Search

Yang Yang,1,2 Zongze Yao,1 Jiazhen Zhang,1 Wei Shao,3 Bo Li,2 Huihui Wu,2 Wenjian Tang,3 Jing Zhang2 1School of Medicine, Anhui University of Science and Technology, Huainan, People’s Republic of China; 2Anhui Province Key Laboratory of Occupational Health, Anhui No.2 Provincial People’s Hospital, Hefei, People’s Republic of China; 3School of Pharmacy, Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Wenjian Tang; Jing Zhang, Tel +86-551-63672601, Email ahmupharm@126.com; hfzj2552@163.comBackground: Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of staph infection that is difficult to treat because of resistance to some antibiotics. A recent study indicated that diarylurea ZJ-2 is a novel antibacterial agent against multi-drug resistant Enterococcus faecium. In this work, we refined the bactericidal mechanism of ZJ-2 as a peptidoglycan (PG) hydrolase by affecting AtlA-mediated PG homeostasis.Methods: A wild-type strain (WT) and a mutant strain (ΔatlA) were used to investigate the effects of ZJ-2 on the cell wall, PG, and autolysin regulatory system by antimicrobial susceptibility testing, hemolytic toxin assay, microanalysis, autolysis assay, qRT-PCR, ELISA and mouse model of pneumonia.Results: The results revealed that ZJ-2 down-regulated the expression of genes related to peptidoglycan hydrolase (PGH) (sprX, walR, atlA, and lytM), and reduced the levels of PG, muramyl dipeptide (MDP), cytokines, and hemolytic toxin, while ΔatlA interfered with the genes regulation and PG homeostasis. In the mouse MRSA pneumonia model, the same trend was observed in the nucleotide oligomerization domain protein 2 (NOD2) and relative proinflammatory factors.Conclusion: ZJ-2 may act as a novel inhibitor of PG hydrolyse, disrupting autolysin-mediated PG homeostasis, and reducing inflammation by down-regulating the MDP-NOD2 pathway. Keywords: MRSA, peptidoglycan hydrolase, homeostasis, autolysis, NOD2

Wei Meng,1 Qing Wang,1 Qingyu Xu,2 Hongli Gao,3 Yunjun Zhou,1 Wei Shao1 1Department of Pediatric Internal Medicine, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang, People’s Republic of China; 2Department of Pediatrics Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang, People’s Republic China; 3Department of Digestive Endoscopy Center, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang, People’s Republic of ChinaCorrespondence: Wei Shao, Department of Pediatrics, Hongqi Hospital Affiliated to Mudanjiang Medical University, No. 5 Tongxiang Road, Aimin District, Mudanjiang, Heilongjiang, 157000, People’s Republic of China, Tel +86-4536602008, Email 3649971511@qq.comBackground: The occurrence of necrotizing enterocolitis (NEC) is a common and severe disease of the digestive system in neonates. This study aims to assess the value of the intestinal tissue oxygen saturation (rintSO2) combined with the levels of procalcitonin (PCT) and mean platelet volume (MPV) in predicting the severity of NEC in preterm infants.Methods: This experiment was a retrospective cohort study conducted in the Department of Pediatrics, Hongqi Hospital Affiliated to Mudanjiang Medical University between January 2017 and July 2022. Premature neonates with NEC were enrolled and divided into mild-moderate NEC group and severe NEC group according to Bell’s stage. The general information data, rintSO2 and blood parameters such as the white blood cell (WBC) count, platelet count (PLT), PCT, MPV, red blood cell distribution width (RDW), hemoglobin (Hb), C-reactive protein (CRP) were compared between the two groups.Results: A total of 122 patients were enrolled, including 79 mild-moderate NEC and 43 severe NEC. The rintSO2 was lower in severe group than in mild-moderate group (P = 0.042), the PCT and MPV were both higher in severe group than in mild-moderate group (P = 0.048, P = 0.049). The results of logistic regression suggested that the rintSO2 (OR = 1.491, P = 0.003), PCT (OR = 3.071, P = 0.001) and MPV (OR = 4.027, P = 0.015) were independent predictive factors for severity of NEC. The area under the curve (AUC) of the rintSO2 combined with PCT and MPV showed good diagnostic ability in the severity of NEC.Conclusion: The rintSO2 combined with PCT and MPV may be considered as the early biomarkers in the severity of NEC and could help us to diagnose the case early with early treatment with better prognosis.Keywords: premature infants, necrotizing enterocolitis, intestinal tissue oxygen saturation, procalcitonin, mean platelet volume

Haoshuang Liu,1,2 Jingfeng Chen,1,2 Weihao Shao,3 Su Yan,1,2 Suying Ding1,2 1Health Management Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2College of Public Health, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 3School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Suying Ding, Department of Health Management Center, the First Affiliated Hospital of Zhengzhou University, Longhu Zhonghuan Road, Jinshui District, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 158 3802 3097, Email fccdingsy@zzu.edu.cnObjective: Numerous pharmacological interventions are now under investigation for the treatment of the 2019 coronavirus pandemic (COVID-19), and the evidence is rapidly evolving. Our aim is to evaluate the comparative efficacy and safety of these drugs.Methods: We searched for randomized clinical trials (RCTs) on the efficacy and safety of novel oral antivirals for the treatment of hospitalized COVID-19 patients until November 30, 2022, including baricitinib, ivermectin (IVM), favipiravir (FVP), chloroquine (CQ), lopinavir and ritonavir (LPV/RTV), hydroxychloroquine (HCQ), and hydroxychloroquine plus azithromycin (HCQ+AZT). The main outcomes of this network meta-analysis (NMA) were in-hospital mortality, adverse event (AE), recovery time, and improvement in peripheral capillary oxygen saturation (SpO2). For dichotomous results, the odds ratio (OR) was used, and the 95% confidence interval (CI) was determined. We also used meta-regression to explore whether different treatments affected efficacy and safety. STATA 15.0 was used to conduct the NMA. The research protocol was registered with PROSPERO (#CRD 42023415743).Results: Thirty-six RCTs, with 33,555 hospitalized COVID-19 patients, were included in this analysis. First, we compared the efficacy of different novel oral antivirals. Baricitinib (OR 0.56, 95% CI: 0.35 to 0.90) showed the highest probability of being the optimal probiotic species in reducing in-hospital mortality and suggested that none of the interventions reduced AE better than placebo. In terms of safety outcomes, IVM ranked first in improving the recovery time of hospitalized COVID-19 patients (mean difference (MD) − 1.36, 95% CI: − 2.32 to − 0.39). In addition, patients were most likely to increase SpO2 (OR 1.77, 95% CI: 0.09 to 3.45). The meta-regression revealed no significant differences between participants using different novel oral antivirals in all outcomes in hospitalized COVID-19 patients.Conclusion: Currently, baricitinib has reduced in-hospital mortality in hospitalized COVID-19 patients, with moderate certainty of evidence. IVM appeared to be a safer option than placebo in improving recovery time, while FVP was associated with increased SpO2 safety outcomes. These preliminary evidence-based observations should guide clinical practice until more data are made public.Keywords: COVID-19, network meta-analysis, pharmacological intervention, efficacy, safety

