Search

Rui Shen,1,2,* Kebin Cheng,3,* Guanyi Li,1 Zhendong Pan,4 Xijier Qiaolongbatu,1 Yuting Wang,1 Cui Ma,1 Xucong Huang,1 Li Wang,1 Wenjing Li,1 Yuanyuan Wang,2 Lili Jing,1 Guorong Fan,2 Zhenghua Wu2 1School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 4Department of Clinical Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenghua Wu, Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-159-0161-7923, Email wuzhenghua@sjtu.edu.cnPurpose: Alisma orientale (AO, Alisma orientale (Sam). Juzep) has been widely employed for the treatment of macular edema (ME) in traditional Chinese medicine due to its renowned water-relief properties. Nonetheless, the comprehensive investigation of AO in alleviating ME remained unexplored. This study aims to identify the active components of AO that target the eye and investigate its pharmacological effects and mechanisms on ME.Methods: The study commenced with UPLC-Triple-TOF/MS analysis to identify the primary constituents of AO. Zebrafish eye tissues were then analyzed after a five-day administration of AO to detect absorbed components and metabolites. Subsequently, network pharmacology, molecular docking, and molecular dynamics simulations were employed to predict the mechanisms of ME treatment via biological target pathways. In vivo experiments were conducted to corroborate the pharmacological actions and mechanisms.Results: A total of 7 compounds, consisting of 2 prototype ingredients and 5 metabolites (including isomers), were found to traverse the blood-eye barrier and localized within eye tissues. Network pharmacology results showed that AO played a role in the treatment of ME mainly by regulating the pathway network of PI3K-AKT and MAPK with TNF-α centered. Computational analyses suggested that 11-dehydro-16-oxo-24-deoxy-alisol A, a metabolite of alisol A, mitigates edema through TNF-α inhibition. Furthermore, zebrafish fundus confocal experiments and HE staining of eyes confirmed the attenuating effects of alisol A on fundus angiogenesis and ocular edema, representing the first report of AO’s ME-inhibitory effects.Conclusion: In this study, computational analyses with experimental validation were used to understand the biological activity and mechanism of alisol A in the treatment of ME. The findings shed light on the bioactive constituents and pharmacological actions of AO, offering valuable insights and a theoretical foundation for its clinical application in managing ME. Keywords: Alisma orientale, macular edema, network pharmacology, zebrafish, TNF-&#x03B1

Zhouyang Hu,1,2,* Xiaobing Yin,3,* Guoxin Fan,1,2 Xiang Liao1,2 1Department of Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China; 3Nursing Department, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoxin Fan; Xiang Liao, Department of Pain Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, People’s Republic of China, Tel +86-18529093630 ; +86-13725595056, Email fan06309@163.com; liaoxiang75@email.szu.edu.cnObjective: Bibliometric analysis is commonly used to visualize the knowledge foundation, trends, and patterns in a specific scientific field by performing a quantitative evaluation of the relevant literature. The purpose of this study was to perform a bibliometric analysis of recent studies in the field of orthopedic biofilm research and identify its current trends and hotspots.Methods: Research studies were retrieved from the Web of Science Core Collection and Scopus databases and analyzed in bibliometrix with R package (4.2.2).Results: A total of 2426 literature were included in the study. Journal of orthopaedic research and Clinical orthopaedics and related research ranked first in terms of productivity and impact, with 57 published articles and 32 h-index, respectively. Trampuz A, Ohio State Univ and the United States ranked as the most productive authors, institutions, and countries. Biofilm formation, role of sonication, biomaterial mechanism and antibiotic loading have been investigated as the trend and hotspots in the field of orthopedic biofilm research.Conclusion: This study provides a thorough overview of the state of the art of current orthopedic biofilm research and offers valuable insights into recent trends and hotspots in this field.Keywords: biofilm, orthopedic infection, bibliometric analysis, hotspot, research trend

