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Objective:To determine lysophosphatidic acid receptor 6 (LPAR6) expression in patients with mycosis fungoides (MF) , a variant of cutaneous T-cell lymphoma (CTCL) , and to investigate its role and mechanism of action in the development and prognosis of CTCL.Methods:A total of 110 patients with confirmed MF were collected from Department of Dermatology, Peking University First Hospital from 2011 to 2020, including 24 with large-cell transformation (LCT) and 25 with non-large cell transformation (NLCT) in the discovery cohort, and 24 with LCT and 37 with NLCT in the validation cohort. RNA sequencing and RT-PCR were conducted to determine the LPAR6 expression in patients in the discovery cohort and validation cohort respectively. LPAR6 expression was compared between patients with LCT and those with NLCT, and its effect on the prognosis of patients was evaluated. Two LPAR6-overexpressing CTCL cell lines MyLa and Sz4 were constructed to evaluate the effect of LPAR6 overexpression on proliferative activity of MyLa and Sz4 cells, with the cells normally expressing LPAR6 as the control group; after the treatment with LPAR6-related ligand lysophosphatidic acid (LPA) , 2S-OMPT, adenosine triphosphate (ATP) or adenosine (ADO) , the effects of LPAR6 activation on the proliferative activity and apoptosis of LPAR6-overexpressing MyLa and Sz4 cells were evaluated by the MTS method and flow cytometry respectively. Log-rank test was used for prognostic analysis, and t test or Mann-Whitney U test was used for comparisons between two groups. Results:As RNA sequencing showed, LPAR6 was one of the significantly underexpressed genes in the LCT group in the discovery cohort; in the validation cohort, LPAR6 expression (median[ Q1, Q3]) was significantly lower in the LCT group (204.90[81.90, 512.70]) than in the NLCT group (809.40[417.50, 1 829.20], U= 242.00, P= 0.002) ; in the two cohorts, the underexpression of LPAR6 was significantly associated with increased risk of poor prognosis (both P < 0.01) . Cell proliferation assay showed no significant difference in the proliferative activity of MyLa or Sz4 cells between the LPAR6 overexpression group and control group at 0, 24, 48 and 72 hours during the experiment (all P > 0.05) ; 48 hours after activation of LPAR6 by LPA, 2S-OMPT, ATP and ADO in MyLa cells, the LPAR6 overexpression group showed significantly decreased cellular proliferative activity (1.38 ± 0.01, 1.04 ± 0.01, 1.09 ± 0.03, 1.23 ± 0.01, respectively) compared the control group (1.73 ± 0.04, 1.23 ± 0.01, 1.24 ± 0.01, 1.42 ± 0.03, t= 30.33, 18.38, 4.78, 5.75, respectively, all P < 0.05) , but significantly increased cell apoptosis rate (17.93% ± 0.88%, 17.75% ± 0.35%, 23.97% ± 0.57%, 31.44% ± 0.34%, respectively) compared the control group (3.98% ± 0.03%, 7.81% ± 0.59%, 11.95% ± 0.85%, 12.02% ± 0.48%, t= 15.93, 14.49, 11.74, 33.01, respectively, all P < 0.05) ; 48 hours after activation of LPAR6 by 2S-OMPT and ADO in Sz4 cells, compared with the control group, the LPAR6 overexpression group also showed significantly decreased cellular proliferative activity (2S-OMPT: 1.29 ± 0.04 vs. 1.48 ± 0.01; ADO: 1.27 ± 0.01 vs. 1.51 ± 0.02; both P < 0.05) , but significantly increased cell apoptosis rate (2S-OMPT: 41.70% ± 0.70% vs. 29.35% ± 0.55%; ADO: 37.05% ± 0.15% vs. 24.60% ± 1.00%; both P < 0.05) . Conclusions:LPAR6 was underexpressed in the patients with LCT, and its underexpression was significantly associated with increased risk of poor prognosis. In vitro activation of LPAR6 could inhibit the proliferation of CTCL cells and promote their apoptosis, suggesting that the decrease of LPAR6 expression may be one of the important mechanisms underlying disease progression in patients with LCT.
ABSTRACT
Mycosis fungoides (MF) is the most common subtype of primary cutaneous T-cell lymphoma, and its pathogenesis remains unclear. Recent studies have uncovered high-frequency chromosomal copy number variations in MF, such as gain of chromosomes7q,1q,17q and loss of 9p21,10q,17p, which lead to the gain of proto-oncogenes and loss of tumor suppressor genes, and finally result in tumor development and progression. Moreover, low-frequency single-nucleotide variants have been found in MF, and these mutated genes are mostly enriched in the pathways associated with cell cycle regulation, cell apoptosis, chromatin remodeling as well as T cell activation. Gene-fusion variation is rarely reported in MF. In addition, large cell transformation may occur in some MF cases, and often indicates poor prognoses such as disease progression and drug resistance. In conclusion, MF is a complex disease with highly molecular genetic heterogeneity, and more extensive and intensive researches on its pathogenesis are needed in the future.
