ERα Gene Promoter Methylation in Cognitive Function and Quality of Life of Patients With Alzheimer Disease.

OBJECTIVE: Alzheimer disease (AD) has been recognized as a progressive neurodegenerative disorder. This study aims to investigate the effects of estrogen receptor α (ERα) gene promoter methylation on the cognitive function and quality of life (QOL) of patients with AD. METHODS: A total of 132 patients with AD and 135 healthy individuals were recruited for this study. The DNA in the peripheral blood was extracted and treated with bisulfite; then methylation-specific polymerase chain reaction and reverse transcription quantitative polymerase chain reaction were performed to determine the methylation status of ERα and ERα messenger RNA (mRNA) expression, respectively. Mini-Mental State Examination (MMSE), activities of daily living (ADL), and Quality of Life-Alzheimer Disease scale were employed to evaluate the cognitive functions, ADL, and QOL of the participants. RESULTS: The methylation group showed a decrease in ERα mRNA expression. The MMSE and ADL scores were indicative of a worse cognitive function in the methylation group. The ERα promoter methylated patients showed a higher rate of abnormal ADL score, while patients in the nonmethylation group enjoyed a better QOL. CONCLUSIONS: The ERα promoter methylation is related to impaired cognitive function and QOL of patients with AD by inhibiting ERα mRNA expression and transcription.

Post-Uterine Artery Embolization: 3-Day MRI Changes and Their Predictive Value for Therapeutic Efficacy in Symptomatic Uterine Fibroids.

OBJECTIVES: To summarize and discuss3-days MRI changes after uterine artery embolization (UAE) and their predictive value for efficacy. METHODS: From August 2016 to April 2023, 52 patients underwent enhanced MRI within 3 days post-embolization. We retrospectively analyzed clinical and imaging data, focusing on MR characteristics at the 3-day mark, comparing pre- and post-embolization images. Patients were categorized based on 3-day MR findings into complete and incomplete necrosis groups, with clinical efficacy compared over 6 months. RESULTS: Our study included 30 cases of multiple leiomyomas and 22 of single leiomyomas. Postoperative MRI revealed complete necrosis in 31 tumors and incomplete necrosis in 21 tumors. At 3 days, MR ADC imaging showed increased signals in necrotic areas, mildly increased signals on T2-weighted images, and minimal changes on T1-weighted images. Six-month follow-up showed no significant difference in symptom improvement between groups (p = 0.524, p = 0.587, p = 0.615). However, a significant difference was found in leiomyoma volume reduction, with 70.63 ± 15.53% in the complete necrosis group and 51.36 ± 25.20% in the incomplete necrosis group (p＜0.001), highlighting the impact of necrosis extent on volumetric reduction. CONCLUSION: Short-term MRI changes after UAE can reflect changes in blood supply to fibroids and normal uterine tissue, and have good predictive value for medium-term embolization efficacy. ADVANCES IN KNOWLEDGE: This study describes short-term MR manifestations of complete and incomplete embolism, aiding in predicting long-term outcome.

Genetic polymorphisms in tumor necrosis factor alpha and interleukin-10 are associated with an increased risk of cervical cancer.

Most cases of cervical cancer are the result of infection with specific high-risk types of human papillomavirus (HPV). Investigating the genetic basis of the host immune response, particularly cytokine function, could help further characterize the progression of cervical HPV infection into neoplasia. Prior studies have demonstrated a correlation between genetic variants of tumor necrosis factor alpha (TNF-α, TNF gene) and/or interleukin-10 (IL-10, IL10 gene) and cervical cancer susceptibility. However, some of the results have been contradictory. We sought to resolve these discrepancies by carrying out our study in a large cohort of Chinese women. In order to assess the association of TNF and IL10 genotypes with cervical cancer susceptibility, the polymorphisms in TNF (-238 G/A, -308 G/A) and IL10 (-592 C/A, -819 C/T, -1082 A/G) were genotyped and odds ratios for the genotype and allele frequencies between cervical cancer patients and healthy controls were calculated. Also, the functional relevance of these polymorphisms was evaluated using enzyme-linked immunosorbent assays (ELISAs) and in vitro lymphocyte proliferation assays. The TNF-238 AA genotype frequency was lower in patients than in controls (p < 0.05). TNF-308 AA, IL10-592 CA/AA, and IL10-819 CC/CT genotype frequencies were higher in cervical cancer patients than in controls (p < 0.05). The frequency of the TNF-238 A allele was significantly lower in patients, while the frequency of the -308 A allele was significantly higher (p < 0.05). No significant differences between patients and controls were found in the genotype or allele frequencies of IL10-1082 A/G (p > 0.05). Furthermore, the combinations of TNF-238 GA or GG and IL10-592 CC; TNF-238 GA or GG and IL10-592 CA or AA; TNF-308 AA and IL10-592 CC; and TNF-308 AA and IL10-592 CA or AA in cervical cancer patients were statistically significant (p < 0.0167). Upon stimulation with PHA, peripheral blood mononuclear cells (PBMCs) with the TNF-308AA genotype exhibited significantly higher proliferation rates, elevated IL-4, TGF-ß levels, and lower IL-2 levels (p < 0.05). For IL10-592C/A, the AA and CA genotypes were significantly associated with higher proliferation rates, elevated IL-4 and IL-10 levels (p < 0.05). We also found that for TNF-308 G/A or IL10-592 C/A variants, the combination of TNF-308 GG or GA with IL10 CA or AA had an association with the severity of cervical cancer. Taken together, these results suggest that TNF-308 AA and IL10-592 CA/AA genotypes may increase susceptibility to cervical cancer by altering the immune response of an individual.