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Ruixue Zhang,1 Hui Xu,1 Xiaoxue Zhang,1 Hui Xiong,2 Fei Tang,3 Liping Lv,3 Xiangdong Mu,4 Wei Tian,5 Yueguang Cheng,6 JianRong Lu,6 Xiuhong Nie,7 Yang Guo,8 Yingying Liu,9 Zhi Zhang,10 Lianjun Lin1 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Emergency, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Interventional Pulmonology, Anhui Province Chest Hospital, Hefei, People’s Republic of China; 4Department of Respiratory, Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 5Department of Geriatrics, Jishuitan Hospital, Beijing, People’s Republic of China; 6Department of Emergency, Jingmei Group General Hospital, Beijing, People’s Republic of China; 7Department of Respiratory, Xuanwu Hospital, Beijing, People’s Republic of China; 8Department of Endoscopic Diagnosis &treatment, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 9CapitalBio Technology Co., Ltd, Beijing, People’s Republic of China; 10Bio Biological Group Co., Ltd, Beijing, People’s Republic of ChinaCorrespondence: Lianjun Lin, Department of Geriatrics, Peking University First Hospital, No. 8 Xishiku Avenue, Beijing, 100034, People’s Republic of China, Email 06474@pkufh.comPurpose: The detection of pathogenic microorganisms plays a significant role in the diagnosis and management of pneumonia that are responsible for a substantial number of deaths worldwide. However, conventional microbiological tests (CMT) have low accuracy and are time-consuming. In this study, we aim to evaluate the clinical value of Chips for Complicated Infection Detection (CCID) in detecting pneumonia pathogens.Patients and Methods: This study was conducted at nine hospitals in China from January 2021 to September 2022. Respiratory samples from adult pneumonia patients were collected from each patient. CMT and CCID were performed in parallel to identify the pathogens.Results: A total of 245 patients were included, with 73% being elderly. CCID identified pathogenic microbes in 78.0% of patients and conventional microbiological tests (CMT) in 57.1% of the patients (p< 0.001). The overall positive and negative percent agreements between CCID and CMT for pathogen detection were 90.07% and 38.46%, respectively. 38.8% of patients were diagnosed with mixed infections with at least two pathogens by CCID. Bacterial infections identified by CCID accounted for 60.0% of 245 patients, with the top 3 being Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecium, respectively. K. pneumoniae was the most common pathogen in elderly patients, with a significantly higher prevalence compared to non-elderly patients (p = 0.0011). Among the 197 patients who had used antibiotics before sample collection, the positive rate of CCID was significantly higher than that of CMT (p < 0.001).Conclusion: This study indicates that compared to CMT, this novel chip has significant advantages in detecting pathogens in pneumonia patients, especially in the elderly.Keywords: pneumonia, elderly, pathogens, chip, LAMP

Changzhen Li,1,&ast; Xiaomei Wang,1,&ast; Jingjing Rao,1,&ast; Ye Zeng,1 Jianjun Liu,2 Feng Tang1 1Department of Laboratory Medicine, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430015, People’s Republic of China; 2Office of the Dean, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Tang; Jianjun Liu, Email tang33feng66@163.com; liujianjun5221@163.comObjective: To analyze bacterial distribution and antibiotic resistance in clinical specimens from a Chinese hospital for evaluating environmental factors’ impact on pathogen prevalence.Methods: From January 2017 to December 2021, we collected 42,854 clinical specimens from hospitalized children and women. The specimens were cultured on various agar plates and incubated at 35°C for 18– 48 h. Their identification was performed using standard biochemical methods and Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF), whereas antibiotic susceptibilities were determined using the VITEK 2 system. Concurrent environmental data from Wuhan were analyzed for correlations with pathogen prevalence using multiple linear stepwise regression.Results: Of the 24,555 bacterial strains isolated, the majority were gram-positive, and sputum was the most common specimen type. Haemophilus influenzae and Escherichia coli were the most prevalent pathogens in sputum and urine samples, respectively. Notably, H. influenzae and Streptococcus pneumoniae affected children under 6 years of age the most. Furthermore, H. influenzae showed high ampicillin resistance but low cefotaxime resistance; S. pneumoniae was sensitive to penicillin G, and E. coli was resistant to ampicillin but sensitive to cefotetan. The prevalence of multidrug-resistant organisms was below national averages. In terms of seasonality, H. influenzae peaked during late winter and early spring, and environmental analysis indicated positive correlations between PM2.5 and PM10, and H. influenzae and S. pneumoniae prevalence. In addition, NO2 levels were positively correlated with increased S. aureus and M. catarrhalis prevalence; E coli prevalence was negatively correlated with ozone levels.Conclusion: This study provides valuable insights into the distribution and antibiotic resistance patterns of bacterial pathogens in maternal and child healthcare facilities in Wuhan, China. Environmental factors significantly influence the epidemiology of certain bacterial pathogens. Implementing integrated health strategies that combine microbial surveillance with environmental monitoring is needed to effectively manage and prevent bacterial infections.Keywords: epidemiology, multidrug-resistant pathogens, seasonality, particulate matter

Shipeng Chen,1– 3 Mengna Li,1– 3 Changning Xue,1– 3 Xiangting Zhou,1– 3 Jianxia Wei,1– 3 Lemei Zheng,1– 3 Yumei Duan,1– 3 Hongyu Deng,1 Faqing Tang,1 Wei Xiong,1– 3 Bo Xiang,1– 3 Ming Zhou1– 3 1NHC Key Laboratory of Carcinogenesis, Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, People’s Republic of China; 2Cancer Research Institute, Central South University, Changsha, 410078, People’s Republic of China; 3The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Central South University, Changsha, 410078, People’s Republic of ChinaCorrespondence: Ming Zhou; Bo Xiang, Email zhouming2001@163.com; xiangbolin@csu.edu.cnPurpose: Cinobufotalin injection has obvious curative effects on liver cancer patients with less toxicity and fewer side effects than other therapeutic approaches. However, the core ingredients and mechanism underlying these anti-liver cancer effects have not been fully clarified due to its complex composition.Methods: Multidimensional network analysis was used to screen the core ingredients, key targets and pathways underlying the therapeutic effects of cinobufotalin injection on liver cancer, and in vitro and in vivo experiments were performed to confirm the findings.Results: By construction of ingredient networks and integrated analysis, eight core ingredients and ten key targets were finally identified in cinobufotalin injection, and all of the core ingredients are tightly linked with the key targets, and these key targets are highly associated with the cell cycle-related pathways, supporting that both cinobufotalin injection and its core ingredients exert anti-liver cancer roles by blocking cell cycle-related pathways. Moreover, in vitro and in vivo experiments confirmed that either cinobufotalin injection or one of its core ingredients, cinobufagin, significantly inhibited cell proliferation, colony formation, cell cycle progression and xenograft tumor growth, and the key target molecules involved in the cell cycle pathway such as CDK1, CDK4, CCNB1, CHEK1 and CCNE1, exhibit consistent changes in expression after treatment with cinobufotalin injection or cinobufagin. Interestingly, some key targets CDK1, CDK4, PLK1, CHEK1, TTK were predicted to bind with multiple of core ingredients of cinobufotalin injection, and the affinity between one of the critical ingredients cinobufagin and key target CDK1 was further confirmed by SPR assay.Conclusion: Cinobufotalin injection was confirmed to includes eight core ingredients, and they play therapeutic effects in liver cancer by blocking cell cycle-related pathways, which provides important insights for the mechanism of cinobufotalin injection antagonizing liver cancer and the development of novel small molecule anti-cancer drugs. Keywords: cinobufotalin injection, liver cancer, cinobufagin, network pharmacology, cell cycle, core ingredients