Xu Chang,1,2 Huiyong Wu,2 Shangkun Ning,3 Xinge Li,4 Yinfa Xie,2 Wenbo Shao,2 Jinming Yu1,5 1Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300000, People’s Republic of China; 2Department of Interventional Therapy II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 3Department of Interventional Therapy I, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China; 4Department of Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250117, People’s Republic of China; 5Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, Shandong, 250117, People’s Republic of ChinaCorrespondence: Jinming Yu, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300000, People’s Republic of China, Tel +86 531-67626306, Email sdyujinming@163.com Wenbo Shao, Department of Interventional Therapy II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250117, People’s Republic of China, Tel +86 531-67626892, Email shaowenbo1974@sina.comPurpose: The treatment of hepatocellular carcinoma (HCC) patients with high-risk features (Vp4, and/or tumor occupancy≥ 50%) has not been standardized and has poor outcomes. The present study aimed to assess the safety, efficacy, and prognostic impact of lenvatinib, hepatic arterial infusion chemotherapy (HAIC), and humanized programmed death receptor-1 (PD-1) in treating high-risk patients and to explore the biomarkers that may predict the efficacy.Methods: HCC patients with high-risk features treated with lenvatinib, HAIC, and PD-1 were analyzed retrospectively. Overall survival (OS), progression-free survival (PFS), duration of response (DOR), objective response rate (ORR), and disease control rate (DCR) were calculated to evaluate the antitumor efficacy. Treatment-related adverse events (TRAEs) were analyzed to assess the safety profiles.Results: Between February 2020 and July 2022, 97 patients were enrolled in this retrospective cohort study. The median follow-up time was 447 days. During analysis, 65 patients had disease progression, and 39 patients died. The median PFS and OS were 295 and 579 days, respectively. According to RECIST 1.1 and mRECIST, the ORR was 64.9% and 78.3%, respectively, and the DCR was 92.8%. The median and intrahepatic DOR was 363 and 462 days, respectively. Treatment-related grade 3 or 4 adverse events occurred in 64 (65.9%) patients, and the most common adverse events were hypertension (9.3%), thrombocytopenia (7.2%), and elevated aspartate transaminase (7.2%). Participants with low levels of serum procalcitonin (PCT) had satisfactory prognosis.Conclusion: Lenvatinib, HAIC, and PD-1 were safe and showed promising antitumor activity against HCC with high-risk features. The initial levels of procalcitonin might be the predictive biomarkers for the combined treatment.Keywords: hepatocellular carcinoma, HAIC, lenvatinib, VP4, PD-1

Mingyuan Li,1 Meng Li,1 Xinyi Li,1 Wanhui Shao,1 Xiujuan Pei,2 Ruyue Dong,1 Hongmeng Ren,1 Lin Jia,1 Shiqin Li,1 Wenlin Ma,1 Yi Zeng,1 Yun Liu,1 Hua Sun,1 Peng Yu1 1College of Biotechnology/Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin University of Science & Technology, Tianjin, 300457, People’s Republic of China; 2Tianjin Shiji Kangtai Biomedical Engineering Co.,Ltd, Tianjin, 300462, People’s Republic of ChinaCorrespondence: Hua Sun; Peng Yu, Email sunhua@tust.edu.cn; yupeng@tust.edu.cnPurpose: In the present study, we prepared collagen liposomes with the addition of polyol, which is expected to not only increase the solubility of collagen but also improve skin penetration.Methods: Collagen liposomes were prepared by the film dispersion method, and their characteristics, integrity and biosafety were evaluated by Fourier transform infrared spectroscopy (FTIR), UV-VIS spectroscopy, polyacrylamide gel electrophoresis (SDS-PAGE), dynamic light scattering (DLS) and transmission electron microscope (TEM). The transdermal absorption of collagen and collagen liposomes were tested by an ex vivo horizontal Valia-Chien diffusion cell system.Results: We first demonstrated that collagen extracted from bovine Achilles tendon was type I collagen. The results of DLS measurement and TEM observation showed that the collagen liposomes were spherical in shape with average diameter (75.34± 0.93 nm) and maintained high stability at low temperature (4°C) for at least 42 days without toxicity. The encapsulation rate of collagen liposomes was 57.80 ± 0.51%, and SDS-PAGE analysis showed that collagen was intact in liposomes. Finally, permeability studies indicated that the collagen-loaded liposomes more easily penetrated the skin compared to collagen itself.Conclusion: This study proposed a new method to improve the bioavailability and permeability of bovine type I collagen, which improves the applicability of collagen in biomedicine, cosmeceuticals and pharmaceutical industries.Graphical Abstract: Keywords: collagen, liposome, physicochemical properties of collagen, skin penetration, drug delivery

Gaili Wang,1 Huizi Tian,2 Kai Kang,2 Shixian Feng,2 Weihao Shao,1 Xiaorui Chen,1 Caifang Zheng,1 Bowen Zhang,1 Pei Pei,3 Weidong Zhang1 1Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 2Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan, 450016, People’s Republic of China; 3Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, 100191, People’s Republic of ChinaCorrespondence: Weidong Zhang, Department of Epidemiology, School of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China, Tel +86-0371-67781964, Email imooni@163.comObjective: Little is known about the effect of age at first childbirth on lung function. We aimed to investigate the association between age at first childbirth and lung function in Chinese women and further test whether this association is mediated by body mass index (BMI).Methods: This cross-sectional study is a partial survey of the China Kadoorie Biobank (CKB) which was conducted in Xinxiang City, Henan Province between 2004 and 2008. A total of 16,584 postmenopausal women aged 30– 79 years were enrolled. Multiple linear and logistic regression were used to investigate the association between age at first childbirth and lung function and overweight/obesity. The mediation analysis was performed using the PROCESS procedure for SPSS.Results: The mean (SD) age at first childbirth was 23.1 (2.7) years. Women with first childbirth aged ≤ 19 years and 20– 22 years had lower lung function than women who gave first childbirth aged 23– 25 years. Per 1-year increase in the age at first childbirth was associated with a 3.31 mL increase in FEV1 (95% CI = 1.27– 5.35), 3.91 mL increase in FVC (95% CI = 1.63– 6.18), 0.15% increase in FEV1, % predicted (95% CI = 0.05– 0.24) and 0.14% increase in FVC, % predicted (95% CI = 0.05– 0.22). There was no clear association between age at first childbirth and FEV1/FVC ratio. BMI played a contribution to the association between age at first childbirth and FEV1 and the proportion was 16.4% (indirect effect: β = 0.65, 95% CI = 0.46– 0.89; total effect: β = 3.96, 95% CI = 1.92– 5.99). Similarly, the proportion to FVC, FEV1, % predicted, and FVC, % predicted was 25.0%, 16.6%, and 25.0%, respectively.Conclusion: Early age at first childbirth was associated with lower lung function and BMI mediated the association. It is important to test lung function and popularize the knowledge of weight control in women who gave first childbirth at an early age.Keywords: first childbirth, lung function, body mass index, mediation, postmenopausal women

