Pulmonary metastasis is a major cause of disease progression and mortality in patients with osteosarcoma. The survival impact of pulmonary metastasectomy and the prognostic relevance of surgery-related factors remain incompletely defined. This systematic review and meta-analysis aimed to evaluate the association between pulmonary metastasectomy and survival outcomes and to identify key prognostic determinants. PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched from inception to December 2025. Studies enrolling patients with histologically confirmed osteosarcoma and lung metastases that examined associations between surgery-related factors and survival outcomes were eligible. Outcomes included post-relapse survival (PRS) and post-metastasectomy overall survival (PMOS). Hazard ratios (HRs) with 95
There is no study on the relationship between peripheral blood different lymphocyte subtypes and the prognosis of osteosarcoma (OS). Therefore, this study aims to investigate the predictive value of T cells and natural killer (NK) cells for the prognosis of OS patients. This study retrospectively analyzed the clinical data and preliminary laboratory indicators of patients with OS admitted from dual-center between January 2014 and January 2021. The receiver operating characteristic (ROC) curve was employed to determine optimal cutoff values for different lymphocyte subtypes, with T cells, NK cells, and B lymphocytes subsequently stratified into high- and low-proportion groups based on their respective optimal cutoff values. Kaplan–Meier curve was employed to analyze the impact of different lymphocyte on survival time and status. Univariate and multivariate Cox analyses were performed on clinical and laboratory indicators to identify independent prognostic factors influencing the prognosis of OS patients. After screening 277 patients with OS, a total of 106 patients were eligible for this study. The median follow-up time was 36.00 months. At the last follow-up, patients were categorized as having a good prognosis if they survived or a poor prognosis if they died: good prognosis (n = 48) and poor prognosis (n = 58). Kaplan–Meier curve revealed that patients with a high proportion of T (Median overall survival: 41 months vs. 32 months, P = 0.007) and NK (Median overall survival: 44 months vs. 32 months, P = 0.004) cells had a better prognosis compared to those with a low proportion. Univariate analysis indicated that age, body mass index (BMI), C-reactive protein (CRP), tumor size, Enneking stage, surgical method, and the proportions of T, NK, and B cells were associated with the prognosis of OS patients (P < 0.05). Multivariate analysis indicated that Enneking stage (II vs. I, HR = 12.543, P = 0.015; III vs. I, HR = 29.078, P = 0.001), and the proportions of T and NK cells (HR = 0.466, P = 0.048; HR = 0.497, P = 0.029) were independent factors influencing the prognosis of OS patients (P < 0.05). The proportions of T and NK cells may serve as efficient and practical prognostic indicators for OS patients, with higher proportions often associated with a better prognosis.
Hepatocellular carcinoma (HCC) is one of the most common types of cancers. Identifying and validating specific and robust cancer biomarkers is paramount for the early screening, timely diagnosis, and accurate prognosis of a cancer. Overexpression of hypochlorous acid (HClO) and beta-galactosidase (beta-gal) in malignant tumors is considered a key biomarker of cancer pathology. We herein present a groundbreaking approach: the design and synthesis of a tandem dual-locked fluorescent probe, named LDMTY. Compared to conventional single-locked probes, LDMTY demonstrates superior potential for enhancing the diagnostic specificity of HCC. LDMTY exhibits excellent sensitivity and specificity toward HClO and beta-gal, with minimum detection limits of 0.046 mu M and 2.54 x 10(-)(4) U/mL, respectively. Because of the reaction between LDMTY and overexpressed beta-gal and HClO present with in cancerous cells, the fluorescence of LDMTY significantly increases (by 220-fold), enabling precise differentiation of between cancerous cells from normal cells (P < 0.0001). Moreover, the galactose modification on LDMTY enhances its hepatic-targeting capabilities, significantly enhancing its HCC imaging accuracy. LDMTY was successfully applied to in vivo imaging studies in mouse HCC models. It demonstrated promising potential as an innovative tandem dual-locked visual analysis tool and would offer value for HCC-specific detection.
Abstract Background Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. Methods Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. Results From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. Conclusions Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.