Xiaochun Zhou,1– 3,&ast; Kaiying He,1,3,&ast; Jing Zhao,1,3 Guohua Wei,3 Qicai You,1,3 Hongxuan Du,1,3 Wenjiao Gu,1,2 Haiyu Niu,1,4 Qiaoying Jin,1,5 Jianqin Wang,3 Futian Tang1,2 1The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 3Department of Nephrology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 4Department of Tumor, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 5Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Futian Tang, Department of Cardiovascular Disease, The Second Hospital & Clinical Medical School, Lanzhou University, No. 82, Cuiyingmen, Lanzhou, Gansu, People’s Republic of China, Tel +8613321330515, Email Tangfutian2023@126.comPurpose: To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD).Methods: Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis.Results: Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p< 0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes.Conclusion: A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.Keywords: diabetic kidney disease (DKD), mixture of astragalus, rhubarb, saffron, transcriptome sequencing, db/db mice

Yang Gu,1– 4,&ast; Xingrui Mu,1,3,4,&ast; Yan Zhang,1,3,4 Yunyan Tang,4,5 Ting Zhang,4,6 Fushan Tang1,3,4 1Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, 563006, People’s Republic of China; 2Department of Pharmacy, People’s Hospital in Hezhang County, Bijie, 553200, People’s Republic of China; 3Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563006, People’s Republic of China; 4The Key Laboratory of Clinical Pharmacy of Zunyi City, Zunyi Medical University, Zunyi, 563006, People’s Republic of China; 5Department of Pharmacy, Affiliated Meitan People’s Hospital of Zunyi Medical University, Zunyi, 564100, People’s Republic of China; 6Department of Pharmacy, Guiyang Hospital of Stomatology, Guiyang, 550002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fushan Tang, Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China, Tel +86851 28642337, Fax +86851 28642334, Email fstang@zmu.edu.cn; fstang@vip.163.comObjective: To investigate the effect of psychological contract of outpatients with hospital pharmacists on medication adherence, providing reference for improving the management of patients’ medication adherence from the perspective of pharmacist-patient relationship and psychological contract.Methods: The 8 patients who received medication dispensing service at the outpatient pharmacies at the First Affiliated Hospital of Zunyi Medical University and the Second Affiliated Hospital of Zunyi Medical University were selected for face-to-face in-depth interviews through a purposive sampling method. In order to get more potential information and adjust flexibly according to the actual situation of the interview, the interviews were set as semi-structured, and the interview content was analyzed by using Colaizzi’s seven-step method of phenomenological analysis and NVivo11.0 software.Results: The following four themes about effects of patients’ psychological contract with hospital pharmacists on medication adherence were extracted: from the perspective of patients, the relationship between pharmacists and patients is generally harmonious; pharmacists can basically fulfil their responsibilities; patients’ medication adherence needs to be improved; the status of patients’ psychological contract with hospital pharmacists may affect medication adherence.Conclusion: The psychological contract of outpatients with hospital pharmacists has a positive effect on their medication adherence. Effective management on medication adherence should involve the management on patients’ psychological contract with hospital pharmacists.Keywords: psychological contract, medication adherence, pharmaceutical care, qualitative study

Stuti Dang,1– 3 Marianne Desir,1– 3 Shiv Lamba,4 Kiranmayee Muralidhar,1 Fei Tang,2 Willy Marcos Valencia5 1Miller School of Medicine, University of Miami, Miami, FL, USA; 2Geriatric Research, Education and Clinical Center, Miami Veterans Affairs Healthcare System, Miami, FL, USA; 3Department of Veterans Affairs Elizabeth Dole Center of Excellence in Veteran and Caregiver Research, Miami, FL, USA; 4Washington University, St. Louis, MO, USA; 5Division of Endocrinology, Diabetes and Metabolic Diseases, Medical University of South Carolina, Charleston, SC, USACorrespondence: Stuti Dang, Email sdang@med.miami.eduIntroduction: Understanding the needs of higher-risk older adult patients can support the delivery of high quality and patient-centered healthcare. We sought to characterize the physical, functional, social and psychological needs of High-Need High-Risk (HNHR) Veterans. We hypothesized that the concept of frailty could be useful in identifying the highest-risk HNHR patients and characterizing their needs.Methods: We conducted a cross-sectional study of Veterans in the Miami Veterans Affairs Healthcare System who were identified as High-Need High-Risk by the Department of Veterans Affairs (VA) using data analytic techniques. We analyzed data of 634 Veterans who completed questionnaires by mail, telephone or in person. We assessed the Veterans’ frailty status and needs in the physical, functional, psychological and social domains. Beyond descriptive statistics, we used Chi-square (χ2) test, one-way ANOVA and Kruskal–Wallis to analyze whether there were differences in Veterans’ needs in relation to frailty status.Results: The HNHR Veterans who participated in the questionnaire had complex needs that spanned the physical, functional, psychological, and social domains. We observed a potential mismatch between functional needs and social support; over two-thirds of respondents endorsed having dependence in at least one ADL but only about a third of respondents reported having a caregiver. Patients with frailty had higher levels of functional dependence and were more likely than the other HNHR respondents to report recent falls, recent hospitalizations, depression, and transportation issues.Conclusion: High-Need High-Risk Veterans have complex needs related to the physical, functional, psychological and social domains. Within the HNHR population, HNHR Veterans with frailty appear to have particularly high levels of risk and multidomain needs. Increased attention to identifying members of these groups and aligning them with biopsychosocial interventions that are targeted to their specific needs may support development of appropriate strategies and care-models to support HNHR Veterans.Keywords: needs assessment, older adults, high need, frailty, biopsychosocial

Hong-Miao Li,1 Fei Tang,2 Qian Huang,3 Hai-Feng Pan,1 Tian-Ping Zhang4 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Interventional Pulmonology and Endoscopic Diagnosis and Treatment Center, Anhui Chest Hospital, Hefei, People’s Republic of China; 3Department of Public Health, Medical Department, Qinghai University, Xining, People’s Republic of China; 4The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of ChinaCorrespondence: Tian-Ping Zhang, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China, Email zhangtianping@ustc.edu.cn Hai-Feng Pan, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China, Email panhaifeng1982@sina.comObjective: Our study aimed to explore the association of IL-13, IL-13RA1, and IL-13RA2 genes polymorphisms with PTB susceptibility and its clinical features.Methods: Nine SNPs were genotyped by improved multiple ligase detection reaction (iMLDR) in 476 PTB patients and 473 controls. The association between these SNPs and PTB risk was analyzed using SPSS software and haplotype analysis was assessed using SHEsis software.Results: The IL-13RA1 rs2495636 GA genotype frequency in PTB patients was significantly decreased, and IL-13RA2 rs5946039 A allele was related to the lower risk of PTB. In IL-13 gene, rs20541 variant was found to be associated with PTB risk under recessive mode. Moreover, IL-13RA1 rs141573089 C allele was significantly lower in PTB presenting with fever, drug resistance, and CC genotype was decreased in PTB presenting with leukopenia. IL-13RA1 rs2495636 polymorphism was associated with drug resistance, pulmonary infection, and IL-13RA2 rs3795175, rs638376 polymorphisms were related to drug resistance in PTB patients.Conclusion: IL-13 rs20541, IL-13RA1 rs2495636, IL-13RA2 rs5946039 polymorphisms might be contributed to the genetic background of PTB in Chinese population.Keywords: pulmonary tuberculosis, Mycobacterium tuberculosis, interleukin-13, single nucleotide polymorphisms