Meixue Yao,1,* Mengda Liu,2,* Xia Chen,3 Jianjun Li,4 Yan Li,5 Yu Run Wei,2 Yong Liu,3 Kang Long Yang,3 Xiaoxiao Duan,5 Weixing Shao,2 Xiangxiang Sun,2 Xiaoxu Fan,2 Shufang Sun,2 Lili Tian,2 Dehui Yin,1 Mingjun Sun2 1Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China; 2Laboratory of Zoonoses, China Animal Health and Epidemiology Center, Qingdao, 266032, People’s Republic of China; 3Yubei Animal Husbandry and Aquatic Products Station, Chongqing, 401120, People’s Republic of China; 4School of Animal Science and Veterinary Medicine, Tianjin Agriculture College, Tianjin, 300384, People’s Republic of China; 5Qingdao Animal Disease Prevention and Control Center, Qingdao, 266000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingjun Sun, Laboratory of Zoonoses, China Animal Health and Epidemiology Center, No. 369 Nanjing Road, Qingdao, 266032, People’s Republic of China, Email sunmingjun@cahec.cn Dehui Yin, Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, People’s Republic of China, Email yindh16@xzhmu.edu.cnBackground: Brucellosis is one of the most important zoonotic diseases in the world. Canine brucellosis, caused mainly by Brucella canis, is seriously neglected, and there is a lack of accurate diagnostic tools.Methods: In this study, to compare BP26, Omp25, Omp31 and a multiepitope-based fusion protein in the serological detection of canine brucellosis, using 34 brucellosis-positive dog sera and 62 negative control sera, the Brucella outer membrane proteins Omp31, BP26, Omp25 and a multiepitope-based fusion protein were evaluated by iELISA for their potential use as antigens in the serological diagnosis of canine brucellosis.Results: The results showed that the multiepitope-based fusion protein performed best in distinguishing brucellosis-positive and brucellosis-negative dog sera, with a positive predictive value (PPV) of 100% and a negative predictive value (NPV) of 98.41%. BP26 and Omp31 showed excellent sensitivity in detecting brucellosis-positive dog sera, but their cross reaction to sera infected with Vibrio parahaemolyticus and Listeria monocytogenes may hinder their application as diagnostic reagents. Omp25 lacked sufficient sensitivity and showed limited ability in distinguishing positive and negative dog sera.Conclusion: The multiepitope-based fusion protein can be used as an ideal antigen for serologically diagnosing canine brucellosis currently prevalent worldwide.Keywords: Brucella, outer membrane protein, multiepitope, canine brucellosis

Songping Liu,1,2,* Junjun Qiu,3,* Xiaoyan Tang,3,* Qinmei Li,1 Wei Shao1 1Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, Zhenjiang Maternal and Child Hospital, Zhenjiang, Jiangsu, People’s Republic of China; 3Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Songping Liu, Email spliu0619@163.comBackground: Long noncoding RNAs (lncRNAs) are involved in the pathogenesis of endometriosis and can be regulated by estrogen. This study aimed to investigate the role of estrogen in regulating the expression and function of lncRNA-H19 in endometriosis.Methods: Endometrial stromal cells (ESCs) were isolated from ectopic, eutopic endometrium with endometriosis and control endometrium without endometriosis, and lncRNA-H19 expression was detected using real-time polymerase chain reaction (RT-PCR). Ectopic endometrial stromal cells (ecESCs) were treated with 17β-estradiol at 10− 8mol/L for 0, 12, 24 and 48 hours, and lncRNA-H19 expressions of cells were evaluated using RT-PCR. After ecESCs were treated with 17β-estradiol for 48 hours, lncRNA-H19 expression was knocked down and cell proliferative and invasive abilities were compared.Results: The expression of lncRNA-H19 in ecESCs was significantly higher than that in eutopic endometrial stromal cells (euESCs) and control ESCs. After treated with 17β-estradiol, ecESCshadupregulatedlncRNA-H19 expression with time-dependent manner. Cell proliferation and invasion increased when estrogen upregulated lncRNA-H19 expression in ecESCs, however, cell proliferation restored and cell invasion did not change when lncRNA-H19 was knocked down in ecESCs.Conclusion: The expression and function of lncRNA-H19 was regulated by estrogen in ecESCs, which probably contributed to the pathogenesis of endometriosis.Keywords: endometriosis, lncRNA-H19, estrogen, proliferation, invasion, ectopic endometrial stromal cells

Bo Wang,1,* Song Gong,2,* Lizhi Han,2 Wenkai Shao,2 Zilin Li,2 Jiawei Xu,2 Xiao Lv,2 Baojun Xiao,2 Yong Feng2 1Department of Rehabilitation, Wuhan No.1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baojun Xiao; Yong Feng, Email drxiao999@sohu.com; fengyong@hust.edu.cnBackground: Histone deacetylase 9 (HDAC9) is a member of the HDAC gene family that plays essential roles in the organization of transcriptional regulation by catalyzing deacetylation of histone proteins. However, the effects of HDAC9 on osteonecrosis of femoral head (ONFH) have not been investigated. The present study aimed to reveal whether histone deacetylase 9 (HDAC9) regulated osteogenic differentiation.Methods: A lentiviral knockdown HDAC9 model was established in hBMSCs. Osteoblast-specific gene expression, such as Runx2, OCN was examined by qRT-PCR and Western blot, respectively. Though transcriptome sequencing and enrichment analysis, related signal pathways caused by down-regulation of HDAC9 were screened. The effect of HDAC9 on MAPK signaling pathway was determined by Western blot. Eventually, tert-Butylhydroquinone (tBHQ) was used to examine the effect of MAPK activation on osteogenesis in HDAC9 knockdown hBMSCs.Results: A lentiviral knockdown HDAC9 model was successfully established in hBMSCs. HDAC9 knockdown significantly inhibited osteoblast-specific gene expression, such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and mineral deposition in vitro. Moreover, a total of 950 DEGs were identified in HDAC9-knockdown hBMSCs. We discovered that the MAPK signaling pathway might be related to this process by pathway enrichment analysis. HDAC9 knockdown significantly reduced the expression level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). Finally, the decreased osteogenesis due to HDAC9 knockdown was partly rescued by a MAPK signaling pathway activator.Conclusion: Taken together, these results suggest that HDAC9 knockdown inhibits osteogenic differentiation of hBMSCs, partially through the MAPK signaling pathway. HDAC9 may serve as a potential target for the treatment of ONFH.Keywords: HDAC9, hBMSCs, osteogenesis, MAPK signaling pathway