Osteoclasts (OCs) and regulatory CD4(+) T cells (CD4(+)Tregs) are important components in the tumor microenvironment (TME) of osteosarcoma. In this study, we collected six osteosarcoma samples from our previous study (GSE162454). We also integrated a public database (GSE152048), which included single cell sequencing data of 11 osteosarcoma patients. We obtained 138,192 cells and then successfully identified OCs and CD4(+)Tregs. Based on the interaction gene set between OCs and CD4(+)Tregs, patients from GSE21257 were distinguished into two clusters by consensus clustering analysis. Both the tumor immune microenvironment and survival prognosis between the two clusters were significantly different. Subsequently, five model genes were identified by protein-protein interaction network based on differentially upregulated genes of cluster 2. Quantitative RT-PCR was used to detect their expression in human osteoblast and osteosarcoma cells. A prognostic model was successfully established using these five genes. Kaplan-Meier survival analysis found that patients in the high-risk group had worse survival (p = 0.029). Therefore, our study first found that cell-cell communication between OCs and CD4(+)Tregs significantly alters TME and is connected to poor prognosis of OS. The model we constructed can accurately predict prognosis for osteosarcoma patients.
Chemotherapy, a primary treatment for osteosarcoma (OS), has limited knowledge regarding its impact on tumor immune microenvironment (TIME). Here, tissues from 6 chemotherapy-naive OS patients underwent single-cell RNA sequencing (scRNA-seq) and were analyzed alongside public dataset (GSE152048) containing 7 post-chemotherapy OS tissues. CD45+ (PTPRC+) cells were used for cell clustering and annotation. Changes in immune cell composition pre- and post-chemotherapy were characterized. Totally, 28,636 high-quality CD45+ (PTPRC+) cells were extracted. Following chemotherapy, the proportions of regulatory T cells (Tregs) and activated CD8 T cells decreased, while CD8 effector T cells increased. GO analysis indicated that differentially expressed genes (DEGs) in T cells were associated with cell activation, adaptive immune response, and immune response to tumor cells. Furthermore, the proportions of plasma cells increased, while naive B cells decreased. B cell surface receptors expression was upregulated, and GO analysis revealed DEGs of B cells were mainly enriched in B cell-mediated immunity and B cell activation. Moreover, M2 polarization of macrophages was suppressed post-chemotherapy. Overall, this study elucidates chemotherapy remodels the OS TIME landscape, triggering immune heterogeneity and enhancing anti-tumor properties.
Background Tumor infiltrating lymphocytes (TILs), the main component in the tumor microenvironment, play a critical role in the antitumor immune response. Few studies have developed a prognostic model based on TILs in osteosarcoma. Methods ScRNA-seq data was obtained from our previous research and bulk RNA transcriptome data was from TARGET database. WGCNA was used to obtain the immune-related gene modules. Subsequently, we applied LASSO regression analysis and SVM algorithm to construct a prognostic model based on TILs marker genes. What’s more, the prognostic model was verified by external datasets and experiment in vitro . Results Eleven cell clusters and 2044 TILs marker genes were identified. WGCNA results showed that 545 TILs marker genes were the most strongly related with immune. Subsequently, a risk model including 5 genes was developed. We found that the survival rate was higher in the low-risk group and the risk model could be used as an independent prognostic factor. Meanwhile, high-risk patients had a lower abundance of immune cell infiltration and many immune checkpoint genes were highly expressed in the low-risk group. The prognostic model was also demonstrated to be a good predictive capacity in external datasets. The result of RT-qPCR indicated that these 5 genes have differential expression which accorded with the predicting outcomes. Conclusions This study developed a new molecular signature based on TILs marker genes, which is very effective in predicting OS prognosis and immunotherapy response.
目的 探讨微信翻转课堂结合案例教学法(CBL)在腰椎间盘突出症见习课中的应用效果.方法 选取广西医科大学临床医学专业大四学生165人为研究对象,按随机数字表法将其分为对照组(n=81)和观察组(n=84).对照组采用传统讲授式教学法,观察组采用微信翻转课堂联合CBL.课程结束后,考核两组学生的理论知识、技能操作,利用满意度调查问卷对两组学生进行教学满意度调查,对比两组学生的理论知识、技能操作成绩及教学满意度.结果 课程结束后,观察组学生的理论考核成绩、技能操作考核成绩均高于对照组,差异均有统计学意义(均P<0.05).观察组学生在加强师生交流、培养团队合作、激发学习兴趣、培养自主学习、培养临床思维和提高教学质量方面的满意度均高于对照组,差异均有统计学意义(均P<0.05).结论 将微信翻转课堂结合CBL应用于腰椎间盘突出症的临床见习课中,取得良好的教学效果,值得在医学院校临床见习教学中进一步推广.