Gang Fan,1,* Jingfen Lu,2,* Jinhui Zha,3,* Weiming Guo,1 Yifei Zhang,4 Yuxin Liu,5 Liyuan Zhang1 1Department of Urology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, People’s Republic of China; 2The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 3Shenzhen University, Shenzhen, 518000, People’s Republic of China; 4The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People’s Republic of China; 5College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liyuan Zhang; Gang Fan, Department of Urology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000, People’s Republic of China, Email liyuan.zhang@uszh.org.cn; gang.fan.med@qq.comAbstract: The maintenance of normal vascular function and homeostasis is largely dependent on the signaling mechanisms that occur within and between cells of the vasculature. TGF-β-activated kinase 1 (TAK1), a multifaceted signaling molecule, has been shown to play critical roles in various tissue types. Although the precise function of TAK1 in the vasculature remains largely unknown, emerging evidence suggests its potential involvement in both physiological and pathological processes. A comprehensive search strategy was employed to identify relevant studies, PubMed, Web of Science, and other relevant databases were systematically searched using keywords related to TAK1, TABs and MAP3K7.In this review, we discussed the role of TAK1 in vascular signaling, with a focus on its function, activation, and related signaling pathways. Specifically, we highlight the TA1-TABs complex is a key factor, regulating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) involved in the processes of inflammation, vascular proliferation and angiogenesis. This mini review aims to elucidate the evidence supporting TAK1 signaling in the vasculature, in order to better comprehend its beneficial and potential harmful effects upon TAK1 activation in vascular tissue.Keywords: TGF-β-activated kinase 1, vascular disease, mitogen-activated protein kinase, transforming growth factor-β, smooth muscle cell, endothelial cell

Ronglin Ma,1,2,* Chunya Ji,1,* Mengdan Shen,2 Shujuan Xu,2 Guojia Fan,3 Chengcheng Wu,1 Qiang Yu,2 Linliang Yin1 1Center for Medical Ultrasound, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, 215002, People’s Republic of China; 3Center for Cytotoxicity Testing, Sanitation & Environment Technology Institute, Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiang Yu, Department of Gastroenterology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Jiangsu, People’s Republic of China, Tel +86 512 62362045, Email yuqiang0102sz@163.com Linliang Yin, Center for Medical Ultrasound, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Jiangsu, People’s Republic of China, Tel +86 13382183478, Email yllsznthello@hotmail.comBackground: Radionuclides have important roles in clinical tumor radiotherapy as they are used to kill tumor cells or as imaging agents for drug tracing. The application of radionuclides has been developing as an increasing number of nanomaterials are used to deliver radionuclides to tumor areas to kill tumor cells. However, promoting the efficient combination of radionuclides and nanocarriers (NCs), enhancing radionuclide loading efficiency, and avoiding environmental pollution caused by radionuclide overuse are important challenges that hinder their further development.Methods: In the present study, a new small molecule compound (3-[[(2S)-2-hydroxy-3-(4-hydroxyphenyl)-1-carbonyl] amino]-alanine, abbreviation: HN, molecular formula: C12H16N2O5) was synthesized as a linker between radionuclide iodine-125 (125I) and NCs to enable a more efficient binding between NCs and radionuclides.Results: In vitro evidence indicated that the linker was able to bind 125I with higher efficiency (labeling efficiency > 80%) than that of tyrosine, as well as various NCs, such as cellulose nanofibers, metal oxide NCs, and graphene oxide. Single-photon emission computed tomography/computed tomography imaging demonstrated the biological distribution of 125I-labeled NCs in different organs/tissues after administration in mice.Conclusion: These results showed an improvement in radionuclide labeling efficiency for nanocarriers and provided an approach for nanocarrier image tracing.Keywords: nanocarriers, radionuclide labeling, radionuclide 125i, SPECT/CT imaging

Understanding reaction kinetics can provide valuable information for the design and optimization of a reaction process. In this study, the reduction degree and carbonitriding ratio of TiO2 in the CH4-H2-N2 system were investigated to understand the kinetics of carbonitriding reduction. The experimental results revealed the following important findings. The reduction degree of TiO2 increased significantly within the temperature range of 1000°C to 1200°C. At the same time, the duration of complete carbonitride time decreased with increasing temperature. However, it was found that excessively high temperatures (1200°C) had a detrimental effect on the degree of reduction. Consequently, the optimal reduction temperature was set at 1100°C, in order to achieve a balance between reduction degree and reaction time. The process of carbonitride reduction of TiO2 in the CH4-H2-N2 system corresponded to the unreacted nuclear model, where the process was mainly controlled by chemical reactions. A calculated apparent activation energy of 99.35 kJ/mol was obtained for the carbonitriding reduction process. The identification of the optimal reduction temperature and the dominant role of chemical reactions provide valuable insights for the design and optimization of carbonitriding processes with titanium compounds.

