Age at menarche and age at natural menopause are associated with causes of substantial morbidity and mortality such as breast cancer and cardiovascular disease. We conducted a joint analysis of two ...genome-wide association studies of these two traits in a total of 17,438 women from the Nurses' Health Study (NHS, N = 2,287) and the Women's Genome Health Study (WGHS, N = 15,151). For age at menarche, we identified ten associated SNPs (P = 1 × 10−7-3 × 10−13) clustered at 6q21 (in or near the gene LIN28B) and 9q31.2 (in an intergenic region). For age at natural menopause, we identified 13 associated SNPs (P = 1 × 10−7-1 × 10−21) clustered at 20p12.3 (in the gene MCM8), 19q13.42 (in or near the gene BRSK1), 5q35.2 (in or near genes UIMC1 and HK3) and 6p24.2 (in the gene SYCP2L). These newly identified loci might expand understanding of the biological pathways regulating these two traits.
Thrombocytopenia or platelet dysfunction is a risk factor for severe infection. Staphylococcus aureus (S. aureus) releases a variety of virulence factors especially toxic shock syndrome toxin 1 ...(TSST-1), which may cause toxic shock syndrome. S. aureus, when carrying the tst gene, is more prone to cause toxic shock syndrome and is responsible for an especially high rate of mortality. However, the effect of TSST-1 protein on platelets is unknown. Patients with the tst gene positive S. aureus bacteremia showed more serious infection, higher mortality and lower platelet count. The tst gene positive S. aureus strains induce more platelet apoptosis and activation and corresponding up-regulation of Bak and down-regulation of Bcl-XL in addition to the activation of Caspase-3. C57BL/6 mice infected with the tst gene positive strains resulted in both a decrease in platelet count and an increase in platelet apoptosis and/or activation events and mortality. Moreover, TSST-1 protein, encoded by tst gene, caused the decrease of platelet count, the increase of platelet apoptosis and activation events and the level of inflammatory cytokines in vivo. However, TSST-1 protein was unable to induce traditional activation and apoptosis on human platelets in vitro. These results suggested that TSST-1 protein may exert indirect effects on platelet activation and apoptosis in vivo.
Associations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like TNBC). In this systematic review and ...meta-analysis, we summarized the associations between reproductive factors and BC subtypes.
Studies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case-control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals.
A total of 75 studies met the inclusion criteria for systematic review. Among the case-control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use.
Identifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.
Inflammatory myofibroblastic tumor (IMT) is a mesenchymal spindle cell tumour with low malignant potential which is extremely rare in breasts. Because of the lack of typical imaging and clinical ...characteristics of IMT, it is easy to misdiagnose before operation. We now report a case of a 37-year-old woman presenting with a mass in her left breast. Ultrasound showed a well-circumscribed lesion in the lower outer quadrant. The patient underwent lumpectomy, and histopathology revealed a tumor which was composed of fusiform cells and inflammatory cells. Immunohistochemistry (IHC) showed tumor cells are positive for vimentin, ALK, BCL2, and SMA. The FISH test demonstrated ALK (2p23) chromosomal translocation (ALK positive). The final diagnosis of breast IMT was rendered with nonclassical morphology. Postoperative 30-month follow-up no evidence showed residual tumor or recurrence. As a very rare tumor, breast IMT could be easily misdiagnosed clinically and pathologically. Complete surgical resection of the tumor is preferred, and it has the risk of recurrence and metastasis.
The data on the prevalence of resistance to mupirocin (MUP), fusidic acid (FA) and retapamulin (RET) in methicillin-resistant Staphylococcus aureus (MRSA) from China are still limited. This study ...aimed to examine these three antibiotics resistance in 1206 MRSA clinical isolates from Eastern China. Phenotypic MUP, FA and RET resistance was determined by minimum inhibitory concentrations (MICs), and genotypic by PCR and DNA sequencing of the mupA/B, fusB-D, cfr, vgaA/Av/A.sub.LC/B/C/E, lsaA-C/E and salA and mutations in ileS, fusA/E, rplC, and 23S RNA V domain. The genetic characteristics of resistance isolates were conducted by pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Overall MRSA MUP, FA and RET resistance was low (5.1, 1.0 and 0.3%, respectively). MupA was the mechanism of high-level MUP resistance. All low-level MUP resistance isolates possessed an equivocal mutation N213D in IleS; of these, 2 reported an additional V588F mutation with an impact on the Rossman fold. FusA mutations, such as L461K, H457Q, H457Y and V90I were the primary FA mechanisms among high-level resistance isolates, most of which also contained fusC; however, all low-level resistance strains carried fusB. Except lsaE gene detected in one isolate, no other resistance mechanisms tested were found among RET-resistant isolates. Additionally, sixteen PFGE types (A-P) were observed, among which type B was the most common (49/76, 64.5%), followed by types E and G (4/76, 5.3% each) and types C and M (3/76, 3.9% each). All resistant strains were divided into 15 ST types by MLST. ST764 (24/76, 31.6%), ST630 (11/76, 14.5%), ST239 (9/76, 11.8%) and ST5 (7/76, 9.2%) were the major types. PFGE type B isolates with the aforementioned STs were mainly found in mupirocin resistant isolates. MUP, FA and RET exhibited highly activity against the MRSA isolates. Acquired genes and chromosome-borne genes mutations were responsible for MUP and FA resistance; however, the mechanism for some RET-resistant isolates remains to be further elucidated. Also, the surveillance to MUP in MRSA should be strengthened to prevent elevated resistance due to the expansion of clones.
Climate change impacts agricultural production negatively. Therefore, rural residents experience large income and consumption fluctuations when dealing with climate change risks. However, little is ...known about whether digital financial inclusion can help rural residents improve their ability to resist climate change. This study uses the Peking University Digital Financial Inclusion Index of China and China Household Finance Survey data, together with historical temperature data from major cities, to study the impact of digital financial inclusion on Chinese rural residents’ consumption in response to climate change. The results suggest that digital financial inclusion significantly promotes rural households’ total consumption and consumption upgrades. Heterogeneity analyses also show that digital financial inclusion predominantly affects low-income households, low-asset households, and households living in China’s central and western regions. The instrumental variable and control function methods were used for robustness, and our main conclusions are robust and reliable. Although climate change reduces rural residents’ consumption and increases their risks, digital finance inclusion significantly mitigates this negative effect. The government can increase the usage depth of digital financial inclusion in rural areas by promoting the construction of digital financial inclusion facilities. The government should strive to deepen the impact of digital financial inclusion on rural household income and consumption to further improve their ability to resist climate risks.
Artificial aphid infestation experiments on the three chrysanthemum cultivars ‘Keiun’, ‘Han6’ and ‘Jinba’ showed that the three cultivars vary markedly in their resistance. Of the three cultivars, ...the most resistant (‘Keiun’) produced the longest, highest and densest trichomes, the largest and fullest gland cells, and the most wax on the lower leaf epidermis. Superoxide dismutase (EC 1.15.1.1), peroxidase (EC 1.11.1.7), ascorbate peroxidase (EC 1.11.1.11), polyphenol oxidase activity (EC 1.14.18.1) and phenylalanine ammonia lyase (EC 4.3.1.5) were enhanced by aphid herbivory. In the two more resistant cultivars (‘Keiun’ and ‘Han6’), the activity of superoxide dismutase and ascorbate peroxidase enzymes rapidly increased following infestation, and their levels remained high from seventy