ABSTRACT
Cervical cancer is known as the possible outcome of genital infection, while the molecular mechanisms of initiation, development, and metastasis of cervical cancer have not yet been fully elucidated. Our study aims to investigate the effects of microRNA-92a (miR-92a) on tumor growth and immune function by targeting PTEN via the MAPK/ERK signaling pathway in tumor-bearing mice. C57BL/6 female mice were used for tumor-bearing mouse models and their tumor and adjacent normal tissues were collected, and normal cervical tissues were obtained from normal mice. Serum levels of tumor necrosis factor-α (TNF-α) and soluble interleukin-2 receptor (sIL-2R) were detected by ELISA. The cells were divided into the normal, blank, negative control (NC), miR-92a mimic, miR-92a inhibitor, siRNA-PTEN, and miR-92a inhibitor + siRNA-PTEN groups. Dual-luciferase reporter assay was adopted to determine the relationship between PTEN and miR-92a. Expressions of miR-92a, PTEN, TNF-α, sIL-2R, ERK1, and ERK2 were tested by RT-qPCR and Western blotting. Cell proliferation was detected by cell count kit-8 (CCK-8); cell cycle and apoptosis were detected by flow cytometry. Compared with the normal cervical tissues and adjacent normal tissues, the cervical cancer tissues exhibited increased expressions of miR-92a, p-ERK1/2, and serum levels of TNF-α and sIL-2R while decreased PTEN expression. PTEN was confirmed to be the target gene of miR-92a. As compared with the blank and NC groups, expressions of miR-92a, ERK1 and ERK2 increased, and expressions of PTEN decreased in the miR-92a mimic group. The miR-92a mimic group exhibited increased expression levels of TNF-α and sIL-2R, cell proliferation, and cell number in S phase but decreased cell apoptosis, and cell number in G0/G1 phase, while the miR-92a inhibitor group followed opposite trends. miR-92a promotes tumor growth and suppresses immune function by inhibiting PTEN via activation of the MAPK/ERK signaling pathway in mice bearing U14 cervical cancer.
ABSTRACT
OBJECTIVE: To investigate the efficacy and pregnancy outcomes of women receiving double-catheter epidural block in labor analgesia, and compare the results with single-catheter epidural block. METHODS: A double-blind clinical trial was conducted on 206 full-term singleton primiparas, aged 25 - 35 and at the 37 - 42 weeks of gestation who delivered at the Department of Obstetrics, Qingdao Municipal Hospital from August 2006 to December 2008, which were randomly divided into two groups: double-catheter epidural block (group D, n = 103) and single-catheter epidural-block (group S, n = 103). Women in group D were given mixture of 0.1% repivacaine hydrochloride and 0.5 mg/L sufentinil 4 - 6 ml as initial dose. Patient control epidural analgesia pump (PCEA) was connected with the upper catheter after 45 minutes. A bolus dose of 4 - 6 ml analgesia mixture was infused according to the condition through the lower catheter. Women in group S received analgesia mixture 10 - 15 ml as initial dose and PCEA pump was connected after 45 minutes. Oxytocin was infused in both groups according to uterine contraction after 30 minutes. The following indexes was observed: (1) visual analogue scales (VAS); (2)modified Bromage Scores; (3) the total dose of analgesia mixture, the percentage of oxytocin infusion, duration of labor and duration of the second stage of labor; (4) fetal birth weight and Apgar scores (1, 5 minutes); (5) mode of delivery; (6) the concentration of plasma cortisol and angiotension II at the beginning of regular uterine contraction and at the time when cervical dilated to 4 cm and 10 cm and fetal disengagement; (7) anesthesia-related complications. RESULTS: (1) The neonatal birth weight and Apgar scores (1, 5 minutes) of group D were (3456 ± 468) g, 9.8 ± 0.6 and 9.9 ± 0.7, respectively, while (3399 ± 569) g, 9.8 ± 0.5 and 9.9 ± 0.7 in group S (P > 0.05). No motor function block was reported in any group and the modified Bromage score was zero. (2) The total dose of analgesia mixture in group D was similar to that in group S [(57 ± 9) ml vs. (58 ± 11) ml, P > 0.05]. However, the percentage of women received oxytocin in group D was smaller [59.2% (61/103) vs. 81.6% (84/103), P < 0.01], and the total time of labor and the duration of second stage of labor in group D were shorter [(532 ± 140) minutes vs. (608 ± 150) minutes; (46 ± 31) minutes vs. (60 ± 34) minutes, P < 0.05]. (3) There were no significant differences in VAS at 30 minutes after initial dose and in the first stage of labor between group D and S (1.2 ± 1.1 vs 1.2 ± 1.1, 1.1 ± 1.1 vs. 1.2 ± 1.0, P > 0.05). VAS at the second stage of labor stage was lower in group D than in group S (1.2 ± 1.1 vs. 4.5 ± 2.2, P < 0.01). (4) The rate of cesarean section, instrumental delivery and episiotomy in group D were lower than in group S (7.8% vs. 17.5%, 7.8% vs. 15.5%, 10.7% vs. 18.4%, P < 0.05). The incidence of fetal distress and meconium-stained amniotic fluid as the indication of cesarean section were similar between the two groups (P > 0.05). Lower incidence of fetal malpresentation and arrested second stage of labor were shown in group D than in group S (2.9% vs. 9.7%, 1.0% vs. 5.8%, P < 0.05). (5) The concentration of plasma cortisol and angiotension II were lower in group D than in group S [(86 ± 25) ng/L vs. (100 ± 20) ng/L, (278 ± 53) nmol/L vs. (311 ± 53) nmol/L, P < 0.05] only at the end of second stage of labor, but not at any other times (P > 0.05). (6) No serious anesthesia-related complications were reported in any groups. Some light backache around the puncture point were complained by 29.1% (30/103) of the women in group D and 31.1% (32/103) in group S (P > 0.05). CONCLUSION: Double-catheter epidural block can provide better analgesia effect during labor than single-catheter epidural block, without any adverse influence on delivery outcomes.
