1.Construction and drug resistance evaluation of cell strains which stably express FIP1L1-PDGFRA protein and its mutants
Jingwen LIU ; Haoxin SONG ; Lei ZHU
Basic & Clinical Medicine 2024;44(1):63-68
Objective To construct mouse BaF3-FIP1L1-PDGFRA(F/P),BaF3-F/P-T674I and BAF3-F/P-D842V pre-B cell strains which stably express F/P fusion protein and its T674I and D842V mutants in order to e-valuate their activity by checking their responses to tyrosine kinase inhibitors(TKIs).Methods Lentivirus infected technique was used to transfect the target gene into BaF3 cells.RT-qPCR was used to detect mRNA expression,and CCK-8 method was used to detect the inhibitory effect of TKIs on the proliferation of stable cell strains.Results The constructed BaF3-F/P,BaF3-F/P-T674I and BAF3-F/P-D842V cell strains all transcripted FIP1L1 and PDGFRA mRNA.They exhibited malignant phenotypic characteristics of proliferation independent of IL-3 and sen-sitivity to corresponding TKIs.Conclusions The pre-B-cell strains stably expressing F/P and its T674I and D842V mutants are successfully constructed,which provide a good cell model for the development of compounds targeting at those molecules.
2.Research on a model of risk perception of venous thromboembolism in pregnant women
Haoxin LIU ; Lili HUANG ; Xiaohua CUI ; Fuying TAO ; Man ZHOU ; Panpan ZHANG ; Yingying TIAN
Chinese Journal of Nursing 2024;59(18):2229-2237
Objective To construct a theoretical model of venous thromboembolism(VTE)risk perception in pregnant women,so as to provide a scientific basis for promoting pregnant women to form a correct risk perception of VTE and actively take preventive behaviors.Methods A qualitative research approach guided by the procedural grounded theoiy was adopted.Data were collected by a semi-structured deep interview on 18 pregnant women who received prenatal examination in the outpatient department of a tertiary A obstetrics and gynecology hospital in Nanjing from June to July 2023,and the data were analyzed by three-level coding and continuous comparison method.Results The VTE risk perception of pregnant women was affected by 6 factors including social coupling system,self health status,life behavior habits,knowledge on disease,compliance behavior and emotional stimulation.Pregnant women perceived VTE risk from 3 aspects:threats to maternal and child safety,increased family economic burden and increased time cost,impact on social roles.Thus,3 health behavior decisions were formed,including taking preventive behaviors,overcoming implementation barriers,and seeking knowledge behaviors,in order to reduce their own risk of VTE,and prevent the occurrence of VTE.Conclusion The theoretical model of VTE risk perception of pregnant women can guide medical staff to comprehensively consider the influencing factors of VTE risk perception of pregnant women,optimize the form and content of VTE health education,give pregnant women individualized and sustainable VTE prevention guidance,and strengthen pregnant women's perception of VTE risk and the benefits of preventive behavior,so as to actively take the correct health behavior decisions.
3.A qualitative study on the dyad coping experience of stress in pregnant women with undifferentiated connective tissue disease and their spouses
Fuying TAO ; Haoxin LIU ; Ruizhe JIA ; Lan WU ; Dongying FU ; Wenqing ZHOU ; Yingying TIAN
Chinese Journal of Nursing 2024;59(22):2760-2765
Objective To explore the dyad coping experience of stress in pregnant women with undifferentiated connective tissue disease and their spouses,providing a basis for developing dyadic coping intervention measures.Methods By purposive sampling,15 pairs of pregnant women and their spouses who visited the outpatient clinic for pregnancy complicated with immune diseases in a matemity hospital in Jiangsu Province from April to August 2023 were selected as the research subjects for semi-structured interviews.Content analysis was conducted using the Colaizzi 7-step method,and an interview outline and integrated themes were developed based on the Developmental Contextual Coping Model.Results 3 themes(coexistence of positive and negative stress experiences;diverse approaches to dyadic coping with stress;growth and challenges following stress adaptation)and 11 subthemes were identified.Conclusion Healthcare professionals should attach importance to the stress coping issues of pregnant women with undifferentiated connective tissue disease and their spouses,take measures to regulate the negative emotions of couples,ensure multi-faceted support,help the couple adopt positive coping strategies,and promote good stress adaptation.
