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Kaidi Zhao,1,* Yang Zhao,2,* Ao Guo,1 Shengxiang Xiao,1 Chen Tu1 1Department of Dermatology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 2National & Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen Tu; Shengxiang Xiao, Email tuchen2023@126.com; xiao_sx@163.comBackground: Psoriasis is a chronic inflammatory skin disease, and its etiology is still unclear. There is increasing evidence suggesting that microorganisms may trigger psoriasis. However, the relationship between psoriasis and oral microbiota remains poorly understood. Our aim is to identify differences in the composition and diversity of the oral microbiota between patients with psoriasis and healthy controls, and to discover oral microbial markers for assessing the severity of psoriasis.Methods: This study recruited 20 psoriasis patients and 20 healthy individuals, collecting their saliva to analyze the composition of the oral microbiota in psoriasis patients. We employed 16S rRNA sequencing technology and utilized various methods for oral microbiome analysis, including the Shannon Index, Gini-Simpson Index, Principal Coordinates Analysis (PCoA), non-metric multidimensional scaling (NMDS), Linear discriminant analysis Effect Size (LEfSe), Wilcoxon test, and Spearman’s rank correlation.Results: The results showed that the alpha diversity of oral microbiota was higher in psoriasis patients. The relative abundances of certain bacterial taxa differed between psoriasis and healthy individuals, including Prevotella, Prevotella 7 and Porphyromonas gingivalis, which are increased in psoriasis. We also found a positive correlation between Alloprevotella, Porphyromonas, and Neisseria with the severity of psoriasis, while Veillonella showed a negative correlation.Conclusion: In summary, this study found significant changes in the composition of the oral microbiota in patients with psoriasis. Some oral bacteria are associated with psoriasis severity. It provides a new perspective on the relationship between the oral microbiota and psoriasis.Keywords: psoriasis, oral microbiota, dysbiosis, comorbidity, 16s rRNA

Fangyuan Kuang,1,2 Yang Gao,3 Qingyun Zhou,4 Chenying Lu,3 Qiaomei Lin,4 Abdullah Al Mamun,5 Junle Pan,6 Shuibo Shi,7 Chaoyong Tu,4,* Chuxiao Shao2,* 1School of Medicine, Shaoxing University, Shaoxing, Zhejiang, 312000, People’s Republic of China; 2Department of Hepatopancreatobiliary Surgery, People Hospital of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, The First Affiliated Hospital of Lishui University, Lishui, Zhejiang, 323000, People’s Republic of China; 3Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China; 4Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China; 5Key Laboratory of Joint Diagnosis and Treatment of Chronic Liver Disease and Liver Cancer of Lishui, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui People’s Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 6First Academy of Clinical Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 7The First Clinical Medical College of Nanchang University, Nanchang City, Jiangxi, 330000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaoyong Tu, Department of Hepatopancreatobiliary Surgery, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, 323000, People’s Republic of China, Email tcy7409@163.comBackground: A limited number of studies have examined the use of radiomics to predict 3-year overall survival (OS) after hepatectomy in patients with hepatocellular carcinoma (HCC). This study develops 3-year OS prediction models for HCC patients after liver resection using MRI radiomics and clinicopathological factors.Materials and Methods: A retrospective analysis of 141 patients who underwent surgical resection of HCC was performed. Patients were randomized into two set: the training set (n=98) and the validation set (n=43) including the survival groups (n=111) and non-survival groups (n=30) based on 3-year survival after hepatectomy. Furthermore, x2 or Fisher’s exact test, univariate and multivariate logistic regression analyses were conducted to determine independent clinicopathological risk factors associated with 3-year OS. 1688 quantitative imaging features were extracted from preoperative T2-weighted imaging (T2WI) and contrast-enhanced magnetic resonance imaging (CE-MRI) of arterial phase (AP), portal venous phases (PVP)and delay period (DP). The features were selected using the variance threshold method, the select K best method and the least absolute shrinkage and selection operator (LASSO) algorithm. By using Bernoulli Naive Bayes (BernoulliNB) and Multinomial Naive Bayes (MultinomialNB) classifiers, we constructed models based on the independent clinicopathological factors and Rad-scores. To determine the best model, receiver operating characteristics (ROC) and Delong’s test were used. Moreover, calibration curves were used to determine the calibration ability of the model, while decision curve analysis (DCA) was implemented to evaluate its clinical benefit.Results: The fusion model showed excellent prediction precision with AUC of 0.910 and 0.846 in training and validation set and revealed significant diagnostic accuracy and value in the calibration curve and DCA analysis.Conclusion: Nomograms based on MRI radiomics and clinicopathological factors have significant predictive value for 3-year OS after hepatectomy and can be used for risk classification.Keywords: hepatocellular carcinoma, hepatectomy, MRI radiomics

Abstract Metal-Organic frameworks (MOFs) have been considered for various gas storage and separation applications. Theoretically, there are an infinite number of MOFs that can be created; however, a finite amount of resources are available to evaluate each one. Computational methods can be adapted to expedite the process of evaluation. In the context of CO2 capture, this paper investigates the method of screening MOFs using machine learning trained on molecular simulation data. New descriptors are introduced to aid this process. Using all descriptors, it is shown that machine learning can predict the CO2 adsorption, with an R2 of above 0.9. The introduced Effective Point Charge (EPoCh) descriptors, which assign values to frameworks’ partial charges based on the expected CO2 uptake of an equivalent point charge in isolation, are shown to be the second most important group of descriptors, behind the Henry coefficient. Furthermore, the EPoCh descriptors are hundreds of thousands of times faster to obtain compared with the Henry coefficient, and they achieve similar results when identifying top candidates for CO2 capture using pseudo-classification predictions.

Rong Liu,1,* Min Zhu,2,* Jiaojiao Chen,3 Junwei Gai,2 Jing Huang,2 Yingqun Zhou,1 Yakun Wan,2 Chuantao Tu4 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2Shanghai Novamab Biopharmaceuticals Co., Ltd, Shanghai, 201318, People’s Republic of China; 3Department of Gastroenterology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, 200434, People’s Republic of China; 4Department of Gastroenterology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuantao Tu; Yakun Wan, Email tuchuantao@hotmail.com; ykwan@novamab.comBackground: No agents are currently available for the treatment or reversal of liver fibrosis. Novel antifibrotic therapies for chronic liver diseases are thus urgently needed. Connective tissue growth factor (CTGF) has been shown to contributes profoundly to liver fibrogenesis, which makes CTGF as a promising target for developing antifibrotic agents.Methods: In this study, we identified a novel nanobody (Nb) against human CTGF (anti-CTGF Nb) by phage display using an immunized camel, which showed high affinity and specificity in vitro. LX-2 cells, the immortalized human hepatic stellate cells, were induced by transforming growth factor beta1 (TGFβ 1) as an in vitro model of liver fibrosis to verify the antifibrotic activity of the anti-CTGF Nb.Results: Our data demonstrated that anti-CTGF Nb effectively alleviated TGFβ 1-induced LX-2 cell proliferation, activation, and migration, and promoted the apoptosis of activated LX-2 cells in response to TGFβ 1. Moreover, the anti-CTGF Nb remarkably reduced the levels of TGFβ 1, Smad2, and Smad3 expression in LX-2 stellate cells stimulated by TGFβ 1.Conclusion: Taken together, we successfully identified a novel Nb against human CTGF, which exhibited antifibrotic effects in vitro by regulating the biological functions of human stellate cells LX-2.Graphical Abstract: Keywords: nanobody, connective tissue growth factor, liver fibrosis, hepatic stellate cells

Abstract Zein, which accounts for around 80% of the total protein composition in corn, is a biocompatible and biodegradable substance derived from renewable sources. Although insoluble in water, its amphiphilic characteristics are utilized to generate nanoparticles, nanofibers, microparticles, and even films. Numerous recent studies have demonstrated the potential of zein as a prospective biomaterial to develop fibrous scaffolds for biomedical functions owing to its biocompatibility, fibrous formation, and encapsulating qualities. Fabrication of zein‐based fibrous scaffolds for biomedical applications is achieved by a wide variety of techniques, including electrospinning, wet spinning, freeze drying, and additive manufacturing. This article overviews current advancements in manufacturing techniques for zein‐based fibrous scaffolds. In addition, it summarizes the most recent biomedical applications and research activities utilizing zein‐based fibrous scaffolds. Overall, zein is proposed as a potential biomaterial for the production of fibrous scaffolds that stimulate cell adhesion and proliferation in a number of exciting biomedical applications due to its biodegradability, biocompatibility, and other unique features related to its structure.

