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Jiamin Li,1,2 Zhenchao Zhong,1,2 Lei Mo1,2 1Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, Guangzhou 510631, People’s Republic of China; 2School of Psychology, Center for Studies of Psychological Application, Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, People’s Republic of ChinaCorrespondence: Lei MoSchool of Psychology, Center for Studies of Psychological Application, Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou 510631, People’s Republic of ChinaEmail molei@m.scnu.edu.cnBackground: Recently, a study revealed that people liked others significantly more than they estimated that others liked them. Thus, the study found that people tended to underestimate how much others liked them, a phenomenon the authors called the Liking Gap. However, the logic and testing of the study existed unclear nature. In order to show whether people underestimate the positivity of impression they left on others, we directly compare the estimate of the impression we left on others with others’ actual impression of us, which make the logic clear. Besides, we explored the new findings with regard to the mechanism of the effect.Methods: Based on this idea, in study 1, we explored whether there is indeed a negative deviation effect in the estimate of the impression people left on others in short interpersonal communication. In study 2, we investigated the potential psychological mechanisms of that effect.Results: In Study 1, the results revealed that people estimated that others liked them significantly less than others actually liked them. That is, a negative deviation effect did occur, and even if people were clear about their liking for others, the effect still existed. In Study 2, we provided evidence that a negative deviation effect existed not just because people are too focused on their own-negative thoughts in conversational performance but rather because people had a psychological defense towards others in their first communication.Conclusion: People significantly underestimate how much they are liked and its reason is that their psychological defense towards others in their initial communication. The results of the study are beneficial for people in social interaction and provide them with new ways of thinking in interpersonal communication and mutual contact.Keywords: impression, negative deviation, negative thoughts, psychological defense

Lin-lin Pei,1,* Wen-zhu Yang,1,* Jing-yuan Fu,1,* Meng-xi Liu,1 Ting-ting Zhang,1 Dong-bo Li,1 Ruo-yue Huang,1 Li Zhang,1 Guang-neng Peng,1 Gang Shu,1 Zhi-xiang Yuan,2 Ju-chun Lin,1 Wei Zhang,1 Zhi-jun Zhong,1 Ling Zhao,1 Hua-lin Fu1 1Department of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, People’s Republic of China; 2College of Pharmacy, Southwest Minzu University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua-lin FuDepartment of Pharmacy, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, People’s Republic of ChinaTel +86 028-86291162Email fuhl2005@sohu.comIntroduction: Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use.Methods: In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated.Results: EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01± 4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD50) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride.Conclusion: EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.Keywords: enrofloxacin mesylate, characterization, antibacterial effect, acute toxicity, pharmacokinetics

Zhiying Shen,1 Guolin Tan,2 Zhuqing Zhong,1 Siqing Ding,1 Fang Wang2 1Nursing Department, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Otolaryngology Head Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Fang WangDepartment of Otolaryngology Head Neck Surgery, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha 410013, People’s Republic of ChinaTel/Fax +86 731-88618624Email wangfang_xy3yy@163.comBackground: Allergic rhinitis (AR) is a common chronic inflammatory disease of nasal mucosa worldwide, and its symptoms seriously affect the lives of patients. Subcutaneous immunotherapy (SCIT) is an effective treatment for AR, but it is also associated with low patient compliance and difficulties in fully achieving therapeutic effects.Objective: In this prospective randomized controlled study, we verified the effects of an interactive network platform named “U breath” in improving patient compliance and the efficacy of SCIT in patients with AR.Methods: A total of 148 patients who received SCIT were recruited as participants and randomly assigned to either the standardized management (SM) or the interactive network platform management (INP) group. The SM group experienced the standard management SCIT process. The INP group experienced a new management approach based on an interactive network platform called “U breath”. The compliance rate, combined symptom and medication score (CSMS), visual analogue scale score and the rhinoconjunctivitis quality of life questionnaire (RQLQ) results were evaluated at baseline and 1-year postintervention for the two groups.Results: Within the first year of treatment, the INP group had a higher compliance rate than did the SM group, with a statistically significant difference (P