4.Preparation of 4-sulfonylcalix6arene-modified cotton for uranium contamination removal
Haoxin GUO ; Yilong WANG ; Zebao ZHENG ; Kunlu LIU ; Rongqing HUANG ; Zhibing ZHENG ; Bo HUANG ; Zhixin WANG ; Meiyu WANG ; Benbo LIU ; Guo CHEN ; Xu WANG ; Zhihua YANG ; Maoxiang ZHU
Chinese Journal of Radiological Health 2023;32(6):603-610
Objective To prepare 4-sulfonylcalix[6]arene-modified cotton fibers for adsorption and removal of uranium based on the specific complexation of calix[6]arene with uranium (VI). Methods Chemical grafting was used for the modification of cotton, which reacted with α-bromoisobutyryl bromide, glycidyl methacrylate, and 4-sulfonylcalix[6]arene. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FTIR) were used to characterize the structure of 4-sulfonylcalix[6]arene-modified cotton (Cotton S-C[6]a). A Franz diffusion cell was used to simulate uranium-contaminated skin. Laser fluorimetry was used to determine the uranium content. Results SEM, XPS, and FTIR showed that cotton fibers were successfully grafted with 4-sulfonylcalix[6]arene. The optimal conditions of Cotton S-C[6]a for the adsorption of uranium (VI) was pH 4.0, duration of 20 min, and 20 mg of adsorbent. The adsorption process fitted well with pseudo-secondary-order kinetics. The uranium removal efficiency of Cotton S-C[6]a was up to 78.46% in aqueous solution and 81.72% on skin. Conclusion The synthesized Cotton S-C[6]a is highly efficient in the removal of uranium (VI) in solution and on contaminated skin.
5.Chain mediating effect of rumination and avoidance coping between information anxiety and suicidal ideation in college students
Shuhao ZHANG ; Dong XUE ; Qiangqing WANG ; Yuxuan YANG ; Zijie LI ; Haoxin LIU
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(12):1123-1128
Objective:To explore the mediating roles of rumination and avoidance coping between information anxiety and suicidal ideation.Methods:In March 2022, a total of 896 college students were surveyed by the information anxiety scale(IAS), ruminative responses scale(RRS), coping style questionnaire(CSQ)and self-rating idea of suicidal ideation scale(SIOSS). The ANOVA analysis, Pearson correlation analysis and mediating effect analysis were performed by the SPSS 22.0 software.Results:The detection rate of suicidal ideation among college students was 9.15%(82/896). The information anxiety score was(73.84±17.29), the rumination score was(47.73±12.16), the avoidance coping score was(3.76±2.52), and the suicidal ideation score was(5.41±4.09). Information anxiety was significantly positively correlated with rumination, avoidance coping and suicidal ideation( r=0.49, 0.36, 0.37, all P<0.05). Rumination was significantly positively correlated with avoidance coping and suicidal ideation( r=0.42, 0.59, both P<0.05). There was a significantly positive correlation between avoidance coping and suicidal ideation( r=0.45, P<0.05). Information anxiety affected suicidal ideation of college students through four paths.The direct effect value of information anxiety on suicidal ideation was 0.06, accounting for 16.67% of the total effect. The effect values of the separate mediating effect of rumination and avoid coping were 0.22 and 0.04, and accounting for 61.11% and 11.11% of the total effect respectively. The chain mediating effect value of rumination and avoid coping was 0.04, accounting for 11.11% of the total effect. Conclusion:Information anxiety can directly affect suicidal ideation of college students and indirectly affect suicidal ideation through rumination and avoidance coping.
6.Discovery of novel exceptionally potent and orally active c-MET PROTACs for the treatment of tumors with MET alterations.
