and TSPO protein were deteeted by qRT-PCR and Western blot, respectively.In order to study the effeet of TSPO on BV2 microglial eells in OGD/R inju¬ry and autophagy, the cell viability was tested by CCK- 8 assey, the cytotoxicity was deteeted by reactive oxy¬gen speeies ( ROS) , autophagy-related mRNA ( p62 mRNA, LC3B mRNA, Beolin-1 mRNA) expressions were detected by qRT-PCR, and the expression levels of autophagy -related proteins ( p62 , LC3 II /LC3 1 , Beclin-1 ) were detected by Western blot in each group.Result The expression of TSPO mRNA and protein increased significantly in OGD/R group while compared to control group, the cell death and cytotox¬icity increased significantly, the expression levels of LC3B mRNA and Beclin-1 mRNA increased, while the p62 mRNA decreased significantly, the levels of LC3 II/LC3 1 and Beclin-1 protein increased, the expres¬sion of p62 protein decreased significantly in OGD/R group, and the autophagy was activated; compared with OGD/R group, the different levels of cell viabili¬ty, cytotoxicity and autophagy in OGD/R + NCshRNA group were not statistically significant.But the survival rate of cells in OGD/R + TSPOshRNA group signifi¬cantly increased, the levels of cytotoxicity and autoph¬agy were significantly reduced.Conclusions The in¬hibition of TSPO has a significant protective effect on OGD/R injury model in BV2 microglial cells, which may be related to the inhibition of autophagy.

PURPOSE: Distribution and survival of sarcoma in Korea are not well described, after the changing of sarcoma classification on 2013. The researchers investigated the distribution and survival in single center 2017 cases of sarcoma.METHODS: Patients with primary sarcoma, who underwent surgery, were investigated. All cases were collected during a 20 year period (1995–2015) from Samsung Medical Center in Korea. Histopathologic types were classified by World Health Organization (WHO) classification (2013). And overall survival rates were analyzed.RESULTS: Between 1995 and 2015, 2017 patients were collected. The most frequent type of sarcoma was gastrointestinal tumor (15%), followed by liposarcoma (12%), leiomyosarcoma (9%), dermatofibrosarcoma (6%), giant cell sarcoma (6%). The most common primary site of sarcoma was the intra-abdominal area (45%, including visceral area). Extremities accounted for 26% of all cases. Sixteen percent of sarcoma were located in retroperitoneal area. The overall survival rate was 70.4% (median follow-up time, 36.8 months; range, 0.1–261.3 months). The best prognosis was dermatofibrosarcoma (100%, 5-year survival rate). The worst prognosis was angiosarcoma (39.3%). Survival analysis by the primary site demonstrated favor prognosis in extremities than head & neck, chest lesion.CONCLUSION: The researchers reported Korean sarcoma characteristics with using the new WHO classification.
Classification ; Dermatofibrosarcoma ; Epidemiology ; Extremities ; Follow-Up Studies ; Giant Cells ; Head ; Hemangiosarcoma ; Humans ; Korea ; Leiomyosarcoma ; Liposarcoma ; Neck ; Prognosis ; Sarcoma ; Survival Rate ; Thorax ; World Health Organization

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-1beta (IL-1beta), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-1beta, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-1beta-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.
Administration, Oral ; Animals ; Cartilage* ; Cartilage, Articular ; Chondrocytes ; Extremities ; Humans ; Immunohistochemistry ; Injections, Intra-Articular ; Interleukin-1beta ; Interleukin-6 ; Joint Diseases ; Knee ; Knee Joint ; Liver Diseases ; Nitric Oxide Synthase Type II ; Nociception ; Osteoarthritis* ; Osteoclasts ; Oxidative Stress ; Rats* ; RNA, Messenger ; Ursodeoxycholic Acid*

The technique of endoscopic submucosal dissection is occasionally used for resection of myogenic tumors originating from muscularis mucosa or muscularis propria of stomach and esophagus. However, endoscopic treatments for esophageal myogenic tumors >2 cm have rarely been reported. Herein, we report a case of large leiomyoma originating from muscularis propria in the upper esophagus. A 59-year-old woman presented with dysphagia. Esophagoscopy and endoscopic ultrasonography revealed an esophageal subepithelial tumor which measured 25x20 mm in size, originated from muscularis propria, and was located at 20 cm from the central incisors. The tumor was successfully removed by endoscopic submucosal dissection and there were no complications after en bloc resection. Pathologic examination was compatible with leiomyoma.
Esophageal Neoplasms/*diagnosis/pathology/surgery ; Esophagus/surgery/ultrasonography ; Female ; Gastroscopy ; Humans ; Leiomyoma/*diagnosis/pathology/surgery ; Middle Aged ; Mucous Membrane/pathology ; Stents ; Tomography, X-Ray Computed

Interleukin (IL)-27 is a novel cytokine of the IL-6/IL-12 family that has been reported to be involved in the pathogenesis of autoimmune diseases and has a pivotal role as both a pro- and anti-inflammatory cytokine. We investigated the in vivo effects of IL-27 on arthritis severity in a murine collagen-induced arthritis (CIA) model and its mechanism of action regarding control of regulatory T (Tregs) and IL-17-producing T helper 17 (Th17) cells. IL-27-Fc-treated CIA mice showed a lower severity of arthritis. IL-17 expression in the spleens was significantly decreased in IL-27-Fc-treated CIA mice compared with that in the CIA model. The Th17 population was decreased in the spleens of IL-27-Fc-treated CIA mice, whereas the CD4+CD25+Foxp3+ Treg population increased. In vitro studies revealed that IL-27 inhibited IL-17 production in murine CD4+ T cells, and the effect was associated with retinoic acid-related orphan receptor gammaT and signal transducer and activator of transcription 3 inhibition. In contrast, fluorescein isothiocyanate-labeled forkhead box P3 (Foxp3) and IL-10 were profoundly augmented by IL-27 treatment. Regarding the suppressive capacity of Treg cells, the proportions of CTLA-4+ (cytotoxic T-lymphocyte antigen 4), PD-1+ (programmed cell death protein 1) and GITR+ (glucocorticoid-induced tumor necrosis factor receptor) Tregs increased in the spleens of IL-27-Fc-treated CIA mice. Furthermore, in vitro differentiated Treg cells with IL-27 exerted a more suppressive capacity on T-cell proliferation. We found that IL-27 acts as a reciprocal regulator of the Th17 and Treg populations in CD4+ cells isolated from healthy human peripheral blood mononuclear cells (PBMCs), as well as from humans with rheumatoid arthritis (RA) PBMCs. Our study suggests that IL-27 has the potential to ameliorate overwhelming inflammation in patients with RA through a reciprocal regulation of Th17 and Treg cells.
Animals ; Arthritis, Experimental/*drug therapy/immunology ; Cells, Cultured ; Humans ; Interleukins/immunology/*therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; T-Lymphocytes, Regulatory/*immunology ; Th17 Cells/*immunology