1.Development of monoclonal antibodies against PD-L1 and preliminary investigation on potential application in treatment of chronic hepatitis B virus in-fection
Yong WU ; Tianying ZHANG ; Liuwei SONG ; Ningshao XIA ; Quan YUAN
Chinese Journal of Immunology 2016;32(7):1004-1008,1012
Objective:To get specific monoclonal antibodies ( mAbs) against PD-L1 which can block PD-1/PD-L1 binding, and explore the feasibility of its application on the treatment of chronic HBV infection preliminarily by in vitro and in vivo model. Methods:E. coli expression and series chromatography purification system were employed to get human and mouse PD-1/PD-L1 that had binding activity in vitro. By immunizing BALB/c mouse with purified recombination proteins of PD-L1,mAb hybridoma cell lines against PD-L1 were obtained. The reactivity with human/mice PD-L1 of individual antibody and the interaction blocking activity of the mAbs to PD-1/PD-L1 in vitro were examined by indirect chemiluminescence immune assay. Results: 8 cell lines against PD-L1 were obtained and 2 Anti-PDL1 mAbs (Ab5 &Ab6) performed strong immune activity to human/mice PD-L1 and blocking activity to PD-1/PD-L1. In the PBMC stimulation experiment of chronic HBV patient,Ab5 and Ab6 could promote theγ-IFN levels. With HBV in-fecting mice model,intravenous injections of these mAbs induced dramatically decrease of HBV DNA copies about 20 times, HBsAg levels in serum reduced to 30% of the baseline level. Conclusion:We obtained 2 PD-L1 mAbs with the reactivity to human/mice PD-L1 and blocking activity to PD-1/PD-L1. The 2 mAbs can promote T cell function in PBMC stimulation culture of chronic HBV patient, have significant antiviral effect in HBV transgenic mice and can be candidates for immunotherapy applications.
2.Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations and prognosis in resected non-small cell lung cancer
Lianmin ZHANG ; Ligang HAO ; Hua ZHANG ; Liuwei GAO ; Daowei WANG ; Zhenfa ZHANG ; Changli WANG
Chinese Journal of Clinical Oncology 2014;(17):1075-1079
Objective:To investigate the relationship between serum carcinoembryonic antigen (CEA) and the predictive value of epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer patients, as well as to analyze further EGFR muta-tions and CEA levels affecting patient survival. Methods:From March 2009 to March 2011, a total of 387 cases were treated in the Lung Cancer Department in Tianjin Cancer Hospital. Preoperative CEA tumor marker and postoperative EGFR gene mutation were used for routine detection. The influence of CEA tumor marker on EGFR mutation and its relationship with the prognosis were ana-lyzed further. Results:A total of 168 cases involved EGFR mutations, the incidence of which is more frequent in women, non-smokers, adenocarcinoma patients, and patients below 60 years old (P<0.05). This study also determined that EGFR mutation was related with tu-mor markers and chemosensitivity indicators. Elevated Cyfra21-1, SCC, and ERCC1-positive are more common in wild-type patients (P<0.05). However, abnormal CEA was more common in EGFR mutation patients (P=0.015). The rate of EGFR gene mutations signifi-cantly increased as the serum CEA level increased. Serum CEA levels were divided into three groups (<5, 5-20, and>20). The positive rates of EGFR mutations were 40.1%, 47.5%and 66.6%(P=0.003). Logistic regression analysis determined that CEA levels are inde-pendent factors in predicting EGFR mutations and independent prognostic factors in patients with non-small cell lung cancer. Conclu-sion:Serum CEA levels can independently predict the prognosis of resected non-small cell lung cancer patients, which is has a close re-lationship with EGFR mutations.
3.Medical image retrieval based on nonlinear texture features.
Wei LIU ; Hong ZHANG ; Qinye TONG
Journal of Biomedical Engineering 2008;25(1):35-38
To extract texture features from medical images, the approaches for multi-scale complexity and multi-scale fractal dimension were proposed in this paper. The extracted texture features were used in the medical image retrieval experiments. The complexity measurements used include permutation entropy and 2D-C0 complexity. The former is used to analyze one dimensional signal, and the latter is used to analyze two dimensional one. Comparison experiments were carried out between our approaches and others' approaches in some literatures. Preliminary experimental results show that our approaches can effectively describe the texture information of medical images. Furthermore, the image retrieval results are encouraging.