Zejun Wang,1,&ast; Shichao Zhang,2,&ast; Chaochao Zheng,3 Kaide Xia,4 Liangquan Sun,4 Xuejie Tang,4 Fulin Zhou,4 Yan Ouyang,2 Fuzhou Tang3 1Department of Gastrointestinal Surgery, The Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, People’s Republic of China; 2Key Laboratory of Infectious Immune and Antibody Engineering in Guizhou Province/School of Biology and Engineering, Guizhou Medical University, Guiyang, People’s Republic of China; 3Immune Cells and Antibody Engineering Research Center of Guizhou province/School of Biology and Engineering, Guizhou Medical University, Guiyang, People’s Republic of China; 4Guiyang Maternal and Child Health Care Hospital, Guiyang Children’s Hospital, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fuzhou Tang, Immune Cells and Antibody Engineering Research Center of Guizhou province/School of Biology and Engineering, Guizhou Medical University, Guiyang, People’s Republic of China, Tel +86 085188174043, Email tangfuzhou@163.com Yan Ouyang, Key Laboratory of Infectious Immune and Antibody Engineering in Guizhou province/School of Biology and Engineering, Guizhou Medical University, Guiyang, People’s Republic of China, Email ouyangyan@gmc.edu.cnBackground: Tumor immune cell infiltration is closely associated with the occurrence and development of tumors. Collagen triple helix repeats containing 1 (CTHRC1), a regulator of collagen expression and cell migration, is involved in the metastasis and invasion of tumors. However, the role of CTHRC1 in breast cancer remains unclear. This study aimed to investigate the prognostic value of CTHRC1, and further explore its association with immune infiltration in breast cancer.Methods: CTHRC1 expression pattern and prognostic value were analyzed using ONCOMINE, PrognoScan, GEPIA, and Kaplan–Meier Plotter databases. We then detected CTHRC1 mRNA levels in breast cancer tissues and paired normal breast tissues by Q-PCR. Subsequently, the University of California Santa Cruz (UCSC) database was used to determine the methylation status of CTHRC1. Furthermore, CTHRC1 mutations were investigated using the Catalogue of Somatic mutations in Cancer (COSMIC) and cBioPortal databases. We also assessed the correlation between CTHRC1 expression and immune cell infiltration using TIMER. In addition, The relationship of CTHRC1 expression with the immune marker sets of various immune cells was evaluated using GEPIA and TIMER.Results: CTHRC1 was highly expressed in a variety of tumors, including breast cancer. Elevated CTHRC1 expression was related to a poor prognosis. Notably, CTHRC1 expression was significantly associated with macrophage infiltration, especially the immune infiltration gene marker set of M2. Copy number variations, DNA mutations and methylation states might be potential mechanisms for regulating CTHRC1 expression. Protein digestion and absorption, human papillomavirus infection, ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways were identified as the potential CTHRC1-driven signaling pathways.Conclusion: These findings suggest that CTHRC1 could be a promising immune-related biomarker for the treatment of breast cancer patients.Keywords: CTHRC1, breast cancer, prognostic, macrophage, biomarker

Hong-Miao Li,1,2,&ast; Li-Jun Wang,2,&ast; Fei Tang,3 Hai-Feng Pan,1 Tian-Ping Zhang4 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 3Anhui Chest Hospital (Anhui Provincial TB Institute), Hefei, Anhui, People’s Republic of China; 4The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tian-Ping Zhang, The First Affiliated Hospital of USTC, 17 Lujiang Road, Hefei, Anhui, 230001, People’s Republic of China, Email zhangtianping@ustc.edu.cn Hai-Feng Pan, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China, Email panhaifeng@ahmu.edu.cnBackground: Recent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) of NEAT1 gene and susceptibility to PTB.Methods: Four SNPs (rs2239895, rs3741384, rs3825071, rs512715) in NEAT1 gene were genotyped in 479 patients with PTB and 476 controls by improved multiple ligase detection reaction (iMLDR) in a Chinese population.Results: We found no significant differences in allele and genotype frequencies of NEAT1 gene rs2239895, rs3741384, rs3825071, rs512715 between PTB patients and controls (all P > 0.05). There was no statistically significant association between genotype frequency distribution of dominant model, as well as recessive model, and genetic susceptibility to PTB patients (all P > 0.05). The TT genotype, T allele frequencies of rs3825071 were significantly increased in sputum smear-positive PTB patients when compared to sputum smear-negative PTB patients (P = 0.010, P = 0.003, respectively). Haplotype analysis shown that NEAT1 haplotype frequency was not associated with PTB susceptibility.Conclusion: NEAT1 gene polymorphisms were not associated with the risk of PTB in Chinese population, and rs3825071 polymorphism might be related to sputum smear-positive in PTB patients.Keywords: long non-coding RNA, NEAT1, pulmonary tuberculosis, single nucleotide polymorphisms

Qiuning Wang,1,&ast; Weiying Chen,2,&ast; Xuefeng Yang,3 Ying Song,4 Xiaowei Sun,5 Guizhou Tao,6 Hong Wang,7 Nan Zhao,7 Yue Huang,1 Erqing Chai,8 Futian Tang9 1Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 2Department of Drug Quality Analysis, Jiuquan Drug Inspection and Testing Center, Jiuquan, Gansu Province, People’s Republic of China; 3Department of Physiology, Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 4Cardiovascular Laboratory, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 5Department of Neurosurgery, China Resources Liaojian Group, General Hospital of Fuxin Mining Group (10th Clinical College of China Medical University), Fuxin, Liaoning Province, People’s Republic of China; 6Internal Medicine-Cardiovascular Department, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 7Allergy and Clinical Immunology Center, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, People’s Republic of China; 8Neurointerventional Department, Emergency General Hospital, Beijing, People’s Republic of China; 9Department of Cardiovascular Disease and Key Laboratory of Digestive System Tumor of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Futian Tang, Department of Cardiovascular Disease and Key Laboratory of Digestive System Tumor of Gansu Province, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People’s Republic of China, Email tangft@163.com Erqing Chai, Neurointerventional Department, Emergency General Hospital, Beijing, People’s Republic of China, Email happybirds998@126.comIntroduction: Astragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, Astragalus membranaceus. The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS).Methods: Animal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels.Results: LPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS.Conclusion: These results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.Keywords: lipopolysaccharides, astragaloside IV, cardiac dysfunction, inflammation, autophagy, miRNA-1

