OBJECTIVE: Hypermethylation of human papillomavirus (HPV) and host genes has been reported in cervical cancer. However, the degree of methylation of different HPV types relative to the severity of the cervical lesions remains controversial. Studies of the degree of methylation associated with the host gene and the HPV genome to the severity of cervical lesions are rare. We examined the association of methylation status between host genes and late gene 1 (L1) regions of HPV16, 18, 52, and 58 in cervical brushings. METHODS: Cervical brushings from 147 HPV-infected patients were obtained. The samples comprised normal (n=28), cervical intraepithelial neoplasia (CIN) 1 (n=45), CIN2 (n=13), and CIN3/carcinoma in situ (n=61). The methylation status of HPV and host genes was measured using bisulfite pyrosequencing and quantitative methylation-specific polymerase chain reaction (PCR). RESULTS: The degree of methylation of L1 in HPV16, 18, and 52 was associated with the severity of the cervical lesion. In HPV52, C-phosphate-G (CpG) sites 6368m, 6405m, and 6443m showed significantly higher methylation in lesions ≥CIN3 (p=0.005, 0.003, and 0.026, respectively). Methylation of most HPV types except HPV52 (r<−0.1) was positively correlated with the degree of methylation of host genes including PAX1 and SOX1 (0.4≤r≤0.7). Combining HPV methylation with PAX1 methylation improved the clustering for ≥CIN2. CONCLUSION: Our study showed that the degree of L1 methylation of HPV16, 18, and 52 but not 58 is associated with the severity of cervical lesions. The association between HPV methylation and host gene methylation suggests different responses of host cellular epigenetic machinery to different HPV genotypes.
Cervical Intraepithelial Neoplasia* ; DNA Methylation ; Epigenomics ; Genome ; Genotype ; Human papillomavirus 16 ; Humans ; Methylation* ; Papillomaviridae ; Polymerase Chain Reaction ; Uterine Cervical Neoplasms

Chronic inflammation is thought to be the leading cause of colorectal cancer, and interleukin-10 (IL10) has been identified as a potent immunomodulatory cytokine that regulates inflammatory responses in the gastrointestinal tract. Although several single nucleotide polymorphisms (SNPs) in IL10 have been associated with the risk of colorectal cancer, their prognostic significance has not been determined. Two hundred and eighty-two colorectal cancer patients were genotyped for two candidate cancer-associated SNPs in IL10. The associations of these SNPs with distant metastasis-free survival and overall survival were evaluated by Kaplan-Meier analysis and Cox regression model. The minor homozygote GG genotype of IL10 rs3021094 was significantly associated with a 3.30-fold higher risk of death compared with the TT+TG genotypes (P=0.011). The patients with IL10 rs3021094 GG genotype also had a poorer overall survival in Kaplan-Meier analysis (log-rank P=0.007) and in multivariate Cox regression model (P=0.044) adjusting for age, gender, carcinoembryonic antigen levels, tumor differentiation, stage, lymphovascular invasion, and perineural invasion. In conclusion, our results suggest that IL10 rs3021094 might be a valuable prognostic biomarker for colorectal cancer patients.
Aged ; Alleles ; Carcinoembryonic Antigen/blood ; Cell Differentiation ; Colorectal Neoplasms/*genetics/mortality/pathology ; Female ; Genotype ; Homozygote ; Humans ; Interleukin-10/*genetics ; Kaplan-Meier Estimate ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; *Polymorphism, Single Nucleotide ; Regression Analysis ; Tumor Markers, Biological/genetics

Objective: Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets). Methods: In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA＋P, n = 57) or DM (30 mg/day, VPA＋DM30, n = 56) or 60 mg/day (VPA＋DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked. Results: Paired t test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA＋P or VPA＋DM30 treatment. VPA＋DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment. Conclusion Hematological molecule levels were lower after long-term treatment with VPA. VPA＋DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.

Objective: Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2 (ALDH2 ) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). Methods: OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors’ Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. Results: We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2＋*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p = 0.03), significantly lower hit reaction time T-scores (p = 0.04), and significantly lower WMS-R visual memory index scores (p = 0.03) than did patients with the ALDH2 1 */*1 (ALDH2 active) genotype. Conclusion OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.