Osteoporosis is a systemic and metabolic bone disease that usually occurs in postmenopausal women, which mainly manifests as bone loss and increased bone fragility that both facilitate fracture. However, few drugs for osteoporosis have shown good efficacy and limited side effects. Vaccarin has demonstrated its antiosteoporosis effects by inhibiting the formation and osteolytic activities of osteoclasts in our previous investigation. In this study, multivariate statistical analysis and ultrahigh-performance liquid chromatography and quadrupole time-of-flight tandem mass spectrometry were used to analyze the serum metabolites of ovariectomized mice treated with or without vaccarin. As a result, 9 serum metabolites were identified as biomarkers. The metabolic levels of 3 crucial biomarkers, namely, lysophosphatidylcholine [22 : 6, (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)], 1-linoleoylglycerophosphocholine and 1-palmitoyl-Sn-glycero-3-phosphocholine, that were correlated with glycerophospholipid metabolism increased and then decreased significantly after vaccarin treatment. Molecular docking analysis and osteoclasts differentiation experiment further revealed that vaccarin may bind with phospholipase A2 and downregulated its activity to reduce the osteoclastogenesis. Therefore, the occurrence of osteoporosis is closely related with glycerophospholipid metabolism disorders, and vaccarin exerts antiosteoporosis effects by reducing the levels of glycerophospholipid metabolites.
目前,骨质疏松症作为全球性的公共卫生健康问题已严重影响人类健康,虽然近年来对骨质疏松症的研究不断深入,但仍不能完整及正确地诠释其相关的发病机制.由于炎症因子在炎症性骨病中发挥重要作用,不但可以作为监测疾病进展的生物标志物,也可作为临床诊疗的诊断指标.大量研究表明,炎症因子可通过激活或抑制相关的信号通路及影响相关酶蛋白的表达量等来影响成骨细胞与破骨细胞的活性和功能,进而在影响骨质疏松症的发生发展中起着至关重要的作用.本文根据炎症因子对骨质疏松症的不同作用分为促进、抑制、双作用炎症因子三大类型,并就它们影响骨质疏松症发病机制中的作用作一简要综述,从而为骨质疏松症的相关研究提供理论依据.
Background: Systemic inflammatory response and nutritional status are closely related to tumor development, and both have been recognized as predictors of tumors. Our study investigated the effect on the prognosis of osteosarcoma by analyzing the ratio of lymphocytes to C-reactive protein (LCR) before surgery. Methods: Patients who were diagnosed with osteosarcoma and underwent surgery in the First Affiliated Hospital of Guangxi Medical University from 2012 to 2019 were included in this retrospective study. The albumin (g/L) +5 × total lymphocyte count (PNI), neutrophil/lymphocyte count (NLR), platelet/lymphocyte count (PLR) and platelet × neutrophil/lymphocyte count (SII) were calculated from preoperative peripheral white blood cells, C-reactive protein and serum albumin. The optimal cutoff values of LCR, PNI, NLR, PLR and SII were determined by receiver operating characteristic (ROC) analysis. According to the Optimal cutoff values, LCR, PNI, NLR, PLR and SII were divided into high and low groups. The Kaplan-Meier method was used to compare the overall survival (OS) between the high and low LCR groups. Univariate analysis was used to determine the influence of age, gender, tumor size, Enneking stage and neoadjuvant chemotherapy on the prognosis of osteosarcoma.The independent predictors of OS were determined by Cox multivariate analysis. Results: The optimal cutoff values for LCR, PNI, NLR, PLR and SII were 0.093, 48.4, 1.23, 157.03 and 314.27, respectively. A low preoperative LCR was significantly correlated with tumor metastasis, stage, NLR, PLR and SII. However, a low preoperative PNI was significantly associated with tumor metastasis, stage, and PLR.Kaplan-Meier survival analysis indicated that the postoperative OS was significantly correlated with preoperative LCR and PNI (P < 0.05). Univariate analysis showed that Enneking stage, metastasis and preoperative LCR, PNI, NLR, PLR and SII were important factors affecting OS (P < 0.05). For multivariate analysis, the results revealed that the preoperative LCR (HR, 0.401; 95% CI, 0.199-0.807; P = 0.01) and Enneking stage (HR, 2.717; 95%CI, 1.067-6.919; P = 0.036) is an independent prognostic factor affecting the postoperative OS of osteosarcoma. Conclusions: The high preoperative LCR is strongly associated with longer survival time in patients with osteosarcoma. Enneking stage and preoperative LCR may be important parameters for the prognosis of osteosarcoma.