Zeyu Wang,1,* Yonghe Zhou,2,3,* Pengzhi Yu,2,3 Yonggang Liu,3,4 Mei Mei,5 Zhuo Bian,2 Wei Shao,2 Jinxia Lv,2 Xin Li,2 Wei Lu,1,3,6 Liang Xu3,6 1Department of Hepatobiliary Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 2Ultrasound department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China; 3Tianjin Research Institute of Liver Diseases, Tianjin, 300192, People’s Republic of China; 4Pathology Department, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China; 5Department of Gastroenterology, Tianjin Haihe Hospital, Tianjin, 300350, People’s Republic of China; 6Department of Hepatology, Tianjin Second People’s Hospital, Tianjin, 300192, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Lu; Liang Xu, Email luwei1966@126.com; xuyangliang2004@sina.comBackground: At present, there is a lack of cheap, effective and convenient detection methods for hepatitis B-related liver fibrosis, especially in the developing area.Aim: To evaluate the non-invasive methods for the significant and advanced fibrosis stage in chronic hepatitis B virus (HBV) patients in basic hospitals and to assess their diagnostic utility.Methods: The study included 436 consecutive naive HBV individuals who had their livers biopsied. They were examined in one week using aspartate aminotransferase-to-aspartate aminotransferase ratio (AAR), age-platelet index (API), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (FIB-4), Forns, gamma-glutamyl transpeptidase-to-platelet ratio (GPR), S-index and transient elastography (TE). Scheuer scoring system was used to determine the histologic fibrosis grades (S0–S4). The diagnostic effectiveness was assessed using AUROCs and the DeLong test, both of which were based on statistical comparisons.Results: For both substantial (≧S2) and advanced (≧S3) fibrosis phases, TE had good diagnostic performance in determining the hepatic fibrosis. Similar diagnostic performance was shown with Forns and S-index when it came to detecting fibrosis stages lower than S3. One model’s diagnostic value was not significantly improved by combining serum models. Correlation coefficients between clinical features and fibrosis phases were greatest for Forns (r = 0.397), S-index (r = 0.382) and TE (r = 0.535) when compared to other variables.Conclusion: This investigation showed that Forns and S-index may be helpful strategies for detecting advanced fibrosis in HBV patients admitted to community hospitals.Keywords: hepatitis B virus, non-invasive, basic hospital, transient elastography, Forns, S-index

In this research, the characteristics of nickel-titanium (NiTi) powders produced by electrode induction melting inert gas atomization (EIGA) technique for additive manufacturing (AM) technology are investigated using various powder characterization technologies. The results show that the particle size distribution (PSD) of pre-alloyed NiTi powders prepared by EIGA has the range of 10 μm to 180 μm. The mean particle size distribution (D50) of the powder is 75 μm. The oxygen increase of the powder is only 0.005% compared to the raw rod. According to the requirements of the characteristics of the metal powder material used for AM, the powders are sieved into three categories, P1 (15-63 μm), P2 (63-150 μm), and P3 (>150 μm), respectively. The flow rates of P1 and P2 are 19.3 and 17.5 s·(50 g)-1, respectively. The surface, crosssectional microstructure, phase structure, and martensitic transformation temperature of the pre-alloyed NiTi powders with different particle sizes are investigated. The results show that powders of different particle sizes are primarily spherical or nearly spherical. The grain size of powders reduces with the decreasing of particle size. Both the bar stock and the powders of P1, P2, and P3 mainly exhibit the B2 phase. Comparing the powders P1, P2, and P3, the transformation temperature reduces with the decrease of particle size. A high density (99.55%) pre-alloyed NiTi specimen is successfully produced by selective laser melting (SLM) technology using P1 powders. The results indicate that the pre-alloyed NiTi alloy powder is appropriate for AM, which also has a good reference value for researchers producing AM powders.

Zhen Sun1,2 *, Zhenhua Lu1 *, Rui Li,1,2 Weiwei Shao,1,2 Yangyang Zheng,1,2 Xiaolei Shi,1 Yao Li,1 Jinghai Song1,2 1Department of General Surgery, Department of Hepato-Bilio-Pancreatic Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 2Graduate School of Peking Union Medical College, Beijing, 100730, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinghai Song Email jhaisong2003@163.comBackground: The aim of this study was to screen and identify immunoautophagy-related genes (IARGs) in HCC patients and clarify their potential prognostic value in HCC patients.Methods: Immune-related genes and autophagy-related gene were downloaded from public databases. Cox regression analysis was used to selected several immunoautophagy-related genes to establish a prognostic model, and patients were divided into high- and low-risk groups based on median risk score. We analyzed the overall survival and clinicopathological characteristics between two groups. Meanwhile, internal validation dataset and external ICGC dataset were used to verify robustness of the model. Associations between six immune cells infiltrates and risk score were analyzed.Results: A prognostic model was established based on CANX and HDAC1. The prognoses of the high-risk group were worse than low-risk group in both TCGA and ICGC datasets. Multivariate Cox regression analysis showed that risk score was an independent prognostic factor for HCC patients. Results showed that the risk score in young group was higher than elderly group. Patients with poorly differentiated tumor may have high risk score and poor survival. The score was positively correlated with immune cells.Conclusion: Our study shows that immunoautophagy-related genes have potential prognostic value for patients with HCC and may provide new information and direction for targeted therapy.Keywords: hepatocellular carcinoma, immune-related genes, autophagy-related gene, overall survival

