Background:Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. Objective:This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. Methods:In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. Results:Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. Conclusions:In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces chemoradiotherapy‑induced muscle loss, weight loss, and malnutrition. This randomized phase II trial evaluated whether a multidisciplinary, mHealth‑based multimodal rehabilitation program could preserve handgrip strength and muscle mass in abdominal cancer patients undergoing CCRT. In this prospective, multicenter, randomized, open‑label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC, n=57) or standard care (SC, n=54). The MRC program was delivered by a dedicated multidisciplinary team comprising oncologists, rehabilitation physicians, nurses, clinical nutritionists, and psychologists. Using the AINST mHealth platform and wearable heart rate monitors, the team provided coordinated, individualized exercise, nutritional, and psychological interventions based on weekly assessments and real‑time data. The SC group received routine oncology care. The primary endpoint was change in handgrip strength from baseline to CCRT completion. Secondary endpoints included body weight, skeletal muscle mass, nutritional biomarkers, quality of life, psychological status, and adverse events. Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high, with 83.9% (47/56) of MRC patients achieving preset exercise targets. Compared with SC, the MRC group demonstrated significantly less decline in handgrip strength at all time points (all p < 0.001). The MRC group also showed better preservation of body weight (mean difference 1.3 kg, p=0.005) and a significantly lower proportion of patients with >5% weight loss (10.7% vs. 32.7%, p=0.005). Skeletal muscle mass was also better preserved (mean difference 1.3 kg, p<0.001). The MRC group had less decline in serum albumin (p=0.009) and prealbumin (p=0.019), and lower incidences of ≥G3 leukopenia (5.4% vs. 19.2%, p=0.037) and ≥G1 thrombocytopenia (16.1% vs. 34.6%, p=0.026). Nutritional and psychological benefits persisted at 4‑week post‑CCRT follow‑up. A multidisciplinary, mHealth‑based multimodal rehabilitation program effectively preserves handgrip strength, muscle mass, and nutritional status while reducing treatment toxicity in abdominal cancer patients undergoing CCRT. The multicenter implementation using standardized digital tools supports its scalability and translation into real‑world clinical pathways. Clinical Trial Registration: ClinicalTrials.gov NCT05325554.Registration Date 03/08/2022.

BACKGROUND:The prognosis of triple-negative breast cancer (TNBC) is notably unfavorable, necessitating the development of novel treatments to enhance therapeutic outcomes. The underlying mechanisms contributing to the pathogenesis of TNBC remain incompletely understood. RNA 5'-phosphate and 3'-OH ligase 1 (RLIG1) was found to be the first RNA ligase in humans and may be related to cancer development, but no reports have been reported. We observe RLIG1 elevated expression levels in TNBC tissues compared to adjacent non-cancerous tissues, with high RLIG1 expression correlating with reduced overall survival in TNBC patients. METHODS:We investigated RLIG1 in TNBC using bioinformatics tools, cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), colony formation, flow cytometry, and western blotting. Mechanistic insights were gained via mass spectrometry, co-immunoprecipitation, and immunofluorescence. RESULTS:Here, we found that interfering with RLIG1 can effectively hinder tumor cell cycle progression and proliferation in vitro, as well as inhibit tumor growth in vivo. Mechanistically, RLIG1 was identified as an oncogene that stimulates the mTORC1 signaling pathway in TNBC cells. Furthermore, the interaction between RLIG1 and ERK was confirmed, with RLIG1 promoting cell cycle transition and proliferation through mediating ERK phosphorylation. CONCLUSIONS:Our research offers novel insights into the biological role of RLIG1, indicating its potential as a therapeutic target for TNBC.

Bone defects caused by trauma, tumors, and degenerative diseases remain a major clinical challenge, necessitating effective strategies for bone repair. Traditional bone grafting approaches are limited by issues such as donor scarcity and immune rejection, highlighting the need for alternative strategies. Stem cell-based regenerative therapies, particularly those utilizing bone marrow mesenchymal stem cells (BMSCs), offer promising solutions due to their osteogenic potential. Herein, we report the synthesis of a porous and biocompatible nanostructured COF-Imine material and systematically evaluate its ability to promote BMSC osteogenic differentiation for bone regeneration. Our findings demonstrate that COF-Imine significantly enhances osteogenesis by activating the Wnt/beta-catenin signaling pathway through multiple mechanisms, which facilitates the expression of key osteogenic genes such as ALP, OCN, COL1, and Runx2. In vivo experiments using a rat calvarial defect model further confirm that COF-Imine accelerates bone defect repair, underscoring its potential as a biomaterial for bone tissue engineering applications.