Hui Gao,1,2 Jin Xu,2 Qiang Ma,2 Feng Tang,1 Qin Ga,1 Yuhong Li,3 Wei Guan,3 Ri-Li Ge,1 Ying-Zhong Yang1,2 1Research Center for High Altitude Medical Sciences, School of Medicine, Qinghai University, Qinghai, People’s Republic of China; 2Basic Medical Sciences, School of Medicine, Qinghai University, Qinghai, People’s Republic of China; 3Department of Respiration, Affiliated Hospital, Qinghai University, Qinghai, People’s Republic of ChinaCorrespondence: Ying-Zhong Yang Tel/Fax +86 971 6143168Email yingzhong-yang@hotmail.comPurpose: Steroid hormone metabolism plays an essential role in high-altitude pulmonary edema (HAPE) progression. This study aimed to investigate the association between polymorphism in seven steroid hormone metabolism genes (STAR, HSD3B1, HSD3B2, CYP17A1, CYP21A2, CYP11B1, and CYP11B2) and HAPE susceptibility among Han Chinese.Patients and Methods: A total of 41 tagSNPs in the seven genes were genotyped using Sequenom MassARRAY SNP assays from 169 HAPE patients (HAPE-p) and 309 matched Han Chinese individuals resistant to HAPE (HAPE-r). The genotypic and allele frequencies, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated.Results: Four SNPs, including the allele C of rs6203 (p = 0.034, OR [95% CI] = 1.344 [1.022− 1.767]) in HSD3B1, allele G of rs3740397 (p = 0.044, OR [95% CI] = 1.314 [1.007− 1.714]) and allele C of rs10786712 (p = 0.039, OR [95% CI] = 0.751 [0.572− 0.986]) in CYP17A1, and allele T of rs6402 (p = 0.006, OR [95% CI] = 0.504 [0.306− 0.830]) in CYP11B1, were significantly associated with HAPE. The distribution of the genotypes of these SNPs also significantly differed between the HAPE-p and HAPE-r groups. Moreover, six haplotypes (the linkage disequilibrium block including rs10883783, rs4919686, rs3740397, rs3824755, and rs10786712) of CYP17A1 were also significantly associated with HAPE.Conclusion: The four SNPs located in HSD3B1 (rs6203), CYP17A1 (rs3740397 and rs10786712), and CYP11B1 (rs6402) and the six haplotypes of CYP17A1 are likely to have an effect on HAPE.Keywords: steroid hormone metabolism gene, SNP, high-altitude pulmonary edema, susceptibility

Chengchen Yin,1– 3 Xing He,1– 3 Kaili Shen,1– 3 Xingrui Mu,1– 3 Fushan Tang1– 3 1Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, 563006, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563006, People’s Republic of China; 3Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi, 563006, People’s Republic of ChinaCorrespondence: Fushan TangDepartment of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi, 563006, People’s Republic of China, Tel +86 851 2864 2337, Fax +86 851 2864 2334, Email fstang@vip.163.comObjective: To investigate the current status of knowledge and behavior about rational drug use in college students in different colleges and universities in a city in southwest China, providing reference for students’ education of rational drug use in colleges and universities.Methods: A questionnaire survey on knowledge and behavior in rational drug use was carried out on the students recruited by occasional sampling method in 6 colleges and universities in Zunyi, China. Statistical analyses on demographic information and answers to questionnaire questions were carried out with SPSS 18.0.Results: A total of 865 valid questionnaires were recovered from 923 questionnaires sent out. Some knowledge and behaviors of the students on drug use were irrational. There was statistically significant difference in some specific questions of the knowledge in rational drug use between medical and non-medical students (P< 0.05); the average score of rational drug use behavior of medical students was lower than that of non-medical students (P< 0.05); the average score of the rational drug use behavior of female students was lower than that of male (P< 0.05); the students’ major types had significantly different influence on their behavior in rational drug use (P< 0.05). The school-carried pharmacy education can effectively improve students’ rational medication; the majority of college students believed that it is necessary to popularize the knowledge of rational drug use on campus; and students’ favorite way to acquire knowledge about rational drug use was to attend related lectures or elective courses.Conclusion: The knowledge and behavior of rational drug use among college students need to be improved. Professional medical education may exert a positive impact on rational drug use among college students. Thus, it is necessary to popularize the knowledge of rational drug use among college students, especially in non-medical colleges and universities.Keywords: college students, rational drug use, knowledge, behavior, ten mistakes in public medication

Hong-Miao Li,1,2 Qian Huang,1 Fen Tang,2 Tian-Ping Zhang3 1Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, Anhui, People’s Republic of China; 2Anhui Chest Hospital (Anhui Provincial TB Institute), Hefei, 230022, Anhui, People’s Republic of China; 3The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, People’s Republic of ChinaCorrespondence: Tian-Ping ZhangThe First Affiliated Hospital of University of Science and Technology of China, 17 Lujiang Road, Hefei, Anhui, 230001, People’s Republic of ChinaEmail zhangtianping@ustc.edu.cnBackground: Reactive oxygen species (ROS) generated by NADPH oxidase has a pivotal role in the nonspecific innate immune response to invading microorganisms including M. tuberculosis (MTB). NCF2 and NOX2 were considered as important functional subunits of NADPH oxidase complex; hence, this study aimed to evaluate the NCF2, NOX2 mRNA expressions in PBMC of pulmonary tuberculosis (PTB) patients.Methods: A total of 79 PTB patients and 73 controls were included in our study. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to measure the NCF2, NOX2 mRNA levels, and receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic value of NCF2, NOX2 in PTB patients.Results: When compared to controls, the NCF2, NOX2 mRNA levels were significantly increased in PBMC from PTB patients (P < 0.001). However, the NCF2, NOX2 mRNA levels were not associated with major clinical and laboratory data of PTB patients. Area under curve (AUC) of ROC curve analysis for NCF2 and NOX2 were 0.686 (95% CI: 0.601, 0.770) and 0.705 (95% CI: 0.623, 0.787), respectively.Conclusion: Altered NCF2, NOX2 mRNA levels in PTB patients implied that these genes might play roles in PTB, and their expression levels might be potential biomarkers for the diagnosis of PTB.Keywords: pulmonary tuberculosis, NADPH oxidase complex, NCF2, NOX2, peripheral blood mononuclear cells