Lan Wei,1 Yuanyuan Han,2 Chao Tu1 1Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, People’s Republic of ChinaCorrespondence: Chao Tu, Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, 213000, People’s Republic of China, Email tcmedical21@czfph.comAbstract: Diabetic kidney disease (DKD) affects an estimated 20– 40% of type 2 diabetes patients and is among the most prevalent microvascular complications in this patient population, contributing to high morbidity and mortality rates. Currently, changes in albuminuria status are thought to be a primary indicator of the onset or progression of DKD, yet progressive nephropathy and renal impairment can occur in certain diabetic individuals who exhibit normal urinary albumin levels, emphasizing the lack of sensitivity and specificity associated with the use of albuminuria as a biomarker for detecting diabetic kidney disease and predicting DKD risk. According to the study, a non-invasive method for early detection or prediction of DKD may involve combining proteomic analytical techniques such second generation sequencing, mass spectrometry, two-dimensional gel electrophoresis, and other advanced system biology algorithms. Another category of proteins of relevance may now be provided by renal tissue biomarkers. The establishment of reliable proteomic biomarkers of DKD represents a novel approach to improving the diagnosis, prognostic evaluation, and treatment of affected patients. In the present review, a series of protein biomarkers that have been characterized to date are discussed, offering a theoretical foundation for future efforts to aid patients suffering from this debilitating microvascular complication.Keywords: diabetic kidney disease, proteomics, diagnostic biomarkers, therapeutic targets

Qi You,1,2,* Minxun Lu,1,2,* Zhuangzhuang Li,1,2 Yong Zhou,1,2 Chongqi Tu1,2 1Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2Sichuan Model Worker and Craftsman Talent Innovation Research Studio, Chengdu, Sichuan Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chongqi Tu; Yong Zhou, Department of Orthopedics, West China Hospital, Sichuan University, No. 37, Guoxuexiang, Chengdu, 610041, Sichuan Province, People’s Republic of China, Email Tucq@scu.edu.cn; zhouyonggk@163.comAbstract: Bone defects that are congenital or the result of infection, malignancy, or trauma represent a challenge to the global healthcare system. To address this issue, multiple research groups have been developing novel cell sheet technology (CST)-based approaches to promote bone regeneration. These methods hold promise for use in regenerative medicine because they preserve cell-cell contacts, cell-extracellular matrix interactions, and the protein makeup of cell membranes. This review introduces the concept and preparation system of the cell sheet (CS), explores the application of CST in bone regeneration, highlights the current states of the bone regeneration via CST, and offers perspectives on the challenges and future research direction of translating current knowledge from the lab to the clinic.Keywords: bone defect, cell sheet technology, bone regeneration, bone tissue engineering

Light-matter interaction can induce changes to the properties of the system by creating hybrid collective states of light and molecular excitations, the so called polaritons. Here the authors use femtosecond pump-probe spectroscopy to explore exciton-polariton dynamics in a photosynthetic protein, light harvesting 2 complexes, and find evidence for rapid energy transfer to dark polariton states.

Rongxin Zhang,1,2 Zhao Hou,2 Kexin Liao,2 Chao Yu,2 Rongrong Jing,1,2 Caixia Tu1,2 1Institute of Integrative Medicine, Dalian Medical University, Dalian, 116044, People’s Republic of China; 2Department of Dermatology, The Second Hospital of Dalian Medical University, Dalian, 116027, People’s Republic of ChinaCorrespondence: Caixia Tu, Department of Dermatology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Dalian, 116027, People’s Republic of China, Tel +8617709872288, Fax +86 411 84672130, Email tucx2010@sina.comPurpose: Circular RNAs (circRNAs) are abundant, stable, and evolutionarily conserved noncoding RNAs with impacts on cell proliferation, differentiation, invasion, apoptosis, and immunity by acting as an miRNA sponge. This study aimed to investigate the expression of circRNAs in vitiligo and analyze the differentially expressed circRNAs (DEcircRNAs) bioinformatically.Patients and Methods: Biopsies of five lesional and five nonlesional skins of patients with vitiligo and five healthy skins (control) were harvested in this study. The expression profiles of circRNAs and DEcircRNAs were determined by microarray analysis and qRT-PCR. Bioinformatics analysis was used to predict target genes of DEcircRNAs binding to miRNAs and their underlying functions. Meanwhile, a competing endogenous RNA (ceRNA) network was constructed using Cytoscape.Results: A total of 817 and 508 DEcircRNAs were identified in lesional and nonlesional skins of patients with vitiligo, respectively. The results of hsa_circRNA_000957 and hsa_circRNA_101798 validation were consistent with our microarray analysis. Furthermore, 32 miRNA response elements (MREs) and related target genes of DEcircRNAs were identified, whose main functions were involved in the pathogenesis of vitiligo. Hsa_circRNA_000957 and hsa_circRNA_101798 might be candidate biomarkers for vitiligo.Conclusion: This study provides scientific clues for understanding the mechanism of vitiligo.Keywords: vitiligo, circular RNAs, microRNAs, miRNA response element, ceRNA