Xiaoning Cen,1,&ast; Yunmei Huang,2,&ast; Zhuangnian Lu,3,&ast; Wenjun Shao,4 Chenyi Zhuo,1 Chongchan Bao,5 Shi Feng,5 Cheng Wei,5 Xiqiang Tang,5 Lijun Cen,5 Wenwen Guo,5 Xinru Tian,5 Qianli Tang,5 Xusen Huang1 1General Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 4Medical college of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 5YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianli TangYouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail htmgx@163.comXusen HuangGeneral Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail hxsfy@163.comBackground: LncRNAs play an important role in tumor initiation and development. However, the underlying involvement of lncRNA expression in colorectal carcinoma remains to be clarified.Methods: All analyses were performed in R software v4.0, SPSS v13.0, and GraphPad Prism 8. The “limma” package was used to identify differentially expressed lncRNAs between two groups with the threshold of |logFC| > 1 and P < 0.05. The “Survival” package was used to conduct survival analysis. HCT8 and SE480 cell lines were used to conduct further phenotype experiments, including transwell, wound-healing, CCK8 and colony formation assay. Gene set enrichment analysis was used to explore the biological pathway difference in high and low IGFL2-AS1 patients.Results: The lncRNA IGFL2-AS1 was highly expressed in colon adenocarcinoma (COAD) tissue and cell lines (HCT116, HCT8, HCT129, and SW480). The COAD patients with high IGFL2-AS1 were associated with a worse prognosis. Meanwhile, the knockdown of IGFL2-AS1 could significantly suppress the proliferation and invasion of COAD cells. Gene set enrichment analysis showed that the top five biological pathways involving IGFL2-AS1 were angiogenesis, epithelial–mesenchymal transition, KRAS signaling, myogenesis, and coagulation. Western blot results showed that the inhibition of IGFL2-AS1 could significantly reduce the N-cadherin, HIF1A and KRAS protein expression, yet increase the E-cadherin protein level. IGFL2-AS1 was also positively correlated with M0 macrophages, M2 macrophages, and neutrophils but negatively correlated with CD4+ memory T cells and CD8+ T cells.Conclusion: IGFL1-AS1 could seriously worsen patient outcomes and facilitate COAD progression, thus serving as an independent tumor marker.Keywords: IGFL2-AS1, lncRNA, colon cancer, immune

Miaoguo Cai,1,* Wei Shao,1,* Huijun Yu,2 Ye Hong,1 Lili Shi3 1Department of Medical Oncology, Luqiao Branch of Taizhou Hospital, Taizhou City, Zhejiang Province, People’s Republic of China; 2Department of Pediatric, Luqiao Branch of Taizhou Hospital, Taizhou City, Zhejiang Province, People’s Republic of China; 3Department of Infection, Luqiao Branch of Taizhou Hospital, Taizhou City, Zhejiang Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei ShaoDepartment of Medical Oncology, Luqiao Branch of Taizhou Hospital, No. 1 Xialiqiao West Road, Luqiao District, Taizhou City 318050, Zhejiang Province, People’s Republic of ChinaTel +86-57682421047Email hmeimw@163.comBackground: Hepatocellular carcinoma (HCC) is one of the most common tumors with high mortality. MicroRNAs (miRNAs) were reported as crucial markers for the diagnosis of HCC. Paeonol exerted many pharmacological effects on tumor progression. This study aimed to elucidate the underlying molecular mechanism of paeonol in HCC progression.Methods: Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was examined by flow cytometry. The levels of Cyclin D1, cyclin-dependent kinase 4 (CDK4), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were detected by Western blot assay. Cell migration and invasion were assessed by transwell assay. The levels of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) were measured by Western blot. The expression of miR-21-5p and kruppel-like factor 6 (KLF6) was detected by quantitative real-time PCR (qRT-PCR) or Western blot assay, respectively. Dual-luciferase reporter assay was performed to analyze the interaction between miR-21-5p and KLF6. The enrichment of miR-21-5p was determined by RNA pull-down assay. Xenograft assay was conducted to analyze tumor growth in vivo.Results: The results demonstrated that cell viability of Hep3B and Huh-7 cells was inhibited, while cell apoptosis was promoted after treatment with paeonol. Transwell assay indicated that cell migration and invasion were blocked in paeonol-treated cells. Moreover, miR-21-5p expression was markedly decreased in paeonol-treated cells and its knockdown suppressed cell viability, migration and invasion, but contributed to cell apoptosis. MiR-21-5p targeted KLF6 and its silencing prominently elevated KLF6 level. Furthermore, the restoration experiment determined that miR-21-5p and KLF6 were antagonisms on cell viability, apoptosis, migration and invasion. Also, paeonol abated the decrease in KLF6 level caused by miR-21-5p up-regulation. Besides, paeonol suppressed tumor growth in vivo.Conclusion: Paeonol impeded cell viability, migration and invasion and triggered apoptosis by regulating miR-21-5p/KLF6 axis in HCC cells. Xenograft assay confirmed that paeonol inhibited tumor growth through miR-21-5p/KLF6 axis in HCC in vivo.Keywords: hepatocellular carcinoma, paeonol, miR-21-5p, KLF6

Xin Wan,1,2,* Dawei Chen,1,* Yan Tan,3 Mengqing Ma,2 Feng Zhang,1 Zhihe Liu,1 Yue Chen,1 Wei Shao,2 Changchun Cao2 1Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changchun CaoDepartment of Nephrology, Sir Run Run Hospital, Nanjing Medical University, No. 109 Longmian Street, Nanjing, Jiangsu 211100, People’s Republic of ChinaEmail caochangchun@njmu.edu.cnPurpose: Little is known about the incidence, risk factors, and prognostic implications of acute kidney injury (AKI) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in China. In this study, we investigated the incidence, risk factors, and short-term outcomes of AKI in these patients.Patients and Methods: We analyzed the records of 1768 patients admitted to Nanjing First Hospital with a principal diagnosis of AECOPD. Of these, 377 patients had AKI.Results: AKI occurred in 377 patients (21%). Independent risk factors for AKI in patients with AECOPD were advanced age, coronary artery disease, anemia, cancer, chronic kidney disease, hypercapnic encephalopathy, acute respiratory failure, and mechanical ventilation. Patients with AKI had worse prognostic implications and were more likely to require mechanical ventilation (38.7% vs 19.1%, P< 0.001); non-invasive mechanical ventilation (38.2% vs 18.9%, P< 0.001); invasive mechanical ventilation (18.3% vs 3.1%, P< 0.001); intensive care unit (ICU) admission (33.7% vs 12.9%, P< 0.001); had a longer ICU stay (9 days vs 8 days, P=0.033) and longer hospitalization (13 days vs 10 days, P< 0.001); and higher in-hospital mortality (18.0% vs 2.7%, P< 0.001) than those without AKI. Multivariable analysis indicated that compared to patients without AKI, those with stage 1, 2, or 3 AKI had a 1.9-fold, 2.1-fold, or 6.0-fold increased risk of in-hospital death, respectively.Conclusion: AKI is common in patients with AECOPD requiring hospitalization. Patients with AKI have worse short-term outcomes. Thus, AKI may be a prognostic predictor of patient survival.Keywords: acute kidney injury, acute exacerbation of chronic obstructive pulmonary disease, incidence, risk factor, prognostic implication

