Association between NUDT17 polymorphisms and breast cancer risk.

BACKGROUND: Breast cancer (BC) is the leading cause of cancer death among women worldwide. The nudix hydrolase 17 (NUDT17) may play notable roles in cancer growth and metastasis. In this study, we explored the importance of NUDT17 gene polymorphism in patients with BC. METHODS: In our study, 563 BC patients and 552 healthy controls participated. We used logistic regression analysis to calculate odds ratios (OR) and 95% confidence intervals (CI), and multifactor dimension reduction (MDR) analysis of SNP-SNP interactions. Finally, UALCAN and THPA databases were used for bioinformatics analysis. RESULTS: The rs9286836 G allele was associated with a decreased the BC risk (p = 0.022), and the carriers of rs2004659 G allele had a 32% decreased risk of BC than individuals with allele A (p = 0.004). In the four genetic models, rs9286836 and rs2004659 reduced the risk of BC. Additionally, we found that the NUDT17 SNPs were associated with BC risk under age, tumor size, and clinical stage stratification. The MDR analysis showed that the five-locus interaction model was the best in the multi-locus model. CONCLUSION: Our study found that NUDT17 single nucleotide polymorphisms are associated with BC susceptibility in Chinese Han population.

The landscape of very important pharmacogenes variants and potential clinical relevance in the Chinese Jingpo population: a comparative study with worldwide populations.

BACKGROUND: Pharmacogenomics is a facet of personalized medicine that explores how genetic variants affect drug metabolism and adverse drug reactions. Therefore, this study aims to detect distinct pharmacogenomic variations among the Jingpo population and explore their clinical correlation with drug metabolism and toxicity. METHODS: Agena MassARRAY Assay was used to genotype 57 VIP variants in 28 genes from 159 unrelated Jingpo participants. Subsequently, the chi-squared test and Bonferroni's statistical tests were utilized to conduct a comparative analysis of genotypes and allele frequencies between the Jingpo population and the other 26 populations from the 1000 Genome Project. RESULTS: We discovered that the KHV (Kinh in Ho ChiMinh City, Vietnam), CHS (Southern Han Chi-nese, China) and JPT (Japanese in Tokyo, Japan) exhibited the smallest differences from the Jingpo with only 4 variants, while ESN (Esan in Nigeria) exhibited the largest differences with 30 variants. Besides, a total of six considerably different loci (rs4291 in ACE, rs20417 in PTGS2, rs1801280 and rs1799929 in NAT2, rs2115819 in ALOX5, rs1065852 in CYP2D6, p < 3.37 × 10-5) were identified in this study. According to PharmGKB, rs20417 (PTGS2), rs4291 (ACE), rs2115819 (ALOX5) and rs1065852 (CYP2D6) were found to be associated with the metabolism efficiency of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, montelukast and tamoxifen, respectively. Meanwhile, rs1801280 and rs1799929 (NAT2) were found to be related to drug poisoning with slow acetylation. CONCLUSION: Our study unveils distinct pharmacogenomic variants in the Jingpo population and discovers their association with the metabolic efficiency of NSAIDs, montelukast, and tamoxifen.

SOWAHB polymorphisms affect thyroid cancer risk in the Chinese Han population.

OBJECTIVES: This study aimed to detect the correlation between SOWAHB polymorphisms and Thyroid cancer (TC) risk in the Chinese Han population. METHODS: We genotyped SOWAHB variants in 510 TC patients and 509 controls using Agena MassARRAY. We assessed the association between SOWAHB polymorphisms and TC susceptibility, with the significant results evaluated through FPRP analysis. We predicted TC risk by the SNP-SNP interaction, analyzed by MDR. RESULTS: Carriers with rs2703129 CC had a lower probability of TC (codominant, recessive: p = 0.002), while subjects with rs1874564 AG had an increased risk of developing TC (codominant, recessive: p = 0.000, log-additive: p = 0.028). In subjects aged > 45 years, rs2703129 may reduce TC predisposition (codominant: p = 0.011, recessive: p = 0.007), but there was an increased association between rs1874564 and TC risk (codominant: p = 0.030, dominant: p = 0.047). Also, rs2703129 was associated with a lower risk of TC among males (codominant: p = 0.018, recessive: p = 0.013). Conversely, rs1874564 was associated with an increased risk of TC in females (codominant: p = 0.001, dominant: p = 0.003). CONCLUSION: SOWAHB SNPs were related to the occurrence of TC, and rs2703129 may be a protective site for TC.

The Role of Endophilin A1 in Lipopolysaccharide-Induced Parkinson's Disease Model Mice.