Hongfeng Wu,1,2 Shuo Liu,1,2 Siyu Chen,1,2 Yuchen Hua,1,2 Xiangfeng Li,1,2 Qin Zeng,1– 3 Yong Zhou,4 Xiao Yang,1,2 Xiangdong Zhu,1,2 Chongqi Tu,4 Xingdong Zhang1– 3 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People’s Republic of China; 2College of Biomedical Engineering, Sichuan University, Chengdu, 610064, People’s Republic of China; 3NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterials & Institute of Regulatory Science for Medical Devices & NMPA Research Base of Regulatory Science for Medical Devices, Sichuan University, Chengdu, 610064, People’s Republic of China; 4Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Qin Zeng; Xiangdong Zhu, National Engineering Research Center for Biomaterials, Sichuan University, NO. 29 Wangjiang Road, Chengdu, 610064, People’s Republic of China, Email qzeng8156@scu.edu.cn; zhu_xd1973@scu.edu.cnBackground: In recent years, using hydroxyapatite nanoparticles (HANPs) for tumor therapy attracted increasing attention because HANPs were found to selectively suppress the growth of tumor cells but exhibit ignorable toxicity to normal cells.Purpose: This study aimed to investigate the capacities of HANPs with different morphologies and particle sizes against two kinds of osteosarcoma (OS) cells, human OS 143B cells and rat OS UMR106 cells.Methods: Six kinds of HANPs with different morphologies and particle sizes were prepared by wet chemical method. Then, the antitumor effect of these nanoparticles was characterized by means of in vitro cell experiments and in vivo tumor-bearing mice model. The underlying antitumor mechanism involving mitochondrial apoptosis was also investigated by analysis of intracellular calcium, expression of apoptosis-related genes, reactive oxygen species (ROS), and the endocytosis efficiency of the particles in tumor cells.Results: Both in vitro cell experiments and in vivo mice model evaluation revealed the anti-OS performance of HANPs depended on the concentration, morphology, and particle size of the nanoparticles, as well as the OS cell lines. Among the six HANPs, rod-like HANPs (R-HANPs) showed the best inhibitory activity on 143B cells, while needle-like HANPs (N-HANPs) inhibited the growth of UMR106 cells most efficiently. We further demonstrated that HANPs induced mitochondrial apoptosis by selectively raising intracellular Ca2+ and the gene expression levels of mitochondrial apoptosis-related molecules, and depolarizing mitochondrial membrane potential in tumor cells but not in MC3T3-E1, a mouse pre-osteoblast line. Additionally, the anti-OS activity of HANPs also linked with the endocytosis efficiency of the particles in the tumor cells, and their ability to drive oxidative damage and immunogenic cell death (ICD).Conclusion: The current study provides an effective strategy for OS therapy where the effectiveness was associated with the particle morphology and cell line.Keywords: hydroxyapatite nanoparticles, osteosarcoma, material features, cell line, mitochondrial apoptosis

Chao Tu, Liangzhi Wang, Lan Wei Department of Internal Medicine, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213000, People’s Republic of ChinaCorrespondence: Lan Wei, Department of Internal Medicine, the Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 0519 68871132, Email weilan06082021@163.comAbstract: Diabetic microangiopathy is among the most common complications affecting patients with diabetes, and includes both diabetic retinopathy (DR) and diabetic nephropathy (DKD). Diabetic microangiopathy remains a persistent threat to the health and quality of life of affected patients. Mechanistically, the severity of DR and DKD is tied to mitochondrial and glucose metabolism abnormalities, with the activation of the glycolytic enzyme pyruvate kinase M2 (PKM2) contributing to mitochondrial and glomerular dysfunction, abnormal renal hemodynamics, and retinopathy. PKM2 can activate inflammatory bodies in macrophages to promote the release of inflammatory mediators, and serves as a key regulator of inflammatory factors, chemokines and adhesion molecules. As such, there is sufficient evidence that PKM2 can be used as a biomarker for the diagnosis of diabetes and diabetic microangiopathy. Here, we survey the mechanisms whereby PKM2 contributes to diabetes-related microvascular diseases, associated regulatory roles, post-translational modifications, and the potential utility of PKM2 as a therapeutic target. Through this literature review, we have determined that PKM2 offers promise as both a diagnostic marker and therapeutic target with direct relevance to research pertaining to diabetic microangiopathy.Keywords: pyruvate kinase M2, inflammation, diabetic retinopathy, diabetic nephropathy, diabetic microangiopathy

Chao Tu,1 Lan Wei,1 Liangzhi Wang,1 Ying Tang2 1Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, People’s Republic of China; 2Department of Rehabilitation Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213000, People’s Republic of ChinaCorrespondence: Ying Tang, Department of Rehabilitation Medicine, The Third Affiliated Hospital of Soochow University, 185 Juqian Road, Changzhou, Jiangsu, 213000, People’s Republic of China, Tel +86 0519 68872146, Email tyczfph@yeah.netBackground: Diabetic nephropathy (DN) is the common cause of renal diseases such as end-stage renal disease (ESRD) and chronic kidney disease (CKD). Various diagnostic applications and treatment methods are used for clinical but remain some prognosis issues. To avoid morbidity and mortality related to DN, early detection of disease complications as well as targeted therapeutic strategies is essential. Considerable evidence indicates that non-coding RNA plays a vital role in the biological processes of various diseases, used as biomarkers and therapeutic targets. And the most known ncRNAs are the microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs).Materials and Methods: Our study aimed to identify potential prognostic ncRNAs involved in DN by bioinformatics analysis and validated expression levels through quantitative polymerase chain reaction (qPCR) and GEO database. Our research focuses on differential expression miRNAs (DEmiRNAs) in DN and their interactions with critical genes.Results: We identified 8 up-regulated DEmiRNAs, including miR-103a-2-5p, miR-297, miR-548x-3p, miR-604, miR-644a, miR-1256, miR-3911 and miR-5047 finally. We further validated these miRNAs in a murine model.Conclusion: Identifying these up-regulated genes and elucidating these miRNAs regulatory network will contribute to a better understanding of the molecular mechanism of DN and how they can be used as new biomarkers and potential therapeutic targets for DN.Graphical Abstract: Keywords: diabetic nephropathy, microRNAs, bioinformatics, biomarkers

Lu Wan,1,2 Wenchao Zhang,1,2 Zhongyue Liu,1,2 Zhimin Yang,1,2 Chao Tu,1,2 Zhihong Li1,2 1Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Chao Tu; Zhihong Li, Tel +86 15974290117; +86 13975112458, Email tuchao@csu.edu.cn; lizhihong@csu.edu.cnPurpose: Metabolic reprogramming, as one of the hallmarks of cancer, shows promising translational potential for cancer diagnosis, treatment and prognostic prediction. This study aims to construct and validate a prognostic prediction model for osteosarcoma based on glutamine metabolism-related genes.Materials and Methods: A group of glutamine metabolism-related genes was identified from a public database and intersected with a list of osteosarcoma survival-related genes, and a risk score model based on sixteen glutamine metabolism-related genes was developed by using LASSO penalized Cox regression analysis.Results: The prognosis of patients in the high-risk group was significantly worse than that of patients in the low-risk group in the training dataset (high- vs low-risk, 5-year overall survival: 11% vs 88%, p < 0.0001) and in two other external validation cohorts (high- vs low-risk, 5-year overall survival: 39% vs 81%, p = 0.015; 50% vs 94%, p = 0.011).In addition, a novel nomogram was constructed by integrating the risk score and clinical characteristics, including age, sex, metastasis status and chemotherapy response. This nomogram had superior predictive power compared with a nomogram composed of only conventional factors. Gene set enrichment analysis indicated that several well-known malignancy-associated gene sets, including MYC targets V1, DNA repair, and unfolded protein response, were enriched in the high-risk subgroup.Conclusion: A novel glutamine metabolism-related prognostic prediction model and nomogram for osteosarcoma was developed and validated in the present study, which could predict the survival of patients with osteosarcoma and may facilitate individualized clinical decision-making for patients.Keywords: bone tumor, survivorship, amino acid metabolism, nomogram

Abstract Addressing climate change challenges by reducing greenhouse gas levels requires innovative adsorbent materials for clean energy applications. Recent progress in machine learning has stimulated technological breakthroughs in the discovery, design, and deployment of materials with potential for high‐performance and low‐cost clean energy applications. This review summarizes basic machine learning methods—data collection, featurization, model generation, and model evaluation—and reviews their use in the development of robust adsorbent materials. Key case studies are provided where these methods are used to accelerate adsorbent materials design and discovery, optimize synthesis conditions, and understand complex feature–property relationships. The review provides a concise resource for researchers wishing to use machine learning methods to rapidly develop effective adsorbent materials with a positive impact on the environment.

