ABSTRACT
The platinum-based chemotherapy is one of the most frequently used treatment protocols for lung adenocarcinoma (LUAD), and chemoresistance, however, usually results in treatment failure and limits its application in the clinic. It has been shown that microRNAs (miRNAs) play a significant role in tumor chemoresistance. In this study, miR-125b was identified as a specific cisplatin (DDP)-resistant gene in LUAD, as indicated by the bioinformatics analysis and the real-time quantitative PCR assay. The decreased serum level of miR-125b in LUAD patients was correlated with the poor treatment response rate and short survival time. MiR-125b decreased the A549/DDP proliferation, and the multiple drug resistance- and autophagy-related protein expression levels, which were all reversed by the inhibition of miR-125b. In addition, xenografts of human tumors in nude mice were suppressed by miR-125b, demonstrating that through autophagy regulation, miR-125b could reverse the DDP resistance in LUAD cells, both in vitro and in vivo. Further mechanistic studies indicated that miR-125b directly repressed the expression levels of RORA and its downstream BNIP3L, which in turn inhibited autophagy and reversed chemoresistance. Based on these findings, miR-125b in combination with DDP might be an effective treatment option to overcome DDP resistance in LUAD.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , MicroRNAs , Tumor Suppressor Proteins , Animals , Mice , Humans , Cisplatin/pharmacology , Cisplatin/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Mice, Nude , Drug Resistance, Neoplasm/genetics , Cell Line, Tumor , Apoptosis/genetics , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Autophagy/genetics , Gene Expression Regulation, Neoplastic , Nuclear Receptor Subfamily 1, Group F, Member 1/genetics , Nuclear Receptor Subfamily 1, Group F, Member 1/metabolism , Nuclear Receptor Subfamily 1, Group F, Member 1/pharmacology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Proto-Oncogene Proteins/geneticsABSTRACT
BACKGROUND: Neuraxial anesthesia with reactivation of a labor epidural catheter is commonly utilized for postpartum tubal ligations (PPTL), although the optimal anesthetic approach is unknown. We assessed institutional anesthesia practices for PPTL, and evaluated the failure rates of reactivation of labor epidural catheters, de novo spinal anesthesia, and spinal anesthesia after failed blocks. METHODS: We conducted a single-center retrospective cohort analysis of 300 consecutive patients who underwent a PPTL and 100 having spinal anesthesia for cesarean delivery. Anesthetic management data (existing labor epidural catheter reactivation, de novo spinal anesthesia or general anesthesia) were collected from electronic medical records. Anesthetic block failure rates were determined for each anesthetic technique. RESULTS: The failure rate was 15% for de novo spinal anesthesia and 23% after failed reactivation of a labor epidural catheter or spinal anesthesia. The epidural catheter reactivation failure rate was 35%. The failure rate of spinal anesthesia for cesarean delivery was 4%. Drug dosage, epidural catheter use in labor, time since epidural catheter placement or delivery, labor neuraxial technique (combined spinal-epidural, epidural), supplemental top-up doses during labor, and anesthesiologist experience did not predict neuraxial anesthesia failures. CONCLUSIONS: Our analysis revealed an unexpectedly high neuraxial anesthesia failure rate even when de novo spinal anesthesia was used for PPTL. The results are consistent with other institutions' recent findings, and are higher than spinal anesthesia failure rates associated with cesarean delivery. Further studies are required to determine optimal anesthesia dosing strategies, and to understand the mechanisms behind high neuraxial anesthesia failures for PPTL.
Subject(s)
Anesthesia, Epidural , Anesthesia, Obstetrical , Anesthesia, Spinal , Sterilization, Tubal , Humans , Female , Retrospective Studies , Sterilization, Tubal/methods , Anesthesia, Obstetrical/methods , Adult , Anesthesia, Spinal/methods , Pregnancy , Anesthesia, Epidural/methods , Cohort Studies , Postpartum Period , Cesarean Section/methodsABSTRACT
Disparities relating to postpartum recovery outcomes in different socio-economic and racial ethnic groups are underexplored. We conducted a planned analysis of a large prospective caesarean delivery cohort to explore the relationship between ethnicity, socio-economic status and postpartum recovery. Eligible patients were enrolled and baseline demographic, obstetric and medical history data were collected 18 h and 30 h following delivery. Patients completed postpartum quality of life and recovery measures in person on day 1 (EuroQoL EQ-5D-5L, including global health visual analogue scale; Obstetric Quality of Recovery-10 item score; and pain scores) and by telephone between day 28 and day 32 postpartum (EQ-5D-5L and pain scores). Socio-economic group was determined according to the Index of Multiple Deprivation quintile of each patient's usual place of residence. Data from 1000 patients who underwent caesarean delivery were included. There were more patients of Asian, Black and mixed ethnicity in the more deprived quintiles. Patients of White ethnicities had shorter postpartum duration of hospital stay compared with patients of Asian and Black ethnicities (35 (28-56 [18-513]) h vs. 44 (31-71 [19-465]) h vs. 49 (33-75 [23-189]) h, respectively. In adjusted models at day 30, patients of Asian ethnicity had a significantly greater risk of moderate to severe pain (numerical rating scale ≥ 4) at rest and on movement (odds ratio (95%CI) 2.42 (1.24-4.74) and 2.32 (1.40-3.87)), respectively). There were no differences in readmission rates or incidence of complications between groups. Patients from White ethnic backgrounds experience shorter postpartum duration of stay compared with patients from Asian and Black ethnic groups. Ethnic background impacts pain scores and recovery at day 1 postpartum and following hospital discharge, even after adjusting for socio-economic group. Further work is required to understand the underlying factors driving differences in pain and recovery and to develop strategies to reduce disparities in obstetric patients.
Subject(s)
Ethnicity , Quality of Life , Pregnancy , Female , Humans , Prospective Studies , Cesarean Section , Postpartum Period , Poverty , PainABSTRACT
The objective of this study was to observe the infection of human cytomegalovirus (HCMV) to human umbilical vein endothelial cells, and its effect on the expression of single-stranded DNA-binding protein (SSBP1) and on lipid metabolism in endothelial cells. We screened the differential expression of mRNAs after HCMV infection by suppression subtractive hybridization and the expression levels of SSBP1 mRNA and protein after HCMV infection by real-time PCR and western blot. After verification of successful infection by indirect immunofluorescent staining and RT-PCR, we found a differential expression of lipid metabolism-related genes including LDLR, SCARB, CETP, HMGCR, ApoB and LPL induced by HCMV infection. The expression levels of SSBP1 mRNA and protein after HCMV infection were significantly down-regulated. Furthermore, we found that upregulation of SSBP1 inhibited the expression of atherosclerosis-associated LDLR, SCARB, HMGCR, CETP as well as the accumulation of lipids in the cells. The results showed that the inhibition of SSBP1 by HCMV infection promotes lipid accumulation in the cells.