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Chang-hong Zhang,1 Ge Li,2 Zhao-ya Fan,1 Xiao-jun Tang,1 Fan Zhang1 1School of Public Health and Management, Research Center for Medicine and Social Development, Collaborative Innovation Center of Social Risks Governance in Health, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing 401331, People’s Republic of ChinaCorrespondence: Fan ZhangSchool of Public Health and Management, Research Center for Medicine and Social Development, Collaborative Innovation Center of Social Risks Governance in Health, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaEmail epicqmu@163.comPurpose: A much higher prevalence of alexithymia has been found in medical students compared with the general population. This study aimed to test the potential mediating effect of psychological capital on the relationship between childhood trauma and alexithymia in Chinese medical students, thereby providing clues for future interventions aimed at dealing with alexithymia in this population.Methods: Convenience cluster sampling was used to recruit 1200 medical students in Chongqing, China. This cross-sectional study utilised the Childhood Trauma Questionnaire Short Form, the Toronto Alexithymia Scale, and the Psychological Capital Questionnaire. A structural equation model with maximum likelihood was used to study the mediating effect presented in the aim, and the significance of the mediating effect was examined by the bootstrap method. Multiple-group invariance analyses were also conducted to confirm the stability of the model.Results: A total of 1018 were identified to have valid responses with a rate of 84.83%. 38.4% were males, 61.6% were females. The prevalence of alexithymia was 16.5%. Results of structural equation model showed that childhood trauma was positively related to alexithymia, with a standard path coefficient of 0.219 (C.R.=6.644, P< 0.001). The partial mediating effect of psychological capital was 0.060 (P< 0.001), accounting for 21.51% of the total effect of childhood trauma on alexithymia. Results of bootstrap method showed that the lower and upper bounds of the 95% confidence interval did not contain 0, and the multiple-group invariance analyses showed that the p values of the changes in the degrees of freedom and chi-square value were greater than 0.05, thus confirming the stability of the model.Conclusion: Childhood trauma was a direct predictor of alexithymia among Chinese medical students, and the relationship between these two was partially mediated by psychological capital. Therefore, interventions aimed at enhancing psychological capital in this population may be effective at diminishing alexithymia.Keywords: childhood trauma, alexithymia, psychological capital, medical students, mediating effect, interventions

Ling Gong,1,2 Guichuan Huang,2 Yi Huang,2 Daishun Liu,2 Xiaoping Tang1 1The First Clinical Medical College, Jinan University, Guangzhou 510632, People’s Republic of China; 2Department of Respiratory Medicine, The First People’s Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi 563000, People’s Republic of ChinaCorrespondence: Xiaoping TangThe First Clinical Medical College, Jinan University, 601 W. Huangpu Avenue, Guangzhou 510632, People’s Republic of ChinaTel +86-13501525993Email txpdoc@126.comDaishun LiuDepartment of Respiratory Medicine, The First People’s Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), 98 Fenghuang North Road, Zunyi 563000, People’s Republic of ChinaEmail ldsdoc@126.comObjective: The aim of this study was to evaluate the efficacy of medical thoracoscopy in the diagnosis and treatment of exudative pleural effusion.Methods: A total of 82 patients with exudative pleural effusion underwent medical thoracoscopy under local anesthesia and mild sedation. The clinical characteristics, pleural fluid routine and biochemical tests, pleural biopsy, and outcomes were retrospectively evaluated.Results: Among 82 patients, the color and transparency of pleural fluid and the levels of white blood cells (WBC), lactate dehydrogenase (LDH), neutrophil proportion, lymphocyte proportion, adenosine deaminase (ADA), and glucose were different among tuberculosis (TB), malignant (M), acute and chronic inflammation (ACI), and purulent (P) cases. Furthermore, 70% of M cases had a low positive rate of exfoliated cells in the sputum and pleural fluid, and more than 90% of TB cases had low positive rates of anti-tuberculosis antibodies and acid-fast bacilli in the sputum and pleural fluid. Pleural biopsy showed that 11% of cases were M, 74.4% were TB, 11% were ACI, and 3.6% were P. Medical thoracoscopy showed that 66.7% of ACI cases had pleural adhesions, 34.4% of TB cases had moderate and 34.4% of TB cases had severe pleural adhesions, 100% of M and TB cases had pleural surface nodules and 77.8% of ACI cases had pleural surface nodules, 49.2% of TB cases showed encapsulated pleural effusion, and 33.3% of M cases showed encapsulated pleural effusion.Conclusion: Medical thoracoscopy has high feasibility and accuracy in the diagnosis and treatment of exudative pleural effusion.Keywords: exudative pleural effusion, medical thoracoscopy, diagnosis, treatment

Hui Chen, Lingyu Li, Yunping Lu, Yajun Shen, Min Zhang, Lihua Ge, Min Wang, Jing Yang, Zhenchuan Tian, Xiaofei Tang Division of Oral Pathology, Beijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Xiaofei TangDivision of Oral Pathology, Beijing Institute of Dental Research, Beijing Stomatological Hospital & School of Stomatology, Capital Medical University, No. 4 Tiantan Xili, Dongcheng District, Beijing 100050, People’s Republic of ChinaTel +86-10-57099311Fax +86-10-57099313Email xftang10@ccmu.edu.cnPurpose: The five-year survival rate of patients with oral cancer is approximately 50%; thus, alternative drugs with higher efficacy are urgently required. Azoxystrobin (AZOX), a natural, novel methoxyacrylate fungicide isolated from mushrooms, has a broad-spectrum, with highly efficient bactericidal effect. However, studies on AZOX have focused on antifungal effects. Here, we explore the potential cancer-preventive effects of AZOX and the underlying mechanisms.Materials and Methods: The effects of AZOX on oral carcinogenesis induced by 4-nitroquinoline-1-oxide (4NQO) were investigated in C57BL/6 mice. Cell proliferation and apoptosis were examined by Ki67 immunohistochemistry and TUNEL staining, respectively. The main organ coefficients of each group were calculated to evaluate the biosafety of AZOX. CCK8 and flow cytometry were used to detect the effects of AZOX on cell viability and apoptosis in oral cancer cell line CAL27 and SCC15 cells in vitro. Cell cycle, mitochondrial complex III activity, intercellular reactive oxygen species (ROS) level, mitochondrial ROS level, and mitochondrial membrane potential (MMP) were detected by flow cytometry in AZOX-treated CAL27 cells.Results: AZOX significantly inhibited the occurrence of 4NQO-induced tongue cancer and delayed the progression of tongue precancerous lesions in mice. High-dose AZOX obviously inhibited cell viability and induced apoptosis in epithelial dysplastic and oral squamous cell carcinoma (OSCC) lesions in mouse tongue mucosa. AZOX was confirmed to have high biosafety. Similarly, in vitro cell viability was suppressed, and apoptosis was induced in AZOX-treated CAL27 and SCC15 cells. AZOX induced cell cycle arrest at the S phase. AZOX inhibited mitochondrial complex III activity, increased intracellular and mitochondrial ROS levels, and decreased MMP in CAL27 cells.Conclusion: AZOX inhibited the development of oral cancer through specific inhibition of the activity of mitochondrial complex III, which led to ROS accumulation, and MMP decrease, ultimately inducing apoptosis. AZOX may be a novel agent for the prevention and treatment of OSCC.Keywords: azoxystrobin, oral cancer, mitochondrial complex III, apoptosis

Han Chen,1,2,* Xiaoying Zhou,1,2,* Xinyu Tang,2,3 Shuo Li,1,2 Guoxin Zhang1,2 1Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2The First Clinical Medical College, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoxin ZhangDepartment of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, 300# Guangzhou Road, Nanjing 210029, People’s Republic of ChinaEmail guoxinz@njmu.edu.cnBackground or Purpose: It is important to predict nodal metastases in patients with early esophageal cancer to stratify patients for endoscopic resection or esophagectomy. This study was to establish a novel artificial neural network (ANN) and assess its ability by comparing it with a traditional logistic regression (LR) model for predicting lymph node (LN) metastasis in patients with superficial esophageal squamous cell carcinoma (SESCC).Methods: A primary cohort was established, composed of 733 patients who underwent esophagectomy for SESCC from December 2012 to December 2019. The following steps were applied: (i) predictor selection; (ii) development of an ANN and a LR model, respectively; (iii) cross-validation; and (iv) evaluation of performance between the two models. The diagnostic assessment was performed with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).Results: The established ANN model had 6 significant predictors: a past habit of alcohol taking, tumor size, submucosal invasion, histologic grade, lymph-vessel invasion, and preoperative CT result. The ANN model performed better than the LR model in specificity (91.20% vs 72.59%, p=0.006), PPV (56.49% vs 39.78%, p=0.020), accuracy (90.72% vs 74.49%, p< 0.0001), C-index (91.5% vs 86.8%, p< 0.001), and IDI (improved by 23.3%, p< 0.001). There were no differences between these two models in sensitivity (87.06% vs 83.21%, p=0.764), NPV (98.17% vs 95.21%, p=0.627), and NRI (improved by − 1.1%, p=0.824).Conclusion: This ANN model is superior to the LR model and may become a valuable tool for the prediction of LN metastasis in patients with SESCC.Keywords: superficial esophageal squamous cell carcinoma, lymph node metastasis, neural network, machine learning

Liuyue Xu,1 Qian Dong,2 Yaoying Long,1 Xiaoqiong Tang,1 Nan Zhang,2 Kai Lu2 1Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaCorrespondence: Kai LuDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing 400016, People’s Republic of ChinaTel/Fax +86 23 89011562Email lukai2013@foxmail.com; zncqmu@126.comBackground: Previous studies indicated that the (neo)adjuvant chemotherapy for breast cancer can cause significant dyslipidemia in patients, but how long this abnormality can persist is unclear so far. The purpose of this study is to investigate whether (neo)adjuvant chemotherapy has a long-term effect on blood lipids in breast cancer patients.Methods: A total of 159 newly diagnosed female breast cancer patients receiving the (neo)adjuvant chemotherapy subsequently and 159 female healthy controls were enrolled into the observational study. All participants’ blood lipid profiles which included TC, TG, HDL-C, and LDL-C before and at the end of the 1st and 12th month after chemotherapy were retrieved from the electronic medical record system. The blood lipid profiles and the percentage of dyslipidemia before and after chemotherapy in breast cancer patients and controls were compared.Results: Compared with the baseline before chemotherapy, TC, LDL-C, and TG increased significantly at the end of the 1st month after chemotherapy, but only the abnormal increase in TG (2.98± 0.71 mmol/L vs 2.82± 0.63 mmol/L, P< 0.05) and LDL-C (1.82± 0.42 mmol/L vs 1.59± 0.42 mmol/L, P< 0.05) continued until the 12th month after chemotherapy. Levels of HDL-C in breast cancer patients and all the blood lipid parameters in controls remained stable during the observation period. The percentage of dyslipidemia in breast cancer patients rose from 41.5% at baseline to 54.1% at the 12th month after chemotherapy. Subgroup analysis demonstrated that the increase in dyslipidemia percentage was more pronounced in patients with low body mass index and aged over 50 years.Conclusion: The (neo)adjuvant chemotherapy used for treating breast cancers can cause significant abnormalities in blood lipid profiles, and the abnormal increase in LDL-C and TG can last at least 12 months after chemotherapy, which indicates long-term management of blood lipid is necessary for those patients.Keywords: breast cancer, dyslipidemia, adjuvant chemotherapy