Yingjian Liang, Xiaobin Zheng, Meizhu Chen, Changli Tu, Cuiyan Tan, Yiying Huang, Zhenguo Wang, Jian Wu, Jing Liu Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of ChinaCorrespondence: Jing Liu; Xiaobin ZhengDepartment of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, 52 East Meihua Road, Zhuhai City, 519000, People’s Republic of ChinaTel/Fax +867562528733Email liujing25@mail.sysu.edu.cn; zhxbin@mail.sysu.edu.cnPurpose: The main objective of this study was to decipher the general epidemiology, clinical characteristic, laboratory finding and chest computed tomography (CT) imaging features of the novel coronavirus disease (COVID-19) patients whose initial detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)is negative.Methods: Nearly 100 confirmed cases admitted to The Fifth Affiliated Hospital of Sun Yat-sen University from 18th January to 26th February, 2020, were screened. Clinical records, laboratory results and CT images were reviewed for nine COVID-19 patients with initially negative RT-PCR detection.Results: Fever and cough were common, and one patient merely present gastrointestinal symptoms. Increasing CRP and decreasing ALB were showed in nearly half of the patients among negative detection and return to normal level after real time polymerase chain reaction (RT-PCR) results converted from positive to negative. Left lower lobe was affected nearly in all the patients. A patient received oxygen support timely according his high Mulbsta score.Conclusion: Our study elucidated on the clinical features of hospitalized patients with initially negative detection of SARS-CoV nucleic acid. Patient merely with symptoms associated with digestive system should be screened for COVID-19. CT scan and repeated RT-PCR are two powerful diagnostic tools. Mulbsta score assessing in the early stage enhances the confidence of severity evaluation in physician.Keywords: COVID-19, negative detection, clinical characteristic, laboratory finding, CT images features

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

Changli Tu,1,* Guojie Wang,2,* Yayuan Geng,3 Na Guo,3 Ning Cui,4 Jing Liu1 1Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China; 2Department of Radiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China; 3Huiying Medical Technology Co., Ltd, Room A206, B2, Dongsheng Science and Technology Park, Beijing, People’s Republic of China; 4Medical Imaging Center, Shiyan Taihe Hospital, Shiyan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Cui; Jing LiuDepartment of Pulmonary and Critical Care Medicine (PCCM), Fifth Affiliated Hospital of Sun Yat-sen University, 52 East Meihua Road, Zhuhai, People’s Republic of ChinaTel +867562528733Email cuixitong@139.com; liujing25@mail.sysu.edu.cnBackground: Coronavirus disease 2019 (COVID-19) is a worldwide public health pandemic with a high mortality rate, among severe cases. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. It is important to ensure early detection of the virus to curb disease progression to severe COVID-19. This study aims to establish a clinical-nomogram model to predict the progression to severe COVID-19 in a timely and efficient manner.Methods: This retrospective study included 202 patients with COVID-19 who were admitted to the Fifth Affiliated Hospital of Sun Yat-sen University and Shiyan Taihe Hospital from January 17 to April 30, 2020. The patients were randomly assigned to the training dataset (n = 163, with 43 progressing to severe COVID-19) or the validation dataset (n = 39, with 10 progressing to severe COVID-19) at a ratio of 8:2. The optimal subset algorithm was applied to filter for the clinical factors most relevant to the disease progression. Based on these factors, the logistic regression model was fit to distinguish severe (including severe and critical cases) from non-severe (including mild and moderate cases) COVID-19. Sensitivity, specificity, and area under the curve (AUC) were calculated using the R software package to evaluate prediction performance. A clinical nomogram was established and performance assessed using the discrimination curve.Results: Risk factors, including demographic data, symptoms, laboratory and image findings, were recorded for the 202 patients. Eight of the 53 variables that were entered into the selection process were selected via the best subset algorithm to establish the predictive model; they included gender, age, BMI, CRP, D-dimer, TP, ALB, and involved-lobe. AUC, sensitivity, and specificity were 0.91, 0.84 and 0.86 for the training dataset, and 0.87, 0.66, and 0.80 for the validation dataset.Conclusion: We established an efficient and reliable clinical nomogram model which showed that gender, age, and initial indexes including BMI, CRP, D-dimer, involved-lobe, TP, and ALB could predict the risk of progression to severe COVID-19.Keywords: clinical nomogram model, COVID-19, progression risk, logistic regression

Ting Qiu,1,* Yintao Lan,1,* Zuwu Wei,2 Yanfen Zhang,3 Yanping Lin,1 Chenggong Tu,1 Guangjuan Mao,1 Lingmin Zhang,3 Bin Yang,1 Jian Zhang1 1The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital, Department of Biomedical Engineering, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, 350025, People’s Republic of China; 3School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhang Email jianzhang@gzhmu.edu.cnBackground: Effective treatment strategy for cervical carcinoma is subject to the limitation of its anatomical location and histological characteristics. Comprehensive imaging before cervical carcinoma treatment is of great significance for the patients. Current imaging methods cannot meet the requirements of high resolution, deep imaging depth and non-invasive imaging at the same time. Fortunately, Photoacoustic imaging (PAI) is a novel imaging method that combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. Moreover, PAI-guided photothermal therapy (PTT) by aid of targeting nanoparticles is an emerging and effective cancer treatment in recent years.Methods: Here, strong near-infrared region (NIR) absorption-conjugated polymer PIIGDTS (PD) nanoparticles with folic acid (FA) modification (namely, PD-FA) that targeted at Hela cell were specifically designed as cervical tumor imaging contrast agents and photothermal agents.Results: The obtained PD-FA nanoparticles exhibited admirable photoacoustic contrast-enhancing ability and desirable PTT behavior with the photothermal conversion efficiency as high as 62.6% in vitro. Furthermore, the PAI performance and PTT efficiency were tested in HeLa tumor-bearing nude mice after injection of PD-FA nanoparticles. In vivo multi-scale, PAI provided B-san and 3D dimension imaging for intuitive and comprehensive information of Hela tumor. Moreover, the Hela tumor can be completely eliminated within 18 days after PTT, with no toxicity and side effects.Conclusion: In summary, PD-FA injection combined with PAI and PTT systems provides a novel powerful tool for early diagnosis and precise treatment of cervical cancer.Keywords: cervical cancer, multi-scale photoacoustic imaging, photothermal therapy, PIIGDTS nanoparticle

Can Tu,1,2 Ming Niu,2 Ai-Wu Wei,3 Jin-Fa Tang,3 Le Zhang,2 Jing Jing,2 Xiao-He Xiao,2 Jia-Bo Wang2,4 1Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 2China Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 3The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China; 4School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, People’s Republic of ChinaCorrespondence: Jia-Bo WangSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, People’s Republic of ChinaEmail pharm_sci@126.comXiao-He XiaoChina Military Institute of Chinese Medicine, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of ChinaEmail pharmacy302xxh@126.comBackground: Drug-induced liver injury is a common adverse effect in clinical practice, with severe cases resulting in liver failure and even death. Identification and prediction of individuals susceptible to idiosyncratic DILI continues to remain a challenge.Methods: In this study, we report that cytokines in human serum can be used to identify and predict individuals susceptible to Polygonum multiflorum-induced DILI (PM-DILI) in retrospective and prospective cohort studies.Findings: In the retrospective pilot study, we compared serum cytokine expression profiles of the PM-DILI group (n=10) and the PM-Tolerant group (n=12) and found 10 cytokines with significant differences. In the replication cohort study, differences in the 10 cytokines between PM-DILI (n =11) and PM-Tolerant (n=13) groups were verified. Among them, 6 cytokines showed no significant differences at two time points, including liver injury and recovery stage of PM-DILI, suggesting that these 6 cytokines have no correlation with PM-DILI, however, they may be related to susceptibility. Furthermore, all the retrospective cohorts were combined, and a PM-DILI susceptibility prediction model was built by screening the 6 cytokines. The combination of (TNF-α and CCL-2) or VEGF showed the highest sensitivity and specificity. Finally, the efficacy of the above 3 cytokine combination models in predicting PM-DILI-susceptible individuals was verified before PM exposure in another independent prospective cohort (n=24), with sensitivity and specificity of 66.7% and 83.3%, respectively.Conclusion: This proof-of-concept study demonstrates that the serum cytokine combination reflecting dysimmunity could be used as a new method to predict PM-DILI, thus providing a new perspective for improving the clinical management of IDILI.Keywords: drug-induced liver injury, Polygonum multiflorum, cytokine, prediction, susceptible individual

