1.From 2D to 3D: transforming malignant bone tumor research with advanced culture models.
Zhengcheng HE ; Haitao HUANG ; Jiale FANG ; Huiping LIU ; Xudong YAO ; Hongwei WU
Journal of Zhejiang University. Science. B 2025;26(11):1059-1075
Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology*
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Humans
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Osteosarcoma/pathology*
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Tumor Microenvironment
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Sarcoma, Ewing/pathology*
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Chondrosarcoma/pathology*
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Animals
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Cell Culture Techniques/methods*
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Cell Culture Techniques, Three Dimensional/methods*
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Cell Line, Tumor
2.Relationship between left ventricular hypertrophy diagnosed by Peguero-Lo-Presti index and recurrence after radiofrequency catheter ablation of paroxysmal atrial fibrillation
Minglong ZHANG ; Yuanyuan FANG ; Xiaopeng SUI ; Xinxin CHEN ; Liudong LI ; Haitao WANG
Tianjin Medical Journal 2024;52(2):210-214
Objective To investigate the relationship between left ventricular hypertrophy(LVH)diagnosed by Peguero-Lo-Presti index and recurrence of paroxysmal atrial fibrillation(AF)after radiofrequency ablation.Methods A total of 652 patients with paroxysmal atrial fibrillation who underwent radiofrequency ablation were selected.According to Peguero-Lo-Presti index,patients were divided into the LVH group(167 cases)and the normal left ventricle group(485 cases).Baseline data were collected,and regular follow-up was performed at 3,6 and 12 months after radiofrequency catheter ablation.The recurrence of AF was assessed.Kaplan-Meier survival curve was used to analyze the recurrence rate of AF in the two groups.Cox proportional hazard model was used to assess risk factors for recurrent atrial fibrillation.Results The median follow-up time was 20.5(15.0,26.0)months.A total of 155 patients(23.8%)developed recurrence of AF,including 95 patients in the LVH group and 60 patients in the LVN group.The recurrence rate without AF was significantly lower in the LVH group than that in the LVN group(64.1%vs.80.4%,Log-rank χ2=26.361,P<0.01).After adjusting for age,sex,body mass index,hypertension,diabetes,coronary heart disease,cardiac dysfunction,left anteroposterior and posterior atrial diameter,left ventricular end-diastolic diameter,and left ventricular ejection fraction,LVH diagnosed by Peguero-Lo-Presti index was still a risk factor for recurrent AF[HR(95%CI):2.359(1.663-3.345),P<0.01].Conclusion In patients with paroxysmal AF,LVH diagnosed by Peguero-Lo-Presti index is a risk factor of AF recurrence after radiofrequency catheter ablation.
3.Mechanism of Qianyang Yuyin Granules Regulating NR3C2/ROS/ERK Pathway to Alleviate Aldosterone-induced Podocyte Injury
Yin LI ; Fang YUAN ; Junyao XU ; Cheng NING ; Yixuan WANG ; Lichao QIAN ; Haitao LI ; Jie LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(13):95-105
ObjectiveTo investigate the protective mechanism of Qianyang Yuyin granules (QYYY) on aldosterone-induced podocyte injury. MethodA total of 30 C57BL/6J mice were randomly divided into five groups: control group, model group, QYYY low dose (QYYY-L) group, QYYY high dose (QYYY-H) group, and spironolactone (SPL) group, with six mice in each group. Except for the control group, mice were implanted with osmotic minipumps and injected continuously with aldosterone (300 μg·kg-1·d-1) to induce renal injury. The drug administration group was given low and high doses (2.6, 5.2 g·kg-1·d-1) of QYYY and SPL (18 mg·kg-1·d-1) for 28 days. The renal pathological changes of mice were observed by hematoxylin-eosin (HE) staining and Masson staining. The expression levels of Nephrin, Desmin, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cleaved Caspase-3, nuclear receptor subfamily 3 group C member 2 (NR3C2), extracellular regulated protein kinases (ERK), and phospho-ERK (p-ERK) in kidney tissue were detected by Western blot. The apoptosis levels of kidney tissue were detected by TdT-mediated dUTP nick and labeling (TUNEL) staining, and the superoxide dismutase (SOD) levels were detected. In vitro, the mice were divided into five groups: Control group, model group (aldosterone concentration of 200 nmol·L-1), QYYY-L group, QYYY medium dose (QYYY-M) group, and QYYY-H group (25, 50, and 100 mg·L-1). The effect of different concentrations of QYYY on the relative viability of aldosterone-induced podocytes was