Hui-Fen Chen,1 Nuo Lei,1 Yan-Min Xu,1 Li Luo,1 Xian-Long Zhang,1 Bei-Ni Lao,1 Fang Tang,2 Li-Zhe Fu,2 Xu-Sheng Liu,3 Yi-Fan Wu3 1The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Chronic Disease Management Outpatient Clinic, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 3Renal Division, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of ChinaCorrespondence: Yi-Fan Wu Email wuyifan007@gzucm.edu.cnBackground: To transfer a paper-version Chinese and Western medication adherence scale for CKD into an electronic scale, and evaluate its validity, internal consistency and clinical implementation, and assess whether the transition is feasible in clinic.Methods: We built an e-version Chinese and Western medication adherence scale based on the Wen-JuanXing platform. CKD subjects’ responses were applied to test the scale’s validity and internal consistency. We retested some of the participants two weeks later randomly. We also tested the clinical application.Results: Of the 434 recruited patients, 228 responded. In exploratory factor analysis (EFA), the Kaiser–Meyer–Olkin (KMO) measure of sampling adequacy = 0.8 and Bartlett’s approx. Chi-Square = 1340.0 (df = 105, p < 0.001). We extracted four common factors which could explain 61.47% of the variance. However, Item 15 “Have you changed a traditional Chinese medicine prescription yourself within the past month?” had factor loading = 0.3 and measure of sampling adequacy (MSA) = 0.5, meaning we could not enter it into the factor analysis. The internal consistency reliability for medication adherence was 0.9, with a Guttman split-half coefficient = 0.5 and a Spearman–Brown coefficient = 0.6. Cronbach’s α was 0.9, 0.4 and 0.5 for the knowledge, belief and behavior domains, respectively. The correlation coefficient r of the test–retest reliability was − 0.8 and was − 0.8, 0.4, − 0.3 in the knowledge, belief and behavior domains, respectively. Patients with comorbidities were more likely to respond. We detected no other significant differences in the clinical profiles between respondents and non-respondents.Conclusion: The e-version Chinese and Western medication adherence scales have undesirable construct validity and internal consistency. Thus, caution is needed in transitioning the paper-version scale into an e-version.Keywords: medication adherence, renal insufficiency, chronic, surveys and questionnaires

Weipeng Wei,1– 3,* Jianhua Tang,4,* Hongfang Li,1– 3 Yongsheng Huang,5 Chengchen Yin,1– 3 Dan Li,6 Fushan Tang1– 3 1Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 3Key Laboratory of Clinical Pharmacy of Zunyi City, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 4Cancer Research UK Manchester Institute, The University of Manchester, Cheshire SK10 4TG, UK; 5Peking Union Medical College, Chinese Academy of Medical Sciences, Institute of Basic Medical Sciences, Beijing 100005, People’s Republic of China; 6State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushan TangDepartment of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Guizhou, People’s Republic of ChinaTel +86851 28642337Fax +86851 28642334Email fstang@vip.163.comDan LiCancer Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaTel +8610 87787107Email eileenld@gmail.comPurpose: To study the in vitro and in vivo antitumor effects of the colloidal suspension-in situ hydrogel of emodin (EM) constructed with the self-assembling peptide RADA16-I and systematically evaluate the feasibility of the delivery system.Methods: The MTT and colony-formation assays were used to determine the viability of normal cells NCTC 1469 and tumor cells Hepa1-6. The uptake of EM in the RADA16-I-EM in situ hydrogel by tumor cells was analyzed by laser confocal microscope and flow cytometry. Flow cytometry was used to detect the cell apoptosis and cell cycle distribution. Transwell assay was used to detect the migration and invasion of tumor cells. The antitumor efficacy of the RADA16-I-EM in situ hydrogel and its toxic effects was further assessed in vivo on Hepa1-6 tumor-bearing C57 mice.Results: The results showed that the RADA16-I-EM in situ hydrogels could obviously reduce the toxicity of EM to normal cells and the survival of tumor cells. The uptake of EM by the cells from the hydrogels was obviously increased and could significantly induce apoptosis and arrest cell cycle in the G2/M phase, and reduce the migration, invasion and clone-formation ability of the cells. The RADA16-I-EM in situ hydrogel could also effectively inhibit the tumor growth and obviously decrease the toxic effects of EM on normal tissues in vivo.Conclusion: Our results demonstrated that RADA16-I has the potential to be a carrier for the hydrophobic drug EM and can effectively improve the delivery of hydrophobic antitumor drugs with enhanced antitumor effects and reduced toxic effects of the drugs on normal cells and tissues.Keywords: self-assembling peptide, emodin, in situ hydrogels, antitumor, drug delivery system

Hongfang Li,1– 3,* Yunyan Tang,1,4,* Yang Wang,1– 3 Weipeng Wei,1– 3 Chengchen Yin,1– 3 Fushang Tang1– 3 1Department of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 3Key Laboratory of Clinical Pharmacy of Zunyi City, Zunyi Medical University, Zunyi 563000, People’s Republic of China; 4Department of Pharmacy, Meitan People’s Hospital, Zunyi 564100, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushang TangDepartment of Clinical Pharmacy, Key Laboratory of Basic Pharmacology of Guizhou Province and School of Pharmacy, Zunyi 563000, People’s Republic of ChinaTel +86 851 2864 2337Fax +86 851 2864 2334Email fstang@vip.163.comBackground: Bupleurum is one of the most important traditional Chinese medicines and an ingredient in many compound preparations. It is widely used together with other drugs in clinical practice, and thus there is great potential for drug–drug interactions. Saikosaponin D (SsD) is a major bioactive triterpenoid saponin extracted from Bupleurum with anti-inflammatory, anticancer, antioxidative, and antihepatic fibrosis effects. Effects of the main components of Bupleurum on cytochromes P450 (CYPs) need to be clarified in the clinical application of combination therapies of formulations containing SsD or Bupleurum.Purpose: This study aimed to investigate the effects of SsD on the CYP1A2 and CYP2D6 mRNAs, protein expression, and relative enzyme activities in HepaRG cells.Methods: HepaRG cells were cultured with SsD at concentrations of 0.5, 1, 5 and 10 μM for 72 hours. mRNA and protein expression of CYP1A2 and CYP2D6 were analyzed with real-time PCR and Western blot analysis. Relative enzyme activities were analyzed with HPLC based on consumption of the specific probe substrate.Results: SsD significantly induced expression of mRNA and increased relative activity of CYP1A2 in HepaRG cells after the cells had been treated with SsD at concentrations of 1, 5 and 10 μM. SsD also induced protein expression of CYP1A2 at concentrations of 5 and 10 μM. SsD exhibited an inductive effect on CYP2D6 mRNA and protein expression, while increasing the relative activity of CYP2D6 at concentrations of 5 and 10 μM.Conclusion: This study is the first to investigate the effect of SsD on CYP1A2 and CYP2D6 in HepaRG cells, and the results may provide some useful information on potential drug–drug interactions related to clinical preparations containing SsD or Bupleurum.Keywords: saikosaponin D, HepaRG cells, drug–drug interactions