Pengyun LI ; Changkai JIA ; Zhiya FAN ; Xiaotong HU ; Wenjuan ZHANG ; Ke LIU ; Shiyang SUN ; Haoxin GUO ; Ning YANG ; Maoxiang ZHU ; Xiaomei ZHUANG ; Junhai XIAO ; Zhibing ZHENG ; Song LI
Acta Pharmaceutica Sinica B 2023;13(6):2715-2735
Various c-mesenchymal-to-epithelial transition (c-MET) inhibitors are effective in the treatment of non-small cell lung cancer; however, the inevitable drug resistance remains a challenge, limiting their clinical efficacy. Therefore, novel strategies targeting c-MET are urgently required. Herein, through rational structure optimization, we obtained novel exceptionally potent and orally active c-MET proteolysis targeting chimeras (PROTACs) namely D10 and D15 based on thalidomide and tepotinib. D10 and D15 inhibited cell growth with low nanomolar IC50 values and achieved picomolar DC50 values and >99% of maximum degradation (Dmax) in EBC-1 and Hs746T cells. Mechanistically, D10 and D15 dramatically induced cell apoptosis, G1 cell cycle arrest and inhibited cell migration and invasion. Notably, intraperitoneal administration of D10 and D15 significantly inhibited tumor growth in the EBC-1 xenograft model and oral administration of D15 induced approximately complete tumor suppression in the Hs746T xenograft model with well-tolerated dose-schedules. Furthermore, D10 and D15 exerted significant anti-tumor effect in cells with c-METY1230H and c-METD1228N mutations, which are resistant to tepotinib in clinic. These findings demonstrated that D10 and D15 could serve as candidates for the treatment of tumors with MET alterations.
7.Antigen presentation and T cell activation by dendritic cells in radiation damage
Qian LI ; Shuang GENG ; Chengming YAN ; Haoxin GUO ; Zhixin WANG ; Meiyu WANG ; Benbo LIU ; Xu WANG ; Yilong WANG ; Zhihua YANG ; Maoxiang ZHU
Chinese Journal of Radiological Health 2022;31(6):657-662
Objective To explore dendritic cells (DCs)-mediated antigen presentation for radiation-injured cells by using the in vitro cell co-culture technology to simulate the in vivo microenvironment of the lung tissue. Methods 60Co γ-irradiated mouse lung epithelial cells (MLE-12) were cultured with bone marrow-derived DCs and/or splenic T lymphocytes for 48 hours. Flow cytometry was used to measure the expression levels of costimulatory molecules (CD80/86) and antigenic peptide recognition complexes (the major histocompatibility complex [MHC] class Ⅰ/Ⅱ) on DCs and T cell activation markers (CD69/28/152) as well as the numbers of CD4+ and CD8+ T cells. Results 60Co γ irradiation significantly increased the apoptosis rate of MLE-12 cells in a dose-dependent manner, and significantly stimulated the expression of CD80/86 and MHC Ⅱ on DCs, without direct activation of T cells. After γ (6 Gy)-irradiated MLE-12 cells were co-cultured with DCs and T lymphocytes for 48 h, there were significant increases in the expression of CD69 and CD28 on T cells, the numbers of CD4+ and CD8+ T cells, and the expression of CD86 and MHC I on DCs, as compared with the control groups. Conclusion Radiation-injured cells can stimulate antigen presentation by DCs and activate T cells.
8.Systematic Review of Methodological Guidelines for Health Technology Assessment at Home and Abroad
Peipei XU ; Wenrui LI ; Linan ZENG ; Dan LIU ; Yang ZHANG ; Xue MI ; Zongyao HUANG ; Haoxin SONG ; Lingli ZHANG
China Pharmacy 2020;31(12):1500-1499
OBJECTIVE:To evaluate guidelines f or health technology assessment (HTA)at home and abroad ,and to provide reference for scientific formulation of HTA guidelines in China. METHODS :Databases including PubMed ,Embase,Guidenlines International Network and 83 official websites from 26 countries governments and academic organizations were searched to collect HTA guidelines from inception to April 2020. Two reviewers independently screened literature and extracted data ,including basic characteristics, content of guideline and assessment content. Then a descriptive analysis was conducted. RESULTS & CONCLUSIONS:A total of 19 guidelines published during 2001 to 2018 were included ,7 guidelines(36.8%)were published in 2015-2020;in addition to 1 guideline from WHO ,14 guidelines (73.7%)were published in Europeand ,2 guidelines(10.5%) in North America and 1 guideline each from South America and Asia (5.3%). There were 11 guidelines(57.9%)developed by academic organizations and 8 guidelines(42.1%)by health administration ;11 guidelines(57.9%)were evidence-based ,while the others weren ’t evidence- based (42.1%). The purpose ,content and object of assessment are demonstrated in 19 guidelines;18 guidelines specified the assessment method (94.7%),and 16 guidelines(84.2%)defined the subject of assessment ;14 guidelines (73.7%)specified the HTA assessment process ;12 guidelines(63.3%)mentioned the conflict of interest in HTA assessment process;7 guidelines(36.8%)mentioned the application of assessment results. There are some differences in the formulation methods and contents of HTA guidelines in foreign countries ,but the core contents ar e basically the same. At present ,there is a lack of HTA guidelines in China. We can refer to foreign guidelines,and establish applicable HTA guidelines which aresuitable for national conditions ,so as to provide scientific guidance for HTA research.