BACKGROUND: Endophilin A1 (EPA1) is encoded by the SH3GL2 gene, and SH3GL2 was designated as a Parkinson's disease (PD) risk locus by genome-wide association analysis, suggesting that EPA1 may be involved in the occurrence and development of PD. OBJECTIVE: To investigate the role of EPA1 in lipopolysaccharide (LPS)-induced PD model mice. METHODS: The mice PD model was prepared by injecting LPS into the substantia nigra (SN), and the changes in the behavioral data of mice in each group were observed. The damage of dopaminergic neurons, activation of microglia, and reactive oxygen species (ROS) generation were detected by immunofluorescence method; calcium ion concentration was detected by calcium content detection kit; EPA1 and inflammation and its related indicators were detected by western blot method. EPA1 knockdown was performed by an adeno-associated virus vector containing EPA1-shRNA-eGFP infusion. RESULTS: LPS-induced PD model mice developed behavioral dysfunction, SN dopaminergic nerve damage, significantly increased calcium ion, calpain 1, and ROS production, activated NLRP1 inflammasome and promoted pro-inflammatory cell release, and SN EPA1 knockdown improves behavioral disorders, alleviates dopaminergic neuron damage, reduces calcium, calpain 1, ROS generation, and blocks NLRP1 inflammasome-driven inflammatory responses. CONCLUSION: The expression of EPA1 in the SN of LPS-induced PD model mice was increased, and it played a role in promoting the occurrence and development of PD. EPA1 knockdown inhibited the NLRP1 inflammasome activation, decreased the release of inflammatory factors and ROS generation, and alleviated dopaminergic neuron damage. This indicated that EPA1 may participating in the occurrence and development of PD.

Genetic polymorphisms in CYP2B6 may be associated with lung cancer risk in the Chinese Han population.

BACKGROUND: Our study aimed to elucidate the association between single nucleotide polymorphisms (SNPs) in CYP2B6 gene and susceptibility to lung cancer (LC). METHODS: Five SNPs in CYP2B6 were genotyped in Chinese Han population (507 cases and 505 controls) utilizing Agena MassARRAY. The relationship between these SNPs and LC susceptibility was assessed using odds ratios, 95% confidence intervals, and χ2 tests. Additionally, multifactor dimensionality reduction was employed to analyze SNP-SNP interactions. Bioinformatics methods were applied to investigate the function of these SNPs. RESULTS: We found that rs2099361 was associated with an increased susceptibility to LC in the codominant model (OR = 1.31, p = 0.045). Stratification analysis revealed the allele G at rs4803418 and the allele T at rs4803420 of CYP2B6 (BMI >24 kg/m2) were significantly linked to decreased susceptibility of LC. Conversely, the allele C at rs12979270 (BMI >24 kg/m2) showed increased susceptibility to LC. Moreover, a robust redundant relationship between rs12979270 and rs4803420 was identified in the study. According to the VannoPortal database, we found that rs4803420, rs12979270 and rs2099361 may modulate the binding affinity of LMNB1, SP1 and HDAC2, respectively. CONCLUSIONS: Our results suggest that SNPs in the CYP2B6 gene play crucial roles in LC susceptibility.

Heterogeneity of Capability Deprivation and Subjective Sense of Gain: Analysis of Factor Mixture Models Based on 892 Rural Households in Six Provinces.

BACKGROUND: The capability approach conceptualizes poverty as capability deprivation. Given that functionings and opportunities as key factors are diverse, the combination of a varied lack of functionings and opportunities will lead to different deprivation patterns. Therefore, we sought to investigate the association between the category of capacity deprivation and the subjective acquisition of rural households. METHODS: Data were collected from the micro survey of 892 households in six provinces. The overall sense of acquisition was measured by self-assessment of life satisfaction and the relative sense of gain was measured by self-assessment of social status and communication confidence. Capability deprivation was assessed through evaluation functionings and opportunities for a better life, such as education, social security, medical and health services, living conditions and spiritual and cultural activities. The factor mixture models were used to investigate the group categories of capability deprivation and ordered probit regression was used to estimate the associations between the categories of capability deprivation and sense of gain. RESULTS: There were mild, moderate and severe differences among the deprivation items reflecting functionings and opportunities. In addition, capability deprivation was grouped into four classes: double deprivation of functionings and opportunities, severe deprivation of opportunities, functionings deprivation and non-poverty. There was a significant negative relationship between deprivation classes and the subjective sense of gain. CONCLUSION: The deprivation from some social participation functions and services led to a reduced sense of acquisition. However, serious deprivations from educational opportunities and social participation opportunities were the main reason for the lower sense of gain. Eliminating the unequal educational opportunities and social participation opportunities for people is imperative to improving the subjective sense of gain.

Loss of Happiness for Land-Expropriated, Urbanised Residents: A Comparison Based on Multiple Groups.

