Objective: Osteosarcoma is a highly aggressive primary bone tumor that predominantly affects pediatric and adolescent populations. This study aims to explore the therapeutic potential and underlying mechanisms of melittin in treating osteosarcoma both in vitro and in vivo. Materials and methods: Two osteosarcoma cell lines, namely 143B and U-2 OS, were utilized to assess the impact of melittin on cellular proliferation, apoptosis, and cell cycle progression. The effect of melittin on cell viability was evaluated using the CCK-8 assay. Flow cytometry was employed to assess apoptosis and cell cycle progression, while Western blotting analyzed the expression of key proteins, including Cdc-2, c-Myc, and ꞵ-catenin. Specifically, we employed small interfering RNA (siRNA) to selectively knock down the expression of β-catenin in two osteosarcoma cell lines. In vivo studies, tumor growth in nude mice was evaluated through measurements of tumor weight, volume. Additionally, immunohistochemical analysis was performed to assess Ki-67 and active ꞵ-catenin expression in tumor tissues. Results: Melittin induced apoptosis in 143B and U-2 OS osteosarcoma cells in a concentration-dependent manner and caused S-phase cell cycle arrest as the drug concentration increased. Mechanistic investigations revealed that melittin's efficacy was associated with the inactivation of the Wnt/ꞵ-catenin signaling pathway. Specifically, melittin treatment reduced the expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3ꞵ) and active ꞵ-catenin. Notably, silencing β-catenin in 143B and U-2 OS osteosarcoma cells significantly enhanced the anti-proliferative and pro-apoptotic effects of melittin. This was evidenced by reduced cell viability and increased apoptosis, thereby further confirming that the anti-tumor efficacy of melittin is dependent on the inhibition of the Wnt/β-catenin signaling pathway. In vivo studies confirmed that melittin significantly inhibited the growth of subcutaneously implanted tumors in nude mice. This inhibition was further supported by Ki-67 analyse and H&E staining, while immunohistochemical analysis revealed an obvious reduction in active ꞵ-catenin expression. Conclusions: Our results offer deeper mechanistic insights into the inhibitory impact of melittin on osteosarcoma progression, at least in part by suppressing the Wnt/β-catenin signaling pathway. We expand upon previous research by providing more comprehensive and robust evidences that underscore the potential of melittin as a viable and safe therapeutic agent for osteosarcoma.

Purpose This study aimed to compare the bone mineral density (BMD) of older women living in rural and urban areas, and evaluate the potential factors affecting the risk of osteoporosis. Methods We recruited 574 women aged 65 years or older from rural areas and 496 from urban areas in Shanghai, China. The BMD values of the lumbar vertebrae and total left hip were measured by a dual energy X-ray absorptiometry densitometer. We also recorded information about education level, family income, medications, reproductive and menstrual history, diet, smoking, and alcohol consumption. Results Women in urban areas had significantly higher BMD in their lumbar spine, and there was a dramatic increase in the proportion of women with osteoporosis in rural areas. The age at menarche was significantly higher among women living in rural areas, and there were more years from menarche to menopause among urban women. Rural women had significantly higher numbers of both pregnancies and parity, and a significantly lower age at first parity. In multiple linear regression analyses, years from menarche to menopause was independently related to high lumbar spine BMD, while age at menarche and parity was independently related to low lumbar spine BMD. Conclusion More older women in rural areas had osteoporosis. Later menarche, less years from menarche to menopause and higher parity might partially contribute to decreased BMD among women in rural areas. More attention should be paid to women in rural areas to prevent bone loss and further bone and health impairment.

OBJECTIVE:To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models.METHODS:PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review.RESULTS:CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate.CONCLUSION:CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.