Feili Yan,1,* Hui Li,1,* Zhirong Zhong,1,* Meiling Zhou,2 Yan Lin,1 Can Tang,1 Chunhong Li1 1Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, People’s Republic of China; 2Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Can Tang; Chunhong LiDepartment of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, 3-319 Zhongshan Road, Luzhou, Sichuan 646000, People’s Republic of ChinaTel +86 18982455783; +86 13679696586Fax +86 08306302050Email 2291691527@qq.com; lispringhong@126.comBackground: Prednisolone (PD) is extremely effective for treating rheumatoid arthritis (RA). However, it distributes nonspecifically throughout the body and its use is associated with serious side effects, which promoted us to compound it into a phytomedicine for greater efficacy and safety.Methods: We combined PD with curcumin (CU), an effective monomer from traditional Chinese medicine, and human serum albumin (HSA) in a nanoparticulate system (N-PD/CU) to compensate for the poor bioavailability of PD and CU. N-PD/CU was prepared by high-pressure homogenization, and its characteristics were evaluated in vitro. Next, we investigated its toxicity and mechanism of anti-inflammatory to macrophages. Finally, its pharmacokinetics, biodistribution and therapeutic efficacy were assessed in rats with adjuvant-induced arthritis (AIA).Results: N-PD/CU showed a narrow size distribution around 150.4 ± 2.4 nm, a polydispersity index of 0.22 ± 0.02 and drug loading efficiency (DLE) of 88.75 ± 1.82% for PD and 85.79 ± 1.43% for CU. N-PD/CU showed sustained release of both drugs in vitro. N-PD/CU had no toxicity to macrophages in vitro on concentrations between 0.1 and 1.2 μmol/mL. In activated macrophages, N-PD decreased levels of pro-inflammatory cytokines, while N-CU increased levels of anti-inflammatory IL-10, and N-PD/CU exhibited best therapeutic effect in vitro, suggesting co-delivery of PD and CU may synergistically control the course of RA. In AIA rats, N-PD/CU accumulated in inflamed joints through the effect of extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS effect) in inflammatory lesion and showed higher therapeutic efficacy than single-loaded nanoparticles, either free drug on its own, or a simple mixture of the two drugs.Conclusion: This codelivery system based on HSA is a promising platform for combination chemotherapy in RA.Keywords: co-delivery, prednisolone, curcumin, human serum albumin, rheumatoid arthritis

OBJECTIVE: Dexmedetomidine has demonstrated potential in preclinical medical research as a protective agent against inflammatory injuries and a provider of neuroprotective benefits. However, its effect on the shortterm prognosis of patients with sepsis-associated encephalopathy remains unclear. This study aims to explore the underlying value of dexmedetomidine in these patients. PATIENTS AND METHODS: This study enrolled patients with sepsis-associated encephalopathy from the Medical Information Mart for Intensive Care (MIMIC)-IV database, and they were divided into two groups based on dexmedetomidine therapy during hospitalization. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to balance the inter-group baseline differences. Kaplan-Meier (KM) curves with logrank test and subgroup analysis were also employed. The primary outcome was 28-day mortality, and the secondary outcomes were in-hospital mortality, intensive care unit (ICU) stay time, hospital stay time, and the incidence of ventilator-associated pneumonia (VAP). RESULTS: After PSM, 1,075 pairs of patients were matched. In contrast to the non-dexmedetomidine cohort, the dexmedetomidine cohort did not exhibit a shortened ICU [4.65 (3.16, 8.55) vs. 6.14 (3.66, 11.04), p<0.001] and hospital stay duration [10.04 (6.55, 15.93) vs. 12.76 (7.92, 19.95), p<0.001], and there was an elevated incidence of VAP [90 (8.4%) vs. 135 (12.6%), p=0.002]. The log-rank test for the KM curves of dexmedetomidine use and 28-day mortality was statistically significant (p<0.001). The results showed that dexmedetomidine was associated with improved 28-day mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.35-0.61, p<0.001] and in-hospital mortality (HR 0.50, 95% CI 0.37-0.67, p<0.001) after adjusting for various confounders. In the following subgroup analysis, dexmedetomidine infusion was associated with decreased 28-day mortality in most subgroups. CONCLUSIONS: Dexmedetomidine administration was significantly associated with reduced short-term mortality among patients with sepsis-associated encephalopathy in the ICU. However, it also prolonged ICU and hospital stays and increased the incidence of VAP. [ABSTRACT FROM AUTHOR]

Wei Liang,1,2,* Chongyi Li,1,* Mengxia Li,1 Dong Wang,1 Zhaoyang Zhong1 1Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, People’s Republic of China; 2Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhaoyang ZhongCancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, No. 10 Changjiang Zhi Rd, Yuzhong District, Chongqing 400042, People’s Republic of ChinaTel +860 236 875 7183Fax +860 236 889 4062Email zhongzhaoyang08@hotmail.comObjectives: Osteosarcoma (OS) is the most common bone cancer diagnosed in children and adolescents. Expression of APE1 is commonly increased in OS, and this is negatively correlated with a sensitivity to platinum and a favorable prognosis. However, the mechanism underlying high APE1 expression in OS is not fully understood.Methods: A bioinformatics analysis of the APE1 3’-UTR combined with previous microarray data was used to identify miRNAs that regulate APE1 expression. The effects of miR-765 on cisplatin (cDDP) sensitivity were estimated in OS cell lines (9901 and HOS) and BALB/c mice (n=4 per group). The relative expression and association between miR-765 and APE1 were assessed in a cohort of OS patients (n=43 in total) with Kaplan-Meier and Cox proportional hazards regression. All statistical tests were two-sided and p