Huachen Song, Xiaonan Tang, Xiang Li, Yufei Wang, Anjun Deng, Wenjie Wang, Haijing Zhang, Hailin Qin, LianQiu Wu State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People’s Republic of ChinaCorrespondence: Haijing Zhang; LianQiu Wu Tel +86 10-63031589Fax +86 10-63035779Email zhanghaijing@imm.ac.cn; wlq@imm.ac.cnIntroduction: Colitis-associated cancer (CAC) accounts for approximately 15% of IBD patient mortalities. However, currently available anti-CAC drugs possess many disadvantages including safety, specificity and side effects. Therefore, the development of novel anti-CAC compounds is imperative. HLJ2 was a monomeric compound synthesized by our institute and reported to have an effect on ulcer colitis.Methods: In vivo the AOM/DSS-induced CAC model was used to evaluate the effects of HLJ2 on ameliorating CAC symptoms, immunohistochemical analysis was used to analyze the pathological damage to colons and epithelial–mesenchymal transition was for changes of cytokines. In vitro, flow cytometric analysis, immunofluorescence and Western blot were used to detect the inhibition effect of HLJ2 on nuclear factor-κB and epithelial–mesenchymal transition in TGF-β 1-stimulated SW480 cells.Results: In the AOM/DSS animal model, HLJ2 was demonstrated to inhibit the secretion of inflammatory cytokines and nuclear factor-κB, levels of tumorigenesis-related proteins including snail, and finally inhibited a key step in metastasis, epithelial–mesenchymal transition. In vitro, HLJ2 was also shown to inhibit nuclear factor-κB and epithelial–mesenchymal transition in TGF-β 1-stimulated SW480 cells in accordance with in vivo results. Meanwhile, the nuclear factor-κB inhibitor could interrupt the effect of HLJ2 on epithelial–mesenchymal transition.Discussion: HLJ2 may ameliorate CAC through inhibiting nuclear factor-κB and then downstream epithelial–mesenchymal transition. The combination of the obvious improvement in effects on CAC without obvious side effects suggests that HLJ2 could be developed as a potential CAC therapeutic candidate.Keywords: inflammatory bowel disease, colitis-associated cancer, EMT

Fang Liu,1 Rong Wu,2 Lina Guan,3 Xuegui Tang1 1Anorectal Department of Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Clinical Medicine of Combination of Chinese and Western Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 3Institute of Anorectal Diseases, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of ChinaCorrespondence: Xuegui Tang Anorectal Department of Integrated Traditional Chinese and Western MedicineAffiliated Hospital of North Sichuan Medical College, No. 1, Maoyuan South Road, Nanchong 637000, Sichuan, People’s Republic of ChinaTel +86-0817-2262120Email L29228273@163.comPurpose: Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) has been revealed to involve in the progression of CRC. However, the precise mechanisms of PVT1 in action remain unclear.Methods: The expression of PVT1, microRNA-106b-5p (miR-106b-5p) and four jointed box 1 (FJX1) was measured using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. Cell proliferation was investigated by 3-(4,5)-dimethylthiahiazo (−z-y1)-3,5-di-phenytetrazoliumromide assay. Transwell assay was used to determine cell migration and invasion. The correlation between miR-106b-5p and PVT1 or FJX1 was confirmed using luciferase reporter assay. The effects of PVT1 in vivo were assessed using mice xenograft model.Results: PVT1 was up-regulated in CRC tissues and cell lines, especially in CRC tissues with high-grade, and highly expressed PVT1 predicted worse prognosis. Functional experiments demonstrated that PVT1 deletion inhibited CRC cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. MiR-106b-5p was confirmed to be a target of PVT1, and inhibition of miR-106b-5p reversed the inhibitory effects of PVT1 knockdown on CRC cell malignant phenotypes. In addition, we found miR-106b-5p directly targeted FJX1, and miR-106b-5p-mediated inhibition on CRC cell proliferation, migration and invasion was attenuated by FJX1 up-regulation. Importantly, it was also proved that PVT1 could indirectly regulate FJX1 expression via targeting miR-106b-5p.Conclusion: Knockdown of PVT1 impaired cell proliferation, migration and invasion in CRCs via regulating miR-106b-5p/FJX1 axis, which provided a novel insight into the development of therapeutic strategies for CRC patients.Keywords: colorectal cancer, PVT1, miR-106b-5p, FJX1, metastasis, apoptosis

Yuehong Li,1 Yue Yang,2 Yun’an Qing,1 Ruiyan Li,1 Xiongfeng Tang,1 Deming Guo,1 Yanguo Qin1 1Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yanguo Qin Email qinyg@jlu.edu.cnAbstract: Prosthesis-associated infections and aseptic loosening are major causes of implant failure. There is an urgent need to improve the antibacterial ability and osseointegration of orthopedic implants. Zinc oxide nanoparticles (ZnO-NPs) are a common type of zinc-containing metal oxide nanoparticles that have been widely studied in many fields, such as food packaging, pollution treatment, and biomedicine. The ZnO-NPs have low toxicity and good biological functions, as well as antibacterial, anticancer, and osteogenic capabilities. Furthermore, ZnO-NPs can be easily obtained through various methods. Among them, green preparation methods can improve the bioactivity of ZnO-NPs and strengthen their potential application in the biological field. This review discusses the antibacterial abilities of ZnO-NPs, including mechanisms and influencing factors. The toxicity and shortcomings of anticancer applications are summarized. Furthermore, osteogenic mechanisms and synergy with other materials are introduced. Green preparation methods are also briefly reviewed.Keywords: antibacterial property, composite material, orthopedic implant, osteogenic activity, zinc oxide nanoparticles

Hongliang Zhang,1,2 Kang Yang,3 Tingting Ren,1,2 Yi Huang,1,2 Xin Liang,1,2 Yiyang Yu,1,2 Wei Wang,1,2 Jianfang Niu,1,2 Jingbing Lou,1,2 Xiaodong Tang,1,2 Wei Guo1,2 1Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, People’s Republic of China; 3Department of Orthopedics, Yangzhou University Affiliated Hospital, Yangzhou, People’s Republic of ChinaCorrespondence: Xiaodong Tang; Wei GuoMusculoskeletal Tumor Center, Peking University People’s Hospital, No. 11 Xizhimen South Street, Beijing 100044, People’s Republic of ChinaTel +86 10 8832 4471Fax +86.10.8837.8544Email tang15877@163.com; guobonetumor@163.comPurpose: Our research aimed to illuminate the role of miR-100-5p in chordoma and potential mechanism.Materials and Methods: We used microRNA array analysis to explore differentially expressed miRNAs in chordoma tissue and then verified by qRT-PCR. Cell proliferation and transwell assay were used to evaluate the function of miR-100-5p. Cell apoptosis was analyzed by flow cytometry, and using biological software, we predicted that the insulin-like growth factor 1 receptor (IGF1R) could be the target gene of miR-100-5p, which was then validated by dual luciferase assays and Western blot.Results: miR-100-5p was downregulated in chordoma tissues. Overexpression of miR-100-5p could suppress the growth of chordoma both in vitro and in vivo, and miR-100-5p could inhibit the migration and invasion of chordoma cells partially by suppressing epithelial–mesenchymal transition (EMT). Furthermore, IGF1R was validated as the target gene of miR-100-5p and expressed in most chordoma tissues.Conclusion: In conclusion, our results showed that miR-100-5p was lowly expressed in chordoma and inhibited tumor malignant progression by targeting IGF1R.Keywords: chordoma, miRNA, miR-100-5p, IGF1R

Shi Zhao,1,2,* Xiujuan Tang,3,* Xue Liang,4,* Marc KC Chong,1,2 Jinjun Ran,5 Salihu S Musa,6 Guangpu Yang,7 Peihua Cao,8 Kai Wang,9 Benny CY Zee,1,2 Xin Wang,3 Daihai He,6 Maggie H Wang1,2 1Division of Biostatistics, JC School of Public Health and Primary Care, Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 2Shenzhen Research Institute of Chinese University of Hong Kong, Shenzhen, People’s Republic of China; 3Shenzhen Center for Disease Control and Prevention, Shenzhen, People’s Republic of China; 4Department of Hematology, The 989th Hospital of the Joint Logistics Support Force of Chinese PLA, Luoyang 471031, People’s Republic of China; 5School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, People’s Republic of China; 6Department of Applied Mathematics, Hong Kong Polytechnic University, Hong Kong, People’s Republic of China; 7Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 8Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 9Department of Medical Engineering and Technology, Xinjiang Medical University, Urumqi 830011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi Zhao; Daihai He Email zhaoshi.cmsa@gmail.com; daihai.he@polyu.edu.hkBackground: Measles, a highly contagious disease, still poses a huge burden worldwide. Lately, a trend of resurgence threatened the developed countries. A measles outbreak occurred in the Hong Kong International Airport (HKIA) between March and April 2019, which infected 29 airport staff. During the outbreak, multiple measures were taken including daily situation updates, setting up a public enquiry platform on March 23, and an emergent vaccination program targeting unprotected staff. The outbreak was put out promptly. The effectiveness of these measures was unclear.Methods: We quantified the transmissibility of outbreak in HKIA by the effective reproduction number, Reff(t), and basic reproduction number, R0(t). The reproduction number was modelled as a function of its determinants that were statistically examined, including lags in hospitalization, situation update, and level of public awareness. Then, we considered a hypothetical no-measure scenario when improvements in reporting and public enquiry were absent and calculated the number of infected airport staff.Results: Our estimated average R0 is 10.09 (95% CI: 1.73− 36.50). We found that R0(t) was positively associated with lags in hospitalization and situation update, while negatively associated with the level of public awareness. The average predicted basic reproduction number, r0, was 14.67 (95% CI: 9.01− 45.32) under the no-measure scenario, which increased the average R0 by 77.57% (95% CI: 1.71− 111.15). The total number of infected staff would be 179 (IQR: 90− 339, 95% CI: 23− 821), namely the measure induced 8.42-fold (95% CI: 0.21− 42.21) reduction in the total number of infected staff.Conclusion: Timely reporting on outbreak situation and public awareness measured by the number of public enquiries helped to control the outbreak.Keywords: measles, outbreak, reproduction number, statistical modelling, public awareness, airport

Lu Xie,1 Jie Xu,1 Xin Sun,1 Kuisheng Liu,1 Xiaowei Li,1 Fangzhou He,1 Xinyu Liu,1 Jin Gu,2 Zhe Lv,3 Rongli Yang,1 Xiaodong Tang,1 Taiqiang Yan,1 Dasen Li,1 Yi Yang,1 Sen Dong,1 Kunkun Sun,4 Danhua Shen,4 Wei Guo1 1Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Surgical Oncology, Peking University Shougang Hospital, Beijing, People’s Republic of China; 3Radiology Department, Peking University Shougang Hospital, Beijing, People’s Republic of China; 4Pathology Department, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wei GuoMusculoskeletal Tumor Center, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, People’s Republic of ChinaTel +86 13701195504Fax +86 10 68318386Email bonetumor@163.comPurpose: For patients who have chondrosarcoma in the unresectable setting, antiangiogenic agents are reportedly effective. This multicenter, retrospective study investigated the antitumor activity of apatinib in patients with unresectable chondrosarcoma to gain insight into the biological behavior of this disease.Methods: All of the patients with unresectable chondrosarcoma who were diagnosed between October 1, 2009, and November 1, 2019, in two sarcoma centers affiliated with Peking University were evaluated. Relevant information was collected from the medical records at both centers, from which patients receiving apatinib for systemic therapy were selected for analysis.Results: In total, efficacy analysis was conducted in 33 patients with a median follow-up time of 22.1 (Q1, Q3, 14.6, 23.0) months. There were 20/33 (60.0%) conventional chondrosarcomas (grades 2– 3), 5/33 (15.2%) dedifferentiated chondrosarcomas, 4/33 (12.1%) mesenchymal chondrosarcomas, 3/33 (9.1%) extraskeletal myxoid chondrosarcoma, and 1/33 (3.1%) clear-cell chondrosarcomas with 87.9% in metastatic and 12.1% in locally advanced states. The objective response rate was 6/33 (18.2%). The median progression-free survival (PFS) was 12.4 months (Q1, Q3, 7.0, 21.2), while the median overall survival has not yet been reached. Rare variants of chondrosarcoma tended to have a longer PFS than conventional chondrosarcoma (P= 0.06). Based on clinicopathological factors Cox and univariate analysis, only extraskeletal myxoid chondrosarcoma and baseline target lesions < 60 mm benefited from the drug apatinib (P=0.14 and P=0.00), respectively. Grade 3 or higher adverse events were frequent in 11/33 (39.3%) of patients who discontinued apatinib due to deterioration of their general condition.Conclusion: Apatinib had clinically meaningful activity in patients with inoperable high-grade chondrosarcoma. However, special caution should be made in managing toxicity due to the indolent behavior and slow growth pattern after using this drug. Patients with a smaller tumor size and extraskeletal myxoid chondrosarcoma subtype might benefit from this therapy more.Clinical Trial Registration: Registered February 7, 2020, with clinicaltrials.gov: NCT04260113.Keywords: chondrosarcoma, apatinib, inoperable, metastasis, locally advanced