Qiong Huang,1,2 Li Luo,1 Bing-qing Xia,1 Ding-Jun Zhang,1 Chen-di Dong,1 Jiao-wang Tan,1,3 Li-zhe Fu,4 Fang Tang,4 Xian-long Zhang,1 Bei-ni Lao,1 Yan-min Xu,1 Hui-fen Chen,1 Xu-sheng Liu,5 Yi-fan Wu5 1The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Blood Purification Center, Heyuan Hospital of Traditional Chinese Medicine, Heyuan, Guangdong, People’s Republic of China; 3Renal Division, Beijing University of Traditional Chinese Medicine Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 4Chronic Disease Management Outpatient Department, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, People’s Republic of China; 5Renal Division, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Yi-fan WuRenal Division, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), No. 111 Dade Road, Yuexiu District, Guangzhou 510120, People’s Republic of ChinaTel/ Fax +86-20-81887233Email wuyifan007@gzucm.edu.cnPurpose: This study aimed to simplify the version-1 Chinese and Western medication adherence scale for patients with chronic kidney disease (CKD) to a version-2 scale using item response theory (IRT) analyses, and to further evaluate the performance of the version-2 scale.Materials and Methods: Firstly, we refined the version-1 scale using IRT analyses to examine the discrimination parameter (a), difficulty parameter (b) and maximum information function peak (Imax). The final scale refinement from version-1 to version-2 scale was also decided upon clinical considerations. Secondly, we analyzed the reliability and validity of version-2 scale using classical test theory (CTT), as well as difficulty, discrimination and Imax of version-1 and version-2 scale using IRT in order to conduct scale evaluation.Results: For scale refinement, the 26-item version-1 scale was reduced to a 15-item version-2 scale after IRT analyses. For scale evaluation using CTT, internal consistency reliability (total Cronbach α = 0.842) and test-rest reliability (r = 0.909) of version-2 scale were desirable. Content validity indicated 3 components of knowledge, belief and behaviors. We found meritorious construct validity with 3 detected components as the same construct of medication knowledge (items 1– 9), medication behavior (items 13– 15), and medication belief (items 10– 12) based upon exploratory factor analysis. The correlation between the version-2 scale and Morisky, Green and Levine scale (MGL scale) was weak (Pearson coefficient = 0.349). For scale evaluation with IRT, the findings showed enhanced discrimination and decreased difficulty of most retained items (items 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15), decreased Imax of items 1, 2, 3, 4, 6, 11, 14, as well as increased Imax of items 5, 7, 8, 9, 10, 12, 13, 14, 15 in the version-2 scale than in the version-1 scale.Conclusion: The original Chinese and Western medication adherence scale was refined to a 15-item version-2 scale after IRT analyses. The scale evaluation using CTT and IRT showed the version-2 scale had the desirable reliability, validity, discrimination, difficulty, and information providedoverall. Therefore, the version-2 scale is clinically feasible to assess the medication adherence of CKD patients.Keywords: chronic kidney disease, traditional Chinese medicine, medication adherence scale, item response theory

Ting Zhang,1– 4,* Chengchen Yin,1– 3,* Yongchen Geng,1– 3 Yan Zhou,1– 3 Shusen Sun,5 Fushan Tang1– 3 1Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 2Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 3The Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 4Department of Pharmacy, Guiyang Hospital of Stomatology, Guiyang 550000, People’s Republic of China; 5College of Pharmacy and Health Sciences, Western New England University, Springfield, MA 01119, USA*These authors contributed equally to this workCorrespondence: Fushan TangDepartment of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaTel/ Fax +86 851 2864 2334Email fstang@vip.163.comObjective: To set up a psychological contract scale for hospital pharmacists to strengthen the management of pharmacists and improve the occupational health of pharmacists.Methods: A psychological contract scale for hospital pharmacists with structured questionnaires was designed according to the professional characteristics of hospital pharmacists and validated through the investigation of pharmacists in 77 public medical institutions in Zunyi, China, which were included through stratified random sampling. Kaiser-Meyer-Olkin (KMO) Measure of Sampling Adequacy and Bartlett’s Test of Sphericity were used to assess the suitability of the sample for factor analysis. Validity of the dimensions was investigated with exploratory factor analysis. The principal component analysis and varimax rotation methods were used to identify the factor structure. The internal consistency was assessed by the Cronbach’s alpha coefficient.Results: The psychological contract scale for hospital pharmacists was composed of pharmacists’ perceptions regarding the hospital, pharmacists themselves, and government/society responsibility. The KMO values of the three perceptions were 0.957, 0.930 and 0.917, respectively, all greater than 0.6. The significance probability of the Bartlett spherical test was 0.000, indicating good structural validity. The Cronbach’s alpha coefficient and half coefficient of the responsibilities in three sub-scales were all greater than 0.6, indicating good internal reliability of the scale. The average scores of the pharmacist responsibility, the hospital responsibility and the government/society responsibility in the pharmacists’ perception were 5.42± 0.637, 4.64± 1.069 and 4.49± 1.134, respectively. In the pharmacists’ perception, their own responsibility has been better fulfilled than those of hospitals and government/society.Conclusion: The psychological contract scale for hospital pharmacists can be a useful tool to evaluate the psychological contract of hospital pharmacists for research and occupational health assessments and management in the area of hospital pharmacy.Keywords: pharmacist, psychological contract, questionnaire

Xingrui Mu,1– 3 Chengchen Yin,1– 3 Xing He,1– 3 Hongfang Li,1– 3 Yuansha Gong,4 Weipeng Wei,1– 3 Yan Zhang,1– 3 Fushan Tang1– 3 1Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 2The Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 3Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 4School of Nursing, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaCorrespondence: Fushan TangSchool of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaTel +86 851 2864 2337Fax +86 851 2864 2334Email fstang@vip.163.comObjective: To investigate the correlation between patients’ medication adherence and their psychological contract with hospital pharmacists under the background of the pharmacist–patient relationship, providing a reference for improving the pharmacist–patient relationship and the patients’ medication adherence based on the patients’ psychological contract with the hospital pharmacists.Materials and Methods: Some of the patients who received medication dispensing service at the outpatient pharmacies at the First Affiliated Hospital of Zunyi Medical University and the Second Affiliated Hospital of Zunyi Medical University were included and investigated as follows: 320 patients were included through the convenient sampling method for psychological contract and medication adherence questionnaire survey with the self-designed scales for patients’ psychological contract with the hospital pharmacists and their medication adherence. SPSS 17.0 was used for reliability and validity testing, correlation analysis, and multiple linear regression analysis.Results: The average score of the psychological contract was 3.80± 0.59. The average score of the patients’ medication adherence was 2.93± 0.70. The patients’ psychological contract with the pharmacists and its dimensions (the responsibility of competence, the responsibility of service, and the responsibility of humanistic care) were positively correlated with medication adherence (P< 0.05). The results of the multiple linear regression analysis showed that the effect of patients’ psychological contract with the pharmacists on medication adherence was statistically significant (P< 0.05).Conclusion: Outpatients’ psychological contract with the pharmacists is positively correlated with their medication adherence. Maintaining the patients’ psychological contract with the pharmacists may be an effective way to improve medication adherence.Keywords: psychological contract, medication adherence, the relationship between pharmacists and patients