Wenbo Shao,1,* Caixia Li,2,* Jun Tang,3 Jinlong Song,1 Zixiang Li,4 Jize Sun,5 Yili Xu,6 Zhaomin Zheng,7 Jingqin Cao,8 Lei Zhang3 1Department of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Interventional Radiology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3Department of Interventional Radiology, Shandong Medical Imaging Research Institute, Jinan, People’s Republic of China; 4Department of Interventional Radiology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 5Department of Interventional Radiology, Qingdao Central Hospital, Qingdao, People’s Republic of China; 6Department of Interventional Radiology, 960 Hospital of People’s Liberation Army, Tai’an, People’s Republic of China; 7Department of Interventional Radiology, Qianfoshan Hospital of Shandong Province, Jinan, People’s Republic of China; 8Department of Interventional Radiology, People’s Hospital of Jining City, Jining, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun TangDepartment of Interventional Radiology, Shandong Medical Imaging Research Institute, 324 Jingwu Road, Jinan, Shandong 250021, People’s Republic of ChinaTel +86 13964031909Email tangjun7925032@163.comJinlong SongDepartment of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, Shandong 250117, People’s Republic of ChinaTel +86 13969080678Email jls7286@163.comObjective: To evaluate the efficacy and safety of raltitrexed plus oxaliplatin-based transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC).Methods: A total of 123 patients with unresectable HCC were recruited into the prospective cohort study. Raltitrexed plus oxaliplatin-based TACE was performed according to the traditional method at monthly intervals and was repeated for up to 4 cycles if no disease progression or intolerable toxicity occurred. The primary efficacy endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and tumor response rate. The Cox proportional-hazards regression model was used to assess the independent prognostic factors of OS. Adverse events were also observed.Results: The median OS time and PFS were 623 days (95% CI: 461, 785) and 338 days (95% CI: 302, 704), respectively. The disease control rate was 95.5% (118/123). The Cox proportional-hazards regression model indicated that age, ECOG performance status and response to TACE as independent prognostic factors of OS. No treatment-related mortality occurred within 30 days of treatment procedure. The most common complications included postembolization syndrome, liver dysfunction and hematological toxicity. Grade 3 pain, transglutaminase abnormality and thrombocytopenia were observed in 16 (13%), 15 (12.2%) and 3 (2.4%) patients, respectively. No grade 4 adverse events were observed.Conclusion: Raltitrexed plus oxaliplatin-based TACE led to high tumor response rate and promising PFS and OS, and was considered safe and tolerable in patients with unresectable HCC.Keywords: raltitrexed, oxaliplatin, hepatocellular carcinoma, transarterial chemoembolization

Chang-chun Cao,1,* Da-wei Chen,2,* Jing Li,2 Meng-qing Ma,2 Yu-bao Chen,3 Yi-zhi Cao,4 Xi Hua,2 Wei Shao,1 Xin Wan2 1Department of Nephrology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 2Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 3Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China; 4The First Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, China *These authors contributed equally to this work Purpose: Previous studies have described the incidence, risk factors, and outcomes for patients with acute exacerbations of COPD (AECOPD) developing acute kidney injury (AKI). However, little is known about the differences between community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) in patients with AECOPD. Thus, in this study, we compared prevalence, risk factors, and outcomes for these patients with CA-AKI and HA-AKI. Patients and methods: This study was conducted from January 2014 to January 2017, and data from adult inpatients with AECOPD were analyzed retrospectively. A total of 1,768 patients were included, 280 patients were identified with CA-AKI and 97 patients were with HA-AKI. Results: Prevalence of CA-AKI was 15.8% and that of HA-AKI was 5.5%, giving an overall AKI prevalence of 21.3%. Patients with CA-AKI had a higher prevalence of chronic kidney disease (CKD) and lower prevalence of chronic cor pulmonale than patients with HA-AKI. Risk factors for developing HA-AKI and CA-AKI were similar, such as being elderly, requirement for mechanical ventilation, and a history of coronary artery disease and CKD. Patients with HA-AKI were more likely to have stage 3 AKI and worse short-term outcomes. In comparison with patients with CA-AKI, those with HA-AKI were more likely to require non-invasive mechanical ventilation (31.3% versus 16.8%; P = 0.003) and had a longer duration of mechanical ventilation (11 days versus 8 days; P = 0.020), longer hospitalization (14 days versus 12 days; P = 0.038), and higher inpatient mortality (32.0% versus 13.2%; P < 0.001). Patients with HA-AKI had worse (multivariate-adjusted) inpatient survival than those with CA-AKI (hazard ratio, 1.7 [95% confidence interval, 1.03–2.81; P = 0.038] for the HA-AKI group). Conclusion: AKI was common in patients with AECOPD requiring hospitalization. CA-AKI was more common than HA-AKI but otherwise demonstrated similar demographics and risk factors. Nevertheless, patients with HA-AKI had worse short-term outcomes. Keywords: acute exacerbation of COPD, community-acquired acute kidney injury, hospital-acquired acute kidney injury, short-term outcomes

Yong-Liang Liu, Peng-Fei Liu, Wei Shao, Hong-Peng Du, Zhen-Zhu Li, Chong Guo, Ze-Fu Li Department of Neurosurgery, Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong, Yantai, People’s Republic of China Objective: At present, there is no consensus regarding the standard treatment for glioblastoma (GBM) in elderly patients with impaired Karnofsky performance status (KPS) scores. This study aimed to determine the effects of temozolomide (TMZ) versus best supportive care (BSC) in this population. Materials and methods: We conducted a retrospective observational study of patients aged ≥65 years with histologically confirmed GBM and KPS scores ≤70 who were treated at our institution between January 2006 and July 2014. Demographic data, treatments, and outcomes were evaluated. Univariate and multivariate analyses were performed to identify the independent prognostic factors of overall survival (OS) and progression-free survival (PFS). The impact of TMZ on survival was analyzed by the application of propensity score matching of clinicopathological factors among patients who received TMZ vs BSC. Results: There were 153 patients (86 men, 56.2%) in this study. The median patient age was 70 years (range: 65–83 years). The median KPS score was 60 (range: 30–70). Seventy-eight patients (51.0%) received TMZ, whereas 75 (49.0%) received BSC. Median OS and PFS were 6.0 and 4.5 months, respectively. Compared with BSC, TMZ was associated with improved OS (hazard ratio [HR]: 0.38, 95% CI: 0.17–0.70; P=0.002) and PFS (HR: 0.41, 95% CI: 0.21–0.76; P=0.003) after propensity score matching. Factors independently associated with OS were KPS score (HR: 2.11, 95% CI: 1.48–7.67; P=0.016), extent of resection (HR: 1.98, 95% CI: 1.45–5.14; P=0.026), and treatment group (HR: 0.49, 95% CI: 0.23–0.87; P=0.019). The most frequent toxicity in the TMZ group was myelosuppression.Conclusion: Compared with BSC, TMZ increased survival with acceptable toxicity in elderly GBM patients with KPS scores ≤70. Keywords: temozolomide, best supportive care, elderly, glioblastoma, prognostic factors