Guimei Fan,1 Mo Yi,2 Xiangmin Qiu,1 Jinfang Zhao1 1Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 2School of Nursing, Peking University, Beijing, People’s Republic of ChinaCorrespondence: Jinfang Zhao, Shandong Provincial Hospital Affiliated to Shandong First Medical University, #324 Jingwuweiqi Road, Huaiyin District, Jinan City, Shandong Province, 250021, People’s Republic of China, Email zjfcqt@qq.comPurpose: This study aims to explore the complicated decision-making dilemma and challenges confronted by parents of children suffering from severe asthma within the Pediatric Intensive Care Unit (PICU) when participating in the development of their children’s discharge care plans.Patients and Methods: Employing a phenomenological methodology, a purposive sampling was performed to engage with 17 parents who participated in in-depth and semi-structured interviews between October 2022 and February 2023. The transcripts of these interviews were transcribed into textual data, which was then subjected to Colaizzi’s seven-step analysis for meticulous coding and comprehensive thematic elucidation.Results: The comprehensive analysis of the factors involved in the intricate decision-making dilemmas faced by parents of children with severe asthma during the process of crafting discharge care plans in the PICU revealed five themes and eight sub-themes: 1) Complexity of asthma-related information; 2) Insufficient provision of comprehensive decision-making support; 3) Encountering negative emotions and wavering confidence; 4) Navigating realistic constraints impacting both parents and HCPs; 5) Balancing the advantages and disadvantages of various plans.Conclusion: Parents of children with severe asthma in the PICU encounter intricate and multifaceted decision-making dilemmas while engaging in the formulation of discharge care plans. These complexities significantly dampen their decision-making enthusiasm and introduce potential risks to the children’s prognosis and recovery. In the future, it is imperative to leverage the guidance provided by healthcare professionals (HCPs) in the decision-making process, develop tailored decision support tools specifically designed for the formulation of discharge care plans for children with severe asthma in the PICU.Keywords: severe asthma, parents, discharge care plan, decision-making dilemma, phenomenological study

Longbin Zheng,1,* Yiteng Wang,2,* Qing Ma,1,* Wenbo Liang,1 Xiaojing Zhang,1 Zhiqiang Ren,1 Weimin Qin,1 Fan Meng,1 Yuhong Li,1 Guoxiang Fan,1 Ning Yin1 1Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Anesthesiology, Xinchang County People’s Hospital, Xinchang, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Yin, Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Avenue, Nanjing, Jiangsu Province, 211112, People’s Republic of China, Email yinning882000@126.comPurpose: Patients with obesity are more susceptible to hypoxemia. Anesthetic management for patients with obesity undergoing painless gastroscopy presents a severe challenge for anesthesiologists. Esketamine is a NMDA antagonist that has been proven to be beneficial for ameliorating respiratory depression owing to its sympathomimetic effect; however, there are no relevant reports on its use in patients with obesity. We designed a randomized controlled trial to evaluate whether esketamine can be the ideal adjuvant to propofol sedation in patients with obesity undergoing painless gastroscopy.Patients and Methods: A total of 104 patients with obesity undergoing painless gastroscopy were randomly divided into group C (propofol+saline) and group S (propofol+esketamine 0.25 mg/kg). Anesthesia was induced by 2 mg/kg propofol with saline or esketamine. The consumption of propofol, hemodynamic parameters, duration of procedure, induction time, postoperative awakening time, and orientation recovery time were recorded. Adverse events and satisfaction scores were also recorded.Results: Propofol consumption was 274.4± 22.6 mg and 201.3± 16.6 mg in groups C and S, respectively. The induction time of groups C and S were 25.4± 2.3 s and 17.8± 1.9 s, respectively. The postoperative awakening times of groups C and S were 6.2± 1.1 min and 4.8± 1.3 min, respectively. Hemodynamic parameters were more stable in group S than in group C. The incidence of adverse events such as injection pain, hypoxemia, hypotension, bradycardia, choking, and body movement were significantly lower in group S. The satisfaction scores of the endoscopist and anesthesiologist were (4.58± 0.49 vs 3.71± 0.83) and (4.75± 0.44 vs 3.33± 0.92), respectively.Conclusion: The combination of propofol and esketamine (0.25 mg/kg) improves the safety and reduces the incidence of adverse events in patients with obesity during painless gastroscopy. Thus, this method is worthy of clinical application.Clinical Trials Registration: ChiCTR 2200062547.Keywords: esketamine, propofol, patients with obesity, painless gastroscopy