Na Qi,1,2 Yu Zhang,3 Xing Tang,3 Aimin Li1 1Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, People’s Republic of China; 2Department of Pharmacy, Guilin Medical University, Guilin 541004, People’s Republic of China; 3Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of ChinaCorrespondence: Aimin Li; Xing Tang Email liaimin2005@163.com; tanglab@126.comBackground: Cationic and anionic polymer-modified nanoparticles offer promising properties for the drug and gene delivery. Our study uses cationic/anionic polyelectrolyte coated vesicular phospholipid gels (VPGs) loaded with cytarabine (Ara-C) that enhance in vitro and in vivo anti-glioma effects.Methods: Sodium cholesteryl sulfate (SCS) or octadecylamine (ODA) incorporated in a phospholipids phase were used to prepare charged VPGs, and cationic ϵ-polylysine (PLL) coated VPGs (PLL-SCS VPGs) and anionic γ-polyglutamic acid (PGA) coated VPGs (PGA-ODA VPGs) were prepared via electrostatic interactions, respectively. The morphology, particle size, zeta potential, rheology properties, and in vitro release were then characterized. The in vitro cytotoxicity and cellular uptake were evaluated on U87-MG glioma cells. The in vivo antitumor effects were studied on BALB/c nude mice bearing a right flank U87-MG glioma model.Results: The TEM images and physicochemical properties of cationic/anionic polyelectrolyte coated VPGs exhibited that polymers covered on the vesicular surface. The results of rheologic property analysis showed that cationic/anionic polyelectrolyte coated VPGs enhanced the viscosity of uncoated VPGs. The in vitro release experiments revealed that cationic/anionic polyelectrolyte coated VPGs kept Ara-C sustained release up to 18 days. Specially, compared with PLL-SCS VPGs, PGA-ODA VPGs demonstrated higher in vitro cytotoxicity and cellular uptake efficiency in U87-MG glioma cells, and enhanced in vivo antitumor effects when subcutaneously injected around the tumor. No severe toxicity appeared in the right flank U87-MG glioma model of BALB/c nude mice.Conclusion: Anionic γ-PGA coated VPGs were superior to cationic PLL coated VPGs in terms of improving the anti-glioma effect for local delivery.Keywords: biodegradable depots, polyelectrolyte coating, sustained release, glioma, local therapy

Hongyang Fan,1,2,* Xiaojia Tang,2,3,* Yuxia Song,2,3,* Peipei Liu,1,2 Yingzhu Chen1,2 1Clinical Medical College, Yangzhou University, Yangzhou City, Jiangsu Province, People’s Republic of China; 2Department of Neurology, Northern Jiangsu Province Hospital, Yangzhou City, Jiangsu Province, People’s Republic of China; 3Department of Neurology, Clinical Medical College of Yangzhou, Dalian Medical University, Yangzhou City, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingzhu Chen; Peipei Liu Email yzchendr@163.com; doclpp87@163.comAbstract: The global spread of COVID-19 has caused a substantial societal burden and become a major global public health issue. The COVID-19 elderly population with hypertension, diabetes, cardiovascular, and cerebrovascular diseases are at risk. Mortality rates are highest in these individuals if infected with COVID-19. Although the lungs are the main organs involved in acute respiratory distress syndrome caused by COVID-19 infection, COVID-19 triggers inflammatory and immune mechanisms, inducing a “cytokine storm” that aggravates disease progression and may lead to death. Presently, effective drugs are lacking, although current studies have confirmed that drugs with therapeutic potential include redaciclovir, lopinavir/ritonavir combined with interferon-β, convalescent plasma, and monoclonal antibodies. Currently, the most reasonable and effective way to prevent COVID-19 is to control the source of infection, terminate routes of transmission, and protect susceptible populations. With the rise of COVID-19 in China and worldwide, further prevention, diagnosis, and treatment measures are a critical unmet need. Cerebrovascular disease has high incidence, disability rate, and fatality rate. COVID-19 patient outcomes may also be complicated with acute stroke. This paper summarizes the influence of COVID-19 on cerebrovascular disease and discusses possible pathophysiological mechanisms to provide new angles for the prevention and diagnosis of this disease.Keywords: novel coronavirus pneumonia, 2019-nCoV, SARS-CoV-2, cerebral vascular disease

Kaili Yang, Jingfang Liu, Songbo Fu, Xulei Tang, Lihua Ma, Weiming Sun, Ying Niu, Gaojing Jing, Qianglong Niu Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, People’s Republic of ChinaCorrespondence: Jingfang LiuDepartment of Endocrinology, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu, Peoples’ Republic of ChinaTel +86-931-8356242Email ljf824168@126.comObjective: To investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and blood glucose and lipid levels in people over 18 years of age in Gansu, China.Subjects and Methods: A total of 1928 volunteers (958 males and 970 females) were selected. The prevalence of abnormal glucose metabolism and lipid metabolism in the vitamin D deficiency group (< 20 ng/mL) and the non-vitamin D deficiency group (≥ 20 ng/mL) were compared. The correlations between serum 25(OH)D and blood glucose and lipid were analyzed.Results: A total of 1681 patients had 25(OH)D deficiency, with an overall prevalence of 87.2% (82.9% in males and 91.4% in females). The levels of 25(OH)D in the diabetic group and the IGT/IFG group were significantly lower than that in the normal group. The level of 25(OH)D was significantly lower in the dyslipidemia group than that in the normal group, and was significantly lower in the fasting plasma glucose (FPG) ≥ 5.6 mmol/L group than that in the FPG < 5.6 mmol/L group (p=0.002). The 25(OH)D level in the serum triglyceride (TG) ≥ 1.7 mmol/L group was significantly lower than that of the TG < 1.7 mmol/L group (p=0.0274). The age, heart rate, TG, TC, FPG and H2PG levels in the vitamin D deficiency group were significantly higher than those in the non-vitamin D deficiency group (p< 0.05). The prevalence of FPG ≥ 5.6 mmol/L in the vitamin D deficiency group was higher than that in the non-vitamin D deficiency group (23.5% vs 16.6%, p=0.016). Multiple linear regression analysis suggested that serum 25(OH)D levels were independently correlated with gender, age, FPG, TG and heart rate (β=− 0.218, − 0.129, − 0.075, β=− 0.103, − 0.058, all p< 0.05).Conclusion: The incidences of dyslipidemia and dysglycemia were higher in the vitamin D deficiency group. The vitamin D level was independently and negatively correlated with FPG and TC, but not with waist circumference, BMI and blood pressure.Keywords: 25(OH)D, lipid metabolism, glucose metabolism

Xiaoyan Tang,1– 3,* Songping Liu,4,* Yan Ding,1– 3,* Chenyan Guo,1– 3 Jingjing Guo,1– 3 Keqin Hua,1– 3 Junjun Qiu1– 3 1Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, People’s Republic of China; 2Department of Obstetrics and Gynecology of Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Shanghai 200011, People’s Republic of China; 4Department of Obstetrics and Gynecology, Zhenjiang Maternal and Child Health Hospital, Zhenjiang, Jiangsu 212001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junjun Qiu; Keqin HuaDepartment of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai 200011, People’s Republic of ChinaTel +86-21-63455050 Ext 8261Fax +86-21-63455090Email qiujunjun1113@163.com; huakeqin@fudan.edu.cnPurpose: Circular RNAs (circRNAs) are novel type of noncoding RNAs that play important roles and serve as noninvasive biomarkers in various cancers. In the present study, we focused on circFoxO3a and aimed to investigate its prognostic value as a novel serum biomarker for squamous cervical cancer (SCC).Patients and Methods: Our study included 103 SCC patients from Obstetrics and Gynecology Hospital of Fudan University. Expression levels of circFoxO3a in the serum of patients with SCC were examined by reverse transcription‑quantitative PCR (RT‑qPCR). The correlation between serum circFoxO3a expression and clinicopathologic factors was analyzed. The Kaplan–Meier method and multivariate Cox regression analysis were applied to evaluate the independent prognostic factors for SCC. A prognostic predictive nomogram was constructed using R software.Results: Levels of serum circFoxO3a were decreased in SCC patients compared with controls. Low expression of circFoxO3a was correlated with deeper stromal invasion and positive lymph node metastasis. Moreover, SCC patients with lower expression of serum circFoxO3a showed poorer prognosis, including both overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox analysis indicated low serum circFoxO3a levels to be an unfavorable prognostic factor for both OS and RFS, independent of positive lymph node metastasis. Notably, the predictive nomogram we established further confirmed that serum circFoxO3a is a useful tool for predicting survival in SCC.Conclusion: Altogether, our findings demonstrated that serum circFoxO3a could serve as a potential novel noninvasive predictive prognostic biomarker and therapeutic target for SCC.Keywords: circular RNA, FoxO3a, squamous cervical cancer, biomarker

Xia Yang, Xin Tang, Yaoqian Cao, Lixia Dong, Yan Wang, Jing Zhang, Jie Cao Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Jie CaoDepartment of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin 300052, People’s Republic of ChinaTel +8613682187319Fax +8602260361720Email tjcaojie@sina.comPurpose: COPD-OSA (chronic obstructive pulmonary disease–obstructive sleep apnea) overlap syndrome is associated with more frequent COPD acute exacerbations than COPD without OSA. With the application of high-resolution computed tomography (HRCT) in COPD, bronchiectasis is commonly detected and is associated with disease severity. Sleep respiratory disease is also associated with bronchiectasis; however, the correlation between OSA and coexisted bronchiectasis in COPD (COPD-Bx) has not been reported yet.Patients and Methods: A total of 124 consecutive patients with stable COPD were enrolled. All subjects completed the chest HRCT and nocturnal polysomnography (PSG). The scores of extent and severity in bronchiectasis were assessed based on the Smith method and the Bhalla scoring system. Clinical data, questionnaire, routine blood test data, blood levels of C-reactive protein (CRP) and Immunoglobulin E, and the lymphocyte subtype were collected.Results: Among all enrolled patients, 56.45% (70/124) were diagnosed as COPD-OSA based on the results of PSG screening. Bronchiectasis was detected in 42.86% (30/70) of the patients with COPD-OSA, but in 18.52% (10/54) of the patients without OSA (χ 2=8.264, p=0.004). PSG screening revealed that COPD with OSA had a significantly higher apnea-hypopnea index and percent of time spent with oxygen saturation below 90% (T90). Higher values of CRP, T90, and lower CD4/CD8 in the COPD-Bx with OSA were detected compared to COPD-Bx without OSA. Correlation analysis showed that the Bhalla severity score was related to CD8 cell count (r=0.446, p< 0.05) and CD4/CD8 (r=− 0.357, p< 0.05) in all the COPD-Bx patients. The Smith extent score was also associated with the values of CD8 count (r=0.388, p< 0.05) and CD4/CD8 (r=− 0.381, p< 0.05).Conclusion: The comorbid bronchiectasis was more common in COPD-OSA overlap syndrome patient and may be related to more severe hypoxia and increased systemic inflammation.Keywords: chronic obstructive pulmonary disease, bronchiectasis, obstructive sleep apnea

