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Lisha Zhang,1,&ast; Yuxiu Wang,2,&ast; Yaokun Ye,2 JunYin Gao,2 Fabei Zhu,1 Lingfeng Min2 1Department of Respiratory and Critical Care Medicine, The Yangzhou School of Clinical Medicine, Dalian Medical University, Yangzhou City, Jiangsu Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Clinical Medical College, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingfeng Min, Department of Respiratory and Critical Care Medicine, Clinical Medical College, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China, Tel +86 19962595724, Email minlingfeng@126.comPurpose: This study aimed to evaluate the clinical outcomes of high-flow nasal cannula (HFNC) compared with conventional oxygen therapy (COT) in patients with hypercapnic chronic obstructive pulmonary disease (COPD), including arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), respiratory rate (RR), treatment failure, exacerbation rates, adverse events and comfort evaluation.Patients and Methods: PubMed, EMBASE and the Cochrane Library were retrieved from inception to September 30, 2022. Eligible trials were randomized controlled trials and crossover studies comparing HFNC and COT in hypercapnic COPD patients. Continuous variables were reported as mean and standard derivation and calculated by weighted mean differences (MD), while dichotomous variables were shown as frequency and proportion and calculated by odds ratio (OR), with the 95% confidence intervals (Cl). Statistical analysis was performed using RevMan 5.4 software.Results: Eight studies were included, five with acute hypercapnia and three with chronic hypercapnia. In acute hypercapnic COPD, short-term HFNC reduced PaCO2 (MD − 1.55, 95% CI: − 2.85 to − 0.25, I² = 0%, p < 0.05) and treatment failure (OR 0.54, 95% CI: 0.33 to 0.88, I² = 0%, p< 0.05), but there were no significant differences in PaO2 (MD − 0.36, 95% CI: − 2.23 to 1.52, I² = 45%, p=0.71) and RR (MD − 1.07, 95% CI: − 2.44 to 0.29, I² = 72%, p=0.12). In chronic hypercapnic COPD, HFNC may reduce COPD exacerbation rates, but there was no advantage in improving PaCO2 (MD − 1.21, 95% CI: − 3.81 to 1.39, I² = 0%, p=0.36) and PaO2 (MD 2.81, 95% CI: − 1.39 to 7.02, I² = 0%, p=0.19).Conclusion: Compared with COT, short-term HFNC reduced PaCO2 and the need for escalating respiratory support in acute hypercapnic COPD, whereas long-term HFNC reduced COPD exacerbations rates in chronic hypercapnia. HFNC has great potential for treating hypercapnic COPD.Keywords: nasal high-flow oxygen therapy, conventional oxygen therapy, hypercapnia, chronic obstructive pulmonary disease, meta-analysis

Taojun Gong,* Yi Luo,* Yitian Wang, Chuanxi Zheng, Jianguo Fang, Li Min, Yong Zhou, Chongqi Tu Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chongqi TuDepartment of Orthopedics, West China Hospital, Sichuan University, Guoxue Xiang No. 37, Chengdu, Sichuan, 610041, People’s Republic of ChinaEmail tuchongqibone@hotmail.comAbstract: Giant cell tumor of bone (GCTB) is a rare, benign, but locally aggressive bone tumor. It has a high tendency for local recurrence, which may increase the incidence of lung metastasis. Currently, an optimal treatment strategy has not been established because of the rarity of pulmonary metastatic GCTB. Denosumab is the preferred regimen for unresectable metastatic lesions; however, there are no alternative treatment options when patients are resistant to denosumab. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively competes for the vascular endothelial growth factor receptor 2 (VEGFR-2) ATP binding site, and several studies have analyzed the effectiveness of apatinib in advanced or metastatic tumors. However, there is no report of apatinib as an anti-angiogenesis therapy for pulmonary metastatic GCTB to date. Here, we present a case of a 26-year-old female who was diagnosed with recurrent and pulmonary metastatic GCTB. Immunohistochemical (IHC) staining indicated that the tumor cells were positive for VEGFR-2. Denosumab was administered to control the metastases; nevertheless, disease progression was confirmed after four months of treatment. Given the IHC results and rapid disease progression, apatinib was added to the treatment strategy. After 42 months of treatment, the patient showed noticeable symptomatic improvement and considerable tumor shrinkage.Keywords: giant cell tumor of bone, pulmonary metastasis, VEGFR-2, denosumab, apatinib

