Two Pathological Fractures in a Patient with Chronic Abnormalities in Serum Markers Following Two Liver Transplantations: A Case Report and Literature Review.

Bone disease is a common complication following liver transplantation, often overlooked in clinical practice. Clinical diagnosis of post-liver transplantation bone disease is challenging, and there have been few case report in the literature. This case report presents a patient who underwent two liver transplant surgeries, exhibited good daily activity, and did not display typical clinical symptoms such as fatigue, bone pain, or spinal deformities associated with prolonged sitting or standing. However, within the fifth year after the second liver transplant, the patient experienced two consecutive fractures. In March 2023, the patient underwent the first bone density test, which revealed osteoporosis. This case highlights the fact that severe fractures after liver transplantation may not necessarily be accompanied by typical symptoms of bone disease. Without timely examination and early prevention, serious consequences may arise. Therefore, this condition requires attention, proactive prevention, early detection, and timely treatment. Additionally, a retrospective analysis of the patient's previous laboratory data revealed persistent abnormalities in serum markers such as hypocalcemia and elevated alkaline phosphatase levels after liver transplantation, emphasizing the importance of monitoring these serum markers.

Therapeutic Effects of Curcumin on Osteoarthritis and Its Protection of Chondrocytes Through the Wnt/Β-Catenin Signaling Pathway.

Context: Osteoarthritis (OA) is a high-incidence, chronic condition, with an extremely high prevalence among older adults. OA seriously compromises the normal living of OA patients, and it's imperative to find a novel therapy as soon as possible to improve their prognosis and life quality. Objective: The study intended to investigate the therapeutic effects of Curcumin (Cur) on OA and to explore its preliminary mechanism of action, with the aim of offering more accurate guidance for use of OA therapy. Design: The research team designed a prospective non-randomized controlled trial. Setting: The study took place in the Department of Orthopedics at Sir Run Run Hospital at Nanjing Medical University in Nanjing, China. Participants: Participants were 107 OA patients treated at the hospital between March 2019 and January 2020. Intervention: Participants were divided into two groups, 51 in the Cur group and 56 in the ibuprofen group. Outcome Measures: The clinical efficacy and safety of the two groups were observed. In addition, the research team performed in-vitro studies. Chondrocytes HC-a and C28/I2 were purchased to evaluate the intracellular inflammatory response and apoptosis rate under the intervention of Cur and Wnt/ß-catenin pathway inhibitors. Results: No significant differences existed in the clinical-efficacy rate between the two groups (P > .05), but the Cur group show higher improvements in safety, joint mobility, and inhibition of inflammation (P < .05). In-vitro experiments showed that Cur inhibited the apoptosis rate of chondrocytes and the levels of inflammatory factors, while the Wnt/ß-catenin inhibitor did the opposite (P < .05). Conclusions: Cur can effectively decrease the pathological results of OA, with a remarkable safety profile; its mechanism may be the activation of the Wnt/ß-catenin signaling pathway to inhibit the inflammatory reaction and apoptosis in chondrocytes.

Treatment of Ulnar Coronoid Process Fracture Using the Anterior Neurovascular Interval Approach: A Retrospective Clinical Study with Short- to Mid-term Follow-up.