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

Jing Zhang,1,2,* Chengchen Yin,1,3,4,* Hongfang Li,1,3,4 Weipeng Wei,1,3,4 Yuansha Gong,5 Fushan Tang1,3,4 1Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 2Department of Respiratory Medicine, Central Hospital in Jinchang City (Worker’s Hospital of Jinchuan Group), Jinchang 737102, People’s Republic of China; 3The Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 4Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 5School of Nursing, Zunyi Medical University, Zunyi 563006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushan TangDepartment of Clinical Pharmacy School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaTel +86 851 2864 2337Fax +86 851 2864 2334Email fushantang@qq.comPurpose: Poor medication adherence can negatively affect health outcomes of patients with asthma from medication and significantly increase the healthcare costs. Management of adherence to inhalers remains a challenging topic in the long-term management of patients with asthma. We aim to evaluate the role of asthma control test (ACT) in the management of adherence to inhalers in outpatients with asthma.Patients and Methods: Six hundred twenty-seven outpatients with asthma admitted to the clinic of respiratory medicine in a tertiary hospital in northwestern China during 2016 to 2019 were randomly divided into observation group (n= 315) and control (n= 312) and received standard inhalant therapy for 6 months and lung function test before and after treatment. The patients in the observation group took ACT questionnaires at the end of each month, while the patients in control only took an ACT at the end of the last month. The ‘Test of Adherence to Inhalers’ (TAI) questionnaire was used to evaluate the patients’ adherence to inhalant therapy.Results: All patients completed the study. The ACT scores in the observation group showed a gradual increase month by month. The TAI results indicated that adherence to inhalers of patients in the observation group was significantly better than that in control and the patients’ non-adherence pattern in the observation group, with significantly lower erratic non-adherence, was also different from that in control. After 6 months of treatment, the lung function indexes and their relative improvement and the ACT scores in the observation group were significantly better or higher than those in control.Conclusion: The once-monthly self-reported ACT can effectively improve the adherence to inhalers of outpatients with asthma mainly by addressing erratic non-adherence and improve the treatment effects, and thus deserves widespread use in the treatment adherence management in patients with asthma.Keywords: asthma control test, ACT, medication adherence, Test of Adherence to Inhalers, TAI, self-management, China

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

Lumbar disc herniation is among the common phenotypes of degenerative lumbar spine diseases, significantly affecting patients' quality of life. The practice pattern is diverse. Choosing conservative measures or surgical treatments is still controversial in some areas. For those who have failed conservative treatment, surgery with or without instrumentation is recommended, causing significant expenditures and frustrating complications, that should not be ignored. In the article, we performed a literature review and summarized the evidence by subheadings to unravel the cons of surgical intervention for lumbar disc herniation. There are tetrad critical issues about surgical treatment of lumbar disc herniation, i.e., favorable natural history, insufficient evidence in a recommendation of fusion surgery for patients, metallosis, and implant removal. Firstly, accumulating evidence reveals immune privilege and auto-immunity hallmarks of human lumbar discs within the closed niche. Progenitor cells within human discs further expand the capacity with the endogenous repair. Clinical watchful follow-up studies with repeated diagnostic imaging reveal spontaneous resolution for lumbar disc herniation, even calcified tissues. Secondly, emerging evidence indicates long-term complications of lumbar fusion, such as adjacent segment disease, pseudarthrosis, implant failure, and sagittal spinal imbalance, which get increasing attention. Thirdly, systemic and local reactions (metallosis) for metal instrumentation have been noted with long-term health concerns and toxicity. Fourthly, the indications and timing for spinal implant removal have not reached a consensus. Other challenging issues include postoperative lumbar stiffness. The review provided evidence from a negative perspective for surgeons and patients who attempt to choose surgical treatment. Collectively, the emerging underlying evidence questions the benefits of traditional surgery for patients with lumbar disc herniation. Therefore, the long-term effects of surgery should be closely observed. Surgical decisions should be made prudently for each patient.

Xiaoshuai Zhang,1 Fang Tang,2 Jiadong Ji,1 Wenting Han,3 Peng Lu3 1School of Statistics, Shandong University of Finance and Economics, Jinan, People’s Republic of China; 2Center for Data Science in Health and Medicine, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Preventive Medicine, School of Public Health and Management, Binzhou Medical University, Yantai, People’s Republic of ChinaCorrespondence: Xiaoshuai ZhangSchool of Statistics, Shandong University of Finance and Economics, Jinan 250014, People’s Republic of ChinaTel +86 13589896463Email zhxiaoshuai@gmail.comObjective: Dyslipidemia has been recognized as a major risk factor of several diseases, and early prevention and management of dyslipidemia is effective in the primary prevention of cardiovascular events. The present study aims to develop risk models for predicting dyslipidemia using Random Survival Forest (RSF), which take the complex relationship between the variables into account.Methods: We used data from 6328 participants aged between 19 and 90 years free of dyslipidemia at baseline with a maximum follow-up of 5 years. RSF was applied to develop gender-specific risk model for predicting dyslipidemia using variables from anthropometric and laboratory test in the cohort. Cox regression was also adopted in comparison with the RSF model, and Harrell’s concordance statistic with 10-fold cross-validation was used to validate the models.Results: The incidence density of dyslipidemia was 101/1000 in total and subgroup incidence densities were 121/1000 for men and 69/1000 for women. Twenty-four predictors were identified in the prediction model of males and 23 in females. The C-statistics of the prediction models for males and females were 0.731 and 0.801, respectively. The RSF model shows better discriminative performance than CPH model (0.719 for males and 0.787 for females). Moreover, some predictors were observed to have a nonlinear effect on dyslipidemia.Conclusion: The RSF model is a promising method in identifying high-risk individuals for the prevention of dyslipidemia and related diseases.Keywords: random survival forest, Cox proportional hazard model, dyslipidemia, risk prediction

Cui Meng,1–3* Weipeng Wei,1,2* Yuhe Wang,1,3 Kunqin Zhang,1,2 Ting Zhang,1,2 Yunyan Tang,1,2 Fushan Tang1,2 1Department of Clinical Pharmacy, School of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of China; 2The Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi 563006, People’s Republic of China; 3Department of Pharmacy, The First Hospital Affiliated to Zunyi Medical University, Zunyi 563003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fushan TangSchool of Pharmacy, Zunyi Medical University, Zunyi 563006, People’s Republic of ChinaTel +8685128642337Email fstang@vip.163.comObjective: This study aimed to investigate the interaction between the ion-complementary self-assembling peptide RADA16-I and the hydrophobic drug mangiferin (MA), and the potential of the self-assembling peptide to be exploited as a drug carrier of MA.Methods: The RADA16-I–MA suspension was prepared by magnetic stirring, followed by fluorescence spectrophotometry, particle size determination, rheological properties analysis, and in vitro release assay to characterize the interaction between RADA16-I and MA. Then, the effects of in situ MA-loaded hydrogel on the proliferation of KYSE 30 and DLD-1 tumor cells and the toxic effect of the hydrogel on 293T renal epithelial cells were studied by the Cell Counting Kit 8 method.Results: The RADA16-I–MA suspension was formed in water under magnetic stirring; the in situ hydrogel was formed when the suspension was added to PBS. The particle size in the RADA16-I–MA suspension was around 300–600 nm with an average size of 492 nm. Within 24 h, the cumulative release of MA from the RADA16-I–MA hydrogel was about 80%. The release rate of MA from the hydrogel was dependent on the concentration of RADA16-I and the release can be fitted with a first-order kinetic equation. The results suggested that the self-assembling peptide can stabilize MA in water to form a relatively stable suspension; the results also indicated that controlled release of MA from the RADA16-I–MA in situ hydrogel formed from the RADA16-I–MA suspension can be achieved by adjusting the concentration of the peptide in suspension. The cell viability studies showed that the RADA16-I–MA in situ hydrogel not only can maintain or enhance the intrinsic proliferation inhibition effects of MA on tumor cells, but also can reduce the toxicity of MA to normal cells.Conclusion: The self-assembling peptide RADA16-I can be a potential candidate for constructing a delivery system of the hydrophobic drug MA.Keywords: RADA16-I, hydrophobic drug, delivery system, antitumor