Osteosarcoma is the most common malignant bone tumor affecting children and adolescents. Currently, the most common treatment is surgery combined with neoadjuvant chemotherapy. Although the survival rate of patients with osteosarcoma has improved in recent years, it remains poor when the tumor(s) progress and distant metastases develop. Therefore, better animal models that more accurately replicate the natural progression of the disease are needed to develop improved prognostic and diagnostic markers, as well as targeted therapies for both primary and metastatic osteosarcoma. The present review described animal models currently being used in research investigating osteosarcoma, and their characteristics, advantages, and disadvantages. These models may help elucidate the pathogenic mechanism(s) of osteosarcoma and provide evidence to support and develop clinical treatment strategies.

Objective To investigate the effect of folic acid-modified liposome quercetin(FLQ)on the proliferation and apoptosis of triple negative breast cancer(TNBC)cells and explore its underlying mech-anism.Methods CCK-8 was used to detect the effect of FLQ on TNBC cell viability.Colony formation assay was conducted to detect the effect of FLQ on TNBC cell proliferation.Flow cytometry was performed to detect the effect of FLQ on TNBC cell apoptosis,the levels of intracellular ROS,and mitochondrial membrane potential.Western blot analysis was conducted to detect the expression levels of JAK2/STAT3 signaling pathway-related and apoptosis-related proteins.Results FLQ inhibited the proliferation and promoted the apoptosis of MDA-MB-231 cells(P=0.023,P<0.001).It promoted mitochondrial membrane potential collapse and increased the intracellular ROS levels of MDA-MB-231 cells(P=0.003,P=0.034);inhibited the phosphorylation levels of JAK2 and STAT3;upregulated the expression levels of the proapo-ptotic proteins Bax,Bak,cytochrome C,and Cleaved-Caspase-3(P<0.001,P<0.001);and downregulated the expression levels of the antiapoptotic proteins Bcl2 and Bcl-xL(P=0.037,0.028).Conclusion FLQ inhibits the proliferation and induces the apoptosis of MDA-MB-231 cells.These effects may be related to the activa-tion of the mitochondrial apoptosis pathway through the inhibition of the JAK2/STAT3 signaling pathway.

There is no unified surgical plan for fibular proximal malignant tumours; therefore, the present study retrospectively analysed the medical records of 19 patients with primary malignant and invasive tumours in the proximal fibula and discussed the postoperative oncological results, complications and postoperative functions of limb salvage surgery. According to pathological classification, there were 10 osteosarcoma cases, 3 chondrosarcoma cases, 2 invasive giant cell osteosarcoma tumour cases, 1 epithelioid sarcoma case, 1 leiomyosarcoma case, 1 fibrosarcoma case and 1 lymphoma case. According to the Enneking instalment, IB stage was found in 2 cases, IIA in 2 cases and IIB in 15 cases. A total of 3 patients underwent Malawer I resection, and 16 patients underwent Malawer II resection. The follow-up period was 11-174 months, with an average of 76.58 months. Local recurrence occurred in three patients and distant metastasis in seven patients; 4 patients succumbed and 15 survived. After biceps femoris tendon reconstruction and lateral collateral ligament insertion, 18 patients had good knee stability. The Musculoskeletal Tumour Society scale ranged between 23 and 29 points, with an average of 27.26 points; the Lysholm Knee Score was 65-84 points, with an average of 83 points. After the resection of proximal fibula primary and invasive tumours, the biceps femoris tendon and lateral collateral ligament insertion point was reconstructed. The data show that this technique can effectively reconstruct stability and restore knee function.