Minxun Lu,1,2 Hongjie Chen,2 Bo Yuan,2 Yong Zhou,1 Li Min,1 Zhanwen Xiao,2 Xiangdong Zhu,2 Chongqi Tu,1 Xingdong Zhang2 1Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xiangdong ZhuNational Engineering Research Center for Biomaterials, Sichuan University, No. 29 Wangjiang Road, Chengdu 610064, People’s Republic of ChinaTel +86-28-85470770Email zhu_xd1973@scu.edu.cnChongqi TuDepartment of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxue Street, Chengdu 610041, People’s Republic of ChinaTel +86-28-85422570Email Tuchongqi@yeah.netPurpose: The aim of research is to fabricate nanostructured hydroxyapatite (HA) coatings on the titanium via electrochemical deposition (ED). Additionally, the biological properties of the ED-produced HA (EDHA) coatings with a plate-like nanostructure were evaluated in vitro and in vivo by undertaking comparisons with those prepared by acid/alkali (AA) treatment and by plasma spray-produced HA (PSHA) nanotopography-free coatings.Materials and Methods: Nanoplate-like HA coatings were prepared through ED, and nanotopography-free PSHA coatings were fabricated. The surface morphology, phase composition, roughness, and wettability of these samples were investigated. Furthermore, the growth, proliferation, and osteogenic differentiation of MC3T3-E1 cells cultured on each sample were evaluated via in vitro experiments. Histological assessment and push-out tests for the bone–implant interface were performed to explore the effect of the EDHA coatings on the interfacial osseointegration in vivo.Results: XRD analysis showed that the strongest intensity for the EDHA coatings was at the (002) plane rather than at the regular (211) plane. Relatively higher surface roughness and greater wettability were observed for the EDHA coatings. Cellular experiments revealed that the plate-like nanostructured EDHA coatings not only possessed an ability, similar to that of PSHA coatings, to promote the adhesion and proliferation of MC3T3-E1 cells but also demonstrated significantly enhanced early or intermediate markers of osteogenic differentiation. Significant osseointegration enhancement in the early stage of implantation period and great bonding strength were observed at the interface of bone and EDHA samples. In comparison, relatively weak osseointegration and bonding strength of the bone–implant interface were observed for the AA treatment.Conclusion: The biological performance of the plate-like nanostructured EDHA coating, which was comparable with that of the PSHA, improves early-stage osteogenic differentiation and osseointegration abilities and has great potential for enhancing the initial stability and long-term survival of uncemented or 3D porous titanium implants.Keywords: electrochemical deposition, hydroxyapatite coatings, nanoscale, osteogenic activity, osseointegration

Chuanxi Zheng,* Yong Zhou,* Yitian Wang, Yi Luo, Chongqi Tu, Li Min Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li MinDepartment of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu 610041, People’s Republic of ChinaTel +86 13760311476Fax +86 028 85582944Email minli1204@scu.edu.cnPurpose: Desmoid fibromatosis (DF) is an aggressive fibroblastic neoplasm with a high propensity for local recurrence. Although multiple therapeutic modalities seem effective for DF, the standard systemic treatment for symptomatic and progressive DF remains controversial. As targeted therapy, tyrosine kinase inhibitors have been recently reported to contribute to the treatment of DF. Thus, the purpose of this study was to assess the efficacy and safety of anlotinib, a novel multi-kinase angiogenesis inhibitor, in patients with DF.Patients and Methods: We retrospectively collected the clinical medical records of patients with extremity DF who received anlotinib between January 2019 and January 2020 in our center. Anlotinib was started with a dose of 8 mg daily and adjusted according to the drug-related toxicity. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors 1.1 criteria. Progression-free survival (PFS) was identified as the primary endpoint and analyzed using the Kaplan–Meier method.Results: In total, 21 (6 male, 15 female) consecutive patients with DF were enrolled. The median medication time was nine months (Q1, Q3: 7.5, 10.5). None of the patients achieved a complete response, but eight (38.1%) patients achieved a partial response and ten patients (47.6%) achieved disease stability. Three (14%) patients developed progressive disease and the 3-, 6-, and 12-month PFS rates were 95.2%, 90.5%, and 84.0%, respectively. The disease control rate was 86.0% (18/21) and the objective response rate was 38.1% (8/21). Moreover, 15/21 (71.4%) patients achieved a reduction in tumor size, accompanied with a decrease in T2-weighted signal intensity on magnetic resonance imaging and clinical benefit.Conclusion: Anlotinib was effective against DF with an acceptable safety profile, and significantly slowed the disease progression. Further, multicenter studies with a longer follow-up time are needed to characterize fully the clinical application of anlotinib in DF.Keywords: desmoid fibromatosis, anlotinib, tyrosine kinase inhibitor, targeted therapy