9.The regulating and mediating effects of resilience on the influence of job resources on anxiety of nur-ses
Xin GUO ; Jing WANG ; Jingjuan PANG ; Yueying LU ; Shaobo LYU ; Lina LI ; Haoxin LIU ; Jie YUAN
Chinese Journal of Behavioral Medicine and Brain Science 2018;27(6):551-555
Objective To explore the relationship between job resources and anxiety on nurses,and investigate the moderating and mediating effects of resilience on job resources and anxiety. Methods Chi-nese nurses ( n=560) from some departments of four hospitals in tangshan city were recruited by random sampling method and interviewed by job resources questionnaire,Connor-Davidson resilience scale and self-rating anxiety scale. Results The scores of nurses'anxiety,resilience and job resources were 40.82±9.63, 9.45±1.82,and 93.24±16.61 respectively.The resilience,job resources and its dimensions were negatively correlated to nurses'anxiety (P<0.05).Resilience played moderating role in the relationship between nurses'anxiety and work autonomy(β=0.168,P<0.01).Resilience served to mediate the relationship between nurses'anxiety and performance feedback,career development opportunities (P<0.05). The mediating effect value of performance feedback and career development opportunities on nurses' anxiety were -0.115881 and-0.068052 respectively ,which were 41.26% and 32.71% of the total effect respectively. Conclusion Job resources and resilience are closely related to nurses'anxiety.Resilience plays partially moderating and medi-ating role in the relationship between nurses'anxiety and job resources.
10.Relationship between mental health service demand, loneliness, anxiety and depression of rural left-behind women
Lina LI ; Jiuju LI ; Shanshan ZHANG ; Haoxin LIU ; Shuhao ZHANG ; Yekun SUN ; Shu SU ; Xiaoyu YU
Chinese Journal of Behavioral Medicine and Brain Science 2018;27(8):763-768
Objective To explore the correlation between psychological health service demand and loneliness and anxiety depression in rural left-behind women.Methods 260 left-behind wo nen in Hebei province were surveyed by psychological health service demand scale,UCLA loneliness scale,trait anxiety scale and the center for epidemiologic studies depression scale (CES-D).Results There were statistically significant differences between the only child and non-only child left-behind women in mental health service demand ((131.72±13.91) vs (122.94±14.76)),loneliness ((52.94±5.65) vs (49.864±5.90)) and anxiety ((50.97±6.38) vs (47.16±4.80)) (t=3.313,2.899,4.151,P<0.01).The mental health service demand,loneliness,anxiety and depression of left-behind women were different in the age of marriage (F=6.196,9.441,5.257,4.221,all P<0.01),husband go out time (F=2.761,27.020,4.550,2.830,all P<0.05) and degree of farm work (F=12.142,6.403,4.115,5.366,all P<0.001).The anxiety of left-behind women was positively correlated with service content,service demand and depression (r=0.138-0.221,P<0.01).Depression was negatively correlated with mental health service demand and service teams (r=-0.352--0.223,P< 0.01).Loneliness was positively correlated with service content,anxiety and depression (r=0.177-0.262,P< 0.01).Multiple linear regression showed that husbands go out time (β=0.326),farm work in very heavy degree (β=-0.376) and relatively heavy degree (β=-0.281),depression (β=-0.194) had a predictive effect on mental health services.Conclusion The mental health service demand of left-behind women are affected by their age,whether the only child,the age of marriage,their husbands' go out time and the degree of heavy farm work.


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