Qiyue Xia,1,2,* Jinxing Huang,1,* Qiyi Feng,1 Xuanming Chen,1 Xinyi Liu,1 Xiaojie Li,1 Ting Zhang,3 Shuwen Xiao,1 Hongxia Li,1 Zhihui Zhong,3,4 Kai Xiao1,41National Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China; 2Toxicology Department, Sichuan Center for Disease Control and Prevention, Chengdu, Sichuan Province, China; 3Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; 4Sichuan Kangcheng Biotech Co., Ltd, Chengdu, Sichuan Province, ChinaCorrespondence: Kai XiaoNational Chengdu Center for Safety Evaluation of Drugs and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, 28 Gaopeng Ave, High-Tech Development Zone, Chengdu 610041, Sichuan Province, People’s Republic of ChinaTel +86 288 332 6313Fax +86 288 517 3043Email xiaokaikaixiao@scu.edu.cn*These authors contributed equally to this workBackground: Gold nanoparticles (AuNPs) have shown great promise in biomedical applications. However, the interaction of AuNPs with biological systems, its underlying mechanisms and influencing factors need to be further elucidated.Purpose: The aim of this study was to systematically investigate the effects of particle size on the uptake and cytotoxicity of AuNPs in normal cells and cancer cells as well as their biological distribution in vivo.Results: Our data demonstrated that the uptake of AuNPs increased in HepG2 cancer cells but decreased in L02 normal cells, with the increase of particle size (5-50 nm). In both cancer cells and normal cells, small (5 nm) AuNPs exhibited greater cytotoxicity than large ones (20 and 50 nm). Interestingly, 5 nm AuNPs induced both apoptosis and necrosis in HepG2 cells through the production of reactive oxygen species (ROS) and the activation of pro-caspase3, whereas it mainly induced necrosis in L02 cells through the overexpression of TLR2 and the release of IL-6 and IL-1a cytokines. Among them, 50 nm AuNPs showed the longest blood circulation and highest distribution in liver and spleen, and the treatment of 5 nm AuNPs but not 20 nm and 50 nm AuNPs resulted in the increase of neutrophils and slight hepatotoxicity in mice.Conclusion: Our results indicate that the particle size of AuNPs and target cell type are critical determinants of cellular uptake, cytotoxicity and underlying mechanisms, and biological distribution in vivo, which deserves careful consideration in the future biomedical applications.Keywords: gold nanoparticles, particle size, uptake, toxicity, biodistribution

Hongru Zhang,1 Joe Antony Jacob,2 Ziyu Jiang,3 Senlei Xu,1 Ke Sun,1 Zehao Zhong,1 Nithya Varadharaju,4 Achiraman Shanmugam21The Second Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 2Department of Environmental Biotechnology, Bharathidasan University, Tiruchirappalli, 620024, Tamil Nadu, India; 3Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, Jiangsu, People’s Republic of China; 4Department of Animal Health and Management, Alagappa University, Karaikudi 630 003, Tamil Nadu, IndiaBackground: Liver plays a vital role in the elimination of xenobiotics that can induce hepatotoxicity in living organisms.Silver nanoparticles have evolved recently as an alternative in various industries and are used for their biomedical applications.Rhizophora apiculata is a least studied mangrove-based plant that has been used in the traditional medicine of Southeast Asia for its healing properties. It is a well-known fact that the generation of free radicals has been associated with oxidative stress. Methods: Hence, in this study we used carbon tetrachloride as a hepatotoxin to induce liver damage. The protective effects of silver nanoparticles synthesized using Rhizophora apiculata on hepatotoxin-induced liver damage in experimental mice were assessed. Results: The results of the assessment indicate that silver nanoparticles were effective in protecting the liver from damages induced by carbon tetrachloride. Conclusion: Among existing literature, this is the first ever approach for hepatoprotective effect of nanoparticles derived using plant extract from mangrove ecosystem.Keywords: mangroves, Rhizophora apiculata, silver nanoparticles, carbon tetrachloride, hepatotoxicity

