BACKGROUND: To date, results on relationship between CYP3A4 gene polymorphism were limited and inconclusive, and no study focused on the influence of CYP3A4 gene-obesity interaction on breast cancer risk, especially in Chinese women. The purpose of this study was to evaluate the impact of four single nucleotide polymorphisms (SNPs) of CYP3A4 gene, the SNP-SNP and gene-environment interactions on the susceptibility to breast cancer in Chinese women. METHODS: Logistic regression was used to explore the relationship between four SNPs of CYP3A4 gene and the risk of breast cancer. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best SNP-SNP and gene-abdominal obesity interaction combinations among four SNPs and abdominal obesity. Haplotype examination among 4 SNPs was conducted using the SHEsis web-based platform. RESULTS: Logistic regression analysis showed that carriers of rs2242480- T allele have significantly higher breast cancer risk, than those with rs2242480- CC genotype, adjusted OR (95%CI) was 1.68 (1.23-2.16) and 2.03 (1.53-2.58) for participants with CT genotype and TT genotype under additive model. We did not find any notable interactions between the four SNPs within the CYP3A4 gene. GMDR model found a significant association in a two-locus model involving rs2242480 and obesity, with a p-value of 0.018. Stratified analysis found that breast cancer risk was the highest in obese participants with rs2242480- CT or TT genotype, compared to those non-obese participants with rs2242480- CC genotype, OR (95%CI) was 3.02 (1.83-4.25). We found that all haplotype combinations were not correlated with breast cancer risk. CONCLUSIONS We found that the T allele of rs2242480 within the CYP3A4 gene and interaction between rs2242480 and obesity were associated with an increased risk of breast cancer. However, the results of this study were only applicable to the Han ethnic group and cannot be generalized to other ethnic groups in China, and more SNPs of CYP3A4 gene should been enrolled in the analysis in the future, to verify the results obtained in this study.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/etiology* ; China/epidemiology* ; Cytochrome P-450 CYP3A/metabolism* ; Gene-Environment Interaction ; Genetic Predisposition to Disease ; Haplotypes ; Obesity/epidemiology* ; Polymorphism, Single Nucleotide ; Risk Factors ; East Asian People

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Objective:Retinal vein occlusion(RVO)is the second most common retinal vascular disease worldwide,and the retinal perfusion status is closely related to the prognosis of the disease.Macular perfusion status is particularly correlated with visual acuity.This study aims to investigate the changes in macular perfusion indicators in RVO using optical coherence tomography angiography(OCTA)and analyze the correlation between macular perfusion status and visual acuity. Methods:This cross-sectional study included 41 RVO patients,who were divided into 2 groups based on the occlusion site:18 cases in the central retinal vein occlusion(CRVO)group and 23 cases in the branch retinal vein occlusion(BRVO)group.Additionally,they were categorized into ischemic RVO(23 cases)and non-ischemic RVO(16 cases)groups based on the presence of ischemia(2 eyes were excluded due to hemorrhage obscuring the peripheral retina,making it impossible to confirm the area of non-perfusion).A control group of 29 healthy individuals matched by sex and age was also recruited.Macular perfusion indicators were measured using OCTA,and the correlation between macular perfusion status and visual acuity was analyzed. Results:Compared with healthy eyes,RVO eyes showed an increased foveal avascular zone(FAZ)area and significantly reduced superficial and deep vessel density(P＜0.001).However,there were no significant differences in central foveal thickness(CFT)or macular perfusion indicators between the CRVO and BRVO groups(P＞0.05).The best corrected visual acuity(BCVA)at the logarithm of the minimum angle of resolution(logMAR BCVA)was significantly negatively correlated with both superficial and deep retinal vessel density in RVO eyes(unstandardized coefficient B=-0.039,B=-0.042;P=0.017,P=0.040).The average BCVA in the ischemic RVO group was significantly worse than that in the non-ischemic RVO group(0.82±0.44 vs 0.45±0.29,P=0.007).The ischemic RVO group also had a larger FAZ area(P=0.003)and lower superficial and deep retinal vessel density(P＜0.001,P=0.008,respectively)compared with the non-ischemic RVO group.The severity of macular ischemia did not correspond directly with the peripheral ischemia severity in RVO. Conclusion:Macular perfusion status is significantly reduced in RVO eyes compared to healthy eyes,which negatively impacts and limits visual acuity in RVO patients.Eyes with ischemic RVO have poorer visual acuity and macular perfusion status than those with non-ischemic RVO.OCTA is advantageous for observing vascular morphology and quantifying macular perfusion status,making it an effective tool for assessing disease progression.

Objective To develop and evaluate the equivalence of the Mandarin test material for tracking of noise tolerance(TNT)test.Methods Six different speech materials were developed(themes including daily life,entertainment,family,festivals,outdoors,and school).Four-minute TNT tests were measured in 21 normal hear-ing subjects using six different test materials.For each session,the tolerable noise level(TNL)and TNT scores were acquired and calculated for 3 time windows(31～240 s,31～120 s,151～240 s).Results Statistic analysis showed significant differences in the TNL(F=43.611,P＜0.05)among the normal hearing listeners.There were statistically significant differences in standardize z-scored TNT scores of the six different materials in the three time windows(P＜0.05).Post-hoc comparisons revealed that all significant differences involved the family and daily life themes.Conclusion Entertainment,festival,outdoors and school themed test materials can serve as the materials of Mandarin tracking of noise tolerance test and can be appied in research and clinical testing.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.

Article 1220 of the Civil Code of the People's Republic of China is specifically formulated for medical in-stitutions and medical personnel to rescue patients with life-threatening conditions,aiming to adjust the contradic-tion between the right of emergency rescue in medical institutions and the right of informed consent of patients.In view of the lack of relevant laws and regulations,poor organizational structure and loopholes in the system,medical institutions may have certain risks when implementing emergency treatment.After sorting out and examining the rele-vant provisions of the current law on emergency treatment in medical institutions,it is found that it is necessary to optimize the relevant legal provisions and judicial interpretations,establish and improve the case evaluation system with ethics committee as the core,improve the medical assistance fund and insurance system,and avoid the dilem-ma of"feeling and reason"for medical personnel.