1.Research progress of magnesium-based biomaterials in the treatment of bone defects induced by osteosarcoma
Jingteng CHEN ; Ling YU ; Shiyu LI ; Weichun GUO
Chinese Journal of Orthopaedics 2025;45(2):109-118
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with a peak incidence between the ages of 10 and 20. It has an extremely high mortality and disability rate. In adults, osteosarcoma is the third most common bone tumor. Despite the advances in chemotherapy, surgical techniques, and radiotherapy that have significantly improved the overall survival rate of osteosarcoma, the long-term prognosis of patients has not shown substantial improvement, especially in cases of tumor metastasis and recurrence. Due to the highly invasive growth of tumor cells, the progression of osteosarcoma is often accompanied by the destruction of surrounding bone tissue and the formation of immature new bone, making treatment challenging, especially in tissue repair and functional recovery following surgical resection. Tumor resection surgery often results in extensive bone loss, particularly in cases involving joints or weight-bearing areas, making the reconstruction of bone structure and function highly complex. Currently, inert materials such as stainless steel or titanium alloy prostheses used in clinical practice exhibit poor biocompatibility and high elastic modulus, often leading to prosthesis loosening and infection. There is an urgent clinical need for multifunctional biomaterials capable of both repairing bone defects and inhibiting tumor recurrence. Magnesium-based biomaterials have shown excellent biodegradability and bioactivity, and the release of magnesium ions and degradation products effectively promotes bone tissue regeneration while demonstrating potential antitumor effects. This paper reviews the application of magnesium-based biomaterials in the treatment of bone defects associated with osteosarcoma, including their adaptation to the acidic conditions of the osteosarcoma microenvironment, their potential to promote osteogenesis, and their antitumor mechanisms. It also analyzes the mechanical compatibility of magnesium-based materials and the use of coating technologies to enhance their corrosion resistance, and explores the prospects of various types of magnesium-based compounds in the treatment of osteosarcoma-related bone defects.
2.Research progress of magnesium-based biomaterials in the treatment of bone defects induced by osteosarcoma
Jingteng CHEN ; Ling YU ; Shiyu LI ; Weichun GUO
Chinese Journal of Orthopaedics 2025;45(2):109-118
Osteosarcoma is the most common primary malignant bone tumor in children and adolescents with a peak incidence between the ages of 10 and 20. It has an extremely high mortality and disability rate. In adults, osteosarcoma is the third most common bone tumor. Despite the advances in chemotherapy, surgical techniques, and radiotherapy that have significantly improved the overall survival rate of osteosarcoma, the long-term prognosis of patients has not shown substantial improvement, especially in cases of tumor metastasis and recurrence. Due to the highly invasive growth of tumor cells, the progression of osteosarcoma is often accompanied by the destruction of surrounding bone tissue and the formation of immature new bone, making treatment challenging, especially in tissue repair and functional recovery following surgical resection. Tumor resection surgery often results in extensive bone loss, particularly in cases involving joints or weight-bearing areas, making the reconstruction of bone structure and function highly complex. Currently, inert materials such as stainless steel or titanium alloy prostheses used in clinical practice exhibit poor biocompatibility and high elastic modulus, often leading to prosthesis loosening and infection. There is an urgent clinical need for multifunctional biomaterials capable of both repairing bone defects and inhibiting tumor recurrence. Magnesium-based biomaterials have shown excellent biodegradability and bioactivity, and the release of magnesium ions and degradation products effectively promotes bone tissue regeneration while demonstrating potential antitumor effects. This paper reviews the application of magnesium-based biomaterials in the treatment of bone defects associated with osteosarcoma, including their adaptation to the acidic conditions of the osteosarcoma microenvironment, their potential to promote osteogenesis, and their antitumor mechanisms. It also analyzes the mechanical compatibility of magnesium-based materials and the use of coating technologies to enhance their corrosion resistance, and explores the prospects of various types of magnesium-based compounds in the treatment of osteosarcoma-related bone defects.