Lina Tang,1,* Yijie Chen,1,* Zhongshi Du,1 Zhaoming Zhong,1 Qin Chen,2 Lichun Yang,3 Ruoxia Shen,3 Yan Cheng,4 Zizhen Zhang,4 Ehui Han,5 Zhihong Lv,5 Lijun Yuan,6 Yong Yang,6 Yinrong Cheng,7 Lei Yang,7 Shengli Wang,8 Baoyan Bai,8 Jun Luo2 1Department of Ultrasound, Fujian Cancer Hospital and Fujian Medical University Cancer Hospital, Fuzhou 350014, Fujian Province, China; 2Department of Ultrasound, Sichuan Provincial People’s Hospital, Chengdu 610072, Sichuan Province, China; 3Department of Ultrasound, The Third Affiliated Hospital of Kunming Medical University and Yunnan Cancer Hospital, Kunming 650118, Yunnan Province, China; 4Department of Ultrasound, Qujing City First People’s Hospital, Qujing 655000, Yunnan Province, China; 5Department of Ultrasound, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi 435000, Hubei Province, China; 6Department of Ultrasound, Tangdu Hospital, Fourth Military Medical University, Xi’an 710032, Shanxi Province, China; 7Department of Ultrasound, Chengdu First People’s Hospital, Chengdu 610000, Sichuan Province, China; 8Department of Ultrasound, Yanan University Affiliated Hospital, Yan’an 716000, Shanxi Province, China *These authors contributed equally to this work Purpose: To evaluate a classification model of contrast-enhanced ultrasound (CEUS) and examine the characteristics of patients with false-negative diagnosis. Patients and methods: A retrospective secondary analysis of a multicenter trial of CEUS for breast cancer diagnosis (from August 2015 to April 2017) was undertaken. Patients (n=1,023) with Breast Imaging Reporting and Data System 4–5 lesions on B-mode ultrasound underwent CEUS. Pathological diagnoses were available from surgical or biopsy specimens for correlation. Lesion maximum diameter (LMD), distance to the papilla (DtP), distance from the superficial edge of the lesion to the skin (DtS), distance from the deep edge of the lesion to the pectoralis muscle (DtPM), and body mass index (BMI) were evaluated. Results: Median age and BMI were 48.0 and 41.2 years and 23.2 and 22.4 kg/m2 for patients with malignant and benign lesions, respectively. Overall sensitivity, specificity, and accuracy of CEUS for malignancy were 89.4%, 65.3%, and 75.8%, respectively. The patients with true-positive and false-negative diagnosis (ie, with malignant lesion) were older than those with false-positive and true-negative diagnosis (ie, with benign lesion). Patients with true-positive and false-positive diagnoses had higher BMI than patients with true-negative and false-negative diagnoses (P=0.004). Patients with true-positive and false-negative diagnoses had larger LMD and DtP, as well as smaller DtS and DtPM. Conclusion: Older age, higher BMI, larger LMD and DtP, and smaller DtS and DtPM were associated with malignant lesions on CEUS. Patients with these characteristics should undergo further imaging. Keywords: breast cancer, ultrasound, contrast-enhanced ultrasound

Na Shen,1,* Songya Liu,2,* Jieke Cui,3 Qing Li,4 Yong You,1 Zhaodong Zhong,1 Fanjun Cheng,1 An-Yuan Guo,5 Ping Zou,1 Guolin Yuan,6 Xiaojian Zhu2 1Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; 2Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; 3Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; 4Department of Hematology, Wuhan No 1 Hospital, Wuhan 430022, China; 5Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; 6Department of Hematology, Xiangyang Central Hospital, The Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441000, China *These authors contributed equally to this work Purpose: Half of the chronic myeloid leukemia (CML) patients with sustained deep molecular response suffer from relapse after discontinuation mainly because tyrosine kinase inhibitors (TKIs) cannot eradicate leukemia stem cells (LSCs). In addition, tumor necrosis factor α (TNF-α) is highly detected in CML patients. Our aim was to explore whether TNF-α is a potential target for LSC elimination.Materials and methods: We applied a CRISPR/Cas9 gene editing technique, colony-forming cell assay, subcutaneous tumor models, miRNA-seq and liquid chromatography-mass spectroscopy (LC-MS) on metabonomics to explore the feasibility and mechanism of TNF-α as a new therapeutic target for CML.Results: We demonstrated that TNF-α knockout remarkably decreased the proliferative, colony-forming and in vivo tumorigenesis capacities of the CML K562 cell line. The apoptosis was increased when TNF-α knockout cells were cultured with imatinib. The mechanisms involved in the abovementioned phenomena were that TNF-α knockout inhibited the citrate cycle and increased starch, sucrose, amino sugar and nucleotide sugar metabolism. In addition, differentially expressed miRNAs between TNF-α knockout and control cells were involved in the cell cycle, CML, P13K-Akt and pathways in cancer.Conclusion: We identified that TNF-α may serve as a new target therapy for CML and described the metabolic pathways associated with TNF-α in CML cells for the first time. Keywords: chronic myeloid leukemia, tumor necrosis factor α, CRISPR/Cas9 gene editing, tumorigenesis, metabolism profile