Xijier Qiaolongbatu,1,* Wenjuan Zhao,1,* Xucong Huang,2,3,* Feng Qian,1 Xinyi Yang,1 Jiaqi Wu,2 Cui Ma,2 Han Qu,1,2 Li Wang,3 Guorong Fan,2 Zhenghua Wu2 1Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, Pharm-X Center, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 3School of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenghua Wu; Guorong Fan, Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-133-0177-7863 ; +86-21-36123711, Email zhenghua.wu@shgh.cn; fanguorong@sjtu.edu.cnBackground: Schisandrol A (Sch A) is the main active ingredient of Schisandra chinensis (Turcz.) Baill. Our previous study showed that Sch A has anti-pulmonary fibrosis (PF) activity, but its metabolic-related mechanisms of action are not clear.Methods: Here, we explored the therapeutic mechanisms of Sch A on PF by ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) metabolomics approach and network analysis. The metabolites of Sch A in mice (bleomycin + Sch A high-dose group) plasma were identified based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS).Results: 32 metabolites were detected reversed to normal level after treating bleomycin (BLM)-induced PF mice with Sch A. The 32 biomarkers were enriched in energy metabolism and several amino acid metabolisms, which was the first report on the therapeutic effects of Sch A on PF through rescuing the disordered energy metabolism. The UPLC-Q-TOF/MS analysis identified 17 possible metabolites (including isomers) of Sch A in mice plasma. Network analysis revealed that Sch A and 17 metabolites were related to 269 genes, and 1109 disease genes were related to PF. The construction of the Sch A/metabolites-target-PF network identified a total of 79 intersection genes and the TGF-β signaling pathway was determined to be the main signaling pathway related to the treatment of PF by Sch A. The integrated approach involving metabolomics and network analysis revealed that the TGF-β 1-ID3-creatine pathway, TGF-β 1-VIM-carnosine pathway were two of the possible pathways Sch A regulated to modulate metabolic disorders, especially energy metabolism, and the metabolite of Sch A M5 was identified as a most likely active metabolite.Conclusion: The results suggested the feasibility of combining metabolomics and network analysis to reflect the effects of Sch A on the biological network and the metabolic state of PF and to evaluate the drug efficacy of Sch A and its related mechanisms.Graphical Abstract: Keywords: schisandrol A, pulmonary fibrosis, mechanism of action, network analysis, metabonomics

Jingjing Liu,1– 3 Guoqing Fan,1– 3 Ningning Tao,4 Feifei Feng,5 Chao Meng,1– 3 Tieying Sun1,2 1Department of Respiratory Medicine and Critical Care, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Beijing, People’s Republic of China; 3The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 4Department of Respiratory & Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 5Department of Respiratory & Critical Care Medicine, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Tieying Sun, Department of Respiratory Medicine and Critical Care, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China, Tel +15153169108, Email suntieying@126.comPurpose: Idiopathic pulmonary fibrosis is a chronic and irreversible fibrotic interstitial pneumonia of unknown etiology and therapeutic strategies are limited. Emerging evidence suggests that the continuous activation of the central nucleotide-binding oligomerization-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in the pathogenesis of pulmonary fibrosis. Ginsenoside Rb1 (G-Rb1) is the most abundant component in the traditional Chinese herb ginseng and has anti-inflammatory and anti-fibrotic activities. The purpose of this study was to explore whether G-Rb1 exerts anti-inflammatory and anti-fibrotic activities in vivo and in vitro by suppressing the activation of the NLRP3 inflammasome and NF-κB pathway.Methods: Forty-eight male C57BL/6 mice were randomly divided into four groups (n=12/group) as follows: control, bleomycin (BLM), BLM/G-Rb1, and G-Rb1. A pulmonary fibrosis model was developed via an intratracheal injection of BLM. Six mice from each group were euthanized on days 3 and 21. The degree of pulmonary fibrosis was examined by histological evaluation and assessing α-smooth muscle actin levels. THP-1 cells were differentiated into macrophages, and stimulated by lipopolysaccharide and adenosine triphosphate. Activation of the NLRP3 inflammasome and NF-κB pathway was determined by Western blotting. Interleukin-1 beta and interleukin-18 levels were measured by ELISA. MRC-5 cells were cultured in the conditioned medium of the treated macrophages, after which markers of myofibroblasts were determined by Western blotting.Results: G-Rb1 ameliorated BLM-induced pulmonary inflammation and fibrosis in mice, and suppressed NLRP3 inflammasome activation and the NF-κB pathway in lung tissues. Moreover, interleukin-1 beta secreted after NLRP3 inflammasome activation in macrophages promoted fibroblast differentiation. G-Rb1 inhibited lipopolysaccharide- and adenosine triphosphate-induced NLRP3 inflammasome activation in macrophages and disturbed the crosstalk between macrophages and fibroblasts.Conclusion: G-Rb1 ameliorates BLM-induced pulmonary inflammation and fibrosis by suppressing NLRP3 inflammasome activation and the NF-κB pathway. Hence, G-Rb1 is a potential novel therapeutic drug for idiopathic pulmonary fibrosis.Keywords: G-Rb1, pulmonary fibrosis, NLRP3 inflammasome, macrophages