Yitian Wang,* Minxun Lu,* Yong Zhou, Sisi Zhou, Xinzhu Yu, Fan Tang, Yi Luo, Wenli Zhang, Hong Duan, Li Min, Chongqi Tu Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li MinDepartment of Orthopedics, West China Hospital, Sichuan University, No. 37 Guoxuexiang, Chengdu 610041, People’s Republic of ChinaTel +86 13980095430Fax +86 028 85582944Email minli1204@scu.edu.cnBackground: Synovial sarcoma (SS) is a highly aggressive soft-tissue sarcoma (STS) with poor prognosis. Tyrosine kinase inhibitor (TKI) has shown a promising impact on advanced STS patients. This study aimed to evaluate the efficacy and safety of apatinib, an oral multi-TKI, which especially inhibited vascular endothelial growth factor receptor, as second-line therapy for patients with advanced SS.Patients and Methods: This retrospective analysis included 21 advanced SS patients, who had a poor response to anthracycline-based chemotherapy alone or combined with ifosfamide at least one cycle. All the patients received an apatinib containing regimen between May 2016 and October 2019 in our institution. Apatinib 500– 750 mg (250 mg for patients younger than 10) was given daily. Tumor responses were assessed by response evaluation criteria in solid tumors. Survival analysis was performed by the Kaplan–Meier test, and a safety profile was recorded.Results: The median follow-up was 15.2 months (95% CI, 12.2-NE). Nine (42.9%) patients had partial response (PR), and eight (38.1%) had stable disease. The median progression-free survival (PFS) was 13.1 months (95% CI, 6.7-NE). The 6- and 12-month PFS rates were 76.2% (95% CI, 60.0– 96.8) and 55.4% (95% CI, 37.3– 82.3), respectively. Additionally, the median overall survival (OS) was 15.5 months (95% CI, 10.7-NE). The 6- and 12-month OS rates were 81.0% (95% CI, 65.8, 99.6) and 64.9% (95% CI, 46.9– 90.0), respectively. Moreover, the objective response rate was 42.9% (9/21) for advanced SS patients. The disease control rate was 81.0% (17/21). For the nine patients with the best response of PR, the median duration of response was 7.7 months.Conclusion: Apatinib was proved to be a potential second-line treatment option for advanced SS patients with chemo-resistance. Apatinib showed promising efficacy and acceptable safety profile in advanced SS, with considerable OS and particularly PFS. Indeed, further multicenter studies with a longer follow-up time are needed to fully determine the clinical application of apatinib in advanced SS.Keywords: synovial sarcoma, apatinib, targeted therapy, efficacy, safety

Daohui Gong,1,* Ying Li,2,* Yuxiu Wang,1,* Beiyuan Chi,1 Jun Zhang,1 Jianjun Gu,1 JunJun Yang,1 Xingxiang Xu,1 Suwei Hu,3 Lingfeng Min1 1Department of Respiratory Medicine, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 2Department of Medical Oncology, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu, People’s Republic of China; 3Medical Genetic Center, Yangzhou Maternal and Child Health Care Service Centre, The Affiliated Hospital of Yangzhou University Medical College, Yangzhou, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lingfeng MinDepartment of Respiratory Medicine, Northern Jiangsu People’s Hospital, Clinical Medical College of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, People’s Republic of ChinaTel +86-18051061783Email minlingfeng@126.comSuwei HuMedical Genetic Center, Yangzhou Maternal and Child Health Care Service Centre, The Affiliated Hospital of Yangzhou University Medical College, Yangzhou, Jiangsu 225002, People’s Republic of ChinaTel +86-18912137872Email husuwei2004@126.comPurpose: AMP-activated protein kinase α 1 (AMPK α 1) associates closely with cancers. However, the relationship between AMPK α 1 and non-small cell lung cancer (NSCLC) is not fully understood. In this study, we aim to explore the role and mechanism of AMPK α 1 in NSCLC initiation and progression.Materials and Methods: A total of 165 clinical NSCLC specimens were included in the formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays. The expression levels of AMPK α 1 and thioredoxin (Trx) in NSCLC cancer tissues and adjacent non-tumor lung tissues were measured through using immunohistochemistry. MTT assay was used to detect cell proliferation. Intracellular ROS levels were measured by using H2DCFDA reagent. Lentiviruses including LV-PRKAA1-RNAi, LV-PRKAA1 and a negative LV-control were used to infect A549 cells to modulate AMPK α 1 expression in vitro. Immunoblotting was used to determine the modulation relationship between AMPK α 1 and Trx. Log rank test and Kaplan–Meier survival analysis were performed to evaluate the significances of AMPK α 1 and Trx expression levels on NSCLC patients’ prognoses.Results: AMPK α 1 was highly expressed in NSCLC cancer tissues and correlated with poor prognosis in patients with NSCLC. In A549 cells, overexpression of AMPK α 1 promoted proliferation, suppressed ROS levels and inhibited apoptosis. Moreover, inhibition of AMPK α 1 expression achieved the opposite effects. Trx was significantly overexpressed in NSCLC cancer tissues; furthermore, Trx expressed much more in cytoplasm when compared with cell nucleus. Trx expression levels were positively correlated with AMPK α 1 expression levels in NSCLC tissues. AMPK α 1 could regulate Trx in A549 cells. No significant correlations were observed between Trx expression variances and prognoses in NSCLC patients. Combination of AMPK α 1 and Trx had no advantage in predicting prognoses of NSCLC patients.Conclusion: These results suggest that AMPK α 1 serves a carcinogenic role at least in part through the regulation of Trx expression, and thus represents a potential treatment target in patients with NSCLC.Keywords: AMPK α 1, ROS, apoptosis, non-small cell lung cancer