detected by cell proliferation and viability assay (CCK-8). The expressions of Nephrin, Desmin, Bax, Bcl-2, cleaved Caspase-3, NR3C2, and p-ERK/ERK were detected by Western blot. AnnexinV-FITC/PI flow cytometry was used to detect the apoptosis levels of podocytes. Reactive oxygen species (ROS) in podocytes were observed by DCFH-DA. ResultCompared with the control group, the model group showed structural pathological changes and fibrotic conditions in the kidney, increased apoptosis levels (P<0.01), and decreased SOD levels (P<0.01). Aldosterone concentration at 200 nmol·L-1 showed a significant decrease in podocyte activity (P<0.05). Podocytes in the model group showed structural pathological changes, disordered arrangement of intercellular microfilaments, increased apoptosis levels (P<0.01), and increased intracellular ROS levels (P<0.01). The protein expressions of Nephrin, Bcl-2, and p-ERK/ERK in kidney tissue and podocytes were decreased (P<0.05, P<0.01). The protein expressions of Desmin, Bax, cleaved Caspase-3, and NR3C2 were increased (P<0.05, P<0.01). Compared with the model group, QYYY alleviated the structural damage and fibrosis of the kidney, decreased the apoptosis levels (P<0.05, P<0.01), and enhanced the SOD content of the kidney (P<0.05, P<0.01). QYYY improved the activity of podocytes (P<0.05, P<0.01), restored the foot process structure of podocytes, and decreased apoptosis levels (P<0.01) and ROS levels of podocytes (P<0.01). The protein expressions of Nephrin, Bcl-2, and p-ERK/ERK in kidney tissue and podocytes were increased (P<0.05, P<0.01), and the protein expressions of Desmin, Bax, cleaved Caspase-3, and NR3C2 were down-regulated (P<0.05, P<0.01). ConclusionQYYY improves aldosterone-induced podocyte injury by regulating the NR3C2/ROS/ERK pathway.
4.Research progress on the influence of ligands on the stability of albumin
Lieqing YANG ; Rongchao YIN ; Lei YANG ; Jinrong JING ; Haitao FANG ; Jiaquan CHEN ; Weixin LIU
Chinese Journal of Blood Transfusion 2024;37(1):120-124
It is necessary to improve the stability of human serum albumin in response to the complex temperature, light and other conditions during the manufacture and storage. In this paper, the stabilization effect and simple stabilization mechanism of ligands on albumin were described from the perspective of ligand binding to albumin.Through review and comparison, it can be concluded that the common ligand sodium octanoate mainly plays a role in improving thermal stability, and the common ligand N-acetyl-L-tryptophan mainly plays a role in improving antioxidant activity, N-acetyl-L-methionine has better antioxidant and anti-photooxidation than N-acetyl-L-tryptophan.
5.Study on a mouse model of aldosterone-induced multi-organ damage
Yu LUO ; Haitao ZHANG ; Yawei ZHENG ; Xianze MENG ; Zhen FANG ; Yating WANG ; Zhuyuan FANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(8):1045-1051
Objective Establishment and evaluation of a mouse model of aldosterone-induced multi-organ damage.Methods Twenty mice were randomly divided into four groups,with five mice in each group:a blank control group(0 μg/(kg·d)),a low-dose aldosterone group(150 μg/(kg·d))),a medium-dose aldosterone group(300 μg/(kg d)),and a high-dose aldosterone group(450 pug/(kg·d)).Aldosterone-containing osmotic minipumps were surgically implanted under the skin,and aldosterone was infused for 4 weeks to establish the aldosterone-induced damage model.The body weight and blood pressure of the mice were recorded weekly.After the 4 week modeling period,the mice were euthanized,and their tissues were collected for observation and analysis of blood pressure and histological morphology of various organs.Results(1)After 4 weeks of aldosterone infusion,the serum aldosterone levels were significantly increased in the medium-dose and high-dose aldosterone groups,but not in the low-dose aldosterone group.(2)After the implantation of osmotic minipumps,the systolic blood pressure was significantly increased in the low-dose,medium-dose,and high-dose aldosterone groups during the second and third weeks,but decreased in all these groups during the fourth week.(3)The kidney and heart in the low-dose,medium-dose,and high-dose aldosterone groups showed varying degrees of damage,interstitial edema,collagen deposition,and fibrotic lesions.The liver in the low-dose aldosterone group showed a small amount of collagen deposition,while the medium-dose and high-dose aldosterone groups showed varying degrees of hepatocyte damage,collagen deposition,and fibrotic lesions.Conclusions Aldosterone can induce multi-organ damage in mice.Under this modeling method,organ damage is mainly manifested as edema,collagen deposition,and fibrotic lesions.