Are land-expropriated, urbanised residents living happily? This question is not only related to the quality of urbanisation but also has important reference for evaluating the reform of the land acquisition system. On the basis of the Chinese General Social Survey data in 2017 and 2018, the HeckProbit model, the ordered probit model and the mediating effect model were used to study the happiness and underlying mechanism of land-expropriated, urbanised residents. The results showed that the older the farmers are, the lower the probability of obtaining urban hukou through land acquisition, and women will be more likely to achieve household registration through land requisition. Education and party status have significant inhibitory effects on hukou conversion through land acquisition. A comparison among multiple groups indicated that the happiness level of each group is ranked as follows: residents who attained urban hukou through education and job recruitment > urban native residents > land-expropriated, urbanised residents > farmers; however, the happiness level of the latter two groups has no significant difference. The propensity score matching method was further used to reduce the endogeneity due to selection bias, and the results were still robust. The lower self-assessment of socioeconomic status indirectly caused the loss of happiness of land-expropriated, urbanised residents. However, the high living expectation 'suppressed' the negative effect of land acquisition on happiness to some extent.

Impact of Internet Use on Multi-dimensional Health: An Empirical Study Based on CGSS 2017 Data.

Based on the data of the Chinese General Social Survey (CGSS) in 2017, the paper divides overall health into physical, mental, and social health, using the ordered probit model to examine the impact of Internet use on multi-dimensional health. It then discusses the possible heterogeneity in different groups and underlying mechanism. Results found that using the Internet can improve the health level in multiple dimensions. After endogenous and robustness tests, the results remain robust. Heterogeneity analysis shows that Internet use has more obvious effects on the health of senior high school education or above, the elderly, and men. Further analysis of the mediating effect model found that information, leisure, and social preferences are important path mechanisms for Internet use to promote physical, mental, and social health, respectively.

The variations of endophilin A2-FoxO3a-autophagy signal in angiotensin II-induced dopaminergic neuron injury mouse model and by biochanin A.

Biochanin A (Bioch A) is a natural plant estrogen, with various biological activities such as anti-apoptosis, anti-oxidation, and suppression of inflammation. In this study, we investigated the protective effects of Bioch A on angiotensin II (AngII) - induced dopaminergic (DA) neuron damage in vivo and on molecular mechanisms. Spontaneous activity and motor ability of mice among groups was detected by open-field test and swim-test. The expression of TH, microtubule-associated proteins light chain 3B II (LC3BII)/LC3BI, beclin-1, P62, forkhead box class O3 (FoxO3), phosphorylated (p) FoxO3a/FoxO3a, FoxO3, and endophilin A2 were determined by Western blot and immunohistochemistry or immunofluorescence staining. Our results showed that AngII treatment significantly increased the behavioral dysfunction of mice and DA neuron damage. Meanwhile, AngII treatment increased the expression of LC3BII/LC3BI, beclin-1, P62, and FoxO3a and decreased the expression of endophilin A2 and p-FoxO3a/FoxO3a, however, Bioch A treatment alleviate these changes. In summary, these results suggest that Bioch A exerts protective effects on AngII-induced mouse model may be related to regulating endophilin A2, FoxO3a, and autophagy-related proteins; however, the specific mechanism is not yet clear and needs further study.

Does Individual Anxiety Play a Mediating Role on the Impact of Psychological Expectation of Class Mobility on Entrepreneurial Choice?

PURPOSE: Under the dual backgrounds of "Chinese dream" and "Mass entrepreneurship and innovation", can psychological expectations influence entrepreneurial activities? There is little literature on this topic. In addition, although psychological expectation can reduce the negative emotions caused by uncertain events, the expectation itself can lead to the activation of related neural circuits and the generation of individual anxiety. According to Maslow's hierarchy of needs, this paper divides the entrepreneurship into the economic status type, the social status type and the self-development type, and attempts to study the psychological mechanism of the psychological expectation of class mobility influencing entrepreneurial choice by constructing the mediating effect model of individual anxiety. METHODS: Based on CGSS 2015 data, entrepreneurial choice was obtained through describing the working status. The individual anxiety in the questionnaire is "How often have you felt depressed or disheartened in the past four weeks?". Psychological expectation of class mobility was calculated by subtracting the current subjective class score from the subjective class score 10 years later. Classical mediating effect models were conducted by stata 15.0. RESULTS: The psychological expectation of class mobility can promote entrepreneurial behavior. According to sub sample study, individual anxiety plays a partial mediating effect between the psychological expectation of class mobility and economic status type entrepreneurships. No mediating effect of individual anxiety occurs for social status type and self-development type entrepreneurships. CONCLUSION: This study provides a psychological mechanism by which the expectation of class mobility affects entrepreneurial choice. The implications are as follows: we should firstly prevent excessive anxiety from triggering irrational entrepreneurship. Secondly, we should establish a fair social mobility mechanism to provide psychological incentives for entrepreneurial groups to flow upward through entrepreneurship. Thirdly, we undertake classification management of entrepreneurial groups and pay attention to social status type and self-development type entrepreneurial.