Dingyun Zhao,1,* Fan Tang,1,* Li Min,1 Minxun Lu,1 Jie Wang,1 Yuqi Zhang,1 Kun Zhao,1,2 Yong Zhou,1 Yi Luo,1 Chongqi Tu1 1Department of Orthopeadics, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 2Department of Orthopeadics, Tianjin Fifth Central Hospital, Tianjin 300450, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chongqi TuDepartment of Orthopedics, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu, Sichuan 610041, People’s Republic of ChinaTel +86-189-8060-1387Fax +86-28-8542-2246Email tcqbonetumor@163.comPurpose: This study aimed to evaluate the early stability, limb function, and mechanical complications of 3D-printed porous prosthetic reconstruction for “ultra-critical sized bone defects” following intercalary tibial tumor resections.Methods: This study defined an “ultra-critical sized bone defect” in the tibia when the length of segmental defect in the tibia was > 15.0 cm or > 60% of the full tibia and the length of the residual fragment in proximal or distal tibia was between 0.5 cm and 4.0 cm. Thus, five patients with “ultra-critical sized bone defects” following an intercalary tibial malignant tumor resection treated with 3D-printed porous prosthesis between June 2014 and June 2018 were retrospectively reviewed. Patient information, implants design and fabrication, surgical procedures, and early clinical outcome data were collected and evaluated.Results: Among the five patients, three were male and two were female, with an average age of 30.2 years. Pathological diagnoses were two osteosarcomas, one Ewing sarcoma, one pseudo-myogenic hemangioendothelioma, and one undifferentiated pleomorphic sarcoma . The average length of the bone defects following tumor resection was 22.8cm, and the average length of ultra-short residual bone was 2.65cm (range=0.6cm– 3.8cm). The mean follow-up time was 27.6 months (range=14.0– 62.0 months). Early biological fixation was achieved in all five patients. The average time of clinical osseointegration at the bone–porous interface was 3.2 months. All patients were reported to be pain free and have no limitations in their walking distance. No prosthetic mechanical complications were observed.Conclusion: Reconstruction of the “ultra-critical sized bone defect” after an intercalary tibial tumor resection using 3D-printed porous prosthesis achieved satisfactory overall early biological fixation and limb function. Excellent primary stability and the following rigid biological fixation were key factors for success. The outcomes of this study were supposed to support further clinical application and evaluation of 3D-printed porous prosthetic reconstruction for “ultra-critical sized bone defects” in the tibia.Keywords: 3D-printed porous, prosthetic reconstruction, intercalary tibial resection, critical sized bone defect

Yitian Wang,* Li Min,* Yong Zhou, Fan Tang, Yi Luo, Wenli Zhang, Hong Duan, Chongqi TuDepartment of Orthopedics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, People‘s Republic of China*These authors contributed equally to this workBackground: Evidence suggests that advanced or metastatic alveolar soft part sarcoma (ASPS) with high metastatic potential is chemo-resistant. However, the benefits of tyrosine kinase inhibitors have been demonstrated for the treatment of ASPS.Purpose: This study aimed to investigate the efficacy and safety of apatinib, aspecific VEGFR-2 inhibitor, in ASPS patients. This retrospective analysis involved six patients with metastatic ASPS not amenable to curative treatment.Patients and methods: Apatinib was administered at a dose of 500mg per day. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) guidelines. Survival analysis was performed using the Kaplan–Meier test, and a safety profile was recorded.Results: The mean age of patients was 26.5 (range, 17–32) years. The median progression-free survival (PFS) was 18.53 months (95% CI, 12.23-NE). However, median overall survival (OS) has not been reached. Twenty-four month PFS and OS rates were 50.0% and 100.0%, respectively. One patient achieved a complete response, and the remaining patients achieved partial responses, with an objective response rate of 100%. Median follow-up was 20.6 (range, 12.43–34.13) months. The most common adverse events included gastrointestinal discomfort (4/6[66.7%]), hair hypopigmentation (4/6[66.7%]) and hand-foot skin reaction (3/6[50.0%]).Conclusion: Apatinib shows beneficial activity in metastatic ASPS patients, and further studies are warranted with more cases and longer follow-up periods to fully characterize clinical efficacy and safety of apatinib in ASPS.Keywords: alveolar soft part sarcoma, apatinib, efficacy, safety, vascular endothelial growth factor