OBJECTIVE: Numerous surgical techniques for addressing ulnar coronoid process fractures are available; however, a consensus on the optimal approach remains elusive. This study aimed to use the anterior neurovascular interval approach for the surgical management of ulnar coronoid process fractures and to evaluate its clinical outcomes over short- to mid-term follow-up. METHODS: This retrospective clinical study included 20 patients with ulnar coronoid process fractures who were treated using the anterior neurovascular interval approach between January 2018 and December 2022. Participants comprised 16 males and four females, aged between 20 and 64 years (mean, 34.3 ± 12.44 years). Clinical and radiological evaluations were based on elbow joint range of motion (ROM), Visual analogue scale (VAS), and Mayo elbow performance score (MEPS). A paired t-test was used to compare the pre-operative and final follow-up VAS and MEPS scores. RESULTS: The follow-up duration for all patients was at least 12 months (average, 12.65 ± 1.60 months). At the final follow-up, measurements of elbow ROM included a mean extension of 2.85 ± 3.17°, mean flexion of 135 ± 7.25°, mean pronation of 86.4 ± 4.56°, and mean supination of 84.85 ± 5.54°. All participants reached their target MEPS, with an average score of 97.25 ± 4.72 points, and the final mean VAS score was 0.2 ± 0.52 points. The VAS score was significantly lower and MEPS score was higher at the final follow-up than those before surgery (p < 0.05). Throughout the follow-up period, all the fractures united, and the stability of the affected elbows was satisfactory. CONCLUSION: Employing the anterior neurovascular interval approach for open reduction and internal fixation to manage coronoid process fractures effectively facilitates anatomical restoration and robust fixation of ulnar coronoid process fractures.

Clinical Analysis of the Frosch Approach in the Treatment of Posterolateral Tibial Plateau Fractures Combined with Lateral Tibial Plateau Fractures.

OBJECTIVE: The treatment of posterolateral tibial plateau fractures is difficult, and providing sufficient exposure and effective fixation is a challenge. There is great controversy regarding the surgical approach for posterolateral tibial plateau fractures. The purpose of the study was to investigate the clinical effects of open reduction and internal fixation using the Frosch approach for the treatment of posterolateral tibial plateau fractures combined with lateral tibial plateau fractures. METHODS: Data from 19 patients with posterolateral tibial plateau fractures combined with lateral tibial plateau fractures treated from May 2018 to January 2022 were retrospectively analyzed. There were nine men and 10 women, ranging in age from 22 to 62 years, with an average age of 45.6 years. All patients were treated using the Frosch approach. Under direct vision, the posterolateral and lateral fractures were reduced, and full bone grafting was performed. We reshaped the oblique "T" shaped plate for the distal radius and placed it on the posterolateral tibial plateau to fix the posterolateral fractures. The lateral inverted "L" shaped locking plate was placed on the lateral tibial plateau to fix the lateral tibial plateau fractures. Within 2 weeks after the operation, the patients were instructed to perform knee joint function exercises within 90°. At the last follow-up, the Rasmussen radiological criteria were used to evaluate the effectiveness of fracture reduction and fixation. And the knee joint function was evaluated using Rasmussen functional score. RESULTS: The operation time ranged from 100 to 180 min, with an average of 134.2 min; intraoperative blood loss ranged from 20 to 150 mL, with an average of 66.8 mL. The follow-up duration ranged from 14 to 58 months, with an average of 36.2 months. There were no complications, such as vascular or nerve injury or incision infection. Fracture healing was achieved in all patients, and the healing time ranged from 10 to 14 weeks, with an average of 11.2 weeks. During the follow-up period, there was no loosening or breakage of the internal fixation, varus or valgus deformity of the knee joint, re-collapse of the articular surface, or instability of the knee joint. At the last follow-up, the effectiveness of fracture reduction and fixation was excellent in 13 patients and good in six patients. And the knee joint function was excellent in 17 patients and good in two patients. CONCLUSION: The Frosch approach for open reduction and internal fixation in the treatment of posterolateral tibial plateau fractures combined with lateral tibial plateau fractures has a definite clinical benefit and is worthy of promotion and application.

Adjustable-Loop Cortical Button Fixation Results in Good Clinical Outcomes for Acute Tibial Avulsion Fracture of the Posterior Cruciate Ligament.

