Sacral tumors are surgically challenging and at a high risk of complications. In recent years, robotic-assisted resection has been gradually applied in sacral tumors, but it is difficult to remove bone tissue by present robotic instruments, which limits the application of surgical robot in sacral tumor. The present study aimed to explore the application range and therapeutic effect of minimally invasive ultrasonic osteotome in robotic-assisted sacral tumor resection. Eighteen patients underwent robotic-assisted sacral tumor resection in the First Affiliated Hospital of Sun Yat-Sen University from May 2015 to March 2021 by the Da Vinci robotic surgical system. Among them three patients who underwent osteotomy with minimally invasive ultrasonic osteotome were enrolled. There were 2 males and 1 female, aged 24, 32, 71 years, respectively. The tumors included 2 schwannomas and 1 ganglioneuroma. The operation time, bleeding volume and postoperative hospitalization days were recorded. The recurrence and complications were evaluated during follow-up. The operative time of the 3 patients was 80, 240 and 300 minutes, and the intraoperative bleeding volume was 30, 30 and 100 ml. Complete resection was performed in 2 cases and intralesional resection in 1 case. The postoperative hospital stay was 5, 3 and 7 days respectively. The follow-up time was 58, 17 and 31 months respectively. No tumor recurrence was found during the follow-up. As regards complications, only one patient had left foot pain after operation, and there were no other intraoperative or postoperative complications. The therapeutic advantages of ultrasonic osteotome combined with the Da Vinci robotic surgical system can achieve precise osteotomy, reduce intraoperative bleeding and accelerate postoperative recovery for certain patients with sacral tumors.

[This corrects the article DOI: 10.1016/j.apsb.2021.08.015.].

Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties, a high incidence of pulmonary metastasis and a poor prognosis. Chemotherapy is the mainstay of treatment for osteosarcoma. Currently, there are no molecular targeted drugs approved for osteosarcoma treatment, particularly effective drugs for osteosarcoma with pulmonary metastases. It has been reported that fibroblast activation protein alpha (FAPα) is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis, demonstrating that FAPα-targeted agents might be a promising therapeutic strategy for osteosarcoma. In the present study, we reported that the FAPα-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPα-positive osteosarcoma cells in vitro and in vivo. Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells. Importantly, it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo. Mechanistically, Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway, leading to inhibition of the growth and metastatic spread of osteosarcoma cells. These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPα-positive osteosarcoma, particularly osteosarcoma with pulmonary metastases.

Objective To investigate whether Wnt/β-catenin signaling pathway mediating the neuroprotection of isoflurane post-conditioning in hippocampal neurons damage induced by ischemia/reperfusion injury in rats.Methods According to the randomized principle, 60 male Sprague-Dawley rats were randomly divided into five groups (12 rats in each group):sham group (group S), model group (group M), ISO+model group (group MI), ISO+model+DKK-1 group (group MDI) and model+DKK-1 group (group MD).A rat model of middle cerebral artery occlusion (MCAO) was established with 90 min ischemia followed by 24 hreperfusion.Group S was only exposed to one side of the internal carotid artery without fishing line.Isoflurane post-conditioning groups (group MI, MDI) were immediately treated with 1.5％isoflurane for 60 min at the onset of reperfusion.DKK-1 (5μg/kg) was injected intracerebroventricularly 30 min before the model established in group MDI and group MD.After reperfusion for 24 h, Longa score method was used for neurological deficit score.HE staining and Tunel fluorescence was employed to observe the morphological changes of neurons.Immunohistochemistry and Western Blot were applied to detect the expression of target protein in CA1 region.Results Compared with group S, the neurobehavioral score, the number of apoptosis and the expression of Bax and GSK-3βprotein in group M all increased (P<0.05), while the expression ofβ-catenin and Bcl-2/Bax ratio decreased (P<0.05) ;Compared with group M, the neurobehavioral score, the number of apoptosis and the expression of Bax protein were significantly decreased (P<0.05), while the expression of Bcl-2, β-catenin protein and the Bcl-2/Bax ratio were significantly increased (P<0.05) in group MI.Compared with group MI, the neurobehavioral score, the number of apoptosis, Bax and GSK-3βprotein in group MDI were significantly increased (P<0.05), while the Bcl-2, β-catenin protein expression, and Bcl-2/Bax ratio were significantly decreased (P<0.05).Conclusion Isoflurane post-conditioning may protect the hippocampus neurons against cerebral ischemic reperfusion-induced damage via the way that the Wnt/β-catenin signaling pathway regulates the expression levels of Bcl-2 and Bax proteins in rats.