Tao Wang,1,* Jie Yu,1,* Min Liu,1,* Yanliang Chen,1 Caiyun Zhu,1 Lin Lu,2 Mingzhu Wang,2 Lingfeng Min,3 Xinxin Liu,4 Xizhi Zhang,1 Johannes A Gubat,5 Yong Chen1 1Department of Medical Oncology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China; 2Department of Medical Oncology, Dalian Medical University, Dalian, Liaoning, China; 3Department of Respiratory Medicine, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China; 4Department of Gastrointestinal Surgery, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China; 5Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden *These authors contributed equally to this work Purpose: Fluoropyrimidine plus platinum (FP) is currently the standard treatment for esophageal cancer (EC). In recent years, taxane-based chemotherapy has also been used and has shown good efficacy in EC. This study aims to investigate the advantages of taxane-based over FP chemotherapy, as well as discuss its drawbacks, in the treatment of EC. Patients and methods: A literature search was done for studies comparing clinical outcomes between taxane-based and FP chemotherapy in EC. Pooled analyses were performed to compare the efficacy and grade 3/4 adverse events in patients who received neoadjuvant chemotherapy (NACT), neoadjuvant chemoradiotherapy (NACRT), or definitive chemoradiotherapy (dCRT). Subgroup analyses were also conducted in esophageal squamous cell carcinoma (ESCC). Results: Thirty-one studies with a total of 3,912 patients were included in the analysis. Better long-term survival was found in patients who received taxane-based NACT (progression-free survival (PFS): pooled HR=0.58, P=0.0008; and overall survival (OS): pooled HR=0.50, P

Jie Xing,1 Li Min,1 Hao Zhang,2 Peng Li,1 Wei Li,1 Fujin Lv,1 Yongjun Wang,1 Zheng Zhang,1 Hengcun Li,1 Qingdong Guo,1 Siyi Wang,1 Yu Zhao,1 Junmin Wang,3 Xiaoyan Shi,4 Anxin Wang,5 Shengtao Zhu,1 Ming Ji,1 Yongdong Wu,1 Shutian Zhang1 On behalf of the NCECS Study Group 1Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, People’s Republic of China; 2Department of Gastroenterology, Jizhong Energy Fengfeng Group Hospital, Handan, Hebei 056200, People’s Republic of China; 3Department of Gastroenterology, Handan Central Hospital, Handan, Hebei 056001, People’s Republic of China; 4Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, People’s Republic of China; 5Department of Epidemiology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100029, People’s Republic of China Background: Endoscopy is the main approach used for esophageal squamous cell carcinoma (ESCC) screening, especially in high-risk areas. However, little consensus has been achieved in recent ESCC screening programs, and endoscopists have selected patients only by age and family history. Patients and methods: To generate a proper strategy for selecting an eligible population for endoscopic screening based on demographic factors, lifestyle, and eating habits, a total of 7,830 residents in an area with a high risk of ESCC were recruited for this study. All participants underwent endoscopic examinations that were conducted by experienced endoscopists. Risk factors for ESCC and other lesions were selected by univariate and multivariate logistic regressions. A nomogram for the prediction of ESCC and premalignant lesions was constructed, which included information on age, sex, occupation, labor intensity, income, and mining exposure. Receiver operating characteristic (ROC) curve analysis was performed to present the predictive accuracy of the nomograms. Results: The area under the curve (95% CI) was 0.749 (0.711–0.788) for this nomogram. By applying this nomogram, we could exclude 60% (4704/7830) of patients before endoscopy screening and detect all ESCC cases as well as most esophageal lesions in the remaining population. Conclusion: In conclusion, we provided a ready-to-use preclinical tool with the potential to select eligible people with high risk of ESCC for endoscopy screening. Keywords: nomogram, endoscopy screening, ESCC, population-based study

Yitian Wang,* Li Min,* Yong Zhou, Yi Luo, Hong Duan, Chongqi Tu Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China *These authors contributed equally to this work Background: Ewing’s sarcoma (ES) is a highly aggressive and metastatic neoplasm occurring mainly in children and young adults. The standard treatment of localized ES requires a combination of surgery, chemotherapy, and radiotherapy. Although the 5-year survival rate for local ES has improved, the survival rate and prognosis are still very poor for metastatic or recurrent ES patients. The aim of this study was to investigate the efficacy and safety of apatinib, a specific vascular endothelial growth factor receptor 2 inhibitor, in ES patients.Methods: This retrospective analysis involved eleven patients with ES not amenable to curative treatment. All patients suffered poor responses to two cycles of chemotherapy (vincristine, doxorubicin, and cyclophosphamide). Apatinib 500 mg (or 250 mg) was given daily. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors 1.1. Survival analysis was performed by the Kaplan–Meier test. The safety profile was also recorded.Results: The mean age of the patients was 18 (range, 10–31) years. The 12-month overall survival and progression-free survival rates were 90% and 72%, respectively. Four patients achieved partial response, and four patients achieved stable disease, with objective response rate of 40%. The median follow-up in our study was 16 months (range, 3–26 months). The most common adverse events included hand–foot skin reaction (n=5; 45%), oral ulcers (n=4; 36%), and gastrointestinal discomfort (n=4; 36%).Conclusion: Apatinib may provide as second- or first-line treatment options for ES patients, particularly in chemoresistant cases. Further studies with more cases and longer follow-up will be necessary to determine the clinical efficacy and safety of apatinib in ES patients. Keywords: Ewing’s sarcoma, apatinib, vascular endothelial growth factor, efficacy, safety