3.Clinical study of internal jugular vein dilatation index in predicting septic shock volume responsiveness
Runze WANG ; Lin ZHANG ; Feng ZHANG ; Jie SHEN ; Weichun MO ; Kunlun WANG ; Peng GUO
Chinese Journal of Emergency Medicine 2022;31(9):1216-1222
Objective:To explore the value of severe ultrasound measurement of internal jugular vein dilation index (ΔIJV) combined with passive leg raising (PLR) in predicting the volume responsiveness of septic shock.Methods:Patients diagnosed with septic shock under complete mechanical ventilation in the ICU of Jinshan Hospital Affiliated to Fudan University from January 2020 to March 2021 were prospectively selected as the research objects. After 500 mL crystals were injected within 30 min, the patients having the "gold standard" left stroke volume (SV) increased by 15% were allocated to the volume response positive group, and patient having an SV increased by less than 15% to the volume response negative group. First, the maximum anterior posterior diameter (IJV max) and the minimum anterior posterior diameter (IJV min) in the respiratory cycle of internal jugular vein were measured by ultrasound, then SV before and after PLR was measured, and finally SV, IJV max and IJV min were measured again after rapid infusion of 500 mL crystals, and ΔIJV=(IJV max-IJV min)/(IJV mean)×100%. The Wilcoxon rank-sum test was used to compare the hemodynamic indexes before and after capacity expansion and PLR. Spearman rank method was used to analyze the change rate of SV (ΔSV) after PLR and the correlation between ΔIJV and ΔSV of the "gold standard". The sensitivity, specificity and relevant cut-off values were obtained by drawing the subject function curve to evaluate the value of ΔIJV and PLR in predicting the volume responsiveness of patients with sepsis. Results:A total of 56 patients were enrolled in the study, and they were divided into two groups: 32 patients in the volume response positive group and 24 patients in the volume response negative group. There was a positive correlation between ΔIJV and ΔSV after capacity expansion ( r=0.778, P<0.01). Taking ΔIJV>17.3% as the threshold, the area under the curve (AUC) was 0.846 (95% CI: 0.716~0.977), the sensitivity was 84.4% and the specificity was 83.3%. PLR was also positively correlated with ΔSV ( r=0.698, P<0.01). Taking ΔSV>15.5% after PLR as the threshold, the AUC was 0.895 (95% CI: 0.796~0.993), the sensitivity was 96.9%, and the specificity was 79.2%. When ΔIJV combined with PLR predicted volume reactivity, the AUC was 0.944 (95% CI: 0.862~1.000), the sensitivity was 99.8% and the specificity was 87.5%. Conclusions:The measurement of internal jugular vein respiratory dilation index by bedside ultrasound is a reliable index to predict volume responsiveness in patients with sepsis. When combined with PLR, the sensitivity and specificity of prediction can be improved.
4.Biological characteristics of NKTcells and theirroles in anti-tumorimmunity
GUO Weichun ; LIANG Junqing ; JIA Shaochang
Chinese Journal of Cancer Biotherapy 2019;26(8):921-924
NKT细胞是一类特殊的T淋巴细胞亚群,既表达NK 细胞受体,也表达T细胞的相关受体。NKT细胞在多种免疫应答 的调节中发挥重要作用,包括感染、自身免疫性疾病、代谢性疾病和癌症,其通过连接固有免疫系统和适应性免疫系统显示出强大 的抗肿瘤活性。NKT细胞不仅能杀伤肿瘤细胞,也可激活其他抗肿瘤免疫细胞间接地发挥抗肿瘤作用,还能在肿瘤微环境中激活 衰竭的免疫细胞,在抗肿瘤免疫中发挥重要的作用。本文就NKT细胞的生物学特性及其在抗肿瘤免疫中的作用作一综述。
5. Effects of oxygen glucose deprivation and reperfusion on gap junction and glucose uptake of astrocytes
Xiangyang ZHANG ; Cuifang WANG ; Weichun GUO ; Yan CHEN
Chinese Journal of Behavioral Medicine and Brain Science 2019;28(11):967-970
Objective:
To explore the relationship between gap junction and glucose uptake of astrocytes under oxygen-glucose deprivation(OGD) and reperfusion.
Methods:
Cerebral cortical astrocyte from 1 day newborn SD rats were undergone the primary culture. The ischemia cell model was established by OGD. This experiment were divided into control group, OGD group and OGD+ CBX group.After different reperfusion time (0 h, 12 h 24 h and 48 h), the glucose uptake of astrocyte was measured by 2-NBDG through flow cytometry analysis and connexin 43(Cx43) gap junction plaques was detected using immunofluorescene.