Mingsheng Zhang, Enda Xue, Wei Shao Department of Pediatric Surgery, Liaocheng People’s Hospital, Liaocheng, Shandong Province, People’s Republic of China Background: Nephroblastoma (Wilms’ tumor [WT]) is the most common malignant renal cancer in children. Although the outcome of WT has significantly improved as a result of the combination of surgery, chemotherapy, and radiotherapy; in some cases WT results in severe complications. Thus, novel strategies that would decrease treatment burden are required. The aim of the current study was to investigate the synergistic antitumor effect of andrographolide (AND) in combination with vincristine (VCR) on WT cells.Methods: Cell Counting Kit-8 assay was used to investigate the synergistic antiproliferation effect of AND and/or VCR on SK-NEP-1 cells in vitro. Meanwhile, SK-NEP-1 xenografts were used to detect the antitumor effect in vivo. Apoptosis and autophagy were then detected by Annexin V, monodansylcadaverine staining. Finally, the underlying signaling transduction was determined with Western blotting.Results: The combination of AND with VCR significantly suppressed SK-NEP-1 cell proliferation in vitro and inhibited xenograft tumor growth in vivo, compared with AND or VCR treatment alone. In addition, the synergistic antitumor effect of AND on the cells was due to an increased apoptosis, not autophagy. Moreover, PI3K-AKT-p53 signaling pathway was involved in the process of combination treatment, which was confirmed when a selective AKT activator was applied.Conclusion: The combination of AND with VCR has a strong synergistic antitumor effect on WT via PI3K-AKT-p53 signaling pathway, thereby representing a potential treatment for WT in the near future. Keywords: andrographolide, vincristine, p53, drug combination

Weiwei Shao,* Quhui Wang,* Feiran Wang, Yasu Jiang, Meirong Xu, Junfei XuDepartment of General Surgery, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China*These authors contributed equally to this workAbstract: The aim of this study was to investigate the calcyphosine (CAPS) expression in human colorectal cancer (CRC) and to explore its clinical and prognostic significances. CAPS expression was measured by Western blot, real-time polymerase chain reaction analysis, and immunohistochemistry. The relationships between the CAPS expression levels and the clinicopathological factors were investigated. The Kaplan–Meier method and log-rank test were used to investigate the overall survival of the patients. Moreover, the effects of CAPS on biological roles of CRC cells were also evaluated by MTT assay, colony formation assay, and transwell assay. CAPS was significantly overexpressed in cancerous tissue and CRC cell lines compared with adjacent nontumor tissue and a normal human intestinal epithelial cell line. Overexpression of CAPS was significantly associated with histological grade (P=0.004), invasive depth (P

Liting Guo,1,* Haijun Zhang,1,* Weiwei Shao,2 Baoan Chen1 1Department of Hematology and Oncology (Key Department of Jiangsu Medicine), The Affiliated Zhongda Hospital, Medical School of Southeast University, Nanjing, 2Department of Pathology, the First People’s Hospital of Yancheng, Yancheng, Jiangsu, People’s Republic of China *These authors contributed equally to this work Abstract: Crizotinib, the first clinically designed and synthesized as a tyrosine kinase inhibitor targeting mesenchymal–epithelial transition factor, indicating marked anticancer activity in patients with advanced, anaplastic lymphoma kinase-positive non-small-cell lung cancer, was approved by the US Food and Drug Administration in 2011. In this review, we focus on the efficacy of crizotinib compared with chemotherapy in advanced anaplastic lymphoma kinase-positive lung cancer and present the role of crizotinib as a personalized alternative in previously treated patients with non-small-cell lung cancer. Keywords: crizotinib, anaplastic lymphoma kinase rearrangement, non-small-cell lung cancer

Wenbo Shao, Fengjuan Zhang, Ning Cong, Jinpeng Li, Jinlong SongDepartment of Surgical Oncology (Interventional Therapy), Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaObjective: To investigate the reactivation of the hepatitis B virus (HBV) following transarterial chemoembolization (TACE) in Chinese hepatocellular carcinoma (HCC) patients with low serum HBV DNA level, and to analyze the factors related to HBV reactivation in HCC patients with low serum HBV DNA level.Methods: From November 2011 to January 2014, 109 patients newly diagnosed with HCC with an HBV DNA level less than 2,000 IU/mL were enrolled in the study. These patients underwent at least two TACE procedures and were followed-up for at least 3 months to assess the reactivation of HBV DNA. Ten variables were compared in patients with and without HBV reactivation to evaluate the factors related to HBV reactivation in HCC patients with low serum HBV DNA level.Results: Of 109 HCC patients with low level HBV DNA, nine patients were HBeAg-positive, the other 100 patients were HBeAg-negative. Twenty-three of 109 (21.1%) patients developed HBV reactivation after TACE. Of nine HBeAg-positive patients, 55.6% (5/9) developed HBV reactivation, while in 100 HBeAg-negative patients, the rate of HBV reactivation was 18% (18/100) (P=0.019). Of ten variables of patients with low level HBV DNA, the levels of AFP and HBeAg status were found to be significantly correlated with HBV reactivation. Nevertheless, on binary logistic regression analysis, only HBeAg-positive status was the independent predictor of HBV reactivation in HCC patients with low serum HBV DNA level (odds ratio, 7.41; P=0.013).Conclusion: HCC patients with low serum HBV DNA level still remain associated with risk of viral reactivation after TACE, and HBeAg-positive HCC patients have a higher risk than patients with HBeAg-negative status.Keywords: HBV DNA, viral reactivation, hepatocellular carcinoma, transarterial chemo­embolization

