OBJECTIVES: To investigate the association of HOTAIR gene rs920778 single nucleotide polymorphism (SNP) with breast cancer susceptibility and response to HER2-targeted therapy in a Chinese population. METHODS: TaqMan probe-based real-time quantitative PCR was used for genotyping of the rs920778 locus (chr12:54,376,218) in peripheral blood genomic DNA from 287 breast cancer patients and 260 healthy individuals from northern Anhui Province. The genotype (GG, GT and TT) and allele (G/T) distribution frequencies were compared between the two groups to evaluate their association with breast cancer risk. Multivariate logistic regression analysis was conducted to assess the relationship between SNP at this locus and aggressive clinicopathological features (including tumor size, lymph node metastasis, ER/PR/HER2 status, and molecular subtypes) of breast cancer. For the HER2-positive subgroup, the association between rs920778 genotype and responses to dual-targeted therapy (trastuzumab [6 mg/kg q3w]+pertuzumab [420 mg q3w] + docetaxel [75 mg/m²]) was analyzed. The primary endpoints included pathological complete response rate (pCR), objective response rate (ORR), and progression-free survival (PFS). RESULTS: The TT genotype of rs920778 was associated with a significantly increased breast cancer susceptibility (OR=1.54, 95% CI: 1.09-2.19; P=0.017), an advanced tumor stage (P<0.001), lymph node metastasis (P<0.001), and the triple-negative subtype (P<0.001). In HER2-positive patients, TT genotype carriers had a markedly reduced objective response rate to dual HER2-targeted therapy (33.3% vs 89.3%, P=0.001) and a lower pathological complete response rate after neoadjuvant therapy (P=0.018). CONCLUSIONS The TT genotype of HOTAIR rs920778 serves as an independent risk factor for breast cancer susceptibility and aggressive progression in Chinese population and may predict the resistance to HER2-targeted therapies, suggesting its potential as a prognostic biomarker for precision oncology.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/drug therapy* ; Case-Control Studies ; China ; Drug Resistance, Neoplasm/genetics* ; Genetic Predisposition to Disease ; Genotype ; Polymorphism, Single Nucleotide ; Receptor, ErbB-2 ; RNA, Long Noncoding/genetics* ; East Asian People/genetics*

Objective To investigate the effects of probiotics combined with sacubitril valsartan and amiodarone on short-term and long-term efficacy of patients with atrial fibrillation after radiofrequency ablation. Methods A total of 90 patients with atrial fibrillation after radiofrequency ablation in the First Hospital of Zhangjiakou City from June 2021 to June 2022 were selected and randomly divided into three groups, with 30 cases in each group. Control group was treated with amiodarone, sacubitril valsartan group was treated with amiodarone and sacubitril valsartan, and probiotics group was treated with probiotics, amiodarone and sacubitril valsartan. The recurrence situation, atrial structure indexes[left atrial diameter (LAD), left ventricular ejection fraction (LVEF), left ventricular end systolic volume index (LVESVI), left atrial volume (LAV), left ventricular end diastolic volume index (LVEDVI)], myocardial fibrosis indexes[galactin-3 (Gal-3), soluble growth stimulation expression gene 2 protein (sST2)], inflammatory response indexes[intercellular adhesion molecule-1 (ICAM-1), C reactive protein (CRP), interleukin-6 (IL-6)], neuroendocrine hormone indexes[aldosterone, norepinephrine (NE), angiotensin Ⅱ (AngⅡ)], metabolites of gut microbiota[total bile acids, trimethylamine oxide (TMAO)] and incidence of adverse events were compared among the three groups. Results At 12 months after treatment, the recurrence rate of the probiotics group was significantly lower than that of the sacubitril valsartan group and the control group (P < 0.05); after 3, 6 and 12 months of treatment, the LAD, LAV, LVESVI, LVEDVI, sST2 and Gal-3 in the probiotics group were significantly lower than those in the sacubitril valsartan group and the control group (P < 0.05), and these indexes in the sacubitril valsartan group were also significantly lower than those in the control group (P < 0.05); after 3, 6 and 12 months of treatment, the LVEF of the probiotics group was significantly higher than that of the sacubitril valsartan group and the control group (P < 0.05), and the LVEF of the sacubitril valsartan group was also significantly higher than that of the control group (P < 0.05); after 3, 6 and 12 months of treatment, the CRP, IL-6, ICAM-1, NE, aldosterone and AngⅡ in the probiotics group were significantly lower than those in the sacubitril valsartan group and the control group, and these indexes in the sacubitril valsartan group were also significantly lower than those in the control group (P < 0.05); after 3, 6 and 12 months of treatment, the TMAO and total bile acids in the probiotics group were significantly lower than those in the control group and the sacubitril valsartan group (P < 0.05); there was no significant difference in the incidence of adverse events among the three groups (P>0.05). Conclusion Probiotics combined with sacubitril valsartan and amiodarone can improve atrial structure after radiofrequency ablation of atrial fibrillation, inhibit myocardial fibrosis, reduce inflammatory response, regulate neuroendocrine hormones and metabolites of gut microbiota, prevent long-term recurrence of atrial fibrillation, and have a high safety.

Objective:To investigate the changes of serum miR-33 in patients with type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD), and analyze the relationship between miR-33 and non-alcoholic fatty liver disease and type 2 diabetes mellitus.Methods:From July 2019 to January 2020, 25 healthy subjects (control group), 25 NAFLD patients (NAFLD group), 25 T2DM patients hospitalized in the department of endocrinology (T2DM group) and 25 T2DM patients with NAFLD (NAFLD combined with T2DM group) were selected. The basic data of the subjects were collected, and the levels of miR-33 and other biochemical indexes in the serum of the four groups were detected. The risk factors for type 2 diabetes mellitus with nonalcoholic fatty liver disease were analyzed.Results:There was no significant difference between T2DM group and T2DM group with NAFLD in course of disease, medication history and incidence of complications ( P<0.05). The levels of serum miR-33 in T2DM group, NAFLD group and T2DM combined with NAFLD group were higher than those in healthy people, and the level of serum miR-33 in the combined group was the highest ( P<0.05). The differences in systolic blood pressure, total cholesterol (TC), fasting blood glucose (FPG), glycosylated hemoglobin, triglycerides (HbA1c), triglycerides (TG), high density lipoprotein (HDL-C), uric acid (UA), serum creatinine (Scr), gamma-glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the four groups were statistically significant ( P<0.05). The level of miR-33 was positively correlated with systolic blood pressure, FPG, HbA1c, TG, UA and GGT ( P<0.05), and negatively correlated with the level of HDL-C ( P<0.05). MiR-33, systolic blood pressure and FPG increased the risk of NAFLD in T2DM patients ( OR=8.999, 1.083, 2.071, P<0.05). Conclusions:Serum miR-33 is the influencing factor of T2DM and NAFLD diseases and the risk factor of T2DM patients with NAFLD. It may affect the occurrence and development of metabolic diseases by participating in the regulation of glycolipid metabolism.