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Objective@#To investigate the influence of maternal age on the health status of pregnant women and the pregnant outcomes.@*Methods@#Data obtained from "Beijing perinatal health management registration system" was analyzed, 263 157 pregnant women with age information were included from October 1st, 2015 to September 30th, 2016, in which 43 594 women delivered at the age of 35 or above (advanced age) . According to the age of maternal age, there were 5 groups. (1) Proper age: 219 563 (83.43%, 219 563/263 157) cases of the age of 18-34 years, including 122 735 cases (46.64%, 122 735/263 157) in the ≤29 years old group and 96 828 cases (36.79%, 96 828/263 157) in 30-34 years old group. (2) Advanced age: there were 43 594 cases (16.57%, 43 594/263 157) ≥35 years old, including 37 395 cases (14.21%, 37 395/263 157) in the 35-39 years old group, 5 790 cases (2.20%, 5 790/263 157) in the 40-44 years old group and 409 cases (0.16%, 409/263 157) in the ≥45 years old group. The trend-based chi-square test and logistic regression were used to analyze the effects of different age groups on maternal complications and pregnant outcomes.@*Results@#(1) The total incidence of high risk pregnancy (HRP) : in advanced age women, the incidence of HRP was 67.83% (29 571/43 594) which was 56.73% (124 550/219 563) in proper age women, the difference was statistically significant (χ2=1 848.91, P<0.000) . In advanced age women, the incidence of severe HRP was 7.64% (3 329/43 594) which was 6.18% (13 571/219 563) in proper age women, the difference was statistically significant (χ2=128.211, P<0.000) . In advanced age women, the incidence of very severe HRP was 1.76% (769/43 594) which was 0.84% (1 838/219 563) in proper age women, the difference was statistically significant (χ2=318.58, P<0.000) . (2) Comparison of the incidence of HRP in 5 groups:the total incidence of HRP increased through the following age group ≤29 years, 30-34 years, 35-39 years, 40-44 years, ≥45 years (53.28%, 61.09%, 67.41%、70.09%, 74.57% respectively) , the difference was statistically significant (linear by linear χ2=3 165.72, P<0.000) . The incidence of very severe HPR increased (0.66%, 1.06%, 1.66%, 2.35%, 2.93% respectively) , the difference was statistically significant (linear by linear χ2=218.31, P<0.000) . The incidence of severe HPR increased (5.77%, 6.70%, 7.48%, 8.34%, 11.49% respectively) , the difference was statistically significant (linear by linear χ2=422.20, P<0.000) . The incidence of general HPR increased (46.84%, 53.34%, 58.26%, 59.40%, 60.15% respectively) , the difference was statistically significant (linear by linear χ2=1 947.51, P<0.000) . (3) As the maternal age group increased, the incidence of adverse pregnancy outcomes increased (5.54%, 6.85%, 8.77%, 9.90%, 18.09%, linear by linear χ2=674.57, P<0.000) . The incidence of perinatal death, premature birth and low birth weight also presented the above trends (perinatal death: linear by linear χ2=34.79, P<0.000; premature birth: linear by linear χ2=692.87, P<0.000; low birth weight: linear by linear χ2=379.20, P<0.000) . (4) Logistic regression analysis with the assisted reproductive technology and multiple pregnancy considered showed the same trend (P<0.000) .@*Conclusion@#The maternal age has an impact on the maternal health status and pregnancy outcomes, and the risk of various types of pregnancy complications and adverse pregnancy outcomes increase with the maternal age group, antenatal care and management should be emphasized in women with advanced maternal age, especially for women ≥40 years old.
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County -level public hospitals reform is an important measure of deepening reform of the medical and health system.Medicare payments system reform is therefore an important part of public hospitals reform.By abolishing drugs addition,registration fee,treating fee and setting up medical service fee instead,our hospital carried on a diversified management style in the aspect of medical insurance total prepaid system.The implementation of the reform measures turns out a good result:reasonably keeping a control on the medicare spending and really embodying the transformed of interests patterns.On the premise of ensuring patients interests,medical personnel′s interests are improved to a new level and medical insurance fund are also brought under a reasonable control.The medicare payments system reform puts equity in access and people benefit as the starting point and footing of county -level public hospitals reform,thus lays a foundation of further development of public hospitals reform.
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Objective To investigate the relationship between anti-trophoblast membrane antigens(TA) antibodies and hypertensive disorders complicating pregnancy(HDCP).Methods Enzyme linked immunosorbent assay(ELISA) was used to detect anti-TA IgG and IgM in both maternal and umbilical serum samples of 40 normal pregnant women and 92 HDCP women(23 gestational hypertension or mild preeclampsia,41 severe preeclampsia and 28 eclampsia).Results The positive rates of anti-TA IgG and IgM in maternal serum samples with HDCP,eclampsia or severe preeclampsia were significantly higher than that in normal pregnant women,the positive rate of anti-TA IgM increased significantly with the aggravation of HDCP(P