Pan-cancer analysis of LRRC59 with a focus on prognostic and immunological roles in hepatocellular carcinoma.

BACKGROUND: LRRC59 is a leucine-rich repeats-containing protein located in the endoplasmic reticulum (ER), it serves as a prognostic marker in several cancers. However, there has been no systematic analysis of its role in the tumor immune microenvironment, nor its predictive value of prognosis and immunotherapy response in different cancers. METHODS: A comprehensive pan-cancer analysis of LRRC59 was conducted from various databases to elucidate the associations between its expression and the prognosis of cancer, genetic alterations, tumor metabolism, and tumor immunity. Additionally, further functional assays were performed in hepatocellular carcinoma (HCC) to study its biological role in regulating cell proliferation, migration, apoptosis, cell cycle arrest, and sensitivity to immunotherapy. RESULTS: The pan-cancer analysis reveals a significant upregulation of LRRC59 in pan-cancer, and its overexpression is correlated with unfavorable prognosis in cancer patients. LRRC59 is negatively correlated with immune cell infiltration, tumor purity estimation, and immune checkpoint genes. Finally, the validation in HCC demonstrates LRRC59 is significantly overexpressed in cancer tissue and cell lines, and its knockdown inhibits cell proliferation and migration, promotes cell apoptosis, induces cell cycle arrest, and enhances the sensitivity to immunotherapy in HCC cells. CONCLUSIONS: LRRC59 emerges as a novel potential prognostic biomarker across malignancies, offering promise for anti-cancer drugs and immunotherapy.

Clinical characteristics analysis of pediatric spinal cord injury without radiological abnormality in China: a retrospective study.

PURPOSE: This study aims to analyze the clinical characteristics of Chinese children with spinal cord injury (SCI) without radiographic abnormality (SCIWORA) and explore their contributing factors and mechanisms of occurrence. METHODS: A retrospective analysis was conducted on the clinical data of pediatric patients diagnosed with SCIWORA from January 2005 to May 2020. Epidemiological, etiological, mechanistic, therapeutic, and outcome aspects were analyzed. RESULTS: A total of 47 patients with SCIWORA were included in this study, comprising 16 males and 31 females. The age range was 4 to 12 years, with an average age of 7.49 ± 2.04 years, and 70% of the patients were below eight. Sports-related injuries constituted 66%, with 70% attributed to dance backbend practice. Thoracic segment injuries accounted for 77%. In the American Spinal Injury Association (ASIA) classification, the combined proportion of A and B grades accounted for 88%. Conservative treatment was chosen by 98% of the patients, with muscle atrophy, spinal scoliosis, hip joint abnormalities, and urinary system infections being the most common complications. CONCLUSION: SCIWORA in Chinese children is more prevalent in those under eight years old, with a higher incidence in females than males. Thoracic spinal cord injuries are predominant, dance backbend as a primary contributing factor, and the social environment of "neijuan" is a critical potential inducing factor. Furthermore, the initial severity of the injury plays a decisive role in determining the prognosis of SCIWORA.

Single-cell RNA-seq reveals T cell exhaustion and immune response landscape in osteosarcoma.

Background: T cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and osteosarcoma (OS) remains unclear. Methods: In our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion. Subsequently, six machine learning algorithms were applied to develop a prognostic model linked with T cell exhaustion. This model was subsequently validated in the TARGETs and Meta cohorts. Finally, we examined disparities in immune cell infiltration, immune checkpoints, immune-related pathways, and the efficacy of immunotherapy between high and low TEX score groups. Results: The findings unveiled differential exhaustion in CD8+ T cells within the OS microenvironment. Three genes related to T cell exhaustion (RAD23A, SAC3D1, PSIP1) were identified and employed to formulate a T cell exhaustion model. This model exhibited robust predictive capabilities for OS prognosis, with patients in the low TEX score group demonstrating a more favorable prognosis, increased immune cell infiltration, and heightened responsiveness to treatment compared to those in the high TEX score group. Conclusion: In summary, our research elucidates the role of T cell exhaustion in the immunotherapy and progression of OS, the prognostic model constructed based on T cell exhaustion-related genes holds promise as a potential method for prognostication in the management and treatment of OS patients.

Clinical efficacy of different surgical approaches in the treatment of thoracolumbar tuberculosis: a multicenter retrospective case-control study with a minimum 10-year follow-up.