[Objective]To comprehensively compare the feasibility of three different treatment strategies consisting of low-dose chemotherapy(LDC),surgery and surgery with adjuvant low-dose chemotherapy(SLDC)for children with solitary bone lesions of eosinophilic granuloma(SBL-EG).[Methods]We retrospectively reviewed the records of 149 pediatric patients with SBL-EG at our institutions from 2002 to 2014. Our study included 86 patients who received LDC ,33 patients who received surgery and 30 patients who received SLDC. The duration of hospital stay ,time to symptom relief,recovery time,cost,complications and relapse-free sur-vival(RFS)of each strategy were analyzed.[Results]Hospital stay,time to symptom relief,recovery time and cost in the LDC group were significantly shorter or less than those in the surgery or SLDC group (P < 0.05). No statistically significant differences were observed in the above-mentioned factors between the surgery and SLDC groups (P > 0.05). Chemotherapy-related adverse events in the LDC and SLDC groups included nausea(8.62%),aminotransferase elevation(7.76%),slight hair loss(4.31%), immunity decline (21.55%),growth retardation (10.34%) and moon face (7.76%). LDC and SLDC treatment resulted in a significantly longer RFS (147 months and 126 months ,respectively) than surgery alone (114 months)(P = 0.005 and 0.019 , respectively). However ,there was no statistically significant difference in RFS between the LDC and SLDC groups (P = 0.732).[Conclusions]Compared with surgery or SLDC,LDC appears to promote more rapid recovery,less invasion,increase safety and eco-nomic treatment strategy for pediatric patients with SBL-EG.

Objective To explore the application value of CT perfusion imaging for predicting the tiny lymph nodes metastasis and micrometastasis of squamous cell carcinoma in cervix after neoadjuvant chemotherapy.Methods The clinical data and CT perfusion parameters of 46 patients with cervical squamous cell carcinoma who underwent neoadjuvant chemotherapy followed by surgery were enrolled in the study.Based on the surgical pathology findings and short-term follow up,the cases were divided into without tiny lymph nodes metastasis (short axle diameter of lymph nodes＜10 mm) group (n=32) and with tiny lymph nodes metastasis group (n=14).All perfusion data were analyzed retrospectively and the diagnostic value were investigated.Results Blood flow (BF),blood volume (BV) and the maximum diameter of tumor per-chemotherapy in with tiny lymph nodes metastasis group were higher than those in without tiny lymph nodes metastasis group (all P＜0.05).The differences of the maximum diameter of tumor after chemotherapy,permeability,time to peak (TTP) between two groups were not statistically significant (all P＞0.05).Multivariate Logistic regression analysis showed BF and the maximum diameter of tumor per-chemotherapy were independent predictors of the tiny lymph nodes metastasis in cervix after neoadjuvant chemotherapy.ROC showed BF (AUC=0.86,P＜0.001,95％CI [0.75,0.96]) had higher predictive value than maximum diameter of tumor per-chemotherapy (AUC=0.70,P=0.02,95 ％ CI [0.54,0.88]).Conclusion CT perfusion imaging shows the significant predictive value for the tiny lymph nodes metastasis of squamous cell carcinoma in cervix after neoadjuvant chemotherapy.

Objective To investigate the expression level and clinical significance of melanoma antigen gene A (MAGEA) in osteosarcoma patients. Methods Compare gene expression profiles in osteosarcoma cell lines and osteoblasts with gene microarrays. Validation of differentially expressed genes was carried out by real-time polymerase chain reaction analysis. Corresponding protein levels were measures by Western blot analysis in osteosarcoma cell lines and by immunohistochemistry in osteosarcoma tissues. The staining intensity of immuno-histochemistry was correlated with clinical outcome , and its prognostic significance was analyzed. Results Sev-eral genes belonging to MAGEA increased significantly in all osteosarcoma cell lines and tumor tissue , but not in normal osteoblast cell. Patients with MAGEA expression has higher risk of lung metastasis (relative risk 2.79, 95% confidence interval, 1.12-6.93; P = 0.028) and lower five-year survival rates (39.6% ± 8.4% vs. 80% ± 8.9%, P = 0.01) compared with patients without MAGEA expression. Conclusions The expression of MAGEA increased in osteosarcoma , which inversely correlating with outcome of osteosarcoma patients.

OBJECTIVETo compare the effects of oral treatment with tetrandrine (TD) and N-acetylcys-teine (NAC) separately or jointly on silica-exposed rats.

METHODS40 sprague-Dawly (SD) rats were randomly divided into normal saline group, quartz group, TD treatment group (50 mg/kg), NAC treatment group (500 mg/kg) and combined treatment group (TD: 50 mg/kg + NAC: 500 mg/kg). Rats in normal saline group and other groups received intratracheal instillation of normal saline and quartz dust suspension respectively. Treatment groups were given TD, NAC separately or jointly via esophagus the next day after instillation, once a day and six times a week for 30 consecutive days. At the end of experiment, the pathological changes of lung tissues were evaluated by the methods of Foot, HE and Masson staining, the level of hydroxyproline (HYP), malondjalde-hyde (MDA), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in lung tissues were measured by alkaline hydrolysis method, the barbituric acid method and enzyme-linked immunosorbent assay (ELISA) respectively.