Changling Tu,1 Yufeng Wang,1 Xianshuo Cheng,2 Ying Zhu,1 Wenli Yuan,3 Jian Dong4 1Department of Cadres Medical Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, People’s Republic of China; 2Department of Colorectal Surgery, Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, Yunnan, People’s Republic of China; 3Department of Clinical Laboratory, The Fourth Affiliated Hospital of Kunming Medical University, Kunming, 650021, Yunnan, People’s Republic of China; 4The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, People’s Republic of ChinaCorrespondence: Jian DongThe Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, No. 519 Kun Zhou Road, Xishan District, Kunming, 650118, Yunnan, People’s Republic of ChinaTel +86-871-68179549Email 3196259175@qq.comPurpose: The purpose of this study was to investigate the mechanism of combination of fluorouracil (FU) and oxaliplatin (OXA) on the progression of colon cancer via miR-183-5p/SOCS3 axis and regulating PD-L1.Methods: HCT116 cells were treated with 4 μM OXA and 10.5 μM FU, or exogenous regulation of the expression of miR-183-5p, SOCS3 and PD-L1 in HCT116 cells. CCK-8 assay was employed to detect cell viability of HCT116 cells. Flow cytometry was performed to assess the apoptosis and cell cycle. The expression level of SOCS3, PD-L1, chemokines (CCL1, CCL4 and CCL7) and immune escapes related proteins (EGFR, STARD1 and STARD3) in HCT116 cells were assessed by Western blotting. In addition, dual-luciferase reporter gene was carried out to verify the targeted relationship between miR-183-5p with SOCS3.Results: Our study demonstrated that the combination of OXA and FU remarkably suppressed proliferation, promoted apoptosis and arrest cells in G0/G1 phrase of HCT116 cells, and observably downregulated the expression of PD-L1, CCL1, CCL4, CCL7, EGFR, STARD1 and STARD3. Meanwhile, the combination of OXA and FU significantly downregulated miR-183-5p expression. Knockdown of miR-183-5p also repressed the proliferation, promoted apoptosis and arrest cells in G0/G1 phrase of HCT116 cells, and downregulated the expression of PD-L1, CCL1, CCL4, CCL7, EGFR, STARD1 and STARD3. In addition, our study proved that miR-183-5p upregulated PD-L1 by targeting downregulated SOCS3 expression. Finally, we demonstrated that the combination therapy of OXA and FU inhibited the proliferation, promote apoptosis and arrest cells in G0/G1 phrase by downregulating PD-L1 via miR-183-5p/SOCS3 axis.Conclusion: The combination therapy of OXA and FU could suppress the malignant biological behavior, and the mechanism was realized by inhibiting PD-L1 through miR-183-5p/SOCS3 axis.Keywords: colon cancer, combination therapy, PD-L1, miR-183-5p, SOCS3

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

Zhenhui Li,1,* Shaoyou Li,2,* Yun Liang,3,* Hongjiang Pu,4 Changling Tu,5 Zhenyu Wu,6 Dingyun You7,8 1Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 2Department of Medical Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China; 4Department of Colorectal Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 5Department of Cadres Medical Oncology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, People’s Republic of China; 6Department of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety and Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, People’s Republic of China; 7The Department of Epidemiology & Biostatistics, School of Public Health, Kunming Medical University, Kunming, Yunnan 650500, People’s Republic of China; 8Yunnan Key Laboratory of Laboratory Medicine, Kunming Medical University, Kunming, Yunnan 650500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dingyun YouYunnan Key Laboratory of Laboratory Medicine, Kunming Medical University, No. 1168 Chunrongxi Road, Chenggong District, Kunming, Yunnan 650500, People’s Republic of ChinaTel/ Fax +86 871-5922935Email youdingyun@qq.comZhenyu WuDepartment of Biostatistics, School of Public Health, Key Laboratory of Public Health Safety and Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, 130 Dongan Road, Shanghai, People’s Republic of ChinaTel/ Fax +86 21‐33563913Email nc.ude.naduf@wyzObjective: Association of postoperative peripheral CD4+ T cells percentage and recurrence in colorectal cancer (CRC) remains to be explored. Therefore, we aimed to investigate the association between the postoperative peripheral CD4+ T cells percentage and recurrence in CRC patients.Patients and Methods: Consecutive stage I–III CRC patients without neoadjuvant treatment undergoing curative resection from January 2010 to July 2016 were identified in two Chinese centers. The association between the postoperative CD4+ T cells percentage, measured within 12 weeks after surgery, and recurrence-free survival (RFS) was analyzed.Results: A total of 1028 patients were identified (training set: 913 patients, validation set: 115 patients). In the training set, the 5-year RFS rate of the 441 patients with abnormal postoperative CD4+ T cells percentage was significantly lower than that of those with normal percentage (70.3% [95% CI 65.7– 75.2%] vs 77.6% [95% CI 73.7– 81.7%] and unadjusted hazard ratio [HR] 1.36 [95% CI 1.04– 1.78], P= 0.02). The result was confirmed in the validation set. Multivariable Cox regression analysis demonstrated that the association of postoperative CD4+ T cells percentage with 5-year RFS was independent both in the training and validation sets. In propensity score matching analysis, patients with normal postoperative CD4+ T cells percentage were found to have a favourable response to adjuvant chemotherapy (HR 0.29 [95% CI 0.12– 0.72], P=0.008).Conclusion: Postoperative peripheral CD4+ T cells percentage is a predictive biomarker for RFS in patients with CRC, which can identify those who will benefit from adjuvant chemotherapy.Keywords: recurrence, peripheral CD4+ T cells, colorectal cancer, adjuvant chemotherapy, propensity score matching analysis