Jingjing Liu,1– 3 Guoqing Fan,1– 3 Ningning Tao,4 Tieying Sun1,2 1Department of Respiratory Medicine and Critical Care, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Graduate School of Peking Union Medical College, Beijing, People’s Republic of China; 3The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, People’s Republic of China; 4Department of Respiratory Medicine and Critical Care, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Tieying Sun, Department of Respiratory Medicine and Critical Care, Beijing Hospital, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86 15153169108, Email suntieying@126.comAbstract: Pyroptosis is an inflammatory type of regulated cell death that is dependent on inflammasome activation and downstream proteases such as caspase-1 or caspase 4/5/11. The main executors are gasdermins, which have an inherent pore-forming function on the membrane and release inflammatory cytokines, such as interleukin (IL)-1β, IL-18 and high mobility group box 1. Emerging evidence demonstrates that pyroptosis is involved in the pathogenesis of various pulmonary diseases. In this review, we mainly discuss the biological mechanisms of pyroptosis, explore the relationship between pyroptosis and respiratory diseases, and discuss emerging therapeutic strategies for respiratory diseases.Keywords: pyroptosis, pulmonary disease, caspase-1, caspase-4/5/11, gasdermins

Xiaofeng Fu,1 Luwei Hong,2 Haiying Gong,3 Guangjuan Kan,4 Pengfei Zhang,1 Ting-Ting Cui,5 Gonglin Fan,6 Xing Si,7 Jiang Zhu1 1Department of Ultrasound, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 3Department of Ultrasound, Yiwu Traditional Chinese Medicine Hospital, Jinhua, Zhejiang, 321000, People’s Republic of China; 4Department of Ultrasound, The Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 5Department of Ultrasound, Taizhou Traditional Chinese Medicine Hospital, Taizhou, Zhejiang, 318000, People’s Republic of China; 6Department of Ultrasound, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China; 7Hangzhou Normal University, Hangzhou, Zhejiang, 310000, People’s Republic of ChinaCorrespondence: Jiang Zhu, Department of Ultrasound, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 31000, People’s Republic of China, Tel +86 13757122629, Email zhujiang1046@zju.edu.cnBackground: Glioma is a common type of tumor in the central nervous system characterized by high morbidity and mortality. Autophagy plays vital roles in the development and progression of glioma, and is involved in both normal physiological and various pathophysiological progresses.Patients and Methods: A total of 531 autophagy-related genes (ARGs) were obtained and 1738 glioma patients were collected from three public databases. We performed least absolute shrinkage and selection operator regression to identify the optimal prognosis-related genes and constructed an autophagy-related risk signature. The performance of the signature was validated by receiver operating characteristic analysis, survival analysis, clinic correlation analysis, and Cox regression. A nomogram model was established by using multivariate Cox regression analysis. Schoenfeld’s global and individual test were used to estimate time-varying covariance for the assumption of the Cox proportional hazard regression analysis. The R programming language was used as the main data analysis and visualizing tool.Results: An overall survival-related risk signature consisting of 15 ARGs was constructed and significantly stratified glioma patients into high- and low-risk groups (P < 0.0001). The area under the ROC curve of 1-, 3-, 5-year survival was 0.890, 0.923, and 0.889, respectively. Univariate and multivariate Cox analyses indicated that the risk signature was a satisfactory independent prognostic factor. Moreover, a nomogram model integrating risk signature with clinical information for predicting survival rates of patients with glioma was constructed (C-index=0.861± 0.024).Conclusion: This study constructed a novel and reliable ARG-related risk signature, which was verified as a satisfactory prognostic marker. The nomogram model could provide a reference for individually predicting the prognosis for each patient with glioma and promoting the selection of optimal treatment.Keywords: glioma, autophagy, risk signature, prognosis, nomogram

