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Xia Zhu,1,2 Kangyang Lu,1 Liyu Cao,1,3 Yong Hu,4 Yu Yin,1,3 Yongping Cai1,3 1Department of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei 230032, People’s Republic of China; 2Department of Pathology, Huadong Hospital, Fudan University, Shanghai 200040, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, People’s Republic of China; 4Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, People’s Republic of ChinaCorrespondence: Yu Yin; Yongping CaiDepartment of Pathology, School of Basic Medical Science, Anhui Medical University, Hefei 230032, People’s Republic of ChinaEmail aydyinyu@aliyun.com; cyply221@163.comBackground: Osteosarcoma (OS) is a highly aggressive bone malignancy that is mostly diagnosed in children and young adults. Increasing evidence indicates that the transcription factor Forkhead Box M1 (FoxM1) plays a key role in the pathogenesis of various tumors. However, the function of FoxM1 in OS has not been clearly elucidated.Methods: In the present study, we first analyzed the expressions of FoxM1 in human OS and myositis ossificans (MO, included as a control) tissues by immunohistochemistry. To investigate the functional significance of FoxM1 in OS tumorigenesis, we examined the effects of FoxM1 downregulation in MG-63 and HOS-MNNG cells by either short hairpin RNA (shRNA)-mediated gene silencing or treatment with thiostrepton, a specific FoxM1 inhibitor.Results: FoxM1 was detected in 82.1% (55/67) of OS vs only 10% (2/20) of MO samples. High expressions of FoxM1 were also detected in three human OS cell lines (HOS-MNNG, MG-63, and U-2OS). FoxM1 downregulation significantly reduced MG-63 and HOS-MNNG cell proliferation, migration, and invasion as well as cell cycle arrest in the G2/M phase and increased apoptotic cell death.Conclusion: The present study demonstrated the critical role of FoxM1 in the pathogenesis of OS. Therefore, FoxM1 may serve as a potential therapeutic target for the treatment of OS.Keywords: osteosarcoma, FoxM1, thiostrepton, shRNA, tumorigenesis

Jia Chen,1 Liuyue Xu,2 Quan He,3 Shouling Wu,4 Dayi Hu,5 Kai Lu3 1Department of Clinical Nutrition, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 3Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 4Department of Cardiology, Kailuan General Hospital, Hebei United University, Tangshan 100816, People’s Republic of China; 5Heart Center, Peking University People’s Hospital, Beijing 100044, People’s Republic of ChinaCorrespondence: Kai LuDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, People’s Republic of ChinaTel/Fax +86 23 89011562Email lukai2013@foxmail.comBackground: This prospective cohort study aimed to evaluate the potential association of ideal cardiovascular health metrics with the plasma levels of highly sensitive C-reactive protein (hs-CRP) among people in North China.Methods: A total of 80,968 participants were included in this study at baseline. Data relating to seven health metrics and plasma hs-CRP levels were collected at baseline and the end of follow-up. The change in health metrics of each individual was compared and recorded. The potential association of gain or loss of each health metric, as well as the change in the total number of health metrics that each individual had during follow-up, with the risk of increased hs-CRP level, were explored by multiple Cox proportional hazards models.Results: A total of 72,321 participants (94.51%) completed the follow-up, and the average follow-up time was 4.1 years. Ideal body mass index (BMI), physical activity, smoking status and total cholesterol all had significant impacts on hs-CRP levels, with ideal BMI having the largest impact. Losing ideal BMI during follow-up raised the probability of hs-CRP increase during the follow-up time by 1.72 (95% CI, 1.59– 1.86) times for men and 2.05 (95% CI, 1.76– 2.39) times for women. The effects of ideal salt intake and blood pressure on hs-CRP levels were uncertain. Changes in the total number of ideal metrics for each individual had a significant cumulative effect on hs-CRP. The hazard ratio of loss of four to six health metrics during follow-up on the risk of hs-CRP increase was 1.69 (95% CI, 1.38– 2.06) for men and 1.52 (95% CI, 1.13– 2.04) for women.Conclusion: Loss or gain of ideal cardiovascular health metrics is associated with significant fluctuations in plasma hs-CRP levels. The cardiovascular benefits brought by the ideal health metrics are mediated at least in part by reducing systemic inflammation in the body.Keywords: ideal cardiovascular health metrics, highly sensitive C-reactive protein, cardiovascular diseases