OBJECTIVE: To evaluate the long-term clinical efficacy of three different surgical approaches in treating thoracolumbar tuberculosis. METHODS: A total of 176 patients with thoracolumbar tuberculosis, treated with open surgery at two hospitals, were retrospectively analyzed. Patients were stratified into three groups based on the surgical approach: anterior-only (AO), posterior-only (PO), and anterior-posterior combined (AP) approaches. Collected data encompassed operative duration, intraoperative blood loss, hospital stay length, complications, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Visual Analog Scale (VAS) score, Oswestry Disability Index (ODI), American Spinal Injury Association (ASIA) classification, and radiographic measurements of segmental lordotic Cobb angles, correction angles, and correction rates. RESULTS: The minimum duration of follow-up among all patients was 10 years. Postoperatively, all patients experienced a reduction in ESR and CRP, with normalization occurring within 3 months and sustained normal at the last follow-up. The AP group had a longer operative duration and higher intraoperative blood loss than the other two groups. The Cobb correction rates for AO, PO, and AP were (56.33±6.62)%, (72.82±5.66)%, and (74.45±5.78)%, respectively. The correction loss of Cobb angles for AO, PO, and AP were (2.85±1.01)°, (1.42±0.97)°, and (1.19±0.89)°, respectively. Patients in all groups showed significant improvement in VAS scores and ODI postoperatively, with no notable intergroup differences. The neurological recovery rates for the AO, PO, and AP groups were 84.62, 87.10, and 83.72%, respectively, while the complication rates were 12.73, 16.98, and 22.06%, respectively. CONCLUSION: An anterior-only approach is recommended for cases with localized lesions and smaller angular deformities. For patients with multisegmental lesions and larger angular deformities, a posterior-only or anterior-posterior combined approach is advised, with a preference for the posterior-only approach.

Pan-cancer analysis shows that IBSP is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including osteosarcoma.

Background: IBSP is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family that plays a vital role in bone formation, renewal and repair. Emerging evidence revealed that IBSP participated in the tumorigenesis and progression in some cancers. However, its significance in tumour prognosis and immunotherapy is still unknown. Methods: In the current study, we studied the role of IBSP in tumorigenesis, tumor diagnosis, genomic heterogeneity, methylation modifications, immune infiltration, and therapy response in pan-cancer. In addition, we constructed a risk score model to assessed the prognostic classification efficiency of IBSP using the co-expression genes of IBSP in osteosarcoma (OS), and analyzed the expression and role of IBSP in OS through a series of assays in vitro. Results: IBSP was upregulated in various cancers compared to the paired normal tissues, and it was strongly correlated with the prognosis, pathological stage, diagnostic accuracy, genomic heterogeneity, methylation modification, immune infiltration, immune and checkpoint. Moreover, the predictive model we established in combination with the clinical characteristics of OS patients showed high survival predictive power in these individuals. The assays in vitro showed that IBSP promoted the proliferation, migration and invasion of OS cells, which further confirmed IBSP's role in cancers. Conclusions: Our research revealed the multifunctionality of IBSP in the tumorigenesis, progression and therapy in various cancers, which demonstrated that IBSP may serve as a potential prognostic biomarker and a novel immunotherapy target in pan-cancer.

CEMIP Promotes Osteosarcoma Progression and Metastasis Through Activating Notch Signaling Pathway.

Cell migration inducing protein (CEMIP) has been linked to carcinogenesis in several types of cancers. However, the role and mechanism of CEMIP in osteosarcoma remain unclear. This study investigated the role of CEMIP in the progression and metastasis of osteosarcoma, CEMIP was found to be overexpressed in osteosarcoma tissues when compared to adjacent non-tumor tissues, and its expression was positively associated with a poor prognosis in osteosarcoma patients. Silencing CEMIP decreased osteosarcoma cells proliferation, migration, and invasion, but enhanced apoptosis in vitro, and suppressed tumor growth and metastasis in vivo. Mechanistically, CEMIP promoted osteosarcoma cells growth and metastasis through activating Notch signaling pathway, silencing CEMIP would reduce the protein expression and activation of Notch/Jagged1/Hes1 signaling pathway in vitro and in vivo, activation of Notch signaling pathway could partially reversed cell proliferation and migration in shCEMIP osteosarcoma cells. In conclusion, our study demonstrated that CEMIP plays a substantial role in the progression of osteosarcoma via Notch signaling pathway, providing a promising therapeutic target in osteosarcoma.