1.The research progress of bile acid efflux pump (BSEP)
Jing ZHAO ; Manyu CHEN ; Lei LI
Chinese Pharmacological Bulletin 2017;33(1):18-21,22
Bile acid efflux pump(BSEP)is the major transporter of bile salts secreted by liver cells into the bile,the variation and inhibition of which are connected with cholestasis and drug-induced liver injury.A deep understanding of the physiological and pathological function of BSEP IS achieved by analysis and summary of diseases.The paper briefly illustrates the structure, expression,regulation,substrates,inhibitors and diseases of BSEP,in order to provide further theoretical and experimental basis for the clinical treatment.
2.Clinical study of fast track surgery in colorectal cancer patients
Donghua WANG ; Manyu CHEN ; Yuzhen WANG ; Zhenggui TAO ; Long LV
International Journal of Surgery 2011;38(9):598-601
ObjectiveControl study on the clinical efficiency and costs of fast track surgery(FTS) and traditional method was carried out in colorectal cancer patients. Methodsone hundred colorectal cancer patients were randomLy selected, 50 cases treated with conventional therapy as control group and 50 cases treated with FTS programme. The postoperative initial venting time, the incidence of complications, the hospital stay and cost index were compared between the two groups. ResultsThe postoperative initial venting time was in advance and postoperative stay was obviously shortened in FTS group. Hospitalization expenditure in FTS group was lower than that in control group. Patients recovered quickly, the result was satisfactory. The complication was not significantly different between the two groups (P > 0.05 ) . ConclusionsFTS treatment can accelerate postoperative rehabilitation and elevate clinical efficiency in colorectal cancer patients during operation period. FTS treatment is a safe and effective method.
3.Survey on the Cognition and Attitude towards Dignity Therapy in College Students
Xiangyu YAN ; Yian FANG ; Shengmin ZHAO ; Jianxia TAN ; Manyu ZHAO ; Huiping CHEN
Chinese Medical Ethics 2017;30(9):1170-1175
Objective:To investigate the cognition of terminal stage patients'dignity therapy,attitude towards its concept and scheme,willingness of its promotion in college students and to gain some recommendations for improvement.Methods:Combined quantitative and qualitative methods,an anonymous questionnaire survey was conducted in a convenience sample of 220 college students,of which 20 students were selected for in-depth interviews.Results:Only 17.73% of students had a correct understanding of dignity therapy,94.98% of them accepted its concept,92.96% of them held a positive attitude,74.38% of them were willing to promote dignity therapy,in which female students were dominated (P =0.041).Interview results showed that the contents of dignity therapy were to some extent stiff and not fit for Chinese patients,which might impede its promotion.Conclusion:College students lack the cognition of dignity therapy.But they hold a positive attitude and are willing to promote dignity therapy when they get to know its concept and contents.As seen,dignity therapy has a good future but there are still some obstructions in the promotion,and need to be localized.
4.The dose-response relationship between low-dose ionizing radiation and thyroid hormone of medical workers
Manyu ZHANG ; Ning LIU ; Huipeng CHEN ; Xiaohua YE ; Zhenjiang YAO ; Xinguang ZHONG
Chinese Journal of Radiological Health 2021;30(4):397-401
Objectives To explore the dose-response relationship between low-dose ionizing radiation and thyroid hormone levels of radiation medical workers and provide theoretical basis for occupational health protection to this population. Methods Using a prospective cohort study design, we collected health examination reports on employees that worked on jobs with occupational exposure to radiation at hospital with individually dose monitoring data for 1 237 workers. The effective cumulative radiation dose was divided into three groups: 0~2.586 mSv, 2.586~3.757 mSv, 3.758~31.272 mSv by the interquartile range. The low-dose group was used as a reference to compare the changes in thyroid hormones of medical workers in different cumulative radiation dose groups. The generalized linear models and restricted cubic spline model were used to examine the association and dose-response relationship between the cumulative effective dose and changing thyroid hormones. Results There were statistically significant differences in changing thyroxine (T4) and Free triiodothyronine (FT3) levels among three different dose groups of 1237 subjects (P < 0.05). The results of generalized linear models analysis revealed that 2.586~3.757 mSv was a significant risk factors of changing T4, with β of 3.514 (95% confidence interval [95% CI]: 0.900~6.128) after adjusting for gender, age, working duration, occupation, medical level and smoking, while the association with changing FT3 was not observed (P > 0.05). The restrictive cubic spline (RCS) model analysis indicated a non-linear dose-response correlation between cumulative radiation dose with changing T4 (P = 0.023). Conclusion Long-term exposure to low-dose ionizing radiation could induce the thyroid damage among medical occupational population. And there is a dose-response relationship between cumulative radiation dose and changing thyroxine.