Jia Chen,1,* Kai Lu,2,* Hong Chen,3 Ning Hu,3 Jie Chen,3 Xi Liang,3 Jian Qin,1 Wei Huang3 1Department of Clinical Nutrition, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 3Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HuangDepartment of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Chongqing 400016, People’s Republic of ChinaTel +86-13883383330Fax +86-23 89011211Email drhuangwei@yeah.netBackground: The study aimed to investigate the potential association of trunk skeletal muscle mass (tSM) and phase angle measured by bioelectrical impedance analysis (BIA) with the chance of femoral neck fractures in very elderly people.Patients and Methods: This case-control study enrolled 78 femoral neck fracture patients aged over 75 years (29 males) and 1:2 matched healthy controls. All participants were subjected to BIA examination by specialists. tSM, the corrected values by height squared of tSM (tSMI) and phase angle were compared between fracture patients and controls. Multivariate logistic regression was performed to explore the strength of association of femoral neck fracture with tSM, tSMI, and phase angle.Results: tSM (kg) of fracture patients was significantly lower than those of controls in all participants (women: 13.49± 0.42 vs 15.44± 0.39, p< 0.05; men: 15.30± 0.71 vs 17.54± 0.78, p< 0.05). In the sarcopenic subgroup, fracture patients also got a lower tSM than controls (women: 12.58± 0.21 vs 13.62± 0.16, p< 0.05; men:14.41± 0.29 vs 16.07± 0.21, p< 0.05). The comparison of tSMI between the two groups was similar to that of tSM. Phase angle (°) at 50 kHz in fracture patients was significantly lower than that of controls in women and men (women: 3.70± 0.32 vs 4.61± 0.21, p< 0.05; men: 3.50± 0.20 vs 3.84± 0.22, p< 0.05). Multivariate logistic regression analysis demonstrated higher fracture chance with significantly associated decreased tSM [women: OR (95% CI): 0.78(0.67– 0.91); men: 0.74(0.64– 0.86)] and tSMI [women: OR (95% CI): 0.72(0.61– 0.85); men: 0.69 (0.59– 0.81)]. In addition, per 1° increase of phase angle in the trunk could decrease the fracture risk by 14% for women [OR (95% CI): 0.86 0.79– 0.94)] and 29% for men [OR (95% CI): 0.71 (0.64– 0.79)].Conclusion: This study indicates a decrease in tSM, tSMI, and phase angle measured by BIA is significantly related to the increased chance of femoral neck fracture in people aged over 75 years. Strengthening the mass and strength of trunk skeletal muscles may help reduce the risk of femoral neck fracture in elderly patients.Keywords: bioelectrical impedance analysis, skeletal muscle mass, phase angle, femoral neck fracture

Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity. [ABSTRACT FROM AUTHOR]

The large yellow croaker (Pseudosciaena crocea), once a vital fishery resource in the East China Sea, has witnessed a substantial decline in its wild population towing to overfishing. The current resource circumstances mainly relies on artificial breeding, with limited contributions from wild populations. However, discriminating between wild and cultured populations of the large yellow croaker in market trade and parent fish selection remains largely dependent on experiential judgment, with precise and efficient discrimination methods lacking. In this study, the framework method was used to quantify the external morphological characteristics of wild and cultured populations. The differences in external morphology between the two populations were visualized using principal component analysis, and they were classified through stepwise discriminant analysis. Results revealed significant differences in the standardized morphological parameters among most large yellow croakers from these two populations. Additionally, their distributions on principal components 2 and 3 were dissimilar. Furthermore, significant sex-based differences were observed in the cultured population, whereas in the wild population, sex differences were comparatively minor. Cross-validation results revealed that the classification accuracy of distinguishing between different populations exceeded that for separating cultured or wild populations according to different sexes. These findings suggest that the framework method is effective for discriminating between cultured and wild populations of large yellow croaker, although it may not be as successful in distinguishing between individuals of different sexes in these populations. The outcomes of this research offer valuable support for large yellow croaker breeding initiatives. [ABSTRACT FROM AUTHOR]

Shanshan Ma,* Tingting Zhang,* Li Jiang,* Wen Qin, Keyu Lu, Yong Zhang, Rensheng WangDepartment of Radiotherapy, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workObjective: This study aimed to investigate the impact of bladder volume on treatment planning and clinical outcomes of radiotherapy for patients with cervical cancer.Materials and methods: One hundred and sixty-six patients with locally advanced cervical cancer were selected in this retrospective study. The patients were divided into four groups according to their average bladder volume during radiotherapy (external beam radiation therapy and intracavitary brachytherapy): group A: V200 mL. The bladder volume and the cumulative dose to planning target (D90), bladder (D2cc), rectum (D2cc), and sigmoid (D2cc) were calculated using the treatment planning system. Treatment outcomes including late adverse events (the maximum grade of radiation-induced proctitis and cystitis), the objective response rate of tumor and lymph node, overall survival (OS), and progression-free survival (PFS) were collected. Additionally, the correlation between bladder volume and the irradiated dose of organs at risk and treatment outcomes was analyzed.Results: The median follow-up time was 28 months. The D90 and D2cc of the rectum in group A were the highest (P