Yi Luo, Fan Tang, Yitian Wang, Yong Zhou, Li Min, Wenli Zhang, Rui Shi, Hong Duan, Chongqi Tu Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China Background: Giant cell tumor (GCT) of bone is an intermittent and locally aggressive tumor with increasing pulmonary metastatic potential. In this study, we evaluated the interim clinical outcome of denosumab in patients with pulmonary metastatic GCT. Materials and methods: We retrospectively reviewed seven patients with pulmonary metastatic GCT who received denosumab treatment after local tumor surgery during January 2014 and July 2016. Denosumab treatment for all patients lasted for at least 12 months. Serial chest computerized tomography scan was used to monitor the drug response and RECIST 1.1 standard was used to evaluate the therapeutic efficacy. Results: All patients experienced chest pain relief in the first month of treatment. Three patients showed partial response. Four patients got stable disease after denosumab treatment. Adverse events included one patient with hypocalcemia and two patients with fever. No treatment-related deaths were reported. No patient with metastatic disease progression was found during an average of 28.6 months follow-up period. Conclusion: We presented a promising interim clinical outcome using denosumab to treat patients with pulmonary metastatic GCT. Denosumab might be considered as the first-line treatment for patients with inoperable metastatic pulmonary GCT. However, Phase II clinical study with larger number of patients and longer follow-up period is needed to detect the further efficacy and safety of this drug for lung metastatic GCT. Keywords: denosumab, giant cell tumor of bone, pulmonary metastasis, RANKL, recurrence

Ling Min, Xiyan Mu, An Tong, Yanping Qian, Chen Ling, Tao Yi, Xia Zhao Department of Gynecology and Obstetrics, Key laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, People’s Republic of China Objectives: This work aims to explore whether HOX transcript antisense intergenic RNA (HOTAIR) polymorphisms are associated with cancer susceptibility. Materials and methods: A comprehensive search was conducted for literature published from January 2007 to July 2017. The pooled odds ratios (ORs) and the corresponding 95% CIs were calculated using the Revman 5.2 software. Eighteen articles of 36 case–control studies were enrolled including six HOTAIR polymorphisms and 10 cancer types. Results: The results showed that cancer risk was elevated in recessive mutation of rs12826786 (TT vs CC+CT: OR =1.55, 95% CI =1.19, 2.03; TT+CT vs CC: OR =1.23, 95% CI =1.04, 1.46; TT vs CC: OR =1.67, 95% CI =1.24, 2.24; T vs C: OR =1.24, 95% CI =1.09, 1.40) and rs920778 (TT vs CC+CT: OR =1.73, 95% CI =1.30, 2.30; TT+CT vs CC: OR =1.40, 95% CI =1.16, 1.70; TT vs CC: OR =1.83, 95% CI =1.25, 2.68; T vs C: OR =1.37, 95% CI =1.18, 1.59), while the results for polymorphisms of rs7958904, rs4759314, rs874945, and rs1899663 were insignificant. The stratified results for Chinese population were consistent with the overall group analysis. Conclusion: Our meta-analysis showed that HOTAIR polymorphisms of rs12826786 and rs920778 were correlated with increased cancer risk, while rs7958904, rs4759314, rs874945, and rs1899663 were not. More studies with different types of cancer are needed to confirm the findings. Keywords: HOTAIR, polymorphism, cancer, susceptibility, meta-analysis

Minxun Lu,* Li Min,* Cong Xiao, Yongjiang Li, Yi Luo, Yong Zhou, Wenli Zhang, Chongqi Tu Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China *These authors contributed equally to this work Introduction: Currently, it is challenging to treat giant cell tumor (GCT) of distal radius. For Campanacci grade III or recurrent GCTs, en bloc resection has been accepted as a better treatment option. Although numerous methods are available for reconstruction, all of them have some limitations in joint function and complications. In this study, our aims were to treat the GCT of distal radius with uncemented three-dimensional (3D)-printed prosthesis and to present and evaluate the surgical techniques and short-term outcomes. Methods: Between September 2015 and March 2017, 11 patients with distal radius GCTs were treated with personalized uncemented 3D-printed prosthesis. The preoperative/postoperative pain, range of motion, and grip strengths of all patients were evaluated. Oncological results, complications, and degenerative changes in the wrist joint were evaluated. Functional outcomes were assessed according to the disabilities of the arm, shoulder, and hand (DASH) questionnaire and Mayo wrist scoring systems. Results: The average follow-up was 14.45 months (range, 8–18 months). There was a significant decrease in the mean postoperative visual analog scale score (2.33) compared with the preoperative score (5.22; p