RESULTSCompared with the quartz group, lymph nodes/body coefficients in all treatment groups and lung/body coefficient in combined treatment group were significantly decreased (P < 0.05). Pathology results showed that the normal saline group demonstrated no obvious evidence of lung damage. The quartz group lungs silicotic lesions focused on II~III level, the TD treatment group was mainly with I level, the NAC treatment group was mainly with I~II level, and the combined treatment group only showed little silicotic nodule, no obvious fibrosis. HYP content in TD treatment group and combined treatment group were significantly lower than that in the quartz group (P < 0.05), while it showed no obvious change in NAC treatment group. MDA content in lung tissues of each treatment group (TD treatment group, NAC treatment group and combined treatment group) were 18.80 ± 2.94, 20.13 ± 4.01 and 17.05 ± 3.52 nmol/ml respectively, which lower than in the quartz group (23.99 ± 3.26 nmol/ml). The level of IL-6 in lung tissues of the quartz group were 89.57 ± 8.78 pg/ml. After TD and NAC monotherapy, the IL-6 content decreased to 79.22 ± 9.65 pg/ml and 81.63 ± 5.72 pg/ml, and it decreased more significantly after combined medication (74.37 ± 3.17 pg/ml). The level of TNF-α in the quartz group were 59.05 ± 4.48 pg/ml. After TD and NAC monotherapy, the TNF-α content decreased to 50.48 ± 2.76 pg/ml and 54.28 ± 4.30 pg/ml, and it decreased more significantly after combined medication (49.10 ± 4.98 pg/ml).

CONCLUSIONNAC and TD could reduce MDA, TNF-α and IL-6 levels in lung tissue, and alleviate SiO2-induced pulmonary fibrosis in rats. Combined treatment with TD and NAC was more effective than TD or NAC treatment separately.

Acetylcysteine ; pharmacology ; Animals ; Benzylisoquinolines ; pharmacology ; Disease Models, Animal ; Dust ; Hydroxyproline ; metabolism ; Interleukin-6 ; metabolism ; Lung ; pathology ; Malondialdehyde ; metabolism ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; Quartz ; toxicity ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Silicosis ; drug therapy ; Tumor Necrosis Factor-alpha ; metabolism

Objective To explore the relationships of quality of life ( QOL ) and functional status in patients with malignant bone tumors after operation. Methods European organization for research and treatment of cancer quality of life questionnaire C30 (EORTC-QLQ-C30), social support revalued scale (SSRS) and Karnofsky performance scale (KPS) were used to investigate the levels of QOL, social support and functional status. The correlations between them were explored. Results The overall score by QOL was (58.33 ± 18.94). The score by KPS was positively related to somatic function, role function, social function, and general health status (P<0.01), but negatively related to tiredness, pains, insomnia and financial burden (P<0.01). Conclusions The QOL in patients with malignant bone tumors after operation is at a lower level and the function is at a medium level. Nurses should assess the function and make out interventional measures for them so as to improve their QOL.

OBJECTIVETo detect the expression of SCUBE3 in human osteosarcoma cell lines and surgical specimens of osteosarcomas and investigate its association with the patients' prognosis.

METHODSThe expression of SCUBE3 protein was detected in 5 osteosarcoma cell lines using Western blotting. CCK8 assay was used to assess the effect of SCUBE3 suppression mediated by two specific small interfering RNAs (siRNAs) on the proliferation of U2OS osteosarcoma cells, and the cell cycle changes were detected using flow cytometry. Immunohistochemistry was performed to detect the expression of SCUBE3 in 60 osteosarcoma tissues, and Kaplan-Meier method was performed for survival analysis of the patients.

RESULTSCompared with osteoblast hFOB1.19 cells, the osteosarcoma cell lines all showed significantly higher expressions of SCUBE3. In U2OS cells, suppression of SCUBE3 expression by siRNA significantly inhibited the cell proliferation (P<0.05). Kaplan-Meier survival analysis indicated that patients with high SCUBE3 expression had worse prognosis than those with low SCUBE3 expression (P=0.036).

CONCLUSIONSCUBE3 is up-regulated in the 5 osteosarcoma cell lines and in primary osteosarcoma tissues to promote the proliferation of osteosarcoma cells. A high SCUBE3 expression in osteosarcoma tissues is associated with a poor prognosis of the patients, suggesting that SCUBE3 can serve as a potential therapeutic target for osteosarcoma.

Bone Neoplasms ; metabolism ; pathology ; Calcium-Binding Proteins ; metabolism ; Cell Cycle ; Cell Line, Tumor ; Cell Proliferation ; Flow Cytometry ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Osteosarcoma ; metabolism ; pathology ; Prognosis ; RNA, Small Interfering ; Up-Regulation