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Objective@#To explore the most economically feasible cervical cancer screening strategies in urban China.@*Methods@#A series of Markov models were constructed to evaluate health and economic outcomes of different screening strategies. There were 24 screening strategies including four screening methods: liquid-based cytology (LBC), human papillomavirus (HPV) DNA genotyping, HPV DNA genotyping with LBC triage (HPV DNA+ LBC), HPV DNA genotyping and LBC co-testing (HPV DNA-LBC), along with three intervals (every 1, 3 or 5 years) and two starting age for screening (30 or 35 years old) were compared. Models parameters were obtained from a cervical cancer screening study in urban China and literature reviews.@*Results@#The cumulative incidence and mortality risk of cervical cancer declined over 69% and 82% respectively for each screening strategy as compared with the no screening scenario. LBC every five years starting from 35 years old strategy cost the least (RMB 690 per capita) and could save life years compared with no screening. The cost effectiveness ratios of 24 strategies ranged from -10 903 to 117 992 RMB per life year saved. All strategies were cost-effective compared to no screening. In the incremental cost-effectiveness analysis, LBC every 5 years starting from 30 strategy, HPV DNA genotyping every 3 years starting from 30 strategy, LBC every 3 years starting from 30 strategy and LBC every year starting from 30 strategy were dominant strategies.@*Conclusions@#Screening can effectively prevent cervical cancer. In urban Chinese areas with insufficient socioeconomic resources, LBC every 5 years from 35 years old strategy is recommended. In relatively more affluent areas, LBC every 5 years from 30 years old strategy, LBC every 3 years from 30 years old strategy, HPV DNA genotyping every 3 years from 30 years old strategy, and LBC every year from 30 years old strategy are recommended successively.
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Objective@#To investigate the effects of β2 glycoprotein Ⅰ/anti-β2 glycoprotein Ⅰ complex (β2/aβ2) on oxidized low density lipoprotein (oxLDL)-mediated lipid accumulation and focal adhesion kinase (FAK) activation in THP-1 macrophage, as well as the role of Toll-like receptor 4 (TLR4) during the process. @*Methods@#THP-1 cells were differentiated into THP-1 macrophage by PMA (100 ng/mL). THP-1 macrophages were treated with RPMI 1640 medium, oxLDL, oxLDL+β2/aβ2 or oxLDL+lipopolysaccharide (LPS). The mRNA expressions of lipid transportation molecules, ACAT1, ABCA1 and ABCG1 were detected by RT-qPCR. Intracellular total cholesterol (TC) and free cholesterol (FC) in THP-1 macrophages were evaluated by Trinder assay, then the content and proportion of intracellular cholesteryl ester (CE) were calculated. The expression and phosphorylation of FAK were detected by immune fluorescence, RT-qPCR and western blot. To evaluate the role of TLR4, THP-1 macrophages were pre-treated with or without TLR4 inhibitor TAK-242 (1 μg/mL). @*Results@#β2/aβ2 treatment significantly inhibited oxLDL-mediated lipid accumulation and FAK expression and phosphorylation in THP-1 macrophages, which could be reversed by TLR4 blockage. @*Conclusion@#β2/aβ2 inhibits the oxLDL-mediated lipid accumulation and FAK activation of THP-1 macrophage, which is related to the function of TLR4.
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Objective@#To investigate the effects of oxidized low-density lipoprotein/β2 glycoproteinⅠ/β2 glycoproteinⅠantibody (oxLDL/β2GPⅠ/β2GPⅠ-Ab) complex on the phenotypic transformation and lipid transpoters on the surface of rat thoracic aorta smooth muscle cell line (A7r5), and their correlation with toll-like receptor 4 (TLR4) signaling pathway. @*Methods@#A7r5 cells were stimulated by oxLDL, oxLDL/β2GPⅠ complex, oxLDL/β2GPⅠ-Ab complex, β2GPⅠ/β2GPⅠ-Ab complex and oxLDL/β2GPⅠ/β2GPⅠ-Ab complex respectively, and then total RNA and protein were collected. The expressions of α-smooth muscle actin (α-SMA), macrophage surface marker CD68, galectin-3 (LGALS3), scavenger receptor class B member 3 (CD36) and ATP-binding cassette transporter A1/G1 (ABCA1/ABCG1) were detected by real-time quantitative PCR (RT-qPCR), western blot and immunofluorescence (IF) respectively. The roles of TLR4 and its downstream signaling molecules in the phenotypic transformation and expression changes of lipid transporters of A7r5 cells induced by oxLDL/β2GPⅠ/β2GPⅠ-Ab complex were investigated by the pretreatment of TLR4 blocker TAK-242 (5 μmol/L) or c-Jun N-terminal kinases 1/2 (JNK 1/2) blocker SP600125 (90 nmol/L). @*Results@#The oxLDL/β2GPⅠ/β2GPⅠ-Ab complex significantly increased the levels of CD68 and LGALS3, and decreased the level of α-SMA, while TAK-242 could reverse this phenomenon. The oxLDL/β2GPⅠ/β2GPⅠ-Ab complex could promote the expression of CD36 and inhibit the expression of ABCA1/ABCG1, while TAK-242 and SP600125 could reverse this process. @*Conclusion@#The oxLDL/β2GPⅠ/β2GPⅠ-Ab complex promotes the phenotypic transformation of A7r5 cells to macrophage-like cells, regulates the expression of lipid transport-related molecules and enhances the ability of lipids transport into cells. TLR4 and JNK1/2 are closely related to this process.
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Objective@#To account the direct cost of uterine cervix carcinoma treatment in China and to explore the related factors which influence the direct financial burden of the disease.@*Methods@#Data was collected through the medical record system and telephone interviews in 14 county-level hospitals and 9 provincial and municipal hospitals from 14 provinces/municipalities enrolled in the Chinese National Health Industry Research Project in 2015. The direct financial burden of uterine cervix carcinoma treatment consisted of the direct medical cost and the direct non-medical cost of treatment in different pathological cervical cancer stages and precancerous lesions. Multiple liner regression method was used to analyze the factors affecting the costs.@*Results@#The age of the 3 246 patients was (46.40±10.43) years, including 2 423 patients from provincial and municipal hospitals and 823 patients from county-level hospitals. The direct financial burden for one patient of pathological uterine cervix carcinoma stage or precancerous lesion ranged from 10 156.3 yuan to 75 716.4 yuan in provincial and municipal hospitals, and for patients from county-level hospitals, the cost was between 4 927.9 yuan and 47 524.8 yuan per person. There was a wide gap between the direct financial burden of patients in different disease stages. The direct financial burden of patients with precancerous lesions ranged from 4 927.9 yuan per person to 11 243.0 yuan per person, as for patients of pathological uterine cervix carcinoma stages, the direct financial burden was between 29 274.6 yuan and 75 716.4 yuan per person. The factors which influence direct financial burden would include: the levels of the hospital, pathological period, medicare reimbursement, days of treatment, and the methods of treatment (P<0.001).@*Conclusion@#The direct financial burden of diseases in patients with pathological uterine cervix carcinoma stage or precancerous lesion differed in different levels of hospital and pathological periods. In addition, medicare reimbursement, days of treatment, and the methods of treatment all had impact on it.