Purpose: To evaluate the clinical outcomes for arthroscopic treatment of acute posterior cruciate ligament (PCL) avulsion fractures with adjustable-loop cortical button fixation device. Methods: Patients with PCL tibial avulsion fractures treated with an adjustable-loop cortical button fixation device between October 2019 and October 2020 were retrospectively identified. Patients with type 1 were treated using plaster fixation as a conservative treatment, whereas patients with type 2 and 3 with displacement were treated using an arthroscopic adjustable-loop cortical button. Operating time, incision recovery, complications, and postoperative fracture healing time were monitored. All patient follow-up was done at 12 months' postoperatively. Lysholm Knee Score and the International Knee Documentation Committee score were used to assess knee function. Results: A total of 30 patients were included in the study (20 male/10 female; mean age 45.5 years, range 35-68 years). The mean operative time was 67.5 minutes (range: 50-90 minutes). The postoperative incision healed at stage A without complications, such as medically induced vascular nerve injury, intra-articular hematoma, or infection. All 30 patients were tracked postoperatively for 12 to 14 months, with a mean follow-up period of 12.6 months. The Lysholm knee function score was 45.93 ± 6.15 before surgery and 87.10 ± 3.71 at 12 months after surgery, and the International Knee Documentation Committee score was 19.27 ± 4.40 before surgery and 95.47 ± 1.87 at 12 months after surgery, with a statistically significant difference. Conclusions: The treatment of PCL avulsion fractures with arthroscopic adjustable-loop cortical button fixation is easy to perform and shows good clinical results in our study. Level of Evidence: IV, therapeutic case series.

Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient.

Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the landscape of human diseases at an unprecedented resolution, particularly in diseases lacking animal models, such as SUPS. We performed scRNA-seq to analyze tumor tissues and paracancer tissues from a SUPS patient. We identified the cell types and the corresponding marker genes in this SUPS case. We further showed that CD8+ exhausted T cells and Tregs highly expressed PDCD1, CTLA4 and TIGIT. Thus, PDCD1, CTLA4 and TIGIT were identified as potential targets in this case. We applied copy number karyotyping of aneuploid tumors (CopyKAT) to distinguish malignant cells from normal cells in fibroblasts. Our study identified eight malignant fibroblast subsets in SUPS with distinct gene expression profiles. C1-malignant Fibroblast and C6-malignant Fibroblast in the TME play crucial roles in tumor growth, angiogenesis, metastasis and immune response. Hence, targeting malignant fibroblasts could represent a potential strategy for this SUPS therapy. Intervention via tirelizumab enabled disease control, and immune checkpoint inhibitors (ICIs) of PD-1 may be considered as the first-line option in patients with SUPS. Taken together, scRNA-seq analyses provided a powerful basis for this SUPS treatment, improved our understanding of complex human diseases, and may afforded an alternative approach for personalized medicine in the future.

Comparison of clinical outcomes between open and modified endoscopic release for carpal tunnel syndrome.

The aim of the present study was to investigate a novel technology, requiring only a single portal and no special equipment, to perform endoscopic treatment of carpal tunnel (CT) syndrome (CTS). This novel technique involves a surgical approach and standard operating procedures and is designed to minimize the potential for complications. Patients with CTS were randomly assigned using a computer-generated random allocation and stratified by site to either the modified endoscopic CT release (MECTR) group (n=48) or open CT release (OCTR) group (n=46). Various medical indexes were compared between the two groups, including operative time, hospitalization time, the time required to resume a normal life or work, intraoperative complications, incision infection rate, the amelioration of symptoms (Kelly grading), post-operative scar pain score, recovery of grip strength and pinch strength, two-point discrimination and the presence of sympathetic dystrophy. The results revealed that all patients had grade A wound healing and the symptoms were completely relieved. No significant differences were observed between the two groups with regards to the incision infection rate, intraoperative complications, grip strength, pinch strength, two-point discrimination, presence of sympathetic dystrophy and clinical symptom amelioration. In addition, compared with the OCTR group, the MECTR group had a decreased operative and hospitalization time, post-operative scar pain score and time required to resume a normal lifestyle. Post-operative electromyographic examination also revealed that the median nerve sensory conduction speed increased compared with that prior to surgery in both groups. In conclusion, the use of MECTR for the treatment of CTS achieved higher patient satisfaction, a shorter operative time and hospitalization time, an earlier return to work time or resumption of a normal life, as well as less post-operative scar pain compared with OCTR. Thus, these results suggested that MECTR may be an effective method for the treatment of idiopathic CTS. Trial registration no. ChiCTR2000041165, retrospectively registered 20th December 2020.