Zhiqing Zhong,1,* Hongyan Li,2,* Hongzhen Zhong,1 Tianbiao Zhou1 1Department of Nephrology, The Second Affiliated Hospital, Shantou University Medical College, 515041 Shantou, China; 2Department of Nephrology, Huadu District People’s Hospital of Guangzhou, Southern Medical University, 510800 Guangzhou, China *These authors contributed equally to this work Background: Long-term treatment programs with low toxicity represent a therapeutic challenge in lupus nephritis (LN). Although a therapeutic benefit of rituximab (RTX) has been reported in LN patients who have failed conventional treatment, the results are controversial. We aimed to assess the clinical efficacy and safety of RTX as a new immunosuppressive medicine in the treatment of LN with a meta-analysis. Methods: Based on predetermined criteria, PubMed, Embase, and Cochrane Library were used to identify the eligible studies. Cochrane Review Manager version 5.3 was applied to pool the data extracted from individual investigations and provide summary effect estimates. Results: Twenty-four studies with 940 patients were analyzed. In case series trials with specific LN assessment, the complete remission (CR) rate at 12 months was 35.9% (95% CI: 24.2%–49.5%), and total remission (TR: CR plus partial remission) was 73.4% (95% CI: 66.0%–79.7%). In controlled trials, RTX was associated with a higher probability of TR (OR =2.02, 95% CI: 1.23–3.32, P0.05). Additionally, RTX treatment significantly decreased proteinuria (mean difference: -2.79, 95% CI: -3.95 to -1.62, P

Yinbing Zhang,1,2 Haifeng Liu,3 Yingqian Zhang,4 Qiong Wu,1 Yanyan Zhang,1,2 Jie Zhang,1,2 Xiangshan Zhou,3 He Jiao,5 Feng Fan,6 Qi Xue,7 Xin Wang,1,2 Zhihui Zhong1,2 1Laboratory of Nonhuman Primate Disease Modeling Research, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; 2Sichuan Kangcheng Biomed Co., Ltd., Chengdu, China; 3Angde Biotech Pharmaceutical Co., Ltd., Liaocheng, China; 4Department of Physiology, Southwest Medical University, Luzhou, China; 5Department of Interventional therapy, West China Hospital, Sichuan University, Chengdu, China; 6Department of Neurointervention, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; 7Food and Drug Administration of Shibei District Government, Qingdao, China Purpose: In order to evaluate the thrombolytic effects of reteplase in pulmonary thromboembolism (PTE), we developed a novel canine PTE model. The efficacy of reteplase against PTE in comparison to alteplase was clarified for the first time, and this PTE model could be further applied to studies of novel thrombolytic therapies. Patients and methods: Twenty-four dogs were divided into four groups: sham operation, vehicle, alteplase, and reteplase. Autologous thrombi/saline were injected into the pulmonary artery, and thrombolytic agents were administrated. Thrombus formation and dissolution were monitored by real-time digital subtraction angiography (DSA), and pulmonary pressures were measured simultaneously. Blood coagulation, blood gas, hematology, and histopathologic examinations were used as subsidiary methods. Results: The canine PTE model was established with a significant decrease of blood flow and ~75% blocking area. Administration of reteplase (0.6 mg/kg) resulted in effective thrombus dissolution with a recovery of over 80% blood flow, as effective as alteplase (1.6 mg/kg). Correspondingly, the elevated pulmonary systolic, diastolic, and mean arterial pressures declined to the normal level. Blood coagulation was changed by reteplase, with a dramatic elongation of prothrombin time, activated partial thromboplastin time, and thrombin time, even longer than alteplase. In contrast to the vehicle group, no obvious pathological changes were found in the two thrombolytic groups. Hematological, blood biochemical, and blood gas results also indicated that reteplase had no adverse reactions in this PTE model. Conclusion: Reteplase proved to be an effective and safe therapy for PTE for the first time, and a small dosage of reteplase exerted an efficacy comparable to the routine dosage of alteplase. Our findings indicated the potential of reteplase as clinical treatment against PTE. This technically innovative, stability- and validity-proved canine PTE model developed by minimally invasive surgery and DSA resembled major clinical features. This may further facilitate our understanding of thrombotic disorders and development of prophylactic and therapeutic approaches. Keywords: reteplase, canine pulmonary thromboembolism model, thrombolytic therapy

Hongzhen Zhong,1,* Tianbiao Zhou,1,* Hongyan Li,2,* Zhiqing Zhong1,* 1Department of Nephrology, The Second Affiliated Hospital, Shantou University Medical College, Shantou, China; 2Department of Nephrology, Huadu District People’s Hospital of Guangzhou, Southern Medical University, Guangzhou, China *These authors contributed equally to this work Introduction: The purpose of this study was to analyze the effects of hypoxia-inducible factor (HIF) stabilizers on anemia in non-dialysis-dependent (NDD) and dialysis-dependent (DD) chronic kidney disease (CKD) patients.Methods: Published studies were extracted from PubMed, China Biological Medicine Database (CBM), Wanfang database, and Cochrane Library on March 10, 2018, and relevant studies were pooled and included in a meta-analysis. Data on hemoglobin (Hb), ferritin, and hepcidin levels, total iron-binding capacity (TIBC), and incidence of adverse events (AEs) were extracted and pooled using Review Manager Version 5.3.Results: Data from nine selected studies were extracted. Meta-analysis of the included studies showed that HIF stabilizers reduced ferritin and hepcidin levels and increased Hb level and TIBC in NDD-CKD patients. However, HIF stabilizers only increased TIBC, and did not affect ferritin, hepcidin, and Hb levels in DD-CKD patients. Furthermore, no notable differences in AEs and severe AEs between NDD-CKD and DD-CKD patients were detected.Conclusion: HIF stabilizers are effective for the treatment of anemia in NDD-CKD patients and safe for short-term use. Keywords: hypoxia-inducible factor stabilizer, anemia, chronic kidney disease, meta-analysis