A carbothermal reduction process simulating EAF process is used to handle the zinc oxide dust, and the zinc in the dust can be extracted and recovered efficiently. The crude zinc and lead-tin alloy were obtained finally. The effects of temperature, holding time, and reductant dosage on zinc volatilization rate were investigated, and the “Pelletizing - Calcination- Carbothermic reduction” experiment was conducted. The results found the optimal reduction condition was as follows: the temperature of 1300℃, reductant dosage of 14.04%, and holding time of 120 min. After the calcination at 900℃ for 120 min, the removal rates of fluorine, chlorine, and sulfur in the dust were 98.18%, 96.38% and 28.58% respectively, and the volatilization rate of zinc was 99.83% in the reduction process. The zinc content of the crude zinc was 68.48%.

Rui Guo,1,2 Lan Li,1,2 Jing Su,1 Sheng Li,1 Sophia Esi Duncan,1 Zhihao Liu,1,2 Guanwei Fan1,2 1Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 2School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of ChinaCorrespondence: Guanwei FanFirst Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 88, Changling Road, Liqizhuang Street, Xiqing District, Tianjin, People’s Republic of ChinaTel +8613752503396Email fgw1005@163.comAbstract: Salvia miltiorrhiza: (Danshen) is a significant (traditional Chinese medication) natural remedy, enhancing blood circulation and clear blood stasis. In this view, it is widely used against several heart diseases, eg, cardiomyopathy, arrhythmia, and congenital heart defects. Tanshinone IIA (tan-IIA) is the main fat-soluble component of Salvia miltiorrhiza. Modern pharmacological study shows that tan-IIA has anti-inflammatory and anti-oxidant activities. Tan-IIA induces remarkable cardioprotective effects via enhancing angiogenesis which may serve as an effective treatment against cardiovascular diseases (CVD). There is also evidence that tan-IIA has extensive immunomodulatory effects and plays a significant role in the development and function of immune cells. Tan-IIA reduces the production of inflammatory mediators and restores abnormal signaling pathways via regulating the function and activation of immune cells. It can also regulate signal transduction pathways, ie, TLR/NF-κB pathway and MAPKs/NF-κB pathway, thereby tan-IIA has an anti-inflammatory, anticoagulant, antithrombotic and neuroprotective role. It plays a protective role in the pathogenesis of cardiovascular disorders (ie, atherosclerosis, hypertension) and Alzheimer’s disease. It has also been revealed that tan-IIA has an anti-tumor role by killing various tumor cells, inducing differentiation and apoptosis, and has potential activity against carcinoma progression. In the review of this fact, the tan-IIA role in different diseases and its mechanism have been summarized while its clinical applications are also explored to provide a new perspective of Salvia miltiorrhiza. An extensive study on the mechanism of action of tan-IIA is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.Keywords: tanshinone-IIA, atherosclerosis, Alzheimer’ disease, cancer, anti-inflammation, anti-oxidative