目的 调查骨质疏松症(osteoporosis,OP)患者的中医体质分布类型,探讨血清骨代谢指标与中医体质的相关性.方法 2016年10月-2017年2月,选取上海市40～70岁中老年常住居民,采用《中医体质分类与判定》标准调查中医体质类型.双能X线吸收检测法测定受试者的腰椎骨密度,并检测血清钙、磷、肌酐、25-羟维生素D[25-hydroxy-vitaminD,25(OH)D]、甲状旁腺素(parathyroid hormone,PTH)、碱性磷酸酶(alkaline phosphatase,ALP)、骨钙素(osteocalcin,OC)、Ⅰ型原胶原N-端前肽(procollagen type Ⅰ N-peptide,PINP)及Ⅰ型胶原交联C-末端肽(beta cross linked C-lelopeptideof type Ⅰ collagen,β-CTX),分析骨代谢指标与中医体质的相关性.结果 共纳入802例调查对象,平均年龄为(61.8±4.4)岁,其中男性184例、女性618例,骨量正常组235例,骨量减少组361例,骨质疏松组206例.骨质疏松组阳虚质构成比大于骨量正常组,差异有统计学意义(27.67％vs 14.89％,P=0.004).骨量减少组和骨质疏松组痰湿质构成比均小于骨量正常组,差异有统计学意义(P=0.004).3组受试者的中医体质构成比在其余7种偏颇体质中,差异均无统计学意义.选取骨质疏松组40例非阳虚质人群与57例阳虚质人群进行匹配,阳虚质人群的肌酐水平低于非阳虚质人群,差异有统计学意义(P＜0.01).2组人群在血钙、血磷、25(OH)D、ALP、β-CTX、PTH及PINP之间差异均无统计学意义.结论 OP患者偏颇体质中阳虚质明显增多,且OP患者阳虚质与血清肌酐水平相关.

目的:探索中老年原发性骨质疏松症人群脉图参数的变化特征.方法:筛选并纳入中老年受试者共计1 062例,根据纳入对象的骨密度(BMD)测定结果将其分为骨量正常组327例、骨量减少组466例、骨质疏松组269例.运用PDA-1型单道脉诊仪采集所有受试者的寸口关部脉象信息,并进行统计分析.结果:随着骨量减少程度加重,三组脉图参数h1、h3、h4、h1/t1呈下降趋势,但组间比较差异无统计学意义(P＞0.05);与骨量正常组比较,骨质疏松组脉图参数h5明显降低,差异有统计学意义(P＜0.05).随着骨量减少程度的加重,三组心率变异参数P_mean、P_PNN、TF呈下降趋势,但组间比较差异无统计学意义(P＞0.05).结论:中老年骨质疏松症人群的大动脉顺应性较正常骨量人群明显下降,大血管硬化程度增加,提示机体脏腑气血相对不足,代谢水平降低,长期可形成重要脏腑气血虚弱,并久虚致瘀,这与原发性骨质疏松症中医发病机制“虚”与“瘀”相符.

Prostate cancer is the second most commonly diagnosed malignancy and the sixth global primary cause of malignancy-associated fatality. Increased invasiveness and motility in prostate cancer cells are associated with ubiquitin proteasome system-regulated epithelial to mesenchymal transition (EMT). Impairment of the endoplasmic reticulum (ER) causes ER stress due to the accumulation of unfolded proteins and altered cell survival. In the current study, the effect and mechanism of matrine on cell apoptosis, viability, migration and invasion of human prostate cancer cells in vivo and in vitro through the unfolded protein response (UPR)/ER stress pathway were investigated. Matrine inhibited proteasomal chymotrypsin-like (CT-like) activity in the prostate carcinoma cellular proteasome. Upregulated vimentin and N-cadherin and downregulated E-cadherin were also observed in vitro and in vivo. In vitro analyses showed that matrine repressed cell motility, viability and invasion, arrested the cell cycle at the G(0)/G(1) phase and induced prostate cancer cell apoptosis. Furthermore, matrine activated the UPR/ER stress signaling cascade in prostate cancer cells and tumor tissues of xcnograft-bearing nude mice. Results also demonstrated that the anti-apoptotic protein Bd-2 was downregulated, the pro-apoptotic protein Bak was upregulated and the cell growth and cell cycle-related proteins c-Myc, Cyclin B1, Cyclin D1 and CDK1 were downregulated. Moreover, matrine inhibited tumor growth and Ki-67 expression in xenograft-bearing nude mice. To the best of our knowledge, the present study indicated for the first time that matrine exerted marked anticancer functions in human prostate carcinoma in vivo and in vitro through activation of the proteasomal CT-like activity inhibition mediated by the UPR/ER stress signaling pathway.

Osteosarcoma, one of the most common primary bone malignances, is a leading cause of cancer death among children and adolescents. Recently, growing studies have found that long non-coding RNAs (lncRNAs) can interfere with the expression of various genes, and participate in the occurrence and development of malignancies. The purpose of this study is to evaluate the potential functions of lncRNAs as diagnostic biomarkers and therapeutic targets for osteosarcoma in mice, thus to direct the strict design for the future preclinical experiments and clinical trials. We systematically searched PubMed, Web of Science, Embase, China Knowledge Resource Integrated Database, VIP, Chinese BioMedical and Wan Fang Database from their initiation date to June 20, 2017. Two researchers independently screened the literatures and withdrew the data, which used the tumor volume and tumor weight as the outcome measures. A total of 10 studies were included, and the results of this meta-analysis revealed that lncRNAs could serve as the diagnostic biomarkers and therapeutic targets for osteosarcoma; and progression of osteosarcoma in mice could be inhibited via rescuing the abnormally expressed lncRNAs. It is necessary to carry out more rigorous basic experiments before lncRNAs can be further investigated in the clinical trials and used in future clinical practices.