Some primary bone tumors are prone to hematogenous metastasis and after that, the therapeutic effect is not that good and prognosis is poor. Circulating tumor cells (CTC) shed from the tumor cells of primary or metastatic focus and then enter into blood circulation. CTC may appear in the early stage of the tumor, which can implant in distant organs to form metastatic sites and self-implant in the primary sites leading to the tumor recurrence; CTC are closely related with the prognosis of patients with tumors. In most primary bone tumors, CTC are heterogeneous compared with primary tumor cells. Studying CTC from various aspects can provide a basis for the early diagnosis and treatment of primary bone tumors. This review summarizes the current researches of CTC in common primary bone tumors, and expects the future of research direction and application practice in clinic.
骨质疏松症是危害人类健康的重要疾病,虽然现在对于骨质疏松症的发病机制及诊疗等方面的研究已有一定的进展,但许多问题丞待解决.代谢组学是系统生物学的组成部分,主要通过对生物体内的代谢物进行定量分析,寻找出代谢物变化与生理病理变化之间的关系,揭示疾病的发病机制并有助于疾病的诊疗及预后评价.本文就代谢组学的基本技术及其在骨质疏松中的发病机制、早期诊断及治疗等方面的应用研究进展作简要综述.
Background. Ewing sarcoma (EWS) is the second most familiar bone or soft-tissue sarcoma, making the identification of EWS biomarkers critically important. This study aimed to explore and validate potential prognostic biomarkers in EWS by bioinformatics analysis and experiments. Methods The microarray dataset GSE119546 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between EWS cells treated with and without Cyclin-dependent kinase 9 (CDK9) inhibitors were analyzed using R package limma. Next, we performed gene enrichment analysis and constructed a protein-protein interaction (PPI) network. The expression level of the top18 hub genes and the overall survival (OS) in patients with sarcoma were validated using the Oncomine and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases. Furthermore, the mRNA expression of Bystin Like (BYSL), Nucleolar Protein 11 (NOL11), and P21-activated protein kinase-interacting protein 1 (PAK1IP1) was detected by RT-PCR in the EWS cell line (A-673), and the protein expression in EWS tissue was verified by immunohistochemistry (IHC). Results Our study identified 343 DEGs, which were associated with various cancer-related functions and pathways. A total of three DEGs, including BYSL, NOL11, and PAK1IP1, were identified as hub genes with prognostic values using GEPAI2 and Oncomine. Finally, RT-PCR results showed the mRNA expression level of BYSL, NOL11, and PAK1IP1 in A-673 cells was higher than that in human mesenchymal stem cells. IHC staining revealed a positive expression ratio of NOL11, BYSL, and PAK1IP1 was 63.6% (14/22), 31.9% (7/22), and 0% (0/22), respectively. Cox regression analysis confirmed NOL11 was a significant prognostic factor for OS. Conclusions . Our findings revealed that NOL11 may be a potential biomarker for EWS prognosis and treatment.
腰椎滑脱是由于先天性发育不良、创伤或劳损等原因造成相邻椎体骨性连接异常,而发生的上位椎体与下位椎体部分或全部相对滑移引起的脊柱疾病,有压迫脊髓和(或)神经根而引起腰骶部疼痛、坐骨神经受累、间歇性跛行等风险.该病好发于 50 岁以上人群,女性发病率高于男性,L4/L5 节段病变较常见,目前主要治疗方法分为保守和手术治疗.腰椎滑脱复位术主要是恢复其正常的生物力学状态,恢复其脊柱的稳定性,达到解除神经牵拉和压迫的目的[1].腰椎滑脱术术后出现肠梗阻并发症的并不多,以结肠梗阻较为常见,而小肠梗阻少见.广西医科大学第一附属医院收治 1 例腰椎滑脱复位内固定术后小肠梗阻坏死,将救治经过介绍如下.
细胞焦亡(pyroptosis)是由多种病理因素(如感染、恶性肿瘤等)触发并由caspase家族蛋白介导的炎症性细胞死亡,其特点是胞膜快速破裂及胞内促炎物质的释放.细胞焦亡的三种路径分别为依赖于caspase-1的经典路径、依赖于caspase-4/5/11非经典路径以及依赖于caspase-3的特殊路径.此外,GSDMD和GSDME也在焦亡过程中发挥了重要作用.细胞焦亡与多种恶性肿瘤关系密切,表现为既可抑制也可促进恶性肿瘤的发生发展.文章就细胞焦亡的路径、细胞焦亡与恶性肿瘤发生发展的关系及其在恶性肿瘤治疗中的研究进展做简要综述.