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

Xi Fu,1 Pin Liu,1 Dingyun Zhao,2 Bo Yuan,1 Zhanwen Xiao,1 Yong Zhou,2 Xiao Yang,1 Xiangdong Zhu,1 Chongqi Tu,2 Xingdong Zhang1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People’s Republic of China; 2Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, 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 8547 0770Email zhu_xd1973@scu.edu.cnChongqi TuDepartment of Orthopaedics, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, People’s Republic of ChinaTel +86 28 8542 2570Email tcqbonetumor@163.comBackground: Angiogenic and osteogenic activities are two major problems with biomedical titanium (Ti) and other orthopedic implants used to repair large bone defects.Purpose: The aim of this study is to prepare hydroxyapatite (HA) coatings on the surface of Ti by using electrochemical deposition (ED), and to evaluate the effects of nanotopography and silicon (Si) doping on the angiogenic and osteogenic activities of the coating in vitro.Materials and Methods: HA coating and Si-doped HA (HS) coatings with varying nanotopographies were fabricated using two ED modes, ie, the pulsive current (PC) and cyclic voltammetry (CV) methods. The coatings were characterized through scanning electron microscope (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectrometer (XPS), and atomic force microscopy (AFM), and their in vitro bioactivity and protein adsorption were assessed. Using MC3T3-E1 pre-osteoblasts and HUVECs as cell models, the osteogenic and angiogenic capabilities of the coatings were evaluated through in vitro cellular experiments.Results: By controlling Si content in ∼ 0.8 wt.%, the coatings resulting from the PC mode (HA-PC and HS-PC) and CV mode (HA-CV and HS-CV) had nanosheet and nanorod topographies, respectively. At lower crystallinity, higher ionic dissolution, smaller contact angle, higher surface roughness, and more negative zeta potential, the HS and PC samples exhibited quicker apatite deposition and higher BSA adsorption capacity. The in vitro cell study showed that Si doping was more favorable for enhancing the viability of the MC3T3-E1 cells, but nanosheet coating increased the area for cell spreading. Of the four coatings, HS-PC with Si doping and nanosheet topography exhibited the best effect in terms of up-regulating the expressions of the osteogenic genes (ALP, Col-I, OSX, OPN and OCN) in the MC3T3-E1 cells. Moreover, all leach liquors of the surface-coated Ti disks promoted the growth of the HUVECs, and the HS samples played a more significant role in promoting cell migration and tube formation than the HA samples. Of the four leach liquors, only the two HS samples up-regulated NO content and expressions of the angiogenesis-related genes (VEGF, bFGF and eNOS) in the HUVECs, and the HS-PC yielded a better effect.Conclusion: The results show that Si doping while regulating the topography of the coating can help enhance the bone regeneration and vascularization of HA-coated Ti implants.Keywords: electrochemical deposition, hydroxyapatite, silicon, coating, morphology, MC3T3-E1 cells, HUVECs

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

Chen Tu, 1 Di-Zheng Wu, 1 Yu-Sheng Huang, 1 Jing-Shen Zhuang, 1 Ji-Huan Zeng, 2 Ping Xu, 1 Ting-Ting Meng, 3 Zhao-Ming Zhong 1 1Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Orthopaedic Surgery, Jiangxi Province People’s Hospital, Nanchang University, Nanchang, People’s Republic of China; 3Department of Anaesthesia, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Zhao-Ming Zhong; Ting-Ting MengNanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou 510515, People’s Republic of ChinaEmail zhongzm@smu.edu.cn; mengtt2012@126.comPurpose: Chronic pain is one of the most common complications of postmenopausal osteoporosis. Since oxidative stress is involved in the pathogenesis of postmenopausal osteoporosis, we explored whether oxidative stress contributes to postmenopausal osteoporotic pain.Methods: Osteoporosis was induced in mice by ovariectomy (OVX). Pain-related behaviours were assessed by measuring sensitivity to mechanical, thermal and cold stimulation. The expression of pain-related transcripts, such acid-sensing ion channel 3 (ASIC3), transient receptor potential vanilloid 1 (TRPV1) and calcitonin gene-related peptide (CGRP), was evaluated. Plasma markers of oxidative stress were also measured. In addition, the effects of the reactive oxygen species scavenger phenyl N-tert-butylnitrone (PBN) on these parameters were assessed.Results: The OVX mice presented hyperalgesia, as demonstrated by decreased paw withdrawal thresholds to mechanical stimulation and withdrawal latencies to thermal and cold stimulation, along with upregulated expression of ASIC3, TRPV1 and CGRP in the dorsal root ganglia, spinal cord and thalamus tissue. OVX elevated the plasma levels of malondialdehyde (MDA) and advanced oxidation protein products (AOPPs). However, the administration of PBN alleviated these effects.Conclusion: Our results indicated that oxidative stress contributes to hyperalgesia in OVX mice. Enhanced oxidative stress may be associated with osteoporotic pain. Antioxidant treatment could help alleviate chronic pain in postmenopausal osteoporotic patients.Keywords: osteoporosis, hyperalgesia, oxidative stress, PBN

Summary: New photocatalysts are traditionally identified through trial-and-error methods. Machine learning has shown considerable promise for improving the efficiency of photocatalyst discovery from a large potential pool. Here, we describe a multi-step, target-driven consensus method using a stacking meta-learning algorithm that robustly predicts bandgaps and H2 evolution activities of photocatalysts. Trained on small datasets, these models can rapidly screen a large space (>10 million materials) to identify promising, non-toxic compounds as candidate water splitting photocatalysts. Two effective compounds and two controls possessing optimal bandgap values (∼2 eV) but not photoactivity as predicted by the models were synthesized. Their experimentally measured bandgaps and H2 evolution activities were consistent with the predictions. Conspicuously, the two compounds with strong photoactivities under UV and visible light are promising visible-light-driven water splitting photocatalysts. This study demonstrates the power of machine learning and the potential of big data to accelerate discovery of next-generation photocatalysts.

Yingjian Liang,* Meizhu Chen,* Cuiyan Tan, Changli Tu, Xiaobin Zheng, Jing Liu Department of Pulmonary and Critical Care Medicine (PCCM), The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jing Liu; Xiaobin ZhengThe Fifth Affiliated Hospital of Sun Yat-Sen University, 52 East Meihua Road, Zhuhai City, 519000, People’s Republic of ChinaTel/Fax +86(0)7562528733Email liujing25@mail.sysu.edu.cn; zhxbin@mail.sysu.edu.cnAbstract: Awareness of the management of coronavirus disease 2019 (COVID-19) and airway diseases can effectively help clinical physician during the coronavirus pandemic. Herein, we elucidated a COVID-19 case coexisting with severe asthma. Budesonide/glycopyrrolate/formoterol fumarate (BGF) was used as sequential medicine to systemic glucocorticoids for his persisted symptoms related to bronchospasms. Our case suggests patients with long-term airway diseases like asthma probably attribute their symptoms to COVID-19 instead of primary diseases, which make it more difficult in the symptom control. BGF is able to be an effective and convenient choice as sequential medicine to systemic glucocorticoids in some refractory asthmatic patients complicated with COVID-19.Keywords: coronavirus disease 2019, asthma, budesonide/glycopyrrolate/formoterol fumarate, sequential treatment