Fan Tang,1,2 Li Min,1,2 Yong Zhou,1 Yi Luo,1 Chongqi Tu1 1Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, Boston, MA, USA Abstract: Low-grade central osteosarcoma is a rare subtype of tumor with low-grade malignancy. Currently, wide resection with negative resection margin is the standard treatment for this disease. The role of neoadjuvant chemotherapy in low-grade central osteosarcoma was controversial and was mostly considered for tumors containing high-grade focal areas. Local tumor recurrences often exhibited a tumor with higher histologic grade or differentiation with the potential for metastases. In low-grade central osteosarcoma, timely wide resection after definite diagnosis can result in 5-year survival for almost 90%. However, the relatively nonspecific radiological and pathological findings make diagnosis very difficult. MDM2 and CDK4 are specific and provide sensitive markers for the diagnosis of low-grade central osteosarcoma, helping to differentiate low-grade central osteosarcoma from some benign lesions, including fibrous dysplasia, bone giant cell tumor, and chondrosarcoma. Here, we report the case of a 19-year-old woman with low-grade central osteosarcoma located at the proximal humerus. The affected site was rare, but the sensitive biomarkers CDK4 and MDM2 were positive. The patient recovered well after wide tumor resection following a proximal humerus endoprosthesis replacement. Our case highlighted the management strategies in low-grade central osteosarcoma. Being familiar with radiographic features, understanding the biological characteristics, and mastering diagnostic biomarkers can help oncologists avoid embarrassing situations in treatment when this rare tumor is highly suspected, even when located at an uncommon site. The discussion in this report focuses on radiographic and pathological features, advances of biomarkers that help in differential diagnosis, and current treatment options in low-grade central osteosarcoma. Keywords: low-grade central osteosarcoma, proximal humerus, differential diagnosis, wide resection, MDM2, CDK4

Fan Tang, Yong Zhou, Li Min, Wenli Zhang, Rui Shi, Yi Luo, Hong Duan, Chongqi TuDepartment of Orthopedics, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaObjective: To evaluate the medium-term outcome of limb-salvage surgery using all-polyethylene tibial endoprosthetic replacement following en-block resection for distal femoral tumors.Methods: Forty-nine patients with distal femoral tumor were treated between June 2006 and June 2012. The follow-up period was 6–110 months (average 53.4 months). The prosthetic survival was analyzed using the Kaplan–Meier method. The classification of failure of limb salvage after reconstructive surgery for bone tumors was adapted. Limb function was evaluated with the scoring system of the Musculoskeletal Tumor Society (MSTS).Results: Complications were observed in six cases (12.2%). Four suffered infection around the prosthesis, of which two cases were treated with debridement, drainage, and antibiotics without removal of the prosthesis, and the other two cases underwent amputation. Two cases were identified as radiographically loose at 7 year follow-up and did not require revision surgery. One patient underwent amputation due to local recurrence. Failure of limb salvage occurred in nine cases (18.4%), of which two cases were of type 1A, two cases of type 2B, three cases of type 4A, one case of type 4B, and one case of type 5A. The mean MSTS score was 84.3%. Twelve cases died due to distant metastases (24.5%), and the average survival time for these patients was 13.5 months. Thirty-seven patients survived (75.5%), for whom the average follow-up time was 66.3 months and the 5-year prosthetic survival rate was 88.2%.Conclusion: The outcome of medium-term and long-term clinical follow-up was satisfactory. All-polyethylene tibial endoprosthetic replacement following en-block resection can be an alternative method of limb salvage for distal femoral tumors.Keywords: limb salvage, endoprosthetic replacement, all-polyethylene tibia, distal femur, tumor

A comparative analysis of invasive plants in China and the USA, the climates of which are similar, revealed both similarities and differences in taxonomic characteristics, morphological characteristics, areas of origin, invaded regions, and histories of introduction. Generally, there were more species from Asteraceae and Poaceae than from other families, and a high proportion of families were represented by only one invasive species. Most invaders had at least one reproductive mode, with sexual reproduction being the main mode, as well as the adaptation of flower, fruit, and seed characteristics for successful seed production and dispersal. Many invasive plants are able to reproduce clonally. An analysis of the invasive species in China and the USA indicated that they are mainly derived from continents with climates similar to that of the invaded area or at latitudes within the same range. Species from tropical areas invaded more easily than those from other climatic zones. Our study of the invasive histories of species introduced into China and the USA demonstrates that it takes about 100 years for an exotic species to become an invasive species. Keywords: Distribution, Invasibility, Invasive capacity, Introduction history, Alien species

Li Min, Fan Tang, Hong Duan, Yong Zhou, Wen-li Zhang, Rui Shi, Chong-qi Tu Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China Introduction: Cemented allograft-prosthesis composite (APC) reconstruction is one option following resection of the proximal femur tumor. However, rare studies have focused on the indications and complications. The goal of the present study was to (1) ascertain the indications for cemented APC arthroplasty in the proximal femur; (2) identify the detailed perioperative management; and (3) illustrate our experiences to avoid the complications of cemented APC. Materials and methods: A total 28 patients who underwent cemented APC reconstruction of the proximal femur after tumor resection were retrospectively evaluated at a median follow-up of 56 months. Clinical records and radiographs were reviewed to evaluate patients’ outcome. Results: In our series, excluding three cases of death that had a short follow-up period, union occurred in 22 (88.0%) patients (range 9–18 months). Nonunion of the greater trochanter was seen in six of the 12 patients (50.0%). Eight (32.0%) hips had resorption. There were two (8.0%) hips that were observed to have asymptomatic wear of the acetabulum. The average Musculoskeletal Tumor Society (MSTS) score was 26.5 points. The average Harris Hip Score (HHS) score was 80.6 points. There were no cases of recurrence, but metastasis was found in two hips. Conclusions: Mastering indications, perioperative management, and complication prevention are all very important in the APC reconstruction after resection of the proximal femur. Keywords: bone tumor, surgical treatment, limb salvage