Quansong Xia,1,* Wei Wang,2,* Juan Xu,3 Xue Chen,2 Zhaoming Zhong,2 Chuanzheng Sun2 1Department of Clinical Laboratory, 2Department of Head and Neck Surgery, The Third Affiliated Hospital of Kunming Medical University, 3Department of Internal Medicine, The People’s Hospital of Guandu District, Kunming, People’s Republic of China *These authors contributed equally to this work Background: Radiotherapy and chemotherapy are the two important postoperative management approaches for anaplastic thyroid carcinoma (ATC), and several studies have suggested that postoperative radiotherapy and chemotherapy can prolong the survival of patients with ATC. However, the results remain inconsistent. Objective: A meta-analysis was performed to address whether postoperative radiotherapy and chemotherapy could prolong the survival of patients with ATC. Methods: Relevant studies were included, and pooled hazard ratios (HRs) together with 95% confidence intervals (CIs) were calculated. Results: Ten relevant studies on factors that affect the prognosis for ATC were included in this meta-analysis, evaluating a total of 1,163 patients. The pooled HR for overall survival (OS) was calculated using a random-effects model. The pooled results demonstrated that for all patients with resectable ATC, the combination of surgery and radiotherapy significantly reduced the risk of death compared with surgery alone (HR =0.51, 95% CI: 0.36–0.73, Z=3.66, P=0.0002). To investigate the prognostic impacts of chemotherapy in patients with ATC, we also calculated the pooled HR of chemotherapy for OS using a random-effects model; however, the pooled results suggested that chemotherapy did not prolong the survival of ATC patients compared with controls (HR =0.63, 95% CI: 0.33–1.21, Z=1.39, P=0.17). Conclusion: This study provided evidence that currently, for patients with ATC, postoperative radiotherapy may prolong survival; in contrast, chemotherapy did not improve long-term survival. Keywords: anaplastic thyroid carcinoma, postoperative radiotherapy, chemotherapy, prognosis, meta-analysis

Zhuoyuan Zhong,1,* Limin Wang,2,* Xiaojun Wen,3 Yunyun Liu,4 Yafei Fan,5 Zhonglin Liu5 1Department of Neurology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; 2Department of Neurology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou, China; 3Department of Neurology, Guangzhou First Municipal People’s Hospital, Guangzhou Medical University, Guangzhou-Birmingham University Brain and Cognition Center, Guangzhou, China; 4Department of Neurology, the Sixth Affiliated Hospital Sun Yat-sen University, Guangzhou, China; 5Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China *These authors contributed equally to this work Background: Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) have been commonly prescribed for depression treatment. However, their effects on blood pressure are unclear.Materials and methods: Effects on blood pressure of depressive patients in two groups (SSRIs versus placebo and SSRIs versus SNRIs) were evaluated. A search was conducted for double-blind, randomized controlled trials (RCTs) in PubMed, EMBASE, ISI Web of Science, PsycNET, CCRCT, and DARE (up to March 2017). The outcomes were systolic blood pressure (SBP) changes and diastolic blood pressure (DBP) changes from baseline to endpoint or to a certain period of treatment duration. Weighted mean differences (WMDs) and 95% CIs were calculated and pooled using random effects models. The χ2 test and I2 statistics were used to assess heterogeneity. Funnel plots, Begg’s test, and Egger’s test were used to estimate publication bias.Results: A total of 23 RCTs involving 13,285 participants were included. Patients on SSRIs showed no significant differences in blood pressure changes compared with placebo. In the group of SSRIs versus SNRIs, overall SBP changes and DBP changes revealed statistical significances (WMD 1.5 mmHg, 95% CI -2.15, -0.84, Z=4.46, P

Arsenic (As) contamination of water can pose a significant threat to human health. Landoltia punctata is a superior water ecological restoration plant that can absorb As and thus manage the problem of As overload in the aquatic environment. Phytohormones play an important role in regulating plant growth and improving heavy metal resistance. In this study, the enrichment effect of phytohormones on As uptake and tolerance mechanism of L. punctata at different concentrations were investigated. The results showed that the application of Indolent-3-acetic (IAA), Abscisic acid (ABA) and Kinetin (KT) were all effective in increasing chlorophyll a (Ca) and carotenoid (Cc) contents. Low concentrations of phytohormones from 0.001 to 1 μmol·L-1 had a facilitative effect on fluorescence parameters in the order of IAA > ABA > KT. The application of high concentrations of phytohormones inhibited the fluorescence parameters. The application of 0.1 μmol·L-1 IAA, ABA and KT treatments were the most effective in promoting As uptake in L. punctata. The effect sequence of different plant hormone on As enrichment was: ABA > IAA ≥ KT. Low concentrations of IAA, ABA and KT treatments all significantly increased superoxide dismutase (SOD) and glutathione reductase (GR) activities, significantly decreased malondialdehyde (MDA) and H2O2 contents and promoted proline synthesis in As-stressed L. punctata. This indicates that the application of phytohormones can improve the antioxidant activity of As-stressed L. punctata, promote the growth of L. punctata and improve its As absorption capacity. This study may provide a scientific basis for phytohormones to promote the remediation of As-contaminated waters by L. punctata, and can provide scientific basis for phytohormones to promote the remediation of Ascontaminated waters by L. punctata. [ABSTRACT FROM AUTHOR]