Jing Wang,1 Menglu Wang,1 Fuying Chen,1 Yihang Wei,1 Xuening Chen,1 Yong Zhou,2 Xiao Yang,1 Xiangdong Zhu,1 Chongqi Tu,2 Xingdong Zhang1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People’s Republic of China; 2Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, People’s Republic of ChinaCorrespondence: Xuening Chen; Xiangdong ZhuNational Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People’s Republic of ChinaEmail xchen6@scu.edu.cn; zhu_xd1973@scu.edu.cnBackground: The hierarchical porous structure and surface topography of calcium phosphate (CaP) bioceramics have a crucial impact on their osteoinductivity.Purpose: To fabricate a biomimetic bone graft with an interconnected porous structure analogous to that of trabecular bone and a bioactive nanostructured surface with excellent osteoinductive potential.Materials and methods: A biphasic CaP (BCP) substrate with highly porous structure was fabricated by an improved sponge replication method. Surface modification was performed by uniformly depositing a hydroxyapatite (HA) nanoparticle layer to create nHA-coated BCP scaffolds. The effects of these scaffolds on osteogenic differentiation of murine bone marrow-derived stem cells (BMSCs) were investigated in vitro, and their osteoinductivity was further assessed in vivo.Results: The BCP and nHA-coated BCP scaffolds had similar trabecular bone-like architectures but different surface structures, with mean grain sizes of ∼55 nm and ∼1 μm, respectively. Compared with the BCP substrate, the nHA-coated BCP scaffolds favored cell adhesion and promoted osteogenic differentiation of BMSCs, as evidenced by upregulated expression of osteogenic genes, enhanced alkaline phosphatase activity, and increased osteocalcin production. This could be attributed to activation of the BMP/Smad signaling pathway, as significantly higher expression levels of BMPRI, Smad1, Smad4, and Smad5 were observed in the nHA-coated BCP group. The nHA-coated BCP scaffold not only maintained scaffold integrity but also induced ectopic bone formation when implanted into rabbit dorsal muscle in vivo for 90 days, whereas the BCP substrate underwent marked biodegradation that led to severe inflammation with no sign of osteogenesis.Conclusion: The present study demonstrates the potential of this biomimetic bone graft with a trabecular framework and nanotopography for use in orthopedic applications.Keywords: nano-hydroxyapatite, calcium phosphate ceramics, porous scaffolds, MSCs, osteoblastic differentiation, osteoinduction

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

Hongfeng Wu,1 Zhongtao Li,2 Jiaoqing Tang,2 Xiao Yang,1 Yong Zhou,3 Bo Guo,4 Lin Wang,2 Xiangdong Zhu,1 Chongqi Tu,3 Xingdong Zhang1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China; 2Department of Dermatology, West China Hospital of Sichuan University, Chengdu 610041, China; 3Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, China; 4Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu 610041, China Background: Treatment for melanoma is a challenging clinical problem, and some new strategies are worth exploring.Purpose: The objective of this study was to investigate the in vitro and in vivo anti-melanoma effects of hydroxyapatite nanoparticles (HANPs) and discuss the involved material factors.Materials and methods: Five types of HANPs, ie, HA-A, HA-B, HA-C, HA-D, and HA-E, were prepared by wet chemical method combining with polymer template and appropriate post-treatments. The in vitro effects of the as-prepared five HANPs on inhibiting the viability of A375 melanoma cells and inducing the apoptosis of the cells were evaluated by Cell Counting Kit-8 analysis, cell nucleus morphology observation, flow cytometer, and PCR analysis. The in vivo anti-melanoma effects of HANPs were studied in the tumor model of nude mice.Results: The five HANPs had different physicochemical properties, including morphology, size, specific surface area (SSA), crystallinity, and so on. By the in vitro cell study, it was found that the material factors played important roles in the anti-melanoma effect of HANPs. Among the as-prepared five HANPs, HA-A with granular shape, smaller size, higher SSA, and lower crystallinity exhibited best effect on inhibiting the viability of A375 cells. At the concentration of 200 µg/mL, HA-A resulted in the lowest cell viability (34.90%) at day 3. All the HANPs could induce the apoptosis of A375 cells, and the relatively higher apoptosis rates of the cells were found in HA-A (20.10%) and HA-B (19.41%) at day 3. However, all the HANPs showed no inhibitory effect on the viability of the normal human epidermal fibroblasts. The preliminary in vivo evaluation showed that both HA-A and HA-C could delay the formation and growth speed of melanoma tissue significantly. Likely, HA-A exhibited better effect on inhibiting the growth of melanoma tissue than HA-C. The inhibition rate of HA-A for tumor tissue growth reached 49.1% at day 23.Conclusion: The current study confirmed the anti-melanoma effect of HANPs and provided a new idea for the clinical treatment of melanoma. Keywords: hydroxyapatite, nanoparticles, melanoma cells, fibroblasts, viability, apoptosis, tumor, suppression

Yingjian Liang,1,* Changli Tu,1,* Cuiyan Tan,1 Mohamed Abd El-Gawad El-Sayed Ahmed,2,3,4 Min Dai,5 Yong Xia,6 Yan Liu,7 Lan-Lan Zhong,2,3 Cong Shen,2,3 Guanping Chen,2,3 Guo-Bao Tian,2,3 Jing Liu,1 Xiaobin Zheng1 1Department of Respiratory Medicine, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China; 2Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; 3Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China; 4Department of Microbiology and Immunology, Faculty of Pharmacy, Misr University for Science and Technology (MUST), 6th of October City, Egypt; 5School of Laboratory Medicine, Chengdu Medical College, Chengdu, China; 6Department of Clinical Laboratory Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; 7Clinical laboratory, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China *These authors contributed equally to this work Purpose: The main objective of this study was to decipher the prevalence, antimicrobial resistance, major virulence genes and the molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolated from different clinical sources in southern China.Materials and methods: The present study was performed on 187 non-duplicate S. aureus clinical isolates collected from three tertiary hospitals in Guangdong Province, China, 2010–2016. Antimicrobial susceptibility testing was performed by the disk diffusion method and by measuring the minimum inhibitory concentration. Screening for resistance and virulence genes was performed. Clonal relatedness was determined using various molecular typing methods such as multilocus sequence typing, spa and staphylococcal chromosomal cassette mec (SCCmec) typing. Whole genome sequencing was performed for three selected isolates.Results: Out of 187 isolates, 103 (55%) were identified as MRSA. The highest prevalence rate was found among the skin and soft tissue infection (SSTI) samples (58/103), followed by sputum samples (25/103), blood stream infection samples (15/103) and others (5/103). Antimicrobial susceptibility results revealed high resistance rates for erythromycin (64.1%), clindamycin (48.5%), gentamicin (36.9%) and ciprofloxacin (33.98%). All isolates were susceptible to vancomycin. Resistance genes and mutation detected were as follows: aac(6’)-aph(2”) (24.3%), dfrG (10.7%), rpoB (21.4%), cfr (0%), fexA (1.94%), gyrA (35.92%), gyrB (0.97%), grlA (20.4%), grlB (10.68%), ermA (21.4%), ermB (18.44%), ermC (21.4%) and lnuA (18.44%). Profiling of virulence genes revealed the following: sea (11.7%), seb (21.4%), sec (0.97%), sed (0.97%), hla (86.41%), hlb (17.48%), hlg (10.68%), hld (53.4%), Tsst-1 (3.9%) and pvl (27.2%). Clonal relatedness showed that ST239-SCCmecA III-t37 clone was the most prevalent clone.Conclusion: Our study elucidated the prevalence, antibiotic resistance, pathogenicity and molecular characteristics of MRSA isolated from various clinical sources in Guangdong, China. We found that the infectious rate of MRSA was higher among SSTI than other sources. The most predominant genotype was ST239-SCCmecA III-t37 clone, indicating that ST239-t30 clone which was previously predominant had been replaced by a new clone. Keywords: MRSA, antibiotic resistance, resistance genes, virulence factors, molecular typing, whole genome sequencing