Yan Xiong,1 Cheng Ren,1 Bin Zhang,1 Hongsheng Yang,1 Yun Lang,1 Li Min,1 Wenli Zhang,1 Fuxing Pei,1 Yonggang Yan,2 Hong Li,2 Anchun Mo,3 Chongqi Tu,1 Hong Duan11Department of Orthopedics, West China Hospital, 2School of Physical Science and Technology, 3Department of Oral Implant, West China College of Stomatology, Sichuan University, Chengdu, People's Republic of ChinaAbstract: The aim of this study was to analyze the behavior of the porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite grafted for bone defect repair through a series of biological safety experiments, animal experiments, and a more than 5-year long clinical follow-up. The biological safety experiments, carried out in accordance with the Chinese Guo Biao and Tolerancing (GB/T)16886 and GB/T16175, revealed that porous n-HA/PA66 composite had no cytotoxicity, no sensitization effect, no pyrogenic reaction, and that its hemolysis rate was 0.59% (less than 5%). Rabbit models of tibia defects with grafted porous n-HA/PA66 composite were established. After 2 weeks, the experiment showed that osteogenesis was detected in the porous n-HA/PA66 composite; the density of new bone formation was similar to the surrounding host bone at 12 weeks. After 26 weeks, the artificial bone rebuilt to lamellar bone completely. In the clinical study, a retrospective review was carried out for 21 patients who underwent serial radiographic assessment after treatment with porous n-HA/PA66 composite grafts following bone tumor resection. All wounds healed to grade A. No postoperative infections, delayed deep infection, nonspecific inflammation, rejection, or fractures were encountered. At a mean follow-up of 5.3 years, the mean Musculoskeletal Tumor Society's (MSTS) 93 score was 29.3 points (range: 28–30 points) and mean radiopaque density ratio was 0.77±0.10. The radiologic analysis showed that porous n-HA/PA66 composite had been completely incorporated with the host bone about 1.5 years later. In conclusion, this study indicated that the porous n-HA/PA66 composite had biological safety, and good biocompatibility, osteoinduction, and osseointegration. Thus, the porous n-HA/PA66 composite is an ideal artificial bone substitute and worthy of promotion in the field.Keywords: biomaterial, artificial bone materials, porous n-HA/PA66 composite (n-HA/PA66), bone defects healing, bone grafting

Hong Duan,1 Hongsheng Yang,1 Yan Xiong,1 Bin Zhang,1 Cheng Ren,1 Li Min,1 Wenli Zhang,1 Yonggang Yan,2 Hong Li,2 Fuxing Pei,1 Chongqi Tu11Department of Orthopedics, 2School of Physical Science and Technology, Sichuan University, Chengdu, People's Republic of ChinaBackground and methods: Guided bone regeneration (GBR) is a new treatment for bone defects, and the property of membrane is critical to the success of GBR. This study focuses on a novel membrane tube for GBR, which was prepared by a nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer (n-CDHA-MAC) composite. The biomechanical strength and degradability of this membrane tube under mechanical loading after immersion in phosphate-buffered solution were investigated to evaluate the effects of mechanical loading on the membrane tube. The membrane-tube group with no mechanical loading and femora bone were used as controls.Results: The compressive strength and bending strength of n-CDHA-MAC membrane tubes were 66.4 ± 10.2 MPa and 840.7 ± 12.1 MPa, which were lower than those of the goats’ femoral bones (69.0 ± 5.5 MPa and 900.2 ± 17.3 MPa), but there were no significant (P > 0.05) differences. In the in vitro degradability experiment, all membrane tubes were degradable and showed a surface-erosion degradation model. The PH of solution fluctuated from 7.2 to 7.5. The weight and mechanical strength of loaded tubes decreased more quickly than nonloaded ones, with significant differences (P < 0.05). However, the strength of the loaded group after degradation achieved 20.4 ± 1.2 MPa, which was greater than the maximum mechanical strength of 4.338 MPa based on goat femoral middle stationary state by three-dimensional finite-element analysis.Conclusions: n-CDHA-MAC membrane tubes have good biomechanical strength during degradation under mechanical loading. Therefore, this membrane tube is an ideal GBR membrane for critical size defects of long bones in goats for animal experiments.Keywords: degradation, membrane tubes, n-CDHA-MAC, biomechanical properties