Ping Zhong,1,2 Xiaolei Gu,1,2 Ru Cheng,1,2 Chao Deng,1,2 Fenghua Meng,1,2 Zhiyuan Zhong1,2 1Biomedical Polymers Laboratory, 2Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, China Abstract: Antibody-mertansine (DM1) conjugates (AMCs) are among the very few active targeting therapeutics that are approved or clinically investigated for treating various cancers including metastatic breast cancer. However, none of the AMCs are effective for the treatment of triple-negative breast cancers (TNBCs). Here, we show that cRGD-decorated, redox-activatable micellar mertansine prodrug (cRGD-MMP) can effectively target and deliver DM1 to αvβ3 integrin overexpressing MDA-MB-231 TNBC xenografts in nude mice, resulting in potent tumor growth inhibition. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays showed that cRGD-MMP had obvious targetability to MDA-MB-231 cells with a low half-maximal inhibitory concentration (IC50) of 0.18 µM, which was close to that of free DM1 and 2.2-fold lower than that of micellar mertansine prodrug (MMP; nontargeting control). The confocal microscopy studies demonstrated that cRGD-MMP mediated a clearly more efficient cellular uptake and intracellular release of doxorubicin (used as a fluorescent anticancer drug model) in MDA-MB-231 cells. Notably, cRGD-MMP loaded with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide (DiR; a hydrophobic near-infrared dye) was shown to quickly accumulate in the MDA-MB-231 tumor with strong DiR fluorescence from 2 to 24 h post injection. MMP loaded with DiR could also accumulate in the tumor, although significantly less than cRGD-MMP. The biodistribution studies revealed a high DM1 accumulation of 8.1%ID/g in the tumor for cRGD-MMP at 12 h post injection. The therapeutic results demonstrated that cRGD-MMP effectively suppressed MDA-MB-231 tumor growth at 1.6 mg DM1 equiv./kg without causing noticeable side effects, as shown by little body weight loss and histological analysis. This MMP has appeared as a promising platform for potent treatment of TNBCs. Keywords: breast cancer, reduction-sensitive, drug conjugates, micelles, cRGD

Yunlong Wang,1,* Yuling Luo,1,* Chunhong Li,1 Xiaoqin Zhang,1 Chao Pi,1 Lu Yu,2 Shurong Wang,1 Zhirong Zhong1 1Department of Pharmaceutical Sciences, School of Pharmacy, 2Department of Chemistry, The Institute of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China *These authors contributed equally to this work Abstract: Invasion and metastasis are the main causes leading to the death of patients with hepatocellular carcinoma (HCC). Multivesicular liposomes loaded with oleanolic acid (OA-MVLs) have been well demonstrated to suppress survival, growth and angiogenesis of HCC cells. Emerging evidence demonstrates that OA was able to suppress the invasion of HCC cells by down-regulating myocyte enhancer factor-2. We hypothesized that the optimized OA-MVLs could inhibit the migration and invasion of HCC cells. In this study, we utilized central composite design and response surface methodology to assess the influence of some parameters on particle size and encapsulation efficiency and obtain the optimized formulation of OA-MVLs. Subsequently, the human HCC cell lines SMMC-7721 and HepG2 were treated with different doses of OA-MVLs and OA, respectively. Cellular survival, adhesion, migration and invasion in vitro were evaluated. We found that the optimized OA-MVLs significantly decreased the ability of HCC cells to adhere, migrate and invade in vitro. Furthermore, OA-MVLs significantly inhibited the survival of HCC cells at 160 µmol/L but showed no obvious inhibition effect on the cell vitality of normal liver cells. Our findings indicate that OA-MVLs did inhibit the cell survival, adhesion, invasion and metastasis of HCC cells in vitro. Although the involved mechanisms are still unclear, our findings can contribute to a better development of a preventive and therapeutic strategy for human HCC. Keywords: oleanolic acid, multivesicular liposomes, central composite design, adhesion, invasion, migration