Ting Zhou,1,* Wei Zhang,1,* Dongliang Cheng,1 Xin Tang,2 Jianfang Feng,3 Wei Wu1 1School of Pharmacy, Guilin Medical University, Guilin 541004, People’s Republic of China; 2School of Public Health, Guilin Medical University, Guilin 541004, People’s Republic of China; 3School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei WuSchool of Pharmacy, Guilin Medical University, 109 North 2nd Huancheng Road, Guilin 541004, People’s Republic of ChinaEmail wuwei@glmc.edu.cnJianfang FengSchool of Pharmacy, Guangxi University of Chinese Medicine, 13 Wuhe Avenue, Nanning 530200, People’s Republic of ChinaEmail fengjianfang@vip.163.comPurpose: In this study, NK4-conjugated hydroxycamptothecin liposomes (NK4-HCPT-Lips) were prepared with the aim of improving drug targeting to the liver.Methods: NK4-HCPT-Lips were prepared using the thin-film dispersion method. In vitro antitumor activities were evaluated by MTT assay. HCPT levels in plasma and tissues were determined via high-performance liquid chromatography (HPLC) with camptothecin as the internal standard, and the characteristics, pharmacokinetics, and bio-distribution of NK4-HCPT-Lips were evaluated.Results: The liposomes showed a regular spherical-shaped morphology, and the entrapment efficiency and drug loading capacity reached 82.5 ± 2.4% and 3.01 ± 0.23%, respectively, with a particle size of 155.6 ± 2.6 nm and a zeta potential of − 24.8 ± 3.3 mV. Inhibition effect experiments found that NK4-HCPT-Lips had a good inhibition on the HepG2 cells. Pharmacokinetic studies revealed an increase in the area under the curve and mean residence time as well as a decrease in plasma clearance (p < 0.05) of the NK4-HCPT-Lips compared to those of HCPT liposomes and a commercial HCPT injection. Tissue distribution studies showed that NK4-HCPT-Lips were present at high levels in the liver but were cleared from the kidneys.Conclusion: These results demonstrate that NK4-HCPT-Lips possess excellent liver-targeting attributes, which could enhance the therapeutic effects of drug treatments for hepatic diseases.Keywords: hydroxycamptothecin, NK4, liposomes, pharmacokinetics, bio-distribution

Xiaoqiong Tang, Yaoying Long, Liuyue Xu, Xinyu Yan Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing City 400016, People’s Republic of ChinaCorrespondence: Xiaoqiong TangDepartment of Hematology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, YuZhong District, Chongqing City 400016, People’s Republic of ChinaTel +86 23-89011508Email cebzpn3@163.comIntroduction: LncRNA mortal obligate RNA transcript (MORT) is downregulated in different types of cancer, indicating its involvement in cancer biology.Methods: In this study, MORT and miRNA-16 were both downregulated in plasma of mantle cell lymphoma (MCL) patients than that in the controls. The low levels of MORT and miRNA-16 were correlated with poor survival of MCL patients. The expression of MORT and miRNA-16 was positively correlated only in MCL patients.Results: Overexpression of MORT and miRNA-16 suppressed cell proliferation but promoted cancer cell apoptosis, while miRNA-16 inhibitor reduced the effects of MORT overexpression. Overexpression of MORT led to upregulated expression of miRNA-16, while overexpression of miRNA-16 had no effect on the expression of MORT.Conclusion: Therefore, MORT may inhibit cancer cell proliferation and promote apoptosis in mantle cell lymphoma by upregulating miRNA-16.Keywords: mantle cell lymphoma, MORT, miRNA-16, prognosis, cancer cell

The current understanding of light hypernuclei, which are sub-atomic nuclei with strangeness, is being challenged and studied in detail by several European research groups and collaborations. In recent years, studies of hypernuclei using high-energy heavy ion beams have reported unexpected results on the three-body hypernuclear state 3ΛH, named the hypertriton. For some time, reports of a shorter lifetime and larger binding energy than what was previously accepted have created a puzzling situation for its theoretical description; this is known as the "hypertriton puzzle". With the inclusion of the most recent experimental measurements, the current status of the hypertriton puzzle is evolving. Additionally, the possible neutral bound state of a Λ hyperon with two neutrons, nnΛ, has raised questions about our understanding of the formation of light hypernuclei either in bound or resonance states. These results have initiated several ongoing experimental programs all over the world to study these three-body hypernuclear states precisely. We are studying these light hypernuclear states by employing heavy ion beams at 2AGeV on a fixed carbon target with the WASA detector system and the Fragment Separator (FRS) at GSI. The WASA-FRS experimental campaign was performed during the first quarter of 2022, and this paper presents a short overview of the campaign and how it seeks to tackle the hypertriton and nnΛ puzzles. Data analysis is ongoing, and several preliminary results will be reported.

Bei Zhu,1 Xingbo Cheng,2 Yilan Jiang,3 Ming Cheng,4 Luping Chen,3 Jiajun Bao,3 Xiaofeng Tang3 1Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China, Department of Endocrinology, Rugao People’s Hospital, Nantong 226500, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Soochow University, Suzhou 215006, People’s Republic of China; 3Department of Endocrinology, Rugao People’s Hospital, Nantong 226500, People’s Republic of China; 4School of Rail Transportation, Soochow University, Suzhou 215131, People’s Republic of ChinaCorrespondence: Xingbo ChengDepartment of Endocrinology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou 215006, People’s Republic of ChinaEmail xbcheng1107@163.comMing ChengSchool of Rail Transportation, Soochow University, 8 Ji Xue Road., Xiangcheng District, Suzhou 215131, People’s Republic of ChinaEmail mchengcm@163.comBackground: Long noncoding RNAs (lncRNAs) can regulate the progression of DN. This research aimed to study the effect of lncRNA KCNQ1OT1 on the oxidative stress and pyroptosis of the renal tubular epithelial cells induced by high glucose (HG).Methods: RT-qPCR analysis detected the KCNQ1OT1 expression in serum with DN and HG-induced HK-2 cells, detect the expression of NLRP3, cleaved-caspase1, P-caspase1, IL-1β, p-IL-1β and GSDMD-N in HG-induced HK-2 cells, and confirm the transfection effects. The expression of NLRP3, cleaved-caspase1, P-caspase1, IL-1β, p-IL-1β and GSDMD-N in HG-induced HK-2 cells was also analyzed by Western blot analysis. ELISA assay detected the levels of TNF-α, IL-6 and MCP-1. The levels of ROS, MDA and SOD were determined by respective ELISA kits and ROS was also detected by the ROS assay kit (containing DCFH-DA).Results: We found that KCNQ1OT1 was increased in the plasma of patients with DN and HG-induced HK-2 cells and KCNQ1OT1 interference could decrease the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells. In addition, KCNQ1OT1 directly targets miR-506-3p. MiR-506-3p was downregulated in the plasma of patients with DN and HG-induced HK-2 cells and KCNQ1OT1 interference promoted the expression of miR-506-3p. MiR-506-3p overexpression suppressed the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells.Conclusion: This study demonstrated that downregulation of KCNQ1OT1 inhibited the inflammation, oxidative stress and pyroptosis of HG-induced HK-2 cells by up-regulating the expression of miR-506-3p, which provide new insights into the treatment of DN.Keywords: LncRNA KCNQ1OT1, oxidative stress, pyroptosis, diabetic nephropathy, renal tubular epithelial cells

Jin Yu, Caifeng Zhu, Jiazhen Yin, Dongrong Yu, Feng Wan, Xuanli Tang, Xue Jiang Department of Nephrology, Guangxing Hospital Affiliated to ZheJiang Chinese Medical University (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou 310007, People’s Republic of ChinaCorrespondence: Xue JiangDepartment of Nephrology, Guangxing Hospital Affiliated to ZheJiang Chinese Medical University (Key Laboratory of Zhejiang Province, Management of Kidney Disease), Hangzhou 310007, People’s Republic of ChinaEmail monica_jiang@163.comObjective: Podocyte damage is common in many renal diseases characterized by proteinuria. Transient receptor potential cation channel protein 6 (TRPC6) plays an important role in renal function through its regulation of intracellular Ca2+ influx and RhoA/ROCK pathways. Chinese herb Stephania tetrandra, with the main active component being tetrandrine, has been used for the treatment of various kidney diseases for several years and has shown a positive effect. This study aimed at investigating the effect and mechanism of tetrandrine in podocyte damage induced by high expression of TRPC6.Methods: Immortalized, differentiated murine podocytes, MPC5 were treated with valsartan (0– 800 μM) and tetrandrine (0– 40 μM) for 48 h. The maximum safe concentrations of valsartan and tetrandrine were selected using a cell viability assay. MPC5 podocytes stably expressing TRPC6 were constructed using a lentivirus packaging system, followed by treatment with valsartan, tetrandrine, and Y-27632 for 48 h and U73122 (10 μM) for 10 min. The RhoA/ROCK pathway and podocyte-specific proteins (nephrin and synaptopodin) levels were quantified. Podocyte apoptosis and intracellular Ca2+ concentration were measured.Results: Maximum safe concentrations of 100 μM valsartan and 10 μM tetrandrine showed no observable toxicity in podocytes. MPC5 podocytes stably expressing TRPC6 had higher intracellular Ca2+ influx, apoptotic percentages, and expression of RhoA/ROCK proteins, but lower expression of nephrin and synaptopodin proteins. U73122 treatment for 10 min did not inhibit TRPC6, but suppressed RhoA/ROCK protein. Y-27632 decreased ROCK1 expression, but did not influence the expression of TRPC6 protein. Both 100 μM valsartan and 10 μM tetrandrine for 48 h significantly inhibited intracellular Ca2+ influx, apoptosis, and RhoA/ROCK pathway, and increased nephrin and synaptopodin proteins in podocytes stably expressing TRPC6.Conclusion: Elevated TRPC6 expression can lead to podocyte injury by inducing intracellular Ca2+ influx and apoptosis of podocytes, and this effect may be mediated by activation of the RhoA/ROCK1 pathway. Tetrandrine can alleviate podocyte injury induced by TRPC6 expression through inhibition of the RhoA/ROCK pathway, suggesting a protective role in podocyte damage.Keywords: tetrandrine, transient receptor potential cation channel protein 6, podocyte, RhoA/ROCK pathway