Cancer metastasis is a major cause of mortality from several tumors, including those of the breast, prostate, and the thyroid gland. Since bone tissue is one of the most common sites of metastasis, the treatment of bone metastases is crucial for the cure of cancer. Hence, disease models must be developed to understand the process of bone metastasis in order to devise therapies for it. Several translational models of different bone metastatic tumors have been developed, including animal models, cell line injection models, bone implant models, and patient-derived xenograft models. However, a compendium on different bone metastatic cancers is currently not available. Here, we have compiled several animal models derived from current experiments on bone metastasis, mostly involving breast and prostate cancer, to improve the development of preclinical models and promote the treatment of bone metastasis.

Background Osteosarcoma is a malignant bone tumor that usually affects adolescents aged 15–19 y. The DNA damage response (DDR) is significantly enhanced in osteosarcoma, impairing the effect of systemic chemotherapy. Targeting the DDR process was considered a feasible strategy benefitting osteosarcoma patients. However, the clinical application of DDR inhibitors is not impressive because of their side effects. Chinese herbal medicines with high anti-tumor effects and low toxicity in the human body have gradually gained attention. 2-Hydroxy-3-methylanthraquinone (HMA), a Chinese medicine monomer found in the extract of Oldenlandia diffusa, exerts significant inhibitory effects on various tumors. However, its anti-osteosarcoma effects and defined molecular mechanisms have not been reported. Methods After HMA treatment, the proliferation and metastasis capacity of osteosarcoma cells was detected by CCK-8, colony formation, transwell assays and Annexin V-fluorescein isothiocyanate/propidium iodide staining. RNA-sequence, plasmid infection, RNA interference, Western blotting and immunofluorescence assay were used to investigate the molecular mechanism and effects of HMA inhibiting osteosarcoma. Rescue assay and CHIP assay was used to further verified the relationship between MYC, CHK1 and RAD51. Results HMA regulate MYC to inhibit osteosarcoma proliferation and DNA damage repair through PI3K/AKT signaling pathway. The results of RNA-seq, IHC, Western boltting etc. showed relationship between MYC, CHK1 and RAD51. Rescue assay and CHIP assay further verified HMA can impair homologous recombination repair through the MYC-CHK1-RAD51 pathway. Conclusion HMA significantly inhibits osteosarcoma proliferation and homologous recombination repair through the MYC-CHK1-RAD51 pathway, which is mediated by the PI3K-AKT signaling pathway. This study investigated the exact mechanism of the anti-osteosarcoma effect of HMA and provided a potential feasible strategy for the clinical treatment of human osteosarcoma. Graphical Abstract

Polyetheretherketone (PEEK) can potentially be used for bone repair because its elastic modulus is similar to that of human natural bone and good biocompatibility and chemical stability. However, its hydrophobicity and biological inertness limit its application in the biomedical field. Inspired by the composition, structure, and function of bone tissue, many strategies are proposed to change the structure and functionality of the PEEK surface. In this review, the applications of PEEK in bone repair and the optimization strategy for PEEK's biological activity are reviewed, which provides a direction for the development of multifunctional bone repair materials in the future.

By using bioinformatics analysis and the experimental techniques of cell biology and molecular biology, we found that DEP domain-containing protein 1B (DEPDC1B) can promote the invasion and migration of breast cancer cells and that DEPDC1B mediates the deubiquitination of β-catenin by ubiquitin-specific protease 5 (USP5), thus activating the wnt/β-catenin pathway. Our findings provide new insights into the carcinogenic mechanism of DEPDC1B, suggesting that DEPDC1B can be used as a potential therapeutic target for breast cancer.

目的:分析老年骨肉瘤临床特征与影像学表现,提高对老年骨肉瘤的诊断水平,避免误诊误治.方法:回顾性分析32例经病理检查诊断证实的老年骨肉瘤患者的临床、病理及影像资料.所有患者均行X线和MRI检查,26例患者行CT检查,17例患者行SPECT-CT检查,评估软组织肿块范围、骨质破坏范围情况.结果:所有病例均为局部单发,股骨远端17例,胫骨近端6例,其他部位9例.X线检查表现为松质骨斑片状的骨质破坏,皮质边缘主要是小而密集的虫蚀样破坏.软组织肿块多表现为圆形或者半圆形,边界模糊不清,肿块内部存在瘤骨.Godman三角是骨肉瘤最常见的X线征象之一.CT检查显示病变区域都存在不规则的骨质破坏表现,内部为高密度的瘤骨影.MRI检查显示所有患者都存在不规则的骨质破坏表现,T1WI为不均匀的低信号,T2WI为高低混杂的信号,骨膜反应和瘤骨都表现为低信号.结论:老年骨肉瘤是临床少见的疾病,综合应用X线、CT、MRI和SPECT-CT检查可以提高诊断准确率.其中X线检查是老年骨肉瘤的首选检查方法,CT能够敏感识别早期骨质病变,MRI在显示肿块与周围组织的结构关系方面更具优势,SPECT-CT可以评估全身转移情况.