5.Research progress of brain imaging in cognitive behavioral therapy for depression
Manyu HE ; Huiying WANG ; Yan LI ; Xinyu WANG ; Chen QIU ; Zihan YU ; Yifang FU ; Jinyu ZHANG ; Yali WANG ; Changhong WANG
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(12):1148-1152
The prevalence and recurrence rate of depressive disorder are high, while the recognition and cure rate are low. Early intervention can improve the quality of life of patients with depression. In clinical practice, it has been found that psychological treatments can effectively improve the symptoms and prognosis of depression.Cognitive behavior therapy(CBT) has been widely used in the treatment of depression, however, its mechanisms are still unclear. In this paper, the neuroimaging studies of patients with depression before and after CBT were summarized, and the structural or functional changes of different brain regions in patients with depression before and after CBT were described. The findings suggest that CBT improved depressive symptoms by increasing gray matter volume, activation level, and functional connectivity strength in the dorsolateral prefrontal cortex, reducing activation levels in the amygdala and parahippocampal gyrus, and restoring abnormal brain network activity or functional connectivity. Larger gray matter volume in anterior cingulate gyrus and higher activation levels in hippocampus and amygdala before treatment can effectively predict the effect of CBT in depressed patients. In the future, machine learning could be combined with brain imaging data to more accurately predict the effectiveness of CBT in treating depression.
6.hsa-miR-124-3p.1 inhibits the migration and invasion of human gastric cancer cells by targeting TRAF6
Zhenggui TAO ; Jinghu DU ; Kui TIAN ; Donghua WANG ; Fengqi HU ; Manyu CHEN
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(6):843-849
【Objective】 To observe the effects of hsa-miR-124-3p.1 in inhibiting epithelial-mesenchymal transition (EMT), migration and invasion of human gastric cancer cells induced by transforming growth factor β1 (TGF-β1) by targeting tumor necrosis factor receptor-associated factor 6 (TRAF6). 【Methods】 A total of 43 gastric cancer tissues and 43 normal para-carcinoma tissues were collected. The human gastric mucosal epithelial cells GES-1 and gastric cancer cells (NCI-N87, MGC-803, BGC-823, SGC-7901, and MKN-45) were cultured. The expressions of miR-124-3p.1 and TRAF6 in tissues and cells were detected by fluorescent quantitative PCR and Western blotting. The targeted relationship between miR-124-3p.1 and TRAF6 was verified by dual-luciferase reporter gene system assay. SGC-7901 cell lines with miR-124-3p.1 and TRAF6 overexpression were constructed. The cells were induced by TGF-β1. The invasion and migration abilities of the cells were evaluated by Transwell chamber assay and scratch test. 【Results】 Compared with normal para-carcinoma tissues and normal gastric mucosal cells, the expression of miR-124-3p.1 was downregulated, while the expressions of TRAF6 mRNA and protein were upregulated in gastric cancer tissues and cells (P<0.05). Compared with control group, expression of E-cadherin in cells was downregulated, expressions of N-cadherin and Vimentin were upregulated, invasion and migration rates of cells were increased in TGF-β1 group (P<0.05). Compared with TGF-β1 group, after cells were transfected with miR-124-3p.1 mimic, the expression of E-cadherin was upregulated, the expressions of N-cadherin and Vimentin were down-regulated, and invasion and migration rates of cells were decreased (P<0.05). Compared with miR-124-3p.1 mimic group, invasion and migration rates of cells were increased in TGF-β1+mimic+TRAF6 group, expressions of TRAF6, N-cadherin and Vimentin were up-regulated, and the expression of E-cadherin was down-regulated (P<0.05). 【Conclusion】 hsa-miR-124-3p.1 is lowly expressed in gastric cancer. Overexpression of miR-124-33p.1 can inhibit EMT, cell invasion and migration induced by TGF-β1. And the action mechanism may be related to the downregulated expression of TRAF6.
7.Design, synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152): a novel triple angiokinase inhibitor for cancer therapy.
Yuqin YAO ; Zhuowei LIU ; Manyu ZHAO ; Zhengxia CHEN ; Peng LI ; Yang ZHANG ; Yuxi WANG ; Chengjian ZHAO ; Chaofeng LONG ; Xiaoxin CHEN ; Jinliang YANG
Acta Pharmaceutica Sinica B 2020;10(8):1453-1475
Angiokinases, such as vascular endothelial-, fibroblast- and platelet-derived growth factor receptors (VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics (PD) and pharmacokinetics (PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152, identified from a series of 4-oxyquinoline derivatives based on a structure-activity relationship study, inhibited the proliferation of vascular endothelial cells (ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFR simultaneously . Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patient-derived tumor xenograft (PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles. In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective triple-angiokinase inhibitor with clear PD and PK in tumor therapy.