Ruihao Zhou, 1, 2,* Xiaofeng Tang, 1,* Liping Li, 3,* Feifei Zhang, 1 Jun Sun, 1 Cheng Ju, 1, 4 Yan Zhou, 5 Renfeng Liu, 1, 4 Yiping Liang, 1 Bin Lv, 1, 4 Zhiping Zhang, 1, 4 Haiyan Hu, 5 Xiao-Bin Lv 1 1Jiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, Nanchang 30008, People’s Republic of China; 2Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 3Department of Clinical Laboratory, The Third Affiliated Hospital of Nanchang University, Nanchang 330008, People’s Republic of China; 4Department of Orthopedics, The Third Affiliated Hospital of Nanchang University,Nanchang 330008, People’s Republic of China; 5Department of Oncology,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital of Shanghai, Shanghai 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Bin LvJiangxi Key Laboratory of Cancer Metastasis and Precision Treatment, The Third Affiliated Hospital of Nanchang University, North 128 Xiangshan Road, Nanchang 30008, Jiangxi, People’s Republic of ChinaEmail nclvxiaobin@sina.cnHaiyan HuDepartment of Oncology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, No. 600 Yishan Road, Xuhui District, Shanghai City 200233, People’s Republic of ChinaEmail xuri1104@163.comIntroduction: Breast cancer metastasis suppressor 1 like (BRMS1-like)was first reported to be a component of the Sin3-HDAC complex, but the role in the progression of cancers was largely unknown. Our previous study reported that BRMS1L promoted the metastasis of breast cancer through facilitating the recruitment of HDAC complex to the promoter FZD10, and hence suppressing the transcription of FZD10.Methods: In this study, we detected the expression level of BRMS1L in esophageal squamous cell carcinoma (ESCC). The effect of BRMS1L in TE-1D (knockdown) and ECA-109 (overexpression) cell lines was explored by transwell assays, wound healing assays, and cell adhesion assays. Quantitative real‑time PCR, Western blot analysis, and luciferase assays were used to detect the interaction of the CBP/P300-BRMS1L-ITGA7 axis.Results: In the present study, we found that knockdown of BRMS1L promoted the migration, invasion, and epithelial–mesenchymal transition (EMT). Conversely, overexpression of BRMS1L inhibited the migration and invasion of ESCC. Mechanistically, BRMS1L exerted their metastasis-suppressing role via transcriptionally repress ITGA7 expression. Moreover, we revealed that CBP/p 300 regulated the expression of BRMS1L and might be responsible for the down-regulation of BRMS1L in ESCC.Conclusion: Collectively, we identified the role of CBP/p300-BRMS1L-ITGA7 axis in the metastasis of ESCC.Keywords: BRMS1L, ESCC, EMT, ITGA7, CBP/P300, cell invasion and migration

Lu Xie, Jie Xu, Xin Sun, Xiaodong Tang, Taiqiang Yan, Rongli Yang, Wei Guo Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wei GuoMusculoskeletal Tumor Center, Peking University People’s Hospital, Xicheng District, Beijing 100044, People’s Republic of ChinaTel +86-13701195504Email bonetumor@163.comAim: Apatinib, a specific tyrosine kinase inhibitor (TKI) that targets mainly vascular endothelial growth factor receptor-2 (VEGFR-2) as well as Ret, c-Kit and c-Src, has been assessed in patients with advanced osteosarcoma (phase II), the primary report of which has been published in PMID 30559126. This sub-study explored the potential signs of Adverse Events (AEs) for apatinib-treated osteosarcoma.Methods: Participants with advanced osteosarcoma progressing upon chemotherapy received apatinib until disease progression or unacceptable toxicity. Toxicities, progression-free survival (PFS), and clinical benefit rate (CBR) following treatment were evaluated.Results: Of the 41 patients recruited to the study, 37 received treatment and constituted the safety population. At data cut-off (December 30, 2017), median follow-up for safety was 7.37 (IQR, 6.33–11.07) months. The most common grade 3–4 AEs were pneumothorax (16.22%), wound dehiscence (10.81%), proteinuria (8.11%), diarrhea (8.11%), and skin reaction (8.11%). Only hypertension was an independent predictive factor for both PFS (hazard ratio [HR], 0.44; P = 0.07) and CBR (P = 0.07). Anorexia was also significantly related to a longer PFS in a Cox regression model (HR, 0.35; P =0.01). For CBR, pneumothorax and hypothyroidism showed more clinical benefit (P = 0.07 and 0.00, respectively).Conclusion: The results of this study suggest that anorexia, hypertension, pneumothorax, and hypothyroidism might be markers for a favorable clinical outcome following apatinib-treated refractory osteosarcoma.Keywords: apatinib, osteosarcoma, prognosis

GuiSen Wu,1 RanPiao Gan,1 ZhiXing Li,1 LiHua Xu,1 XiaoChen Tang,1 YanYan Wei,1 YeGang Hu,1 HuiRu Cui,1 HuiJun Li,2 YingYing Tang,1 Li Hui,3 XiaoHua Liu,1 ChunBo Li,1 JiJun Wang,1,4,5 TianHong Zhang1 1Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai 200030, People’s Republic of China; 2Florida a & M University, Department of Psychology, Tallahassee, FL 32307, USA; 3Institute of Mental Health, The Affiliated Guangji Hospital of Soochow University, Soochow University, Suzhou 215137, Jiangsu, People’s Republic of China; 4Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai, People’s Republic of China; 5Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: TianHong Zhang; JiJun WangShanghai Key Laboratory of Psychotic Disorders (No.13dz2260500), Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, 600 Wanping Nan Road, Shanghai 200030, People’s Republic of ChinaTel +86-21-34773065Fax +86-21-64387986Email jijunwang27@163.comBackground: The clinical high-risk (CHR) state is identified as a critical period for early prevention and intervention during the development of psychosis and early treatment may reduce the risk of conversion to psychosis. However, it remains controversial whether antipsychotics are effective in CHR populations. Limited previous randomised controlled trials of antipsychotic treatment of CHR individuals indicated possible short-term efficacy on psychotic symptoms with unclear long-term effects. To answer this question, it is necessary to establish a high-quality real-world cohort study with large sample size to explore the effectiveness and safety of antipsychotics in CHR individuals.Methods: We plan to consecutively recruit 600 CHR individuals from Shanghai Mental Health Centre in the ongoing SHARP-2 (ShangHai At Risk for Psychosis-Phase 2) project between 2019 and 2022. At baseline, participants will be assessed by the Structured Interview for Prodromal Syndromes, the MATRICS Consensus Cognitive Battery, demographic information, and clinical medication history. They will be followed up in a naturalistic way in which the research team will not prescribe antipsychotics or provide pharmacological consultation. First, CHR participants and their families will be trained to record their medication daily and self-evaluate symptoms through smart-phone application-based assessment and report their information weekly. Second, telephone calls will be arranged monthly so that the researchers are informed about the participants’ symptoms, medications and daily functions. Third, face-to-face interviews will be conducted annually for repeating assessment of baseline. The primary outcomes will include conversion to psychosis and functional outcome (scored with less than 60 in the Global Assessment of Function) at the end of the follow-up period.Conclusion: The current study will improve our knowledge on the effectiveness and safety of the use of antipsychotics at the prodromal phase, and will eventually facilitate optimisation of individualised interventions for psychosis prevention and treatment.Keywords: clinical high-risk, early interventions, antipsychotics, subgroup

Xiaohuan Tang, Jiaming Zhu, Yuanda Liu, Chao Chen, Tianzhou Liu, Jingjing Liu Department of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jingjing LiuDepartment of Gastrointestinal Nutrition and Hernia Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, Jilin 130041, People’s Republic of ChinaTel +86-431-81136210Email jingjingstarone@163.comAbstract: Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. Advanced diagnosis and high rates of relapse and metastasis are associated with the poor prognosis of this disease. GC has a complex etiopathogenesis of which the underlying mechanisms remain to be explored. Studies on circular RNAs (circRNAs), noncoding RNAs that may be potential targets in GC, have made substantial progress over the past few years. CircRNAs exert important effects on the onset and progression of GC. Hence, this article aims to summarize the findings of recent studies of circRNAs related to GC and to describe the underlying mechanisms and potential applications. The findings indicate that circRNAs participate in GC regulation, proliferation, invasion, and metastasis through regulating microRNAs, proteins, genes, and signaling pathways. In addition, dysregulated circRNAs may be used as novel diagnostic and prognostic biomarkers or therapeutic targets. This review is expected to facilitate a better understanding of GC, and it suggests novel circRNA-based methods to inhibit or prevent GC.Keywords: gastric cancer, circular RNA, biomarkers, diagnosis, prognosis

Xia Tang,1,2 Qian Tong,3 Zhujun Li,4 Zhiyi Chen,2 Mengjia Weng,1 Xiaoyu Zhang,1 Sijing Huang,1 Yang Chen,5 Zhenqi Chen6 1Department of Orthodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Orthodontics, Shanghai Xu Hui Dental Clinic, Shanghai, People’s Republic of China; 3Department of Pediatric Dentistry, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Orthodontics, Shanghai Jing-an Dental Clinic, Shanghai, People’s Republic of China; 5Department of Oral and Craniomaxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of China; 6Department of Orthodontics, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, People’s Republic of ChinaCorrespondence: Zhenqi Chen; Yang ChenShanghai Ninth People’s Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, No. 639, Zhi Zao Ju Road, Huangpu District, Shanghai 200001, People’s Republic of ChinaTel/Fax +86-021-23271699-5056Email orthochen@yeah.net; whitesurgeon@163.comPurpose: Based on Q methodology, this study investigated the motivation of orthodontic treatment for patients and their parents. Through investigation, this paper attempts to explore the motivational factors of CLP and NON-CLP children and their parents, which are different or general.Patients and methods: Q methodology involves 4 phases. (1) Interviews of CLP (N=5), NON-CLP (N=5) patients generated 30 statements (Q-set 1) and CLP (N=5), NON-CLP (N=5) patients’ parents produced 36 statements (Q-set 2) about different reasons to pursue orthodontic care. (2) P-set: recruitment participants. The sample comprised 40 CLP patients (G1) and 40 NON-CLP patients (G2) aged 9–16 years, 40 CLP patients’ parents (G3) and 40 NON-CLP patients’ parents (G4) wanting their children to have orthodontic treatment. (3) Q-sort: 4 groups ranked statements in order of comparative significance using enforced distribution grids (G1, G2 ranked Q-set 1; G3, G4 ranked Q-set 2). (4) Analysis: using the PQMehtod 2.35 vision to analyze data.Results: Three factors in each group were identified as representing the most widespread views of the majority of the participants, described as G1: (1) aesthetics, (2) preparation for other oral treatments, (3) timely. G2: (1) admiration of others, aesthetics, (2) oral function, (3) oral hygiene and improvement of smile. G3: (1) worrying about the future of children, parents’ responsibilities, children’s feelings; (2) mental health, timely; (3) parents’ responsibilities, ready for treatment. G4: (1) aesthetics, children’s will; (2) future problems, timely; (3) timely, parents’ responsibility and no need to worry about physical problems.Conclusion: CLP and NON-CLP patients and parents have different orthodontic treatment motives, yet, they still shared 3 global motivation themes, respectively. Consideration of these motives may help clinicians develop their treatment discussions with patients and parents, which could consequently improve their cooperation and may achieve a more satisfactory outcome.Keywords: cleft lip and/or palate patient, parent, orthodontic, Q methodology, cooperation

