Background: Breast cancer is the prevailing malignancy among women, exhibiting a discernible escalation in incidence within our nation; hormone receptor‐positive (HR+) human epidermal growth factor receptor 2‐negative (HER2−) breast cancer is the most common subtype. In this study, we aimed to search for a non‐invasive, specific, blood‐based biomarker for the early detection of luminal A breast cancer through proteomic studies.Methods: To explore new potential plasma biomarkers, we applied data‐independent acquisition (DIA), a technique combining liquid chromatography and tandem mass spectrometry, to quantify breast cancer‐associated plasma protein abundance from a small number of plasma samples in 10 patients with luminal A breast cancer, 10 patients with benign breast tumors, and 10 healthy controls.Results: The proteomes of 30 participants in all cohorts were analyzed using the DIA method, and a total of 517 proteins and 3584 peptides were quantified. We found that there were significant differences in plasma protein expression profiles between breast cancer patients and non‐breast cancer patients, and breast cancer was mainly related to lipid metabolism pathways. Finally, the optimal protein combinations for the diagnosis of breast cancer were PON3, IGLV3‐10, and IGHV3‐73 through multi‐model analysis, which had a high prediction accuracy for breast cancer (AUC = 0.92), and the model could also distinguish breast cancer from HC (AUC = 0.92) and breast cancer from benign breast tumor (AUC = 0.91).Conclusions: The study revealed proteomic signatures of patients with luminal A breast cancer, identified multiple differential proteins, and identified three plasma proteins as potential diagnostic biomarkers for breast cancer. It provides a reference for the screening of biomarkers for breast cancer.

Diabetic kidney disease (DKD) represents the predominant and severe microvascular complication associated with diabetes, frequently culminating in End-Stage Kidney Disease (ESKD). The escalating prevalence of diabetes has correspondingly led to a rise in DKD incidence, imposing significant challenges on both individuals and society. The etiology of DKD is multifaceted and remains devoid of definitive therapeutic interventions. This article examines the pharmacological actions and mechanisms of different drugs used for the prevention and treatment of DKD that are currently in clinical use or undergoing development. The goal is to offer insights for early intervention based on therapeutic combinations to potentially slow kidney disease progression.

Background. The differences in the antihypertensive treatment with angiotensin type II receptor blockers (ARBs) may be attributed to polymorphisms in genes involving drug-targeted receptor and drug metabolism. The present study aimed to investigate whether the antihypertensive effect of the ARB drug valsartan was associated with angiotensin II type 1 receptor (AGTR1) gene polymorphism (A1166 C) and cytochrome P450 enzyme 2C9 (CYP2C9) gene polymorphism (CYP2C9∗3). Methods. 281 patients with hypertension who received valsartan monotherapy in the past month were included in this retrospective study. Polymerase chain reaction-melting curve analysis was performed to genotype the AGTR1 and CYP2C9 gene polymorphisms. Based on the systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the time of visit, the patients were divided into well-controlled group (n = 144, SBP/DBP <140/90 mmHg) and poorly controlled group (n = 137, SBP/DBP ≥140/90 mmHg). Results. Older age, decreased history of drinking, a higher proportion of mild-to-moderate hypertension, lower alanine aminotransferase levels, and higher high-density lipoprotein cholesterol levels were observed in the well-controlled group than the poorly controlled group. Higher frequencies of the C allele and AC + CC genotype of AGTR1 A1166C were detected in the well-controlled than the poorly controlled patients ( = 0.005 and = 0.006). After adjustment for demographic and environmental factors, the CC + AC genotype of AGTR1 A1166C was markedly linked to better hypertension control with valsartan treatment compared to the AA genotype (odds ratio: 2.836, 95% confidence interval: 1.199–6.705, = 0.018). No significant difference was observed in the allele or genotype distribution of CYP2C9∗3 polymorphism between well-controlled and poorly controlled patients. Conclusions. The current data suggested that the AGTR1 A1166 C polymorphism may be associated with the antihypertensive effect of valsartan, and carriers with AC and CC genotypes may have a better antihypertensive efficacy response to valsartan treatment.