6.Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy
Qiang ZENG ; Yuan TANG ; Haitao ZHOU ; Ning LI ; Wenyang LIU ; Silin CHEN ; Shuai LI ; Ningning LU ; Hui FANG ; Shulian WANG ; Yueping LIU ; Yongwen SONG ; Yexiong LI ; Jing JIN
Chinese Journal of Oncology 2024;46(4):335-343
Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (<8), intermediate (8-16), and high (>16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P<0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P<0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P<0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P<0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P<0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.
7.Effect of transcutaneous electrical acupoint stimulation on postoperative fatigue syndrome in patients with Parkinson′s diseases undergoing bilateral deep brain electrical stimulation
Tong FU ; Mingming HAN ; Fang KANG ; Xiang HUANG ; Haitao WANG ; Bufan KAN ; Juan LI
Chinese Journal of Anesthesiology 2024;44(4):396-400
Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative fatigue syndrome in patients with Parkinson′s diseases undergoing bilateral deep brain electrical stimulation.Methods:Sixty patients with Parkinson′s disease, aged 60-80 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with body mass index of 18.5-29.9 kg/m 2, undergoing elective bilateral deep brain electrical stimulation, were divided into transcutaneous electrical acupoint stimulation group (TEAS group) and sham stimulation group (Sham group), with 30 patients in each group, using the random number table method. The TEAS of bilateral Zusanli and Sanyin points was performed on admission to the operating room with alternative stimulation at a frequency of 2/10 Hz and an intensity of 6-15 mA. The stimulation was stopped when the neurosurgeon performed the microelectrode recording, and TEAS was continued until the end of operation after the microelectrode recording was finished. In Sham group, electrode pads were only placed at the acupoint with no stimulation. The Christensen score was assessed at 1 day preoperatively (T 0) and 1, 3 and 7 days postoperatively (T 1-3) to evaluate the occurrence of postoperative fatigue syndrome. The 15-item Quality of Recovery scale score, emergence agitation and rescue analgesia within 48 h after surgery were recorded. Results:Compared with Sham group, Christensen scores were significantly decreased at T 1-3, 15-item Quality of Recovery scale scores were increased, and the incidence of postoperative fatigue syndrome and emergence agitation and rate of rescue analgesia were decreased in TEAS group than in Sham group ( P<0.05). Conclusions:TEAS can reduce the development of postoperative fatigue syndrome in the patients with Parkinson′s diseases undergoing bilateral deep brain electrical stimulation.
8.A case of successful plasma exchange in the treatment of acute renal failure related to infective endocarditis
Ying SUN ; Haitao WANG ; Fang FANG ; Songlan WANG ; Xin LIU ; Yonghui MAO
Chinese Journal of Nephrology 2024;40(6):484-486
A 65-year-old male was admitted because of anorexia, gross hematuria, skin purpura and acute renal insufficiency. Cardiovascular interventional examination was performed in other hospital 3 months before admission. During hospitalization, multiple blood cultures suggested positive Streptococcus gordonii, decreased blood complement and increased rheumatoid factor. Echocardiography revealed mitral valve vegetations (4 mm), and renal biopsy revealed endocapillary proliferative glomerulonephritis, diagnosed as infective endocarditis-associated glomerulonephritis. The combination of effective antibiotics and plasma exchange therapy significantly improved clinical symptoms and acute renal failure. The case suggests that plasma exchange is effective and safe in the treatment of immune complex-mediated glomerulonephritis caused by infective endocarditis, providing a new option for the treatment of such diseases.
9.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
10.Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy
Qiang ZENG ; Yuan TANG ; Haitao ZHOU ; Ning LI ; Wenyang LIU ; Silin CHEN ; Shuai LI ; Ningning LU ; Hui FANG ; Shulian WANG ; Yueping LIU ; Yongwen SONG ; Yexiong LI ; Jing JIN
Chinese Journal of Oncology 2024;46(4):335-343
Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (<8), intermediate (8-16), and high (>16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P<0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P<0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P<0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P<0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P<0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

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