Yuehong Li,1 Yue Yang,2 Ruiyan Li,1 Xiongfeng Tang,1 Deming Guo,1 Yun’an Qing,1 Yanguo Qin1 1Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yun’an Qing; Yanguo QinOrthopaedic Medical Center, The Second Hospital of Jilin University, Changchun People’s Republic of ChinaEmail qingyunan@hotmail.com qinyg@jlu.edu.cnAbstract: Prosthesis-associated infections are one of the main causes of implant failure; thus it is important to enhance the long-term antibacterial ability of orthopedic implants. Titanium dioxide nanotubes (TNTs) are biomaterials with good physicochemical properties and biocompatibility. Owing to their inherent antibacterial and drug-loading ability, the antibacterial application of TNTs has received increasing attention. In this review, the process of TNT anodizing fabrication is summarized. Also, the mechanism and the influencing factors of the antibacterial property of bare TNTs are explored. Furthermore, different antibacterial strategies for carrying drugs, as well as modifications to prolong the antibacterial effect and reduce drug-related toxicity are discussed. In addition, antibacterial systems based on TNTs that can automatically respond to infection are introduced. Finally, the currently faced problems are reviewed and potential solutions are proposed. This review provides new insight on TNT fabrication and summarizes the most advanced antibacterial strategies involving TNTs for the enhancement of long-term antibacterial ability and reduction of toxicity.Keywords: antibacterial property, drug delivery, titanium dioxide nanotube, orthopedic implant, surface modification

Xiao Liang, Xiuhui Tang, Jiebing Yang, Jiayuan Zhang, Haobo Han, Quanshun Li Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, People’s Republic of ChinaCorrespondence: Haobo Han; Quanshun LiKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, People’s Republic of ChinaTel +86 4 318 515 5201Fax +86 4 318 515 5200Email hanhb1310@mails.jlu.edu.cn; quanshun@jlu.edu.cnBackground: Therapeutic proteins have been widely used in the treatment of various diseases, and effective carriers are highly required for achieving protein delivery to obtain favorable treatment potency.Materials and methods: A protein–polymer hybrid system was constructed through the genipin-mediated crosslinking of polyethyleneimine with a weight-average molecular weight of 25,000 g/mol (PEI25K) and ribonuclease A (RNase A), namely RGP.Results: The RGP nanoparticles were observed to be easily internationalized in HeLa cells owing to the introduction of positively charged PEI25K, thereby triggering the antiproliferative effects by cleaving RNA molecules in the tumor cells. Moreover, red fluorescence could be obviously visualized in the tumor cells after RGP delivery, which was attributed to the intrinsic characteristics of genipin.Conclusion: The protein–polymer hybrid system prepared via the genipin-mediated crosslinking has exhibited potential to be used as a theranostic platform for both in vivo imaging and delivering diverse therapeutic proteins.Keywords: genipin, polyethyleneimine, ribonuclease A, protein delivery, antitumor efficacy

Xiaohan Tang,1–3 Xiang Yan,1–3 Houde Zhou,1,3–4 Xilin Yang,5 Xiaohong Niu,6 Jing Liu,7 Qiuhe Ji,8 Linong Ji,9 Xia Li,1–3 Zhiguang Zhou1–3 On behalf of the National Clinical Research Center for Metabolic Diseases Study Group1Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, Changsha, People’s Republic of China; 3National Clinical Research Center for Metabolic Diseases, Changsha, People’s Republic of China; 4Hunan Key Laboratory for Metabolic Bone Diseases, Changsha, People’s Republic of China; 5Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, People’s Republic of China; 6Department of Endocrinology, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, People’s Republic of China; 7Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, People’s Republic of China; 8Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China; 9Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Zhiguang ZhouDepartment of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, No.139 Renmin Middle Road, Furong District, Changsha, Hunan 410011, People’s Republic of ChinaTel +86 7 318 529 2154Email zhouzhiguang@csu.edu.cnAim: This study aimed to estimate the prevalence of latent autoimmune diabetes of adults (LADA) and classic type 1 diabetes mellitus (T1DM) in newly diagnosed adult diabetes in China.Method: This cross-sectional study involved 17,349 newly diagnosed diabetes in adults aged ≥30 years from 46 hospitals within 31 months. Demographic characteristics, clinical features, and medical history were collected by trained researchers. T1DM as a whole was comprised of classic T1DM and LADA. Classic T1DM was identified based on the clinical phenotype of insulin-dependency, and LADA was differentiated from patients with initially an undefined diabetes type with standardized glutamic acid decarboxylase autoantibody testing at the core laboratory. The age and sex distributions from a large national survey of diabetes in China conducted in 2010 were used to standardize the prevalence of classic T1DM and LADA.Results: Among 17,349 adult patients, the prevalence of T1DM was 5.49% (95% CI: 4.90–6.08%) (5.14% [95% CI: 4.36–5.92%] in males and 6.16% [95% CI: 5.30–7.02%] in females), with 65% of these having LADA. The prevalence of classic T1DM decreased with increasing age (p0.05). The prevalence of T1DM in overweight or obese patients was 3.42% (95% CI: 3.20–3.64%) and 2.42% (95% CI: 1.83–3.01%), respectively, and LADA accounted for 76.5% and 79.2% in these two groups.Conclusion: We draw the conclusion that T1DM, especially LADA, was prevalent in newly diagnosed adult-onset diabetes in China, which highlights the importance of routine islet autoantibodies testing in clinical practice.Keywords: diabetes, autoimmune, metabolism, differentiation

Jingfang Liu, Chenge Wang, Xulei Tang, Songbo Fu, Gaojing Jing, Lihua Ma, Weiming Sun, Yujuan Li, Dan Wu, Ying Niu, Qianglong Niu, Huiping Guo, Pei SongDepartment of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, People’s Republic of ChinaCorrespondence: Jingfang Liu; Xulei TangDepartment of Endocrinology, The First Hospital of Lanzhou University, 1 Donggang West Road, Lanzhou, Gansu 730000, People’s Republic of ChinaTel +86 0 931 835 6470Email ljf824168@126.com xulei_tang@126.comObjective: This study aimed to analyze the relationship between the metabolic syndrome (MetS) and its components with the occurrence of thyroid nodules.Methods: A total of 2719 volunteers from some areas of Gansu Province, China, who participated in the national survey of thyroid diseases and iodine nutrition status (Tide) and diabetes prevalence, were selected. Their height, weight, waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure were recorded. The fasting plasma glucose (FPG), 2-h plasma postprandial glucose (2hPG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glycosylated hemoglobin (HbA1C) levels were measured. The prevalence of MetS and thyroid nodules was evaluated, and the correlation between each component of MetS and thyroid nodules was studied.Results: The prevalence of MetS and thyroid nodules was 15.4% and 17.2%, respectively. WC, SBP, body mass index, FPG, 2hPG, TG, TC, and thyroid-stimulating hormone levels were significantly higher in the thyroid nodule group. The prevalence of thyroid nodules was significantly higher in the MetS group. A positive correlation was found between the degree of metabolic disorder and the occurrence of thyroid nodules. WC was found to be a risk factor for the occurrence of thyroid nodules. For WC≥90 cm, an increase in the independent variables led to a significant rise in the incidence of thyroid nodules.Conclusion: The prevalence of thyroid nodules was higher in the MetS group. The WC of the MetS components might be an independent risk factor for the occurrence of thyroid nodules.Keywords: metabolic syndrome, risk factors, thyroid nodules, waist circumference

Lu Xie,1 Jie Xu,1 Sen Dong,1 Jian Gao,2 Xiaodong Tang,1 Taiqiang Yan,1 Rongli Yang,1 Wei Guo11Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Catheterization Room & Radiology Department, Peking University People’s Hospital, Beijing, People’s Republic of ChinaPurpose: We intend to analyze the gain and loss from transcatheter intra-arterial (IA) limb infusion of cisplatin for extremity osteosarcoma in the past six years.Patients and methods: Between December 2009 and August 2014, a total of 99 patients were analyzed for efficiency and followed up for long-term survival. Based on the different administration methods of cisplatin, we divided them into the following two cohorts: IA infusion of cisplatin (n=48) and intravenous (IV) infusion of cisplatin (n=51). Except for cisplatin, all the other drugs were given intravenously. Cisplatin was given intra-arterially with an infusion time of 3 hrs or 6 hrs using a pump, whereas historical controls received IV infusion of cisplatin within 60 mins. Tumor neovascularity (TNV) was analyzed before infusion, and subsequent arteriograms were compared with the baseline to determine percent changes. Definitive surgery with intended wide resection and postoperative pathological evaluation were performed in all these patients.Results: No local or overall survival benefit was found in the patients preoperatively treated with IA infusion of cisplatin compared with IV infusion (P=0.336 and 0.173, respectively). Furthermore, serial arteriography was used to predict a good histologic response with an accuracy of 73.1% and a sensitivity of 100%. There were sporadic cases with the telangiectatic subtype, which did not respond very well to IV chemotherapy, but later, the tumor obviously shrank after IA infusion of cisplatin. Our study also showed that the rates of the complication of skin and muscle necrosis were not so low as reported.Conclusion: We did not observe any survival advantage of chemotherapy using IA infusion in osteosarcoma of the extremities. Arteriography for TNV can be used to predict the tumor histologic response. Malposition of the catheter might severely increase the complication of skin or muscle necrosis.Keywords: intra-arterial chemotherapy, tumor neovascularity, telangiectatic osteosarcoma, complications

Qing Yang,1,2,* Shanshan Liu,3,* Yongwei Gu,1,2 Xiaomeng Tang,3 Ting Wang,1,2 Jianhua Wu,4 Jiyong Liu1–31Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China; 4Department of Dermatology, Changhai Hospital, Second Military Medical University, Shanghai 200433, People’s Republic of China*These authors contributed equally to this workBackground: Sulconazole (SCZ) is a broad-spectrum transdermally administered anti-fungicidal agent. However, the therapeutic effect of SCZ is generally limited by its poor water solubility. This present study aimed to develop and evaluate sulconazole-loaded nanoemulsions (SCZ-NEs) for enhancement of the transdermal permeation and antifungal activity.Methods: A spontaneous titration method was applied to prepare the SCZ-NEs. And the optimized formulation of SCZ-NEs was screened by central composite design (CCD). In addition, the characteristics of the SCZ-NEs were evaluated, including particle size, zeta potential, drug loading (DL%) and encapsulation efficiency (EE%). The morphology of SCZ-NEs was observed by transmission electron microscopy (TEM). Franz diffusion cells were used to evaluate the transdermal permeability of the SCZ-NEs. The antifungal activity of the SCZ-NEs was measured by a zone of inhibition (ZOI) test.Results: The optimized SCZ-NEs possessed a moderate particle size of 52.3±3.8 nm, zeta potential of 23.3±1.2 mV, DL% of 0.47±0.05% and EE% of 87.1±3.2%. The ex vivo skin permeation study verified that the cumulative permeability (Qn) and penetration rate (Js) of the optimized SCZ-NEs were about 1.7-fold higher than that of a commercial reference, miconazole (MCZ) cream and 3-fold higher than that of SCZ-DMSO solution. The optimized SCZ-NEs exhibited zone of inhibition (ZOI) values of 23.5±2.4 and 20.4±2.5 mm against C. albicans and T. rubrum, which were larger compared with these of the MCZ cream and SCZ-DMSO solution.Conclusion: SCZ-NEs were effectively developed to overcome the poor solubility of SCZ, promote SCZ permeation through the skin and improve its antifungal activity. Thus, the SCZ-NEs are a promising percutaneous administration for skin fungal infections induced by C. albicans and T. rubrum.Keywords: sulconazole, nanoemulsion, central composite design, transdermal delivery, antifungal activity