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

Xiang Fang,1,* Zeping Yu,1,* Yan Xiong,1 Fang Yuan,2 Hongyuan Liu,3 Fan Wu,4 Wenli Zhang,1 Yi Luo,1 Liuhong Song,5 Chongqi Tu,1 Hong Duan1 1Department of Orthopedics, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Radiology, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Orthopedics, Sichuan Provincial Fifth People’s Hospital, Chengdu, Sichuan, People’s Republic of China; 4Department of Orthopedics, Fourth People’s Hospital of ZiGong, Sichuan, People’s Republic of China; 5Department of Orthopedics, People’s Hospital of Pengzhou, Sichuan, People’s Republic of China *These authors contributed equally to this work Purpose: We sought to assess the early clinical outcome of 3D-multimodality image (3DMMI)-based virtual surgical planning for resection and reconstruction of malignant giant pelvic tumors.Patients and methods: In this retrospective case-control study, surgery was planned and performed with 3DMMI-based patient-specific instruments (PSI) in 13 patients with giant pelvic malignancy and without 3DMMI-based PSI in the other 13 patients. In the 3DMMI group, 3DMMI was utilized, taking advantages of computed tomography (CT), contrast-enhanced CT angiography (CTA), contrast-enhanced magnetic resonance imaging (MRI), contrast-enhanced magnetic resonance neurography (MRN), which could reveal the whole tumor and all adjacent vital structures. Based on these 3DMMI, virtual surgical planning was conducted and the corresponding PSI was then designed. The median follow-up was 8 (3–24) months. The median age at operation was 37.5 (17–64) years. The mean tumor size in maximum diameter was 13.3 cm. Surgical margins, intraoperative and postoperative complications, duration of surgery, and intra-operative blood loss were analyzed.Results: In the non-3DMMI group, the margins were wide in six patients (6/13), marginal in four (4/13), wide-contaminated in two (2/13), and intralesional in one (1/13). In the 3DMMI group, the margins were wide in 10 patients (10/13), marginal in three (3/13), and there were no wide-contaminated or intralesional margins. The 3DMMI group achieved shorter duration of surgery (P=0.354) and lower intraoperative blood loss (P=0.044) than the non-3DMMI group.Conclusion: The 3DMMI-based technique is advantageous to obtain negative surgical margin and decrease surgical complications related to critical structures injury for malignant giant pelvic tumor. Keywords: surgical planning, 3D-multimodality image, pelvic tumor, patient-specific instruments, surgical margin

Xiang Fang,1 Hongyuan Liu,1 Yan Xiong,1 Wenli Zhang,1 Yi Luo,1 Fan Wu,2 Yong Zhou,1 Liuhong Song,3 Zeping Yu,1 Chongqi Tu,1 Hong Duan1 1Department of Orthopedics, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthopedics, Fourth People’s Hospital of ZiGong, ZiGong, Sichuan, People’s Republic of China; 3Department of Orthopedics, People’s Hospital of Pengzhou, Pengzhou, Sichuan, People’s Republic of China Purpose: Arthrodesis is one of the most widely accepted surgical recommended methods for tumors of the talus, but it may be associated with poor limb functions. The aim of this study was to present a novel reconstruction with ankle function preserved after en bloc talus tumor resection.Patient and method: A 43-year-old female with mesenchymal sarcoma of the talus was admitted in West China Hospital. Total talar replacement with three-dimensional (3D) printed modular prosthesis was prepared for reconstruction. The 3D printed modular prosthesis was designed exactly as the mirror image of the contralateral talus with complete filling of the sinus tarsi and subtalar joint space. The upper modular component of prosthesis was made of ultra high molecular weight polyethylene, and the lower component, titanium alloy. Pre-drilled holes in three directions were prepared for screw fixation of the subtalar joint.Results: The patient underwent en bloc talus resection through anterior approach, followed by reconstruction with the 3D printed prosthesis. The whole procedure took 2 hours, and intra-operative blood loss was 50 mL. At the last follow-up, our patient was disease free and she could walk almost normally without any aid or pain. The Musculoskeletal Tumor Society score was 26/30. The American Orthopedic Foot and Ankle Society score was 91/100. The range of motion for dorsiflexion and plantar flexion was 40°. And no abnormalities were observed in the roentgenograph.Conclusion: Total talar replacement with a 3D printed modular prosthesis may be an effective procedure for patients with tumors of the talus as it could maintain ankle function. Keywords: bone tumors, sarcoma, reconstructive surgery, ultra high molecular weight polyethylene, limb salvage, en bloc resection

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

Jin Lou,1,2 Junjie Huang,1 Zitong Wang,3 Bingbing Wen,1 Chuanqing Tu,4 Wangxiang Huang,5 Zhimin Zhai,2 Xin Du1 1Department of Hematology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, China; 2Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China; 3School of Medicine, University of Sydney, Sydney, NSW, Australia; 4Department of Hematology, People’s Hospital of Baoan District, Shenzhen 518101, China; 5Department of Hematology, Longgang District Central Hospital of Shenzhen, Shenzhen 518116, China Background: Treatment-free remission (TFR) is becoming an essential goal for chronic myeloid leukemia (CML) patients in clinical practice. Few studies have emphasized patient attitudes or preferences about discontinuing tyrosine kinase inhibitors treatment. This study aimed to evaluate the characteristics of Chinese CML patients and their views and perspectives on TFR. Methods: A total of 329 CML patients participated in this multicenter, questionnaire-based, standardized, semi-structured, interview-guided, open-ended, cross-sectional study. Information about demographics, diagnosis information, treatment history, quality of life (QoL), and TFR preference was collected. Results: The adherence rate was 50% (N=163) and sex dependent (males, OR=2.24, 95% CI=1.40–3.58). Physical activity, symptom burden, mood impact, and daily impact were found to be better among adherent patients. Thirty-four percent of the patients were willing to attempt TFR positively. The reasons for preferring TFR were due to side effects (56%) followed by high cost (52%), inconvenience (42%), and pregnancy need (41%). Multivariate analysis indicated that patients who were younger (OR=0.96, 95% CI=0.94–0.99) with shorter disease duration (OR=0.90, 95% CI=0.82–0.98) and higher disease symptom burden (OR=1.08, 95% CI=0.98–1.21) were more likely positive about TFR. Conclusion: Patients who were younger with shorter disease duration and higher disease symptom burden were more likely to try TFR. They expressed several perceived noncost factors of TFR. Our data may help promote the management of CML and designing of clinical trials for TFR in some developed regions of China. Keywords: CML, TKI, TFR, preference, perception

The evaluation and interpretation of the behavior of construction materials under fire conditions have been complicated. Over the last few years, artificial intelligence (AI) has emerged as a reliable method to tackle this engineering problem. This review summarizes existing studies that applied AI to predict the fire performance of different construction materials (e.g., concrete, steel, timber, and composites). The prediction of the flame retardancy of some structural components such as beams, columns, slabs, and connections by utilizing AI-based models is also discussed. The end of this review offers insights on the advantages, existing challenges, and recommendations for the development of AI techniques used to evaluate the fire performance of construction materials and their flame retardancy. This review offers a comprehensive overview to researchers in the fields of fire engineering and material science, and it encourages them to explore and consider the use of AI in future research projects.

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

Chao Tu, Lianwen Yuan, Jianping Zhou Department of Geriatric Surgery, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of ChinaWith great interest, we read an article entitled “The clinicopathological significance of CDH1 in gastric cancer: a meta-analysis and systematic review” by Zeng et al,1 which was published in Drug Design, Development and Therapy in April 2015. In this meta-analysis, the investigators systematically reviewed the studies on correlation between CDH1 hypermethylation and gastric cancer (GC), and concluded that CDH1 hypermethylation levels in GC and adjacent gastric mucosa are both significantly higher when compared with normal gastric mucosa. Meanwhile, CDH1 hypermethylation is found markedly correlated with Helicobacter pylori status. Taken together, CDH1 hypermethylation is positively associated with overall GC risk and the H. pylori-positive GC risk.1 It is a valuable study. Nevertheless, there are several queries that we would like to communicate with the authors.View original article by Zeng et al.