PurposeTo examine clinical outcomes of a specialized modular prosthesis used to fill a bone deficiency following removal of femoral shaft metastases.MethodsEighteen patients with femoral shaft metastases who underwent en bloc resection and implantation of a personalized modular prosthesis between December 2014 and December 2019 were retrospectively analyzed. Pain, limb function, and quality of life were evaluated using the visual analog scale (VAS), Musculoskeletal Tumor Society (MSTS) scale, International Society of Limb Salvage (ISOLS) scoring system, Karnofsky Performance Status (KPS) scale, and Nottingham Health Profile (NHP) scale. The Kaplan–Meier technique was used to analyze patient survival.ResultsThe operation duration was 90–150 min (mean, 115 min), and the osteotomy length was 9–16 cm (mean, 11.72 cm). The patients were followed for 12–62 months (mean, 25.28 months). The VAS and NHP ratings were lower at 3, 6, and 12 months after surgery than before surgery, while the MSTS, ISOLS, and KPS scores were higher after surgery than they had been before. These differences were statistically significant (P<0.05). The survival period was between 7 and 62 months (mean, 20.89 months), and the rates of survival at 1-year and 2-year were 72.22% and 27.78%, respectively. Except for two patients with aseptic prosthesis loosening during the follow-up period, there were no problems.ConclusionEn bloc excision and implantation of a personalized modular prosthesis can reduce pain and improve the ability of patients with femoral shaft metastases to perform daily activities, thereby improving their quality of life.

目的 基于网络药理学和分子对接技术探究白花蛇舌草治疗骨肉瘤的作用机制.方法 借助中药系统药理学数据库与分析平台(TCMSP)和中药综合数据库(TCMID)平台,检索白花蛇舌草化学成分和作用靶点,并通过基因卡(GeneCards)、人类在线孟德尔遗传数据库(OMIM)和疾病靶点预测数据库(TTD)获取骨肉瘤相关靶点,预测白花蛇舌草治疗骨肉瘤的共同靶点,构建"中药-活性成分-靶点-疾病"网络图.通过STRING平台构建靶点蛋白互作网络(PPI),并使用R语言对PPI中的靶点进行基因本体(GO)功能及京都基因和基因组(KEGG)信号通路富集分析.将相关度最高的前 5 位靶点和白花蛇舌草的活性成分进行分子对接,对结合能最大的活性成分-靶点构建对接模型.结果 共筛选出白花蛇舌草中 8 个活性成分,179 个对应的靶点.检索得到3596个骨肉瘤相关靶点,经R语言取交集得到 124 个共同靶点."中药-活性成分-靶点-疾病"网络提示,白花蛇舌草的 6 个活性成分作用于 124 个靶点基因以治疗骨肉瘤.PPI图中,124 个靶点相互作用关系密切,其中AKT1、TP53、IL-6、MAPK1、TNF等为核心靶点,与活性成分分子对接稳定,结合能最高的是槲皮素与MAPK1,结合能为-8.6 kcal/mol.GO分析显示,靶点涉及氧化应激反应、活性氧反应、DNA结合转录因子活性的调控、脂多糖反应、细菌源性分子反应、肌细胞增殖、类固醇反应等生物过程;KEGG信号通路包括IL-17 信号通路、TNF信号通路、前列腺癌、脂质与动脉粥样硬化、人巨细胞病毒感染、糖尿病并发症中的AGE-RAGE信号通路、MAPK信号通路、Toll样受体等信号通路.结论 白花蛇舌草的活性成分如槲皮素通过多靶点多途径治疗骨肉瘤.