Yongtao Gao,1 Haiyang Qian,2 Xue Tang,1 Xiling Du,3 Gang Wang,2 Hairong Zhang,2 Fei Ye,2 Te Liu41The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People’s Republic of China; 2Department of Imaging, Dahua Hospital, Shanghai, 200237, People’s Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai 200092, People’s Republic of China; 4Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200031, People’s Republic of ChinaBackground: Previously, our group confirmed the presence of a subset of cancer stem cells in the tissues of endometrial carcinoma (ie, human endometrial carcinoma stem cells [HuECSCs]). However, the mechanisms by which microRNAs regulate the growth of HuECSCs remain elusive.Methods: We loaded miR-326 onto superparamagnetic iron oxide nanoparticles (miR-326@SPION) and transfected them into HuECSCs.Results: In the present study, we found that the expression levels of members of the G-protein coupled receptor 91 (GPR91)/signal transducer and activator of transcription 3 (STAT3)/vascular endothelial growth factor (VEGF) pathway were significantly elevated in CD44+/CD133+ HuECSCs. Luciferase reporter assays indicated that the succinate receptor 1 (SUCNR1) gene, also known as the G-protein coupled receptor 91 (GPR91) gene, was one of the potential targets of miR-326. Transmission electron microscopy revealed that the SPIONs could cross the cell membrane and accumulate in the cytoplasm. The overexpression of miR-326 significantly inhibited the proliferation and cell cycle progression of HuECSCs in vitro. MiR-326 overexpression also effectively inhibited the invasion and angiogenic capacities of HuECSCs in the extracellular matrix. Meanwhile, miR-326 overexpression significantly inhibited the tumorigenicity and tumour neovascularization capacity of HuECSCs in nude mice. Both quantitative real-time PCR and Western blotting confirmed that overexpression of miR-326 significantly reduced the expression of members of the GPR91/STAT3/VEGF pathway in HuECSCs, and the activity (level of phosphorylation) of key molecules in this pathway was also reduced.Conclusion: Collectively, we confirmed that SPIONs are highly efficient nanocarriers for nucleic acids, on which the loading of miR-326 inhibited the activation of the GPR91/STAT3/VEGF signaling pathway and significantly attenuated the activity of stem cells in endometrial carcinoma, both in vitro and in vivo.Keywords: human endometrial carcinoma stem cells, superparamagnetic iron oxide nanoparticles, microRNA, succinate receptor 1

Xianhui Kang,1,* Xiaodong Tang,1,* Yang Yu,1 Fangping Bao,1 Shuyuan Gan,1 Wei Zheng,1 Jian Zhang,2 Shengmei Zhu1 1Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; 2Department of Anesthesiology, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, China *These authors contributed equally to this work Purpose: This retrospective cohort study aimed to investigate the association between intraoperative dexmedetomidine infusion and emergence agitation (EA), and recovery profiles after lung surgery in adult patients. It was hypothesized that dexmedetomidine was associated with reduced EA and improved recovery profiles. Patients and methods: A single-center chart review was conducted on elective lung surgeries in adults between January and December 2016. The primary outcome was the incidence of EA in postanesthesia care units (PACUs). The secondary outcomes included rescue analgesia, shivering, time to extubation, residual sedation, postoperative pulmonary events, duration of PACU stay, length of hospital stay, and intraoperative hemodynamic changes. Univariate and multivariate regression analyses were used to analyze data. Results: Among 2,468 patients, 814 received an intraoperative dexmedetomidine infusion. Intraoperative dexmedetomidine infusion was associated with a lower incidence of EA (10.9% vs 15.0%; adjusted OR, 0.67; 95% CI, 0.51–0.87; P=0.003), rescue analgesia (7.6% vs 12.2%; adjusted OR, 0.63; 95% CI, 0.47–0.86; P=0.003), shivering (4.2% vs 6.6%; adjusted OR, 0.58; 95% CI, 0.38–0.88; P=0.010), and intraoperative bradycardia (18.6% vs 12.6%; adjusted OR, 1.51; 95% CI, 1.19–1.92; P=0.001). No differences were observed in residual sedation, duration of PACU stay, postoperative pulmonary events, and length of hospital stay between the groups. Conclusion: This retrospective study suggested that intraoperative dexmedetomidine infusion was associated with a lower incidence of EA, rescue analgesia, and shivering in adults after lung surgery. Intraoperative bradycardia was the main side effect. Keywords: dexmedetomidine, emergence agitation, intraoperative administration, lung surgery, recovery profiles

Fei Tong,1 Xiangyuan Tang,2 Daojun Liu2 1Department of Pathology and Pathophysiology, Provincial Key Discipline of Pharmacology, Jiaxing University Medical College, Jiaxing, Zhejiang Province, PR China; 2Department of Pharmaceutical Chemistry, Medical College, Shantou University, Shantou, PR China Background: Hepatic ischemia/reperfusion-induced pancreatic islet injury (HI/RIPII) was an important pathophysiological phenomenon in clinics. In the present study, we observed the effects of phycocyanin on HI/RIPII. However, the half-life of phycocyanin was extremely short and limited its use in vivo. Materials and methods: In order to overcome this shortcoming, poly(ethylene glycol)-b-(poly(L-glutamic acid)-g-polyethylenimine) (PEG-b-(PG-g-PEI)) was synthesized and estimated as a nanocarrier for lengthening delivery of phycocyanin through the abdominal subcutaneous injection in rats. Phycocyanin (isoelectric point=4.3) was encapsulated with PEG-b-(PG-g-PEI) via electrostatic interactions at pH 7.4. Results: In vitro phycocyanin was fast and efficiently encapsulated and showing efficient loading and sustained release. In vivo the anti-HI/RIPII function of phycocyanin/PEG-b-(PG-g-PEI) complex was surveyed in rats using free phycocyanin as the controls, and the results showed that phycocyanin/PEG-b-(PG-g-PEI) complex reduced HI/RIPII property and enlarged islet functionality. Conclusion: These results suggested that PEG-b-(PG-g-PEI) might be treated as a potential phycocyanin nanocarrier. Keywords: phycocyanin, PEG-b-(PG-g-PEI), HI/RIPII, pancreatic islets

Yingwei Zhu,1,* Hong Tang,2,* Lili Zhang,1 Lei Gong,1 Gaojue Wu,1 Jingbin Ni,1 Xuejun Tang1 1Department of Gastroenterology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu 214002, People’s Republic of China; 2Department of Pathology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu 214002, People’s Republic of China *These authors contributed equally to this work Background: TNF-related apoptosis-inducing ligand (TRAIL) functions as a selective apoptosis-inducing ligand in cancer cells with normal cells remaining unaffected; however, resistance limits its anticancer properties. Cancer stem cells (CSCs) are involved in the treatment of resistant cancer cases including liver cancer (LC). The aim of this study was to look into the approaches for increasing the sensitivity of liver cancer stem cells (LCSCs) toward TRAIL. Methodology: PLC, HepG2 and Huh7 LC cell lines were used in this study. Quantitative reverse transcription PCR (qRT-PCR) analysis was done for evaluating the expression of miR-21-3b. Fluorescent-activated cell-sorting equipment was used for separation and identification of LCSCs and non-LCSCs. The cells were transfected with RNA along with miR-21-3p mimics, anti- miR-21-3p, miR-NC and the phosphatase and tensin homologue (PTEN) siRNA. MTT assay for cell viability, Luciferase assay for luciferase activity, Western blots for the expression of proteins and flow cytometry for the measurement of ROS and apoptosis, respectively, were carried out. Tumor xenografts nude mice were used for tumor growth in vivo. Results: We found that miR-21-3p was overexpressed in LCSCs compared to non-LCSCs and that the suppression of miR-21-3p along with anti-miR-21-3p enhanced the sensitivity of LCSCs to TRAIL-mediated apoptosis. We further found that miR-21-3p regulated the expression of PTEN in Huh7-LCSCs directly and that the suppression of miR-21-3p enhanced the levels of PTEN. The study confirmed that inhibition of the PI3K/Akt/Bad signaling pathway was involved in enhancing TRAIL-mediated apoptosis of LC cells. Conclusion: The study suggested that overexpression of miR-21-3p suppresses the sensitivity to TRAIL in LCSCs. This study concludes that the suppression of miR-21-3p is a potential approach for enhancing the sensitivity of LC cells toward TRAIL by PI3K/Akt/Bad cascade via the miR-21-3p/PTEN axis. Keywords: TRAIL, liver cancer, miR-21-3p, PI3K, Akt, Bad, PTEN

Yanjun Xu,1,* Yang Zhang,2,* Xiaojun Cai,1,2 Wei Gao,1,2 Xiuzhen Tang,3 Yini Chen,1,2 Jie Chen,1,2 Li Chen,1,2 Qiwei Tian,4 Shiping Yang,4 Yuanyi Zheng,1,3 Bing Hu2 1Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 2Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China; 3Department of Ultrasound in Medicine, Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; 4Department of Chemistry, Shanghai Normal University, Shanghai 200234, China *These authors contributed equally to this work Background: The intrinsic properties of Prussian blue (PB) nanoparticles make them an attractive tool in nanomedicine, including magnetic resonance imaging (MRI), photoacoustic imaging (PAI), and photothermal therapy (PTT) properties. However, there still remains the challenge of their poor dispersible stability in the physiological environment. In this study, we developed an efficient hydrothermal method to address the poor dispersible stability of PB nanoparticles in the physiological environment. Materials and methods: The concentration of H+, the mass of polyvinylpyrrolidone (PVP), and iron sources (K3[Fe(CN)6]) are very vital in the preparation of PB nanoparticles. Through exploring the preparation process, optimized PB nanoparticles (OPBs) with excellent physiological stability were prepared. Hydrodynamic diameter and UV-vis absorption properties were measured to verify the stability of the prepared OPBs. Properties of dual-mode imaging, including MRI/PAI, and PTT of OPBs were investigated both in vitro and in vivo. In addition, the in vivo biosafety of OPBs was systematically assessed. Results: OPBs were stable in different environments including various media, pH, and temperatures for at least 90 days, indicating that they are suitable for biomedical application via intravenous administration and easily stored in a robust environment. Compared with other research into the synthesis of PB nanoparticles, the “in situ modification” synthesis of PB nanoparticles had advantages, including a simple process, low cost, and easy mass preparation. OPBs showed no significant signs of toxicity for 90 days. As a proof of concept, the OPBs served as dual-mode image contrast agents and photothermal conversion agents for cancer diagnosis and therapy both in vitro and in vivo. Conclusion: Our findings suggest a facile but efficient strategy with low cost to address the poor dispersible stability of PB nanoparticles in physiological environments. This will promote the development of further clinical transformations of PB nanoparticles, especially in cancer theranostics. Keywords: nanomedicine, magnetic resonance imaging, photoacoustic imaging, photothermal therapy, stability

Zeting Yuan,1,* Yuxia Yuan,1,* Lin Han,2 Yanyan Qiu,1 Xiaqin Huang,3 Feng Gao,3 Guohua Fan,1 Yixi Zhang,1 Xueyao Tang,1 Xue He,1 Ke Xu,1 Peihao Yin1,4,5 1Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, People’s Republic of China; 2Experimental Research Center, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People’s Republic of China; 4Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, People’s Republic of China; 5Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Anhui 230022, People’s Republic of China *These authors contributed equally to this work Background: Multidrug resistance (MDR) is the major reason for the failure of chemotherapy in colon cancer. Bufalin (BU) is one of the most effective antitumor active constituents in Chansu. Our previous study found that BU can effectively reverse P-glycoprotein (P-gp)-mediated MDR in colon cancer. However, the clinical application of BU is limited due to its low solubility in water and high toxicity. In the present study, a multifunctional delivery system based on vitamin-E-succinate grafted chitosan oligosaccharide (VES-CSO) and cyclic (arginine-glycine-aspartic acid peptide) (RGD)-modified d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by emulsion solvent evaporation method for targeted delivery of BU to improve the efficacy of drug-resistant colon cancer therapy.Methods: The cytotoxicity of BU-loaded micelles against drug-resistant colon cancer LoVo/ADR and HCT116/LOHP cells was measured by CCK-8 assay. The cellular uptake, Rho123 accumulation, and cell apoptosis were determined by flow cytometry. The expression of apoptosis-related protein and P-gp was measured by Western blot assay. The antitumor activity of BU-loaded micelles was evaluated in LoVo/ADR-bearing nude mice.Results: BU-loaded VES-CSO/TPGS-RGD mixed micelles (BU@VeC/T-RGD MM) were 140.3 nm in diameter with zeta potential of 8.66 mV. The BU@VeC/T-RGD MM exhibited good stability, sustained-release pattern, higher intracellular uptake, and greater cytotoxicity in LoVo/ADR cells. Furthermore, the mechanisms of the BU@VeC/T-RGD MM to overcome MDR might be due to enhanced apoptosis rate and P-gp efflux inhibition. Subsequently, in vivo studies confirmed an enhanced therapeutic efficiency and reduced side effects associated with BU@VeC/T-RGD MM compared with free BU, owing to the enhanced permeation and retention effect, improved pharmacokinetic behavior, and tumor targeting, which lead to MDR-inhibiting effect in LoVo/ADR-bearing nude mice.Conclusion: Our results demonstrated that VeC/T-RGD MM could be developed as a potential delivery system for BU to improve its antitumor activity against drug-resistant colon cancer. Keywords: bufalin, colon cancer, multidrug resistance, mixed micelle, tumor targeting, P-gp