Extracellular vesicles derived from LPS-preconditioned human synovial mesenchymal stem cells inhibit extracellular matrix degradation and prevent osteoarthritis of the knee in a mouse model.

BACKGROUND: Previous studies report that lipopolysaccharide (LPS)-preconditioned mesenchymal stem cells have enhanced trophic support and improved regenerative and repair properties. Extracellular vesicles secreted by synovial mesenchymal stem cells (EVs) can reduce cartilage damage caused by osteoarthritis (OA). Previous studies show that extracellular vesicles secreted by LPS-preconditioned synovial mesenchymal stem cells (LPS-pre EVs) can improve the response to treatment of osteoarthritis (OA). This study sought to explore effects of LPS-pre EVs on chondrocyte proliferation, migration, and chondrocyte apoptosis, as well as the protective effect of LPS-pre EVs on mouse articular cartilage. METHODS: Chondrocytes were extracted to explore the effect of LPS-pre EVs on proliferation, migration, and apoptosis of chondrocytes. In addition, the effect of LPS-pre EVs on expression level of important proteins of chondrocytes was explored suing in vitro experiments. Further, intraarticular injection of LPS-pre EVs was performed on the destabilization of the medial meniscus (DMM)-induced mouse models of OA to explore the therapeutic effect of LPS-pre EVs on osteoarthritis in vivo. RESULTS: Analysis showed that LPS-pre EVs significantly promoted proliferation and migration of chondrocytes and inhibited the apoptosis of chondrocytes compared with PBS and EVs. Moreover, LPS-pre EVs inhibited decrease of aggrecan and COL2A1 and increase of ADAMTS5 caused by IL-1ß through let-7b. Furthermore, LPS-pre EVs significantly prevented development of OA in DMM-induced mouse models of OA. CONCLUSIONS: LPS pretreatment is an effective and promising method to improve therapeutic effect of extracellular vesicles secreted from SMSCs on OA.

Alleviation of Cartilage Destruction by Sinapic Acid in Experimental Osteoarthritis.

Sinapic acid (SA) modulates the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in chondrocytes. In order to test the hypothesis that SA is protective against the development of osteoarthritis (OA), primary mouse chondrocytes were treated in vitro with SA and the promoter transactivation activity of heme oxygenase 1 (HO-1), nuclear translocation of Nrf2, and protein expression of HO-1 were assayed. To test the hypothesis in vivo, a destabilization of the medial meniscus (DMM) model was used to induce OA in the knees of mice and SA was delivered orally to the experimental group. The chondrocytes were harvested for further analysis. The expression of HO-1 was similarly upregulated in cartilage from both the experimental mice and human chondrocytes from osteoarthritic knees. SA was found to enhance the promoter transactivation activity of heme oxygenase 1 (HO-1) and increase the expression of Nrf2 and HO-1 in primary chondrocytes. Histopathologic scores showed that the damage induced by the DMM model was significantly lower in the SA treatment group. The addition of a HO-1 inhibitor with SA did not show additional benefit over SA alone in terms of cartilage degradation or histopathologic scores. The expression of TNF-α, IL-1ß, IL-6, MMP-1, MMP-3, MMP-13, ADAMTS4, and ADAMTS5 was significantly reduced both in vitro and in vivo by the presence of SA. Protein expressions of HO-1 and Nrf2 were substantially increased in knee cartilage of mice that received oral SA. Our results suggest that SA should be further explored as a preventative treatment for OA.

7,8-Dihydroxyflavone activates Nrf2/HO-1 signaling pathways and protects against osteoarthritis.