Xi Fan,1,2,* Zeting Yuan,1,* Chenting Shou,3,* Guohua Fan,1 Hong Wang,2 Feng Gao,3 Yuanpeng Rui,4 Ke Xu,1 Peihao Yin1,2,5,6 1Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2School of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China; 3Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 4Department of Image, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 5Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 6Shanghai Putuo Central School of Clinical Medicine, Anhui Medical University, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peihao YinDepartment of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaTel +86-21-2223 3836Fax +86-21-5266 5957Email yinpeihao@shutcm.edu.cn Ke XuInterventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaTel +86-21-2223 3222Email kexu2577@shutcm.edu.cnBackground: Photothermal therapy (PTT) has great potential in the clinical treatment of tumors. However, most photothermal materials are difficult to apply due to their insufficient photothermal conversion efficiencies (PCEs), poor photostabilities and short circulation times. Furthermore, tumor recurrence is likely to occur using PTT only. In the present study, we prepared cyclo (Arg-Gly-Asp-d-Phe-Cys) [c(RGD)] conjugated doxorubicin (DOX)-loaded Fe3O4@polydopamine (PDA) nanoparticles to develop a multifunctional-targeted nanocomplex for integrated tumor diagnosis and treatment.Materials and methods: Cytotoxicity of Fe3O4@PDA-PEG-cRGD-DOX against HCT-116 cells was determined by cck-8 assay. Cellular uptake was measured by confocal laser scanning microscope (CLSM). Pharmacokinetic performance of DOX was evaluated to compare the differences between free DOX and DOX in nanocarrier. Performance in magnetic resonance imaging (MRI) and antitumor activity of complex nanoparticles were evaluated in tumor-bearing nude mice.Results: Fe3O4@PDA-PEG-cRGD-DOX has a particle size of 200–300 nm and a zeta potential of 22.7 mV. Further studies in vitro and in vivo demonstrated their excellent capacity to target tumor cells and promote drug internalization, and significantly higher cytotoxicity with respect to that seen in a control group was shown for the nanoparticles. In addition, they have good thermal stability, photothermal conversion efficiencies (PCEs) and pH responsiveness, releasing more DOX in a mildly acidic environment, which is very conducive to their chemotherapeutic effectiveness in the tumor microenvironment. Fe3O4@PDA-PEG-cRGD-DOX NPs were used in a subcutaneous xenograft tumor model of nude mouse HCT-116 cells showed clear signal contrast in T2-weighted images and effective anti-tumor chemo-photothermal therapy under NIR irradiation.Conclusion: According to our results, Fe3O4@PDA-PEG-cRGD-DOX had a satisfactory antitumor effect on colon cancer in nude mice and could be further developed as a potential integrated platform for the diagnosis and treatment of cancer to improve its antitumor activity against colon cancer.Keywords: Fe3O4 nanoparticles, polydopamine, cRGD, magnetic resonance imaging, MRI, chemo-photothermal therapy, tumor target

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

Tight-binding approaches, especially the Density Functional Tight-Binding (DFTB) and the extended tight-binding schemes, allow for efficient quantum mechanical simulations of large systems and long-time scales. They are derived from ab initio density functional theory using pragmatic approximations and some empirical terms, ensuring a fine balance between speed and accuracy. Their accuracy can be improved by tuning the empirical parameters using machine learning techniques, especially when information about the local environment of the atoms is incorporated. As the significant quantum mechanical contributions are still provided by the tight-binding models, and only short-ranged corrections are fitted, the learning procedure is typically shorter and more transferable as it were with predicting the quantum mechanical properties directly with machine learning without an underlying physically motivated model. As a further advantage, derived quantum mechanical quantities can be calculated based on the tight-binding model without the need for additional learning. We have developed the open-source framework—Tight-Binding Machine Learning Toolkit—which allows the easy implementation of such combined approaches. The toolkit currently contains layers for the DFTB method and an interface to the GFN1-xTB Hamiltonian, but due to its modular structure and its well-defined interfaces, additional atom-based schemes can be implemented easily. We are discussing the general structure of the framework, some essential implementation details, and several proof-of-concept applications demonstrating the perspectives of the combined methods and the functionality of the toolkit. [ABSTRACT FROM AUTHOR]

BACKGROUND: Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. PATIENTS AND METHODS: Chemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. RESULTS: Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). CONCLUSIONS: While elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Supramolecular nanosubstrate-mediated delivery (SNSMD) leverages the power of molecular self-assembly and a nanostructured substrate platform for the low toxicity, highly efficient co-delivery of biological factors encapsulated in a nanovector. Human fibroblasts are successfully reprogrammed into induced pluripotent stems and transdifferentiated into induced neuronal-like cells.