Xun Tang,1 Hui-Ying Wang,1 Min Wang,2 Xiao-Hua Ren,3 Fu-Rong Jiang,1 Jian-Ling Li1,3 1Clinical Psychology Department of Xiangya Hospital, Xiangya Medical School, Central South University, Changsha, China; 2Department of HIV, The First Hospital of Changsha, Changsha, China; 3Traning Department of Xiangya Hospital, Central South University, Changsha, China Introduction: People living with HIV/AIDS (PLWHA) have a higher rate of suicide compared to the general population. Psychosocial factors closely correlate with suicidal ideation and it is essential to explain the relationships between related factors among PLWHA.Objectives: To establish a structural equation model and examine direct and indirect effects of social support, coping strategy, depression symptoms and suicidal ideation among PLWHA.Patients and methods: A total of 504 PLWHA completed a set of questionnaires in the HIV clinic of Changsha Infectious Disease Hospital between December 2015 and January 2016.Results: Among the 504 respondents, a total of 27.2% (n=137) had experienced suicidal ideation in their lifetime. The goodness of fit for the two structural equations model was highly satisfactory. Depression symptoms had a significant direct impact on suicidal ideation (β1=0.401, β2=0.422), while problem-focused coping (β=-0.067), emotion-focused coping (β=-0.081) and social support (β=-0.137) had a significant indirect effect with suicidal ideation via depression symptoms. Factors of total effects were ranked from large to small as follows: depression, social support, emotion-focused coping and problem-focused coping.Conclusion: Findings provide more understanding of direct and indirect associations between variables, suggesting that depression screening services, and the strengthening of social support and psychological care services among PLWHA can potentially prevent suicide. Keywords: SEM, PLWHA, depression, problem-focused coping, emotion-focused coping

Xin Tang,1 Yicong Xu,2,3 Lin Lu,2,3 Yang Jiao,2,3 Jianjun Liu,2,3 Linlin Wang,2,3 Hongbo Zhao2,3 1School of Rehabilitation, Kunming Medical University, Kunming, China; 2Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China; 3Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Kunming, China Purpose: Cervical cancer (CC) is one of the most common malignant tumors among women. The present study aimed at integrating two expression profile datasets to identify critical genes and potential drugs in CC.Materials and methods: Expression profiles, GSE7803 and GSE9750, were integrated using bioinformatics methods, including differentially expressed genes analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and protein–protein interaction (PPI) network construction. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis websites. Connectivity Map (CMap) was used to query potential drugs for CC.Results: A total of 145 upregulated genes and 135 downregulated genes in CC were identified. The functional changes of these differentially expressed genes related to CC were mainly associated with cell cycle, DNA replication, p53 signaling pathway, and oocyte meiosis. A PPI network was identified by STRING with 220 nodes and 2,111 edges. Thirteen key genes were identified as the intersecting genes of the enrichment pathways and the top 20 nodes in PPI network. Survival analysis revealed that high mRNA expression of MCM2, PCNA, and RFC4 was significantly associated with longer overall survival, and the survival was significantly better in the low-expression RRM2 group. Moreover, CMap predicted nine small molecules as possible adjuvant drugs to treat CC.Conclusion: Our study found key dysregulated genes involved in CC and potential drugs to combat it, which might provide insights into CC pathogenesis and might shed light on potential CC treatments. Keywords: cervical cancer, bioinformatics, cell cycle, biomarker, drug

Yun’an Qing,1 Lin Cheng,2 Ruiyan Li,1 Guancong Liu,1 Yanbo Zhang,1 Xiongfeng Tang,1 Jincheng Wang,1 He Liu,1 Yanguo Qin1 1Orthopaedic Medical Center, The Second Hospital of Jilin University, Changchun 130041, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun 130041, People’s Republic of China Abstract: Infection, as a common postoperative complication of orthopedic surgery, is the main reason leading to implant failure. Silver nanoparticles (AgNPs) are considered as a promising antibacterial agent and always used to modify orthopedic implants to prevent infection. To optimize the implants in a reasonable manner, it is critical for us to know the specific antibacterial mechanism, which is still unclear. In this review, we analyzed the potential antibacterial mechanisms of AgNPs, and the influences of AgNPs on osteogenic-related cells, including cellular adhesion, proliferation, and differentiation, were also discussed. In addition, methods to enhance biocompatibility of AgNPs as well as advanced implants modifications technologies were also summarized. Keywords: antibacterial mechanism, biocompatibility, osteogenic-related cells, orthopedic implants, silver nanoparticles, surface modification

Tingting Che,1 Xiaochun Teng,1 Qun Huang,1 Yanfei Mu,2 Xianjun Tang,2 Xiaosong Mu,2 Youneng Wei1 1Department of Endocrinology, Chongqing Public Health Medical Center, Chongqing, China; 2Chongqing Cancer Institute, Hospital and Cancer Center, Chongqing, China Background: Depressive and anxiety symptoms could seriously affect the quality of life of type 2 diabetes mellitus (T2DM) subjects. Currently, little is known about the efficacy and acceptability of agomelatine versus fluoxetine in treating these symptoms in T2DM subjects. Therefore, this study was performed to find out which one was better in treating these symptoms in T2DM subjects.Materials and methods: T2DM subjects with depressive and anxiety symptoms were randomly assigned to receive either fluoxetine (30–40 mg/day) or agomelatine (25–50 mg/day). The treatment was continued for 12 weeks. The data of the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) were collected (at baseline and also at weeks 4, 8 and 12) to assess the depressive and anxiety symptoms, respectively. The metabolic parameters, including body mass index (BMI), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c), were assessed at baseline and after 12 weeks of treatment. The treatment-related adverse events during the scheduled treatment period were recorded to compare the acceptability of these two drugs.Results: After 12 weeks of treatment, the average HDRS and HARS scores were significantly decreased in both groups. The average HDRS scores were not significantly different between the two groups, although the agomelatine group had a lower average HDRS score. The response and remission rates were similar between the two groups, and these two drugs had no significant effects on BMI and FPG. However, compared with the fluoxetine group, the agomelatine group had the significantly lower average HARS score (p=0.0017) and lower average HbA1c level (p

Cuilin Li,1,2 Hecun Zou,1–3 Zhifei Wang,4 Xinyue Tang,1,2 Xitang Fan,4 Ke Zhang,1,2 Jianqiu Liu,1,2 Zhi Li1,2 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China; 2Institute of Clinical Pharmacology, Central South University and Hunan Key Laboratory of Pharmacogenetics, Changsha, China; 3Institute of Life Sciences, Chongqing Medical University, Chongqing, China; 4Department of Neurosurgery, Third Xiangya Hospital of Central South University, Changsha, China Background/aim: Repressor element silencing transcription factor (REST) is a transcription repressor, expressed in several malignancies. This study aims to evaluate the prognostic values of REST and its splicing variant REST4 in glioma, and investigate the potential correlation between REST and REST4. Methods: REST and REST4 expression values were evaluated by qRT-PCR in 89 patients with gliomas and 10 with normal brain tissues. Results: Upregulation of REST was related to higher World Health Organization (WHO) grade, larger tumor size, higher ki67, and higher p53 positive rate. After radiotherapy+temozolomide (RT+TMZ) treatment, low REST expression patients could get better therapeutic efficacy (P=0.031). The positive rate of REST4 expression was only 13.5% in glioma tissues, and REST4 expression was not associated with clinical characteristics and REST expression in this study. Conclusions: REST was a prognostic factor in glioma, while REST4 was not. REST expression can be a predictor in evaluating the survival outcome of gliomas patients treated with RT+TMZ after surgery. Keywords: REST, REST4, glioma, radiotherapy, chemotherapy, prognosis

Zhu Y, Ren F, Zhu Y, et al. Nat Sci Sleep. 2020;12:1067–1074. The authors have advised that the name of last author on page 1067 is incorrect. Mingwen Zheng should be Minwen Zheng. The authors apologize for this error. Read the original article

Xiaoshuang Tang,1,2 Feng Li,1 Jing Jia,1 Chao Yang,1 Wei Liu,1 Ben Jin,1 Xinyang Wang,1 Ruixia Gao,3 Dalin He,1,4 Peng Guo1,4 1Department of Urology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, 3Institute of Analytical Science, School of Science, Xi’an Jiaotong University, 4Key laboratory for Tumor Precision Medicine of Shaanxi Province, Xi’an, Shaanxi, People’s Republic of China Purpose: Androgen plays an important role in the progression of prostate cancer. In the present study, novel magnetic molecularly imprinted polymers (MMIPs) with good biocompatibility were produced for the selective separation and inhibition of testosterone in prostate cancer cells. Materials and methods: MMIPs were prepared by using magnetic nanospheres, gelatin, and testosterone as the supporting materials, functional monomer, and the template molecule, respectively. The characterization of the resultant products was investigated by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry. To test whether MMIPs can remove testosterone in biologic samples, human LNCaP (androgen-dependent) and C4-2 (androgen-independent) prostate cancer cells were selected as cell models. The translocation of androgen receptor (AR) was detected by immunofluorescence assay, and the expression of PSA mRNA was detected by real-time quantitative polymerase chain reaction analysis. Cell flow cytometry analysis was performed to detect cell cycle arrest. Results: The synthesized nanomaterials (MMIPs) possessed high crystallinity, satisfactory superparamagnetic properties, and uniform imprinted shell, and exhibited high adsorption capacity, fast kinetics, and high selectivity for testosterone. Moreover, the obtained imprinted nanomaterials could selectively enrich and detect testosterone in the LNCaP cell samples as a solid-phase extractant coupled with high-performance liquid chromatography. In addition, the MMIPs could freely enter prostate cancer cells and suppress the translocation of AR into the cell nucleus. We further found that MMIPs inhibited upregulation of AR downstream target genes in LNCaP and C4-2 cells; also, MMIPs inhibited cell growth and induced obvious cell cycle arrest in androgen-dependent LNCaP cells, but had no obvious effect on androgen-independent C4-2 cells. Conclusion: Our results indicate that the obtained imprinted nanomaterials can specifically and effectively bind testosterone and recover it from prostate cancer cells. Moreover, the MMIPs can freely enter prostate cancer cells and block the activation of testosterone-AR pathway. Thus, the MMIPs may be a new option for antiandrogen therapy in prostate cancer. Keywords: magnetic separation, solid-phase extraction, testosterone, prostate cancer, androgen deprivation therapy, androgen receptor