Guoqun Wang,1 Jiaojiao Zhao,2 Meiling Zhang,1 Qian Wang,1 Bo Chen,3 Yayi Hou,2,4 Kaihua Lu11Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing 210093, People’s Republic of China; 3Institute of Materials Science and Devices, Suzhou University of Science and Technology, Suzhou 215009, People’s Republic of China; 4Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing 210093, People’s Republic of ChinaPurpose: Drug resistance is a major challenge for epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) treatment of lung cancer. Ferumoxytol (FMT) drives macrophage (MΦ) transformation towards a M1-like phenotype and thereby inhibits tumor growth. CpG oligodeoxynucleotide 2395 (CpG), a toll-like receptor 9 (TLR9) agonist, is an effective therapeutic agent to induce anticancer immune responses. Herein, the effect of co-administered FMT and CpG on MΦ activation for treating non-small cell lung cancer (NSCLC) was explored.Methods: The mRNA expression levels of M1-like genes in RAW 264.7 MΦ cells stimulated by FMT, CpG and FMT and CpG (FMT/CpG) were evaluated by quantitative reverse transcription PCR (qRT-PCR). Then, the effects of FMT/CpG-pretreated MΦ supernatant on apoptosis and proliferation of H1975 cells were detected by flow cytometry, and the expression of EGFR and its downstream signaling pathway in H1975 cells were explored by western blotting. Finally, a H1975 cell xenograft mouse model was used to study the anti-tumor effect of the combination of FMT and CpG in vivo.Results: FMT and CpG synergistically enhanced M1-like gene expression in MΦ, including tumor necrosis factor-α, interleukin (IL)-12, IL-1α, IL-1β, IL-6 and inducible nitric oxide synthase (iNOS). FMT/CpG-pretreated MΦ supernatant inhibited proliferation and induced apoptosis of H1975 cells, accompanied by down-regulation of cell cycle-associated proteins and up-regulation of apoptosis-related proteins. Further studies indicated that the FMT/CpG-pretreated MΦ supernatant suppressed p-EGFR and its downstream AKT/mammalian target of rapamycin signaling pathway in H1975 cells. Furthermore, FMT/CpG suppressed tumor growth in mice accompanied by a decline in the EGFR-positive tumor cell fraction and increased M1 phenotype macrophage infiltration.Conclusion: FMT acted synergistically with CpG to activate MΦ for suppressed proliferation and promoted apoptosis of NSCLC cells via EGFR signaling. Thus, combining FMT and CpG is an effective strategy for the treatment of NSCLC with EGFRL858R/T790M, mutation.Keywords: ferumoxytol, CpG oligodeoxynucleotide, macrophages, non-small cell lung cancer, epidermal growth factor receptor

Yuanyuan Kong,1,* Bo Li,2,* Shuaikang Chang,1 Lu Gao,1 Zhijian Xu,2 Wan He,1 Guang Yang,1 Bingqian Xie,1 Gege Chen,1 Liangning Hu,1 Kang Lu,1 Yingcong Wang,1 Xiaosong Wu,1 Weiliang Zhu,2 Jumei Shi11Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University Cancer Center, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China; 2CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People’s Republic of China*These authors contributed equally to this workPurpose: The present study investigates the effect of DCZ0814 in multiple myeloma (MM) cells, and determines the molecular mechanism of its antitumor activity against MM.Methods: The effects of DCZ0814 were evaluated in vitro using human MM cell lines (ARP1 and OCI-MY5) and in vivo in a murine xenograft MM model. Cell viability was measured with the CCK-8 assay and mitochondrial membrane potential (MMP) was assessed with the JC-1 dye. Apoptosis and cell cycle distribution were examined by flow cytometry. Inhibition of mTORC1 and mTORC2 was assessed by western blot analysis, and the synergistic effect of DCZ0814 and known MM drugs was assessed by calculating the combination index value, using the CalcuSyn software.Results: DCZ0814 effectively inhibited proliferation in MM cells, an effect that was associated with the induction of apoptosis, G0/G1 cell cycle arrest, MMP reduction and reactive oxygen species (ROS) generation. Meanwhile, DCZ0814 repressed the mTOR signaling via dual mTORC1/C2 inhibition and overcame the protective effect of the bone marrow (BM) microenvironment in myeloma cells. In addition, co-treatment with DCZ0814 and other anti-MM agents induced synergistic effects. Finally, the efficacy of the DCZ0814 treatment was confirmed in an MM xenograft mouse model.Conclusion: DCZ0814 exhibits potent anti-MM activity and abrogates the activation of the mTOR/Akt signaling pathway mediated by the BM stroma-derived cytokines. Our results provide a theoretical basis for the development of novel therapeutic strategies in MM using DCZ0814 as a natural product combination compound.Keywords: DCZ0814, multiple myeloma, mTOR, bone marrow microenvironment, apoptosis