Single-nucleotide polymorphisms (SNPs) inMYH9-APOL1gene regions have been reported to be associated with diabetic kidney disease (DKD) in the American population. We examined the association between polymorphisms inMYH9-APOL1and DKD susceptibility in a Chinese Han population.MYH9rs3752462 (T>C) andAPOL1rs136161 (C>G) were genotyped in 303 DKD patients and 364 type 2 diabetes mellitus (T2DM) patients without kidney disease using the TaqMan SNP genotyping assay. Chi-squared test and multivariate logistic regression were used to evaluate the association. We observed that onlyMYH9rs3752462 was associated with DKD (genotype,P=0.004; allele,P=0.002). Genetic model analysis revealed that rs3752462 was associated with increased risk of DKD under a dominant model adjusted by age and sex (adjusted odds ratio (aOR), 1.675; 95% CI 1.225–2.289;P=0.001) and an additive model (TC versus TT: aOR, 1.649; 95% CI 1.187–2.290; CC versus TT: aOR, 1.817; 95% CI 0.980–3.367;P=0.005). The combined effect of rs3752462 TC + rs136161 CC genotype showed an association of DKD adjusted by age and sex (aOR, 1.732; 95% CI 1.128–2.660;P=0.012). After a Holm-Bonferroni correction for multiple tests, the C allele frequencies of the rs3752462 and the TC + CC genotype in the dominant model were considered statistically significant with a markedly increased risk of DKD (P<0.00208;P<0.002). Our results suggest thatMYH9rs3752462 is significantly associated with an increased risk of DKD in Chinese Han individuals.

The aim of this study was to investigate the relationship between EPHX2 rs751141 (R287Q polymorphism) and diabetic nephropathy (DN) in Chinese type 2 diabetes (T2D). This case-control study explored the association between EPHX2 rs751141 and DN in a total of 870 Chinese T2D patients (406 T2D patients with DN and 464 T2D patients without DN). DNA was extracted from peripheral leukocytes of the patients and rs751141 was genotyped. The A allele frequency of rs751141 was significantly lower in DN patients (20.94%) compared with non-DN controls (27.8%) (P=0.001), and the A allele of rs751141 was associated with a significantly lower risk of DN after adjustment for multiple covariates in the additive genetic model (OR = 0.68, 95% CI = 0.52–0.88, P=0.004). Significant association between rs751141 and homocysteine (Hcy) level on the risk of DN was observed, indicating that in patients with the highest Hcy levels, the A allele showed marked association with lower risk of DN in all three genetic models. In conclusion, the A allele of exonic polymorphism in EPHX2 rs751141 is negatively associated with the incidence of DN in the Chinese T2D population, which could be modulated by Hcy level status.

Background. Epoxide hydrolase 2 (EPHX2) gene coding for soluble epoxide hydrolase is a potential candidate in the pathogenesis of hypertension. Objectives. We aimed to assess the association of a missense mutation, R287Q, in EPHX2 gene with primary hypertension risk and examine its association with enzyme activity of soluble epoxide hydrolase. Methods. This study involved 782 patients with primary hypertension and 458 healthy controls. Genotyping was done using TaqMan technique. Activity of soluble epoxide hydrolase fusion proteins was evaluated by the conversion of 11,12-EET to corresponding 11,12-DHET using ELISA kit. Results. After taking carriers of R287Q variant GG genotype as a reference, those with GA genotype had a significantly reduced risk of hypertension (adjusted odds ratio: 0.72, 95% confidence interval: 0.56 to 0.93, P = 0.013). Five significant risk factors were identified, including age, body mass index, total cholesterol, homocysteine, and R287Q variant. These five risk factors for hypertension were represented in a nomogram, with a descent prediction accuracy (C-index: 0.833, P<0.001). Enzyme activity of soluble epoxide hydrolase was significantly lower in the R287Q group than in the wild type group. Conclusions. We provide evidence that R287Q mutation in EPHX2 gene was associated with reduced risk of primary hypertension and low activity of soluble epoxide hydrolase.