Automation
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Diagnostic Imaging
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Humans
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Information Storage and Retrieval
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methods
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Nonlinear Dynamics
4.Reliability and validity of Driving Anger Scale in professional drivers in China
Zhen LI ; Yaming YANG ; Cong ZHANG ; Yang LI ; Jie HU ; Liuwei GAO ; Yixi ZHOU ; Xujun ZHANG
Chinese Journal of Epidemiology 2017;38(11):1476-1479
Objective To assess the reliability and validity of the Chinese version of Driving Anger Scale (DAS) in professional drivers in China and provide a scientific basis for the application of the scale in drivers in China. Methods Professional drivers, including taxi drivers, bus drivers, truck drivers and school bus drivers, were selected to complete the questionnaire. Cronbach's α and split-half reliability were calculated to evaluate the reliability of DAS, and content, contract, discriminant and convergent validity were performed to measure the validity of the scale. Results The overall Cronbach'sα of DAS was 0.934 and the split-half reliability was 0.874. The correlation coefficient of each subscale with the total scale was 0.639-0.922. The simplified version of DAS supported a presupposed six-factor structure, explaining 56.371% of the total variance revealed by exploratory factor analysis. The DAS had good convergent and discriminant validity, with the success rate of calibration experiment of 100%. Conclusion DAS has a good reliability and validity in professional drivers in China, and the use of DAS is worth promoting in divers.
5.Research of the core items of Physical Literacy Guidelines for Children and Adolescents
Chinese Journal of School Health 2021;42(11):1698-1702
Objective:
Physical literacy is the breakthrough point and fundamental goal to achieve the integration of sports and education, sports and public health and expand the function of physical education. Studying the children and adolescents physical literacy is a common responsibility for children and adolescents health, sports and health education workers. This article was based on the latest research evidence and expert opinions in China, aiming to develop the core items of physical literacy guidelines for Chinese children and adolescents.
Methods:
This article systematically combed the dimensions and index system of children and adolescents physical literacy through systematic literature review. After five rounds of Delphi methods, the core items were extracted.
Results:
The core items included four interrelated dimensions of body, emotion, behavior, and cognition, which were specifically composed of four components: physical ability, emotional experience, physical activity related behaviors, and knowledge understanding and application ability.
Conclusion
Children and adolescents are the key periods, sensitive periods, and window periods to cultivate physical literacy. The core items can provide framework recommendations for further refining guidelines. More empirical studies should be carried out in the future, in order to accumulate enough evidences and further to improve Physical Literacy guidelines, better to guide physical literacy promotion.
6.The influence of serum triggering receptor expressed on myeloid cells 1 level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome
Jianping YANG ; Hua FAN ; Wen LI ; Yao YAO ; Meijia SHEN ; Liuwei ZHANG ; Xiaoxia REN ; Hongbo ZHANG
Chinese Journal of Geriatrics 2023;42(6):715-719
Objective:To study the influence of serum triggering receptor expressed on myeloid cells 1(TREM-1)level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome(ARDS).Methods:A total of 100 elderly patients with sepsis were selected as the research objects.All the patients with sepsis were divided into sepsis ARDS group and sepsis non-ARDS group.General data and TREM-1 level were compared between the two groups.The patients with sepsis ARDS were divided into death group and survival group according to the survival status during the 28-day follow-up.TREM-1 level, acute physiology and chronic health evaluation(APACHE)Ⅱ score and SOFA score were compared between the two groups.The correlation between serum TREM-1 level and procalcitonin(PCT), APACHE Ⅱ score and SOFA score was analyzed.The survival rate of high TREM-1 level group and low TREM-1 level group was compared.Results:The age, white blood cell(WBC), PCT, APACHE Ⅱ score, SOFA score and TREM-1 level of sepsis ARDS patients were significantly higher than those of non-ARDS patients( t=2.722, 6.088, 11.55, 6.889, 4.661, 6.122, all P<0.05). The incidence of sepsis ARDS patients with chronic obstructive pulmonary disease was significantly higher than that of non-ARDS patients( χ2=7.895, P<0.05). Serum TREM-1 level, APACHE Ⅱ score and SOFA score of ARDS patients in death group were significantly higher than those in survival group( t=3.293, 6.173, 4.255, all P<0.05). Serum TREM-1 level was positively correlated with PCT, APACHE Ⅱ score and SOFA score( t=0.553, 0.602, 0.636, P<0.001). The Kaplan-Meier survival curve showed that the survival rate of high TREM-1 level group was significantly lower than that of low TREM-1 level group( χ2=3.999, P=0.036). Cox regression analysis showed that TREM-1 level was a risk factor for the prognosis of ARDS patients with sepsis( HR=1.893, 95% CI: 1.049-3.414). Conclusions:Serum TREM-1 level is significantly increased in elderly patients with sepsis ARDS, which is closely related to the prognosis and can be used as a potential prognostic biomarker.