绝经后骨质疏松症(PMO)一般好发于女性绝经后5~10年,其特点是骨质疏松相关脆性骨折的发生率和发病率很高,雌激素水平下降是诱发PMO的主要原因.因此,雌激素替代疗法(ERT)是治疗绝经后骨质疏松症的主要方案之一,雌激素及雌激素类似物可直接与骨组织中的雌激素受体(ER)结合,发挥调节骨代谢功能,从而防治PMO.文章对近年来雌激素在绝经后骨质疏松症治疗中的研究进展进行综述,旨在为治疗绝经后骨质疏松症提供参考与思路.
Malignant bone tumors, one of the most common bone tumors includes osteosarcoma, Ewing's sarcoma, multiple myeloma, and metastatic bone tumors etc. These tumors are often accompanied by distant metastatic lesions at time of diagnosis, leading to low 5-year survival rates. At present, the use of biomarkers for early detection in order to facilitate early treatment are very limited. Therefore, most medical researchers are exploring the roles of exosomes in detecting malignant bone tumors. Exosomes are extracellular microvesicles secreted by different types of cells, which exist in a variety of body fluids. They are new intercellular information carriers that play important physiological roles. Current literature have reported that the RNA contained in exosomes (such as mRNA, miRNAs, lncRNAs and circRNAs) play important roles in the incidence as well as development of malignant bone tumors. However, the previous studies mostly focused on the roles of exosomal RNA in malignant bone tumor diseases, in tumor cell proliferation or apoptosis, transfers, evasion of immune surveillance and chemotherapy drug resistance etc. However, exosomal RNAs may function in the whole process of the disease progression via regulation networks. Our review of existing literature revealed that exosomal RNAs affacted the proliferation, metastasis, immune evasion and drug resistance of five common malignant bone tumors; Osteosarcoma, Ewing sarcoma, Chondrosarcoma, multiple myeloma, and metastatic bone tumors. Therefore, by elucidating on the mechanism of exosomal RNAs in the occurrence and development of malignant bone tumors, this study, could provide new ideas for early diagnosis, concomitant diagnosis, efficacy estimation (chemotherapy, radiotherapy and immunotherapy, etc.) as well as assessing the prognosis of malignant bone tumors.
To retrospectively analyze the tumor resection method used in 20 patients with clavicular tumors and evaluate its clinical efficacy. A total of 9 patients with clavicular benign tumors underwent intracapsular resection, and 11 patients with clavicular malignant tumors underwent tumor resection from May 2012 to May 2017. Of the 11 patients, 5 underwent clavicular reconstruction using the plate-cement complex. Surgical efficacy was assessed using the Musculoskeletal Tumor Society, Constant-Murley, and American Shoulder and Elbow Surgeons shoulder outcome scores preoperatively until 12 months postoperatively. The average duration of follow-up care was 33.7 (12–71) months. Of the 20 patients, 3 patients died, 3 survived with tumor recurrence or metastasis, and 14 survived with no tumor recurrence. Among the 5 patients who underwent resection of malignant clavicular tumors and reconstruction, 2 underwent a re-operation because of a loose screw and plate displacement. In the functional assessment of the shoulder joint, patients with benign and malignant clavicular tumors showed significantly higher scores postoperatively compared with preoperative scores. For malignant clavicular tumors, no significant improvement was observed when comparing the non-reconstruction and reconstruction groups. Surgery is an optimal treatment for clavicular tumors. In patients with benign clavicular tumors, simple intracapsular resection can achieve a satisfactory prognosis. Reconstruction of a clavicular defect after resection of a clavicular malignant tumor is not recommended.
A series of hydroxychalcone derivatives have been designed, synthesized and evaluated for human xanthine oxidase (XO) inhibitory activity. Most of the tested compounds acted moderate XO inhibition with IC50 values in the micromolar rang. Molecular docking and kinetic studies have been performed to explain the binding modes of XO with the selected compounds. In addition, in vitro antioxidant screening results indicated that some of the hydroxychalcones possessed good anti-free radical activities. Furthermore, the preferred compounds 16 and 18 were able to significantly inhibit hepatic xanthine oxidase activity and reduced serum uric acid level of hyperuricemic mice in vivo. In summary, compounds 16 and 18 with balanced activities of antioxidant, XO inhibition and serum uric acid reduction, which are promising candidates for the treatment of hyperuricemia and gout.