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and chemotherapy. Chemotherapy drugs act by interfering with tumor growth and inducing the death of cancer cells. Anti-tumor drugs were developed to induce apoptosis, but some patient's show apoptosis escape and chemotherapy resistance. Therefore, other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer treatment. Ferroptosis is a newly discovered iron-dependent, non-apoptotic type of cell death that is highly negatively correlated with cancer development. Ferroptosis is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox homeostasis. This review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

目的:探讨程序性死亡因子配体1(PD-L1)在骨肉瘤细胞和组织中的表达及对患者预后的影响.方法:采用Western Blot检测PD-L1在骨肉瘤细胞系和成骨细胞系中的表达,并用免疫组织化学(IHC)方法检测肿瘤及癌旁组织中PD-L1的表达,用Kaplan-Meier法进行生存分析.结果:PD-L1在骨肉瘤细胞株中的表达高于正常成骨细胞,而且其在骨肉瘤组织中的表达也显著高于癌旁组织,差异有统计学意义(P＜0.05).Kaplan-Meier生存分析显示PD-L1高表达患者预后较低表达患者差,差异有统计学意义(P＜0.05).结论:PD-L1在骨肉瘤中高表达,其高表达与患者预后不良有关,提示PD-L1可作为潜在的治疗靶点.

Background Anal squamous cell carcinoma (ASCC) is the main subtype of anal cancer and has great heterogeneity in prognosis. We aimed to construct a nomogram for predicting their 1-, 3-, and 5-year overall survival (OS) rates. Methods Patients with ASCC, enrolled between January 1, 2010 and December 31, 2017, were identified from the SEER database. They were divided into a training group and a validation group in a ratio of 7:3. Univariate and multivariate Cox analyses were used to identify the prognostic factors for OS. Then a prognostic nomogram was established and validated by Harrell consistency index (C-index), area under the curve (AUC) of the receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results We identified 761 patients in training group and 326 patients in validation group. Four prognostic factors including age, sex, AJCC stage, and radiotherapy were identified and integrated to construct a prognostic nomogram. The C-index and AUC values proved the model's effectiveness and calibration plots manifested its excellent discrimination. Furthermore, in comparison to the AJCC stage, the C-index, AUC, and DCA proved the nomogram to be of good predictive value. Finally, we constructed a risk stratification model for dividing patients into low-risk, medium-risk, and high-risk groups, and there were obvious differences in OS. Conclusions A prognostic nomogram was firstly established for predicting the survival probability of ASCC patients and helping clinicians improve their risk management.

Osteosarcoma (OS) is a malignant solid tumor prone to lung metastasis that occurs in adolescents aged 15-19 years. Neoadjuvant chemotherapy and surgical treatment aimed at curing OS have gained limited progress over the last 30 years. Exploring new effective second-line therapies for OS patients is a serious challenge for researchers. Quercetin, a multiple biologically active polyphenolic flavonoid, has been used in tumor therapy. However, the exact mechanism of quercetin is still unknown, which limits the application of quercetin. In the current study, we found that quercetin could inhibit JAK2 through the JH2 domain in a non-covalent manner, resulting in the inhibition of OS proliferation and immune escape via the JAK2-STAT3-PD-L1 signaling axis. More importantly, to overcome the shortcomings of quercetin, including low water solubility and low oral availability, we encapsulated it with folic acid-modified liposomes. The transportation of quercetin by folic acid-modified liposomes may provide a feasible strategy to cure OS.

Pyruvate kinase M2 (PKM2) plays an important role in the consumption of glucose and the production of lactic acid, the striking feature of cancer metabolism. The association of PKM2 with osteosarcoma (OS) has been reported but its role in OS has yet to be elucidated. To study this, PKM2-bound RNAs in HeLa cells, a type of cancer cells widely used in the study of molecular function and mechanism, were obtained. Peak calling analysis revealed that PKM2 binds to long noncoding RNAs (lncRNAs), which are associated with cancer pathogenesis and development. Validation of the PKM2-lncRNA interaction in the human OS cell line revealed that lncRNA colon cancer associated transcript-1 (lncCCAT1) interacted with PKM2, which upregulated the phosphorylation of sterol regulatory element-binding protein 2 (SREBP2). These factors promoted the Warburg effect, lipogenesis, and OS cell growth. PKM2 appears to be a key regulator in OS by binding to lncCCAT1. This further extends the biological functions of PKM2 in tumorigenesis and makes it a novel potential therapeutic for OS.