Wei Shao1, Arghya Paul1, Sana Abbasi1, Parminder S Chahal2, Jimmy A Mena2, Johnny Montes2, Amine Kamen2, Satya Prakash11Biomedical Technology and Cell Therapy Research Laboratory, Department of Biomedical Engineering and Artificial Cells and Organs Research Centre, Faculty of Medicine, McGill University, 2Animal Cell Technology, Bioprocess Centre, Biotechnology Research Institute, National Research Council, Montreal, Quebec, CanadaBackground: Systemic delivery of small interfering RNA (siRNA) is limited by its poor stability and limited cell-penetrating properties. To overcome these limitations, we designed an efficient siRNA delivery system using polyethyleneimine-coated virus-like particles derived from adeno-associated virus type 2 (PEI-AAV2-VLPs).Methods: AAV2-VLPs were produced in insect cells by infection with a baculovirus vector containing three AAV2 capsid genes. Using this method, we generated well dispersed AAV2-VLPs with an average diameter of 20 nm, similar to that of the wild-type AAV2 capsid. The nanoparticles were subsequently purified by chromatography and three viral capsid proteins were confirmed by Western blot. The negatively charged AAV2-VLPs were surface-coated with PEI to develop cationic nanoparticles, and the formulation was used for efficient siRNA delivery under optimized transfection conditions.Results: PEI-AAV2-VLPs were able to condense siRNA and to protect it from degradation by nucleases, as confirmed by gel electrophoresis. siRNA delivery mediated by PEI-AAV2-VLPs resulted in a high transfection rate in MCF-7 breast cancer cells with no significant cytotoxicity. A cell death assay also confirmed the efficacy and functionality of this novel siRNA formulation towards MCF-7 cancer cells, in which more than 60% of cell death was induced within 72 hours of transfection.Conclusion: The present study explores the potential of virus-like particles as a new approach for gene delivery and confirms its potential for breast cancer therapy.Keywords: adeno-associated virus type 2, virus-like particles, small interfering RNA delivery, breast cancer therapy, nanomedicine

A Master Sintering Curve (MSC) for rutile TiO2 was constructed for Pressure-less sintering using constant heating rate dilatometry data based on the combined-stage sintering model. Construction of the master sintering curve is described and the validation is proved with rutile TiO2 under different thermal histories. The concept of master sintering can be used to predict the sintering shrinkage and final density and calculate the activation energy, and a value of 105 KJ/mol for TiO2 was obtained. With one temperature dependent parameter determined experimentally, it became possible to describe accurately the densification behavior of TiO2 from the initial to final stages of sintering. .

Using the particle swarm optimization algorithm, we conducted an extensive search for the high-pressure stable structure of technetium diboride (TcB2) within the pressure range of 0–400 GPa. At zero pressure, the P63/mmc (hP6-TcB2) structure is considered the ground state configuration. As the pressure increases, a structural transition from hP6-TcB2 to P6/mmm (hP3-TcB2) occurs at approximately 174.9 GPa. We discuss the bonding between the two distinct phases and analyze the contribution of different atomic bonds to maintaining their structural stability. Meanwhile, the temperature–pressure phase diagram of TcB2 was successfully determined for the first time through the quasi-harmonic approximation method. It is predicted that the transition pressure from hP6-TcB2 to hP3-TcB2 can be reduced to about 164 GPa at a room temperature of 300 K. These results provide valuable insights into the behavior of TcB2 under different temperature and pressure conditions and open up new possibilities for exploring its potential applications in a variety of environments. [ABSTRACT FROM AUTHOR]

The proliferation of urban sensing, IoT, and big data in cities provides unprecedented opportunities for a deeper understanding of occupant behaviour and energy usage patterns at the urban scale. This enables data-driven building and energy models to capture the urban dynamics, specifically the intrinsic occupant and energy use behavioural profiles that are not usually considered in traditional models. Although there are related reviews, none investigated urban data for use in modelling occupant behaviour and energy use at multiple scales, from buildings to neighbourhood to city. This survey paper aims to fill this gap by providing a critical summary and analysis of the works reported in the literature. We present the different sources of occupant-centric urban data that are useful for data-driven modelling and categorise the range of applications and recent data-driven modelling techniques for urban behaviour and energy modelling, along with the traditional stochastic and simulation-based approaches. Finally, we present a set of recommendations for future directions in data-driven modelling of occupant behaviour and energy in buildings at the urban scale.

Abstract Background Quantitative proteomics is an emerging field that encompasses multiplexed measurement of many known proteins in groups of experimental samples in order to identify differences between groups. Antibody arrays are a novel technology that is increasingly being used for quantitative proteomics studies due to highly multiplexed content, scalability, matrix flexibility and economy of sample consumption. Key applications of antibody arrays in quantitative proteomics studies are identification of novel diagnostic assays, biomarker discovery in trials of new drugs, and validation of qualitative proteomics discoveries. These applications require performance benchmarking, standardization and specification. Results Six dual-antibody, sandwich immunoassay arrays that measure 170 serum or plasma proteins were developed and experimental procedures refined in more than thirty quantitative proteomics studies. This report provides detailed information and specification for manufacture, qualification, assay automation, performance, assay validation and data processing for antibody arrays in large scale quantitative proteomics studies. Conclusion The present report describes development of first generation standards for antibody arrays in quantitative proteomics. Specifically, it describes the requirements of a comprehensive validation program to identify and minimize antibody cross reaction under highly multiplexed conditions; provides the rationale for the application of standardized statistical approaches to manage the data output of highly replicated assays; defines design requirements for controls to normalize sample replicate measurements; emphasizes the importance of stringent quality control testing of reagents and antibody microarrays; recommends the use of real-time monitors to evaluate sensitivity, dynamic range and platform precision; and presents survey procedures to reveal the significance of biomarker findings.

As a multifunctional flower with both ornamental and nutritional value, the chrysanthemum has been cherished worldwide. To explore the effects on growth, yield, and quality of Chrysanthemum morifolium x 'Yanshan Jinhuang' under different agroforestry intercropping models, the growth status, photosynthesis, antioxidant leaf substances, and nutrient content of chrysanthemum flowers under nine Acer buergerianum - Chrysanthemum morifolium x 'Yanshan Jinhuang' intercropping modes, and three chrysanthemum monoculture modes with different planting densities were investigated. The results revealed that the canopy closure of Acer buergerianum had significant impacts on the growth of chrysanthemum flowers, and the accumulation of nutrients in major petals. The stomatal conductance and superoxide dismutase activities of leaves were the primary factors that affected the accumulation of secondary metabolites in petals. When the canopy closure ranged from 0.2-0.39 and the chrysanthemum planting density was 40 x 40 cm, the flower yield of chrysanthemum reached 10137 kg·ha-1. This was 34.29% - 38.14% higher than under a single planting mode and the nutrient content was also higher. This study showed that moderate shading improved the flower yield and quality of chrysanthemums in eastern China. Thus, we recommend that growing edible chrysanthemums under forests with proper shade can reduce the investments required for cultivation facilities, while obtaining good quality high-yielding chrysanthemum products. [ABSTRACT FROM AUTHOR]