The aim of the present study was to investigate the effect of 7,8-dihydroxyflavone (7,8-DHF) against osteoarthritis (OA) and examine its regulatory role in the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway in chondrocytes. Primary mouse chondrocytes were treated with 7,8-DHF to examine the expression of Nrf2 and downstream heme oxygenase 1 (HO-1). The surgical destabilization of the medial meniscus model was used to assess the effectiveness of 7,8-DHF in protecting the cartilage from damage, with knee cartilage harvested from mice for histological analysis. The results revealed that 7,8-DHF activated the Nrf2 signaling pathway in primary chondrocytes. Cartilage degradation in the 7,8-DHF-treated group was reduced significantly compared with that in the vehicle-treated group, according to histological evaluation. The gene expression of matrix metalloproteinase (MMP)1, MMP3, MMP13, interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α were reduced in the cartilage of OA mice following 7,8-DHF treatment. Genetic and protein analyses indicated that the expression levels of HO-1 were upregulated in the cartilage of the knee with OA, and 7,8-DHF treatment further promoted the induction of HO-1. These results suggest that 7,8-DHF may serve as a potential therapeutic agent in OA.

Tissue microarray staining reveals PLD1 and Sp1 have a collaborative, pro-tumoral effect in patients with osteosarcomas.

It has been reported that phospholipase D1 (PLD1) - a key enzyme involved in lipid metabolism - is important for the initiation and progression of various human solid cancers; however, its biological significance and regulation in human osteosarcomas remain elusive. In this study, We found that PLD1 and Specificity Protein 1 (Sp1) expression were elevated in 137 osteosarcoma specimens with immunohistochemical staining. Our results showed that both PLD1 and Sp1 were expressed at much higher rates in the cancerous tissue compared to adjacent normal tissue. A correlation analyze also indicated that PLD1 was significantly associated with lactate dehydrogenase expression (p = 0.041) and the Enneking stage (p = 0.000), while Sp1 was significantly associated with the nuclear grade (p = 0.024). Furthermore, survival analyses showed that elevated PLD1 confers a poor prognosis on patients with osteosarcomas, acting as an independent prognostic factor. Of note, we showed a positive correlation between PLD1 and Sp1 expression in the cancer tissues (r = 0.357; p < 0.001). High co-expression of the two molecules results in the worst prognosis for the patients, and can also be regarded as independent prognostic factor (p = 0.001; HR = 2.71; 95% CI 1.53-4.80).

MMC controlled-release membranes attenuate epidural scar formation in rat models after laminectomy.

Epidural scar formation after laminectomy impede surgical outcomes of decompression. Mitomycin C (MMC) has been demonstrated to have significant inhibitory effects on epidural scar. This study was undertaken to develop an effective MMC controlled­release membrane and to investigate its effects on epidural scar in rat models of laminectomy. A total of 72 rats that underwent laminectomy were divided into three groups. Among them, 24 were treated with mitomycin C­polylactic acid (MMC-PLA) controlled­release membrane, 24 with mitomycin C-polyethylene glycol (MMC-PEG) controlled-release membrane, and no treatment was performed for the remaining 24 rats (control group). In the following 4 weeks, magnetic resonance image (MRI), macroscopic observation, histology and hydroxyproline (Hyp) concentration analysis were performed to explore the effects of these three therapies on epidural scar. MRI revealed a significant reduction of epidural fibrosis in MMC-PLA and MMC-PEG treatment groups, compared with the control group. Histological results also showed that collagen deposition was significantly reduced after being treated with MMC-PLA or MMC-PEG membranes. Likewise, Hyp concentrations of the epidural scar tissue in MMC-PLA and MMC-PEG groups were markedly lower than those in the control group. However, regarding the effects on reducing epidural scar, no significant difference was found between the MMC-PLA and MMC-PEG groups. In conclusion, MMC-PLA and MMC-PEG membranes are safe and effective in reducing fibrosis. Thus, MMC-controlled-release membranes promises to be a potential therapeutic in preventing epidural scar formation after laminectomy.