Results:
Compared with the control group, the glucose uptake of astrocyte was up-regulated induced by OGD following different reperfusion time.The glucose uptake of OGD group was (2.32±0.43)nmol/μgDNA in 24 hours reperfusion time and was (0.95±0.28)nmol/μgDNA in control group. The up-regulation was up to 2.63-fold increase (
6.Notch signaling pathway regulates osteosarcoma stem cell characteristics by inhibiting Eph pathway
Tian GAO ; Zhiwei FANG ; Ling YU ; Jingteng CHEN ; Jiayong LIU ; Shu LI ; Chujie BAI ; Ruifeng XUE ; Lu ZHANG ; Weichun GUO ; Zhengfu FAN
Chinese Journal of Orthopaedics 2018;38(10):612-619
Objective To investigate the role of Notch signaling pathway to maintain the stem cell-like characteristics of osteosarcoma and its underlying mechanism.Methods Lentiviral NICD1 or Numb-shRNA was transduced into MG63 osteosarcoma cells to activate Notch activity in vitro.The impact of Notch on osteosarcoma stem cells were assessed by the tumor sphere formation assay and flow cytometry analysis of cell surface markers STRO-1/CD117.The expression of stem cell related genes (Sox2,Oct4) were evaluated by Western blot and qPCR.The nude mice were randomly divided into 3 groups:the NICD1 overexpression (NICD-OE) group,the DAPT group and the control (CON) group.The tumor growth was monitored for 8 weeks and the tumor volume and weight were recorded weekly.To investigate whether Notch regulates Eph pathway,Eph pathway related protein EphB,pEphB was measured by Western blot.The impact of ephrinB 1 on NICD overexpression cell were assessed by tumor sphere formation assay.The expression of Sox2 and Oct4 was evaluated by Western blot.Results NICD1 overexpression or Numb-shRNA increased the activity of Notch pathway.The Notch-activated osteosarcoma showed enhanced in vitro tumor spheroid formation capacity,increased Stro-1/CD117double positive ratio,and upregulated expression of Sox2 and Oct4 in vitro.In animal experiments,it was found that activation of Notch pathway promoted tumor formation in vivo and Notch inhibition decreased it.The primary osteosarcoma cells were obtained from mice xenograft treated with DAPT and its tumor sphere formation capacity was significantly reduced.Finally,The Notch pathway inhibits the phosphorylation of EphB,as well as the downstream signal pathway of EphB,but there is no significant change in total EphB.The activation of Eph pathway inhibited Notch induced up-regulation of tumor sphere formation and Sox2 and Oct4 expression.Conclusion Notch signaling pathway maintains the stem cell-like characteristics of osteosarcoma probably by inhibiting the Eph pathway.
7.Doxorubicin induces enrichment of stem-like cells in osteosarcoma by activating Notch signaling
Ling YU ; Tian GAO ; Zhengpei ZHANG ; Chunjie TAO ; Weichun GUO ; Zhiwei FANG ; Zhengfu FAN
Chinese Journal of Clinical Oncology 2017;44(11):527-531
Objective:Cancer stem cells (CSCs) are resistant to chemotherapy. Our study aimed to investigate the stem cell-like proper-ties of doxorubicin-resistant osteosarcoma cell line 143B and its correlation with Notch signaling. Methods:We generated doxorubicin-resistant osteosarcoma cells by treating them with 2μm doxorubicin. Stem cell-like properties such as morphology change, Stro-1/CD117 double positive ratio, stem cell-related gene expression, sphere formation efficiency, and EMT character were assessed on day 5 after doxorubicin withdrawal. Notch receptor and its target genes were examined using qPCR and Western blot analysis. The stem cell-like properties of doxorubicin-resistant osteosarcoma cells were assessed when pretreated with Notch inhibitor or vehicle. The an-ti-tumor effect of Notch inhibitor was tested using a xenograft model. Results:Doxorubicin-resistant osteosarcoma cells were enriched in Stro-1+/CD117+cells, which showed obvious increased expression of stem cell-related genes, and exhibited enhanced spheroid for-mation and evident mesenchymal characteristics unlike doxorubicin-sensitive cells. qPCR and Western blot assays showed that Notch intracellular domain 1 (NICD1) and target genes Hes1 and Hey1 were upregulated in doxorubicin-resistant osteosarcoma stem cells compared with those in vehicle cells. Furthermore, pretreatment with a γ-secretase inhibitor (GSI) to prevent Notch signaling en-hanced chemo-sensitivity and inhibited doxorubicin-enriched osteosarcoma stem cell activity in vitro. Finally, the Notch inhibitor pre-vented tumor growth in mice xenograft models. Conclusion: Doxorubicin induced the enrichment of osteosarcoma stem-like cells through Notch signaling, and inactivation of Notch could be useful for overcoming drug resistance and eliminating osteosarcoma.