Jiaowang Tan,1,2 Li Luo,3 Min Zhang,3 Huifen Chen,3 Dingjun Zhang,3 Chendi Dong,3 Bingqing Xia,3 Lizhe Fu,1 Fang Tang,1 Xusheng Liu,1 Qinxiang Tan,2 Yifan Wu11Renal Division, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou, People’s Republic of China; 2Renal Division, Beijing University of Chinese Medicine Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 3The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Yifan WuRenal Division, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), No.111, Dade Road, Yuexiu District, Guangzhou 510120, People’s Republic of ChinaTel +86 13 56 032 4448Email wuyifan007@gzucm.edu.cnObjective: The self-reported scale is a widely used method to assess patients’ medication adherence in clinical practice, but there is still a lack of medicine adherence measurement scale for patients with Chronic Kidney Disease (CKD). Therefore, this study aimed to develop a medication adherence measurement scale of traditional Chinese medicine and Western medicine, providing a tool for evaluating medicine adherence of CKD patients.Methods: In the preliminary stage, we formed the prediction scale after three rounds Delphi method and it was filled by 20 patients, who were selected randomly. After pre-investigation and language adaption, we adjusted the prediction measurement scale which included 31 items based on Knowledge-Attitude-Belief Theory. Then, 222 CKD patients in Guangdong Hospital of traditional Chinese Medicine were investigated by this 31-item scale. We screened 31 items by Items analysis theory, including critical ratio, item correlation analysis, internal consistency analysis, principal component analysis and other methods. The left 26 items made up a formal scale. We collected and analyzed data of the 26-item scale and Chinese version of MGL scale, and took their scores correlation analysis as the criterion validity of the 26-item scale. At the same time, we evaluated content validity, Cronbach alpha coefficient and retest reliability of the 26-item scale.Results: We developed a scale with 26 items and 5 dimensions finally. In the validation analysis, the scale had good construct validity and content validity. The Pearson relation index between respective scores of the scale and Chinese version of MGL scale was 0.426, P

To date, comparatively little empirical research has been done on Generation Z globally, and the studies that do exist, while informative, have arrived at different, often loosely tied, conclusions. Seeing as how Generation Z is in the process of joining the professional workforce, it is important for decision makers to understand this generation’s value differences and cultural orientation in order to mitigate intergenerational conflicts and ensure a productive workforce going forward. China, meanwhile, is a rising superpower, and its Generation Z will have a significant impact globally. With the generational mix at work changing to accommodate this new generation, this paper presents a critique of current empirical research on this topic in a cross-cultural context and offers recommendations regarding future research directions as these relate to generational shift in China and other non-Western contexts. It is only by better understanding Generation Z that organizations can develop strategies and policies that will ensure a productive, profitable and collaborative environment in the future, one that better takes into account this newest generation’s needs and outlook.

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

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

Bo Tang,1,2,* Fang Tang,1,2,* Zhenran Wang,1,2,* Guangying Qi,3 Xingsi Liang,1,2 Bo Li,1,2 Shengguang Yuan,1,2 Jie Liu,1,2 Shuiping Yu,1,2 Songqing He1,2 1Department of Hepatobiliary Surgery, Guilin Medical University Affiliated Hospital, 2Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, 3Department of Pathology and Physiopathology, Guilin Medical University, Guilin, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Primary liver cancer is globally the sixth most frequent cancer, and the second leading cause of cancer death and its incidence is increasing in many countries, becoming a serious threat to human health. Many researches focused on the treatment and prevention of liver cancer. However, due to the underlying molecular mechanism of liver cancer still not fully understood, the studies and development of treatments were forced to be delayed. Akt has been suggested to play an essential role in the progression of inflammation response and apoptosis. Hence, in this study, Akt-knockout mice and cells of liver cancer were used as a model to investigate the molecular mechanism of Akt-associated inflammatory and apoptotic signaling pathway linked with NF-κB and Bcl-2-associated death promoter (Bad) for the progression of liver cancer. Carnosic acid (CA), as a phenolic diterpene with anticancer, antibacterial, antidiabetic, as well as neuroprotective properties, is produced by many species from Lamiaceae family. Administration of CA nanoparticles was sufficient to lead to considerable inhibition of liver cancer progression. The results indicated that, compared to the normal liver cells, the expression of Akt was significantly higher in liver cancer cell lines. Also, we found that Akt-knockout cancer cell lines modulated inflammation response and apoptosis via inhibiting NF-κB activation and inducing apoptotic reaction. Our results indicated that the downstream signals, including cytokines regulated by NF-κB and caspase-3-activated apoptosis affected by Bad, were re-modulated for knockout of Akt. And CA nanoparticles, acting as Akt-knockout, could inhibit inflammation and accelerate apoptosis in liver cancer by altering NF-κB activation and activating caspase-3 through Bad pathway. These findings demonstrated that the nanoparticulate drug CA performed its effective role owing to its ability to reduce inflammatory action and enhance apoptosis for the overexpression of NF-κB and Bad via Akt signaling pathway, playing a direct role in liver cancer progression. Thus, nanoparticle CA might be an important and potential choice for the clinical treatment in the future. Keywords: liver cancer, Akt-knockout, carnosic acid nanoparticle, inflammation, apoptosis

We carry out X-ray absorption spectroscopy experiment at the oxygen K edge in croconic acid (C5H2O5) crystal as a prototype of ferroelectric organic molecular solid, whose electric polarization is generated by proton transfer. The experimental spectrum is well reproduced by the electron-hole excitation theory simulations from configuration generated by ab initio molecular dynamics simulation. When inversion symmetry is broken in the ferroelectric state, the hydrogen bonding environment on the two bonded molecules become inequivalent. Such a difference is sensitively probed by the bound excitation in the pre-edge, which is strongly localized on the excited molecules. Our analysis shows that a satellite peak in the pre-edge will emerge at higher excitation energy, which serves as a clear signature of ferroelectricity in the material.

Although the richness of spatial symmetries has led to a rapidly expanding inventory of possible topological crystalline (TC) phases of electrons, physical realizations have been slow to materialize due to the practical difficulty in ascertaining band topology in realistic calculations. Here, we integrate the recently established theory of symmetry indicators of band topology into first-principles band-structure calculations, and test it on a database of previously synthesized crystals. On applying our algorithm to just 8 out of the 230 space groups, we are able to efficiently unearth topological materials and predict a diversity of topological phenomena, including: a screw-protected three-dimensional TC insulator, β-MoTe 2 , with gapped surfaces except for one-dimensional helical hinge states; a rotation-protected TC insulator, BiBr, with coexisting surface Dirac cones and hinge states; non-centrosymmetric Z 2 topological insulators undetectable using the well-established parity criterion, AgXO (X = Na, K, Rb); a Dirac semimetal MgBi 2 O 6 ; a Dirac nodal-line semimetal AgF 2 ; and a metal with three-fold degenerate band crossing near the Fermi energy, AuLiMgSn. Our work showcases how recent theoretical insights into the fundamentals of band structures can aid in the practical goal of discovering new topological materials.