This study presents multiphysics analyses of the electron target cooling system of the accelerator-driven system (ADS) of the Kharkiv Institute of Physics and Technology (KIPT) using MCNP and Fluent computer programs. MCNP has been used to transport electrons, gammas, and neutrons, and to calculate the energy deposition in the target materials. The MCNP mesh-tally data have been imported into Fluent by a C subroutine that has been compiled and linked to Fluent as a user-defined function. The KIPT ADS is located in Ukraine and was in operation until February 2022. The Fluent model is based on the computer-aided design files from the manufacturing process of the target assembly. The Fluent results for the reference case match very well the literature results obtained by STAR-CCM+ during the design phase. Other cases that differ from the reference one have been analyzed; in these cases, it is assumed a malfunction of the electron accelerator or of the water cooling system. The target cooling system operates normally for all the analyzed cases except when the inlet water mass flow rate is decreased. The transient analysis showed that the target cooling system can operate for 180 s with full power when the inlet water mass flow rate is decreased down by 75%. [ABSTRACT FROM AUTHOR]

Jihui Wang, Qinling Wei, Xiaoli Wu, Zhiyong Zhong, Guanying Li Department of Psychiatry, The Third Affiliated Hospital of Sun-Yat Sen University, Guangzhou, Guangdong, People’s Republic of China Objective: To evaluate the efficacy of brief behavioral treatment for insomnia (BBTI) in treating patients with treatment-resistant insomnia.Methods: Seventy-nine adults with treatment-resistant insomnia were randomly assigned to receive either individualized BBTI (delivered in two in-person sessions and two telephone “booster” sessions, n=40) or sleep hygiene education (n=39). The primary outcome was sub­jective (sleep diary) measures of self-report symptoms and questionnaire measures of Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), Epworth sleeping scale (ESS), and dysfunctional beliefs and attitudes about sleep scale (DBAS).Results: The repeated-measures analysis of variance showed significant time effects between pretreatment and posttreatment in the scale ratings of PSQI, ESS, DBAS, ISI, sleep latency (SL), time in bed (TIB), sleep efficiency (SE), and wake after sleep onset (WASO) in both groups and group × time interaction (FPSQI =3.893, FESS =4.500, FDBAS =5.530, FISI =15.070, FSL =8.909, FTIB =7.895, FSE =2.926, and FWASO =2.595). The results indicated significant differences between BBTI and sleep hygiene in change scores of PSQI, ESS, DBAS, ISI, SL, TIB, SE, and WASO. Effect sizes were moderate to large.Conclusion: BBTI is a simple and efficacious intervention for chronic insomnia in adults. Keywords: brief behavioral treatment, treatment-resistant, insomnia

We present systematic investigation on texture evolution in nanocrystalline Ta under planar shock wave loading at different impact velocities. Seven representative initial textures and two loading directions are studied via large-scale molecular dynamics simulations. Orientation mapping and texture analysis, including orientation distribution functions, pole figures, and inverse pole figures, are performed. Shock compression induces a ⟨ 221 ⟩ texture in nanocrystalline Ta initially with no texture, ⟨ 100 ⟩ fiber texture, { 100 } ⟨ 100 ⟩ texture, and θ + γ rolling texture via twinning, which can be traced back to grains initially with ⟨ 100 ⟩. A ⟨ 100 ⟩ texture is induced via twinning for nanocrystalline Ta initially with no texture, ⟨ 110 ⟩ fiber texture, and α + γ rolling texture and can be traced back to ⟨ 110 ⟩. Dislocation slip and grain boundary sliding lead to the movement of ⟨ 110 ⟩ toward ⟨ 111 ⟩ , and the strengthening of ⟨ 100 ⟩ and ⟨ 111 ⟩ orientation densities. The generation of new textures is observed for most cases. However, no new texture is found in the ⟨ 111 ⟩ fiber texture case for shock loading parallel to the fiber, and a much slower elastic–plastic transition occurs due to the lack of deformation twinning. [ABSTRACT FROM AUTHOR]

We investigate with large-scale molecular dynamics simulations texture evolution in nanocrystalline Cu under planar shock wave loading. Five representative initial textures are explored under varying impact strengths. On the basis of Euler angles, we perform orientation mapping and texture analysis, including orientation distribution functions, pole figures, and inverse pole figures. Shock compression induces a weak but apparent ⟨ 110 ⟩ textures in nanocrystalline Cu initially with no texture, and a ⟨ 100 ⟩ fiber texture, and an incomplete weak ⟨ 110 ⟩ texture in nanocrystalline Cu initially with a { 100 } ⟨ 100 ⟩ recrystallization texture; such texture changes can be attributed to deformation twinning and dislocation slip and traced back to grains initially with ⟨ 100 ⟩. A ⟨ 100 ⟩ texture and a { 100 } ⟨ 100 ⟩ cube texture component are induced via twinning in nanocrystalline Cu initially with the ⟨ 111 ⟩ and β fiber textures, respectively, and can be traced back to grains initially with ⟨ 111 ⟩. [ABSTRACT FROM AUTHOR]