8.miR-429 Negatively Regulates Osteosarcoma Stem Cell-like Properties by Targeting Sox2
Ling YU ; Zhengpei ZHANG ; Xiangran SUN ; Di ZHENG ; Weichun GUO
Journal of China Medical University 2017;46(10):874-877,886
Objective To investigate the role of miR-429 in osteosarcoma stem cells.Methods We employed different approaches to test the expression of miR-429 in osteosarcoma stem cells.miR-429-high and miR-429-low cells were separated using molecular probes and their stem cell-like properties were compared.The effect of miR-429 on osteosarcoma stem cell-like properties was further tested through transfection assays.Furthermore,the miR-429 downstream target gene was confirmed by luciferase assay.Results The expression of miR-429 in osteosarcoma stem cells was much lower than that in control cells.miR-429-high cells displayed fewer stem celllike properties than did miR-429-low cells.These observations were confirmed by transfection assays.Additionally,our luciferase assays showed that miR-429 regulates Sox2 at the post-transcriptional level.Conclusion miR-429 negatively regulates osteosarcoma stem celllike properties by targeting Sox2.
9.Efficacy and prognostic factors of percutaneous intervertebral foramen BEIS technique in the treatment of recurrent lumbar disc herniation
Weichun GUO ; Sheng ZHOU ; Min XIONG
Journal of Clinical Surgery 2017;25(12):926-929
Objective To evaluate the efficacy of percutaneous endoscopic BEIS technique in the treatment of recurrent lumbar disc herniation and to analyze its possible prognostic factors.Methods A total of 39 patients who are diagnosed as lumbar disc herniation and treated with percutaneous endoscopic BEIS technique were selected from March 2013 to March 2015.The clinical efficacy was evaluated according to VAS,ODI,JOA and modified MacNab criteria in the follow-up,and the possible prognostic factors were analyzed.Results The average follow-up time was 14 months(12 ~ 18 months).According to the MacNab standard,the excellent and good rate was 82.1%.The average score of back and leg pain VSA was reduced from(7.33 ± 1.01)before operation to(2.69 ± 1.50)after operation,t =16.111,the difference was statistically significant (P < 0.05);ODI and JOA were used to evaluate lumbar function,the score of ODI was reduced from (59.08 ± 7.16) to (13.54 ± 3.36),t =35.946,and that of JOA was increased from(14.92 ±3.37) to(26.05 ± 1.76),t =-18.526,the difference was statistically significant (P < 0.05).Patients with symptoms lasting no more than 3 months and with no lateral recess stenosis were able to obtain good therapeutic effect.Conclusion This study indicates that percutaneous endoscopic BEIS technique is effective in the treatment of recurrent lumbar disc herniation,and duration of symptoms and lateral recess stenosis are important prognostic factors.
10.Discuss the function of docosahexaenoic acid in the early inflammatory response after acute spinal cord injury
Journal of Clinical Surgery 2017;25(4):301-303
Objective To explore the effect of docosahexaenoic acid(DHA)on the neuro-logical outcome as well as the expression of interleukin-1β,interleukin-6 and interleukin-10 after acute spinal cord injury(SCI).Methods One hundred and eight Sprague-Dawley rats were randomly divided into a spinal cord injury group(group A),a DHA treatment group(group B)and a sham operation group(group C),each with 36 rats.SCI models were established in the rats of groups A and B using a version of Allen's weight drop method(T10 level).Group C had removal of the lamina only.Ten minutes later,group A was injected with 5% ethanol in saline(the MT solvent)and group B with 500 mg/kg of DHA preparation.Basso beattie bresnahan locomotor rating scale(BBB)was used to detect locomotors function at 10,24,48 and 72 hours after operation.Rats were sacrificed at 72 h after operation,IL-1β,IL-6 and IL-10 levels in serum were detected in 6 rats of each group.Results BBB locomotor rating scale indicated that hindlimb motor function in Groups B was higher than that in Group A at 10,24,48 and 72 hours after operation.There was a significant difference in locomotor rating score between DHA injection group and control group(P<0.05).The specimens of group A showed inflammatory reaction and ulceration at 72 h:Group C showed the highest levels of IL-10 in serum ,while Group A showed the lowest level.The differences were statistically significant.Group A had the highest levels of IL-1β and IL-6 while group C had the lowest.The difference between group B and groups A and C was significant.Conclusion DHA could play protective role by balancing the reconstruction of the anti-inflammatory response and inflammation in rats with acute spinal cord injury.

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