7.Protective effect of hydroxysafflor yellow A on lung injury associated with severe acute pancreatitis in mice
Jin ZHAO ; Lichao SUN ; Wenjing WU ; Jianping YANG ; Yiqiang XIE ; Liuwei ZHANG ; Meijia SHEN
Chinese Journal of Emergency Medicine 2022;31(6):789-793
Objective:To investigate the protective effect and mechanism of hydroxysafflor yellow A (HSYA) on severe acute pancreatitis (SAP) related lung injury.Methods:Fifty mice were randomly (random number) divided into five groups: the sham-operated group, SAP group and different doses (20, 40 and 80 mg/kg) of HSYA pretreatment group. Mice were pretreated with HSYA 24 h before SAP induction, pancreatic and lung tissues were isolated for histopathological examination at 72 h after modeling, and bronchoalveolar lavage fluid (BALF) was collected for biochemical analysis. Results:Compared with the sham-operated group, serum amylase activity, lung injury pathological score and BALF protein concentration in the SAP group were significantly increased [(2120.44 ± 354.50) U/L vs. (226.72 ± 20.84) U/L; (6.91 ± 0.28) vs. (0.53±0.18); (2563.25±348.22) μg/mL vs. (345.62±56.35) μg/mL, all P<0.05]. Inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels and myeloperoxidase (MPO) activity were increased [(120.5±14.25) pg/mL vs. (31.5±4.82) pg/mL; (214.72±10.62) pg/mL vs. (39.26±5.66) pg/mL; (4.52±0.34) U/mg vs. (1.03±0.17) U/mg]. Compared with the SAP group, HSYA pretreatment significantly attenuated SAP-related pancreatic and lung tissue damage and the activities of the inflammatory factors TNF-α, IL-6 and MPO in BALF. In addition, HSYA promoted the expression of the antioxidant protein heme oxygenase-1 and blocked the activation of the NF-κB signaling pathway. Conclusions:HSYA exerts anti-inflammatory and antioxidant activities to inhibit SAP-related lung injury, which indicated that HSYA may be a potential therapeutic drug for SAP-induced lung injury.
8. Clinical significance of serum level changes of heart-type fatty acid-binding protein and S-100B protein in elderly patients with chronic heart failure
Xu CHEN ; Hongbo ZHANG ; Wen LI ; Yao YAO ; Yunyun XUE ; Meijia SHEN ; Liuwei ZHANG ; Lichao SUN
Chinese Journal of Geriatrics 2019;38(9):971-975
Objective:
To investigate serum level changes of heart-type fatty acid-binding protein(H-FABP)and S100 calcium-binding protein B(S-100B)protein in elderly patients with chronic heart failure and their clinical significance.
Methods:
A total of 160 patients with chronic heart failure treated at our hospital were recruited, and 80 healthy individuals receiving regular check-ups were enrolled as normal controls.Serum levels of H-FABP and S-100B and cardiac function index scores were compared between patients with different cardiac function grades.Correlations of serum H-FABP and S-100B levels with N-terminal pro-B-type natrlure tiepeptide(NT-proBNP)and with cardiac function index scores in heart failure patients were analyzed.The sensitivity, specificity and accuracy of serum H-FABP, S-100B and NT-proBNP for heart failure detection were compared.
Results:
Serum levels of H-FABP, S-100B and NT-proBNP in elderly patients with chronic heart failure were elevated with increased cardiac function grading(
9.A novel biological sources consistency evaluation method reveals high level of biodiversity within wild natural medicine: A case study of Amynthas earthworms as "Guang Dilong".
Zhimei XING ; Han GAO ; Dan WANG ; Ye SHANG ; Tenukeguli TULIEBIEKE ; Jibao JIANG ; Chunxiao LI ; Hong WANG ; Zhenguo LI ; Lifu JIA ; Yongsheng WU ; Dandan WANG ; Wenzhi YANG ; Yanxu CHANG ; Xiaoying ZHANG ; Liuwei XU ; Chao JIANG ; Luqi HUANG ; Xiaoxuan TIAN
Acta Pharmaceutica Sinica B 2023;13(4):1755-1770
For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.