ABSTRACT
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.
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Objective:To explore and analyze the high risk factors of puerperal infection in eastern He'nan province, and to provide scientific basis for prevention of postpartum infection.Methods:The clinical data of 1 521 cases of puerpera in the First People's Hospital of Shangqiu and the People's Hospital of Xiayi County from August 2014 to October 2018 were retrospectively analyzed.Of the 1 521 cases, 91 cases with puerperal infection were enrolled in puerperal infection group, and 1 430 patients without puerperal infection were enrolled in puerperal uninfected group.The correlation of perineum incision, amniotic fluid contamination, soft birth canal injury, prenatal anemia, mode of delivery, placental residual, hemoglobin, birth process time, rupture time and bedtime with puerperal infection was explored.Results:The puerperal infection was associated with perineal incision, amniotic fluid contamination, prenatal anemia, postpartum hemorrhage, delivery mode and placental residue(χ 2=6.439, 5.269, 10.188, 4.862, 4.125, 6.663, all P<0.05). The duration of membrane rupture, hemoglobin, length of labor and bed rest in the puerperal infection group were (10.1±2.1)h, (110.5±10.8)g/L, (8.2±1.4)h, (2.8±0.6)d, respectively, which in the non-infection group were (11.2±2.5)h, (103.2±12.1)g/L, (11.7±1.8)h, (4.2±0.7)d, respectively, the differences between the two groups were statistically significant( t=-4.786, 6.205, -22.689, -21.355, all P<0.05). Conclusion:There are many factors that can cause puerperal infection, we should take preventive measures to against these risk factors in clinical practice, and to reduce the incidence of postpartum infection.
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Objective To understand the effects of drinking water and source water on DNA breakage of human peripheral blood lymphocytes (HPBL). Methods The organic compounds in drinking water and source water were adsorbed by GDX_102 resin for solid phase of gas choromatography. DNA damages of lymphocytes were detected by single cell gel electrophoresis. Results At the same exposure doses to organic extracts of water, the DNA damages of HPBL exposed to organic extracts of surface water were heavier than those exposed to organic extracts of deep underground water, and heavier DNA damages were also observed in HPBL exposed to organic extracts of finished water from water plant treating ground source water compared with those exposed to organic extracts of finished water from water plant treating deep underground source water. Significant dose_response relationships were observed between the exposure doses of organic extracts of water samples and the degrees of DNA damages of HPBL. Conclusion The organic extracts of source water samples collected from surface water and ground water and its tap water samples could cause DNA breakages of HPBL in different degrees in a certain city.