骨肉瘤也称为成骨肉瘤,是青少年及儿童最常见的恶性骨肿瘤,是一种复发率极高,且极难治愈的原发性恶性肿瘤.现如今,随着各类医学技术的发展,骨肉瘤的诊治得到了很大的提高,但是由于骨肉瘤本身恶性度高、生长迅速、早期转移且治疗后极易复发,骨肉瘤的治疗和治疗后控制依然是临床上的一大难题.因此找到一种能够更大程度地减少患者痛苦、降低人体损伤的治疗方法迫在眉睫,而免疫治疗为骨肉瘤的生物学治疗提供了一种崭新的治疗方向.因此,现对骨肉瘤免疫治疗的研究现状作一综述,望为骨肉瘤的研究及临床进展提供一定的方向.

Growing studies have confirmed that long non-coding RNAs (lncRNAs) involve in the occurrence and development of various cancers. XIST, as a lncRNA, was dysregulated in different cancers. This meta-analysis was performed to evaluate the prognostic potential of XIST in malignant tumors. Eight databases of PubMed, Web of Science, Embase, Cochrane library, CNKI, VIP, SinoMed and Wang Fang were comprehensively searched from their initiation date to August 15, 2017. A total of nine studies with 853 cancer patients met the including criteria were finally included in this meta-analysis after independently screening the literatures by two researchers. Any discrepancies were resolved by a consensus. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for the primary endpoints were extracted and pooled for meta-analysis. Our results showed that expression level of XIST was markedly associated with overall survival (function as oncogene, HR = 0.53, 95% CI: 0.42-0.68, p < 0.00001; function as tumor suppressor, HR = 2.25, 95% CI: 1.15-4.37, p = 0.02), disease free survival (DFS)(HR = 0.45; 95% CI: 0.31-0.67, p < 0.0001), tumor type (digestive system carcinoma, HR = 0.50; 95% CI: 0.37-0.69, p < 0.00001; non-digestive system carcinoma, HR = 0.58; 95% CI: 0.39-0.87, p = 0.008), lymph node metastasis (OR = 0.32, 95% CI: 0.20-0.52, p < 0.00001), distant metastasis (OR = 0.36, 95% CI: 0.22-0.60, p < 0.0001) and tumor stage (OR = 0.43, 95% CI: 0.31-0.60, p < 0.00001). In conclusion, the pooled results in our current work suggest that XIST is an important prognostic biomarker in cancer patients.

骨肉瘤是一种常见的原发性恶性骨肿瘤,好发于儿童和青少年.由于其高度的复发性和转移性,患者多预后不良,因此寻求一种新型的治疗靶点非常迫切.近年来,大量研究发现microRNA(miRNA)可干扰多种基因的表达,对肿瘤的发生和发展具有重要的调控作用.随着miRNA对骨肉瘤的作用机制不断被揭示,多种新型分子靶点被挖掘,为深入研究骨肉瘤的发病、转移、诊断、治疗和预后提供了新的方向.本文结合近年的最新报道,对影响骨肉瘤的相关miRNA及其与骨肉瘤作用机制的研究进展进行综述.

Osteosarcoma is the most common primary bone cancer in children and adolescents. In spite of aggressive treatment, osteosarcoma has a high mortality rate with minimal improvements in survival over past few decades. Polyphyllin I (PPI), a component in the traditional Chinese medicinal herb Paris polyphylla Smith, has been shown to have anti-tumor properties. However, its mechanism as an anti-osteosarcoma agent has not been well elucidated. In this study, we found that PPI suppressed osteosarcoma cell viability, arrested cell cycle in G2/M phase, induced apoptosis and inhibited invasion and migration of osteosarcoma cells. Moreover, PPI significantly suppressed intratibial primary tumor growth in xenograft orthotopic mouse model without any obvious side effects. These therapeutic efficacies were associated with inactivation of Wnt/β-catenin pathway, as PPI treatment decreased the amount of p-GSK-3β, leading to down-regulated levels of active β-catenin. PPI induced inhibition of osteosarcoma cell viability was abolished upon addition of GSK-3β specific inhibitor, CHIR99021, while PPI induced inhibition of osteosarcoma cell viability and migration were potentiated by β-catenin silencing. These findings suggested that, in vitro and in vivo, PPI treatment inhibited osteosarcoma, at least in part, via the inactivation of Wnt/β-catenin pathway. Thus, PPI could serve a novel therapeutic option for osteosarcoma patients.

Osteosarcoma (OS) is the most common primary malignant bone carcinoma with high morbidity that happens mainly in children and young adults. As the key components of gene-regulatory networks, microRNAs (miRNAs) control many critical pathophysiological processes, including initiation and progression of cancers. The objective of this study is to summarize and evaluate the potential of miRNAs as targets for prevention and treatment of OS in mouse models, and to explore the methodological quality of current studies. We searched PubMed, Web of Science, Embase, Wan Fang Database, VIP Database, China Knowledge Resource Integrated Database, and Chinese BioMedical since their beginning date to 10 May 2016. Two reviewers separately screened the controlled studies, which estimate the effects of miRNAs on osteosarcoma in mice. A pair-wise analysis was performed. Thirty six studies with enough randomization were selected and included in the meta-analysis. We found that blocking oncogenic or restoring decreased miRNAs in cancer cells could significantly suppress the progression of OS in vivo, as assessed by tumor volume and tumor weight. This meta-analysis suggests that miRNAs are potential therapeutic targets for OS and correction of the altered expression of miRNAs significantly suppresses the progression of OS in mouse models, however, the overall methodological quality of studies included here was low, and more animal studies with the rigourous design must be carried out before a miRNA-based treatment could be translated from animal studies to clinical trials.

Osteosarcoma (OS) is the most common primary malignant bone carcinoma with high morbidity that happens mainly in children and young adults. As the key components of gene-regulatory networks, microRNAs (miRNAs) control many critical pathophysiological processes, including initiation and progression of cancers. The objective of this study is to summarize and evaluate the potential of miRNAs as targets for prevention and treatment of OS in mouse models, and to explore the methodological quality of current studies. We searched PubMed, Web of Science, Embase, Wan Fang Database, VIP Database, China Knowledge Resource Integrated Database, and Chinese BioMedical since their beginning date to 10 May 2016. Two reviewers separately screened the controlled studies, which estimate the effects of miRNAs on osteosarcoma in mice. A pair-wise analysis was performed. Thirty six studies with enough randomization were selected and included in the meta-analysis. We found that blocking oncogenic or restoring decreased miRNAs in cancer cells could significantly suppress the progression of OS in vivo, as assessed by tumor volume and tumor weight. This meta-analysis suggests that miRNAs are potential therapeutic targets for OS and correction of the altered expression of miRNAs significantly suppresses the progression of OS in mouse models, however, the overall methodological quality of studies included here was low, and more animal studies with the rigourous design must be carried out before a miRNA-based treatment could be translated from animal studies to clinical trials.

Osteosarcoma is a most common highly malignant bone tumor in children and adolescents. Polyphyllin I (PPI) is an ethanol extraction from Paris polyphylla Smith var.yunnanensis (Franch.) Hand.-Mazz, which belongs to antipyretic-detoxicate family and has been used as a natural medicine in the treatment of infectious disease and cancer in China for centuries. The proteasome activity inhibitory and anti-osteosarcoma effects of PPI have not been known. Here we found PPI exhibited a selective inhibitory effect on proteasomal chymotrypsin (CT)-like activity, both in purified human proteasome and in cultured osteosarcoma cellular proteasome, and caused an accumulation of ubiquitinated proteins. PPI also inhibited viability, proliferation, migration, and invasion of MG-63, Saos-2, and U-2 OS osteosarcoma cells and resulted in S phase arrest and apoptosis. Furthermore, we explored the molecular targets involved. Exposure of osteosarcoma cells to PPI caused an inactivation of the intrinsic nuclear factor κB (NF-κB) and activation of unfolded protein response (UPR)/endoplasmic reticulum (ER) stress signaling cascade in osteosarcoma cells, followed by down-regulation of anti-apoptotic proteins, with up-regulation of pro-apoptotic proteins. We also demonstrated down-regulation of c-Myc, Cyclin B1, Cyclin D1, and CDK1, which are involved in the cell cycle and growth. Finally, we identified down-regulation of Vimentin, Snail, Slug, and up-regulation of E-cadherin, which are integral proteins involved in epithelial–mesenchymal transition (EMT). Taken together, our data provide insights into the mechanism underlying the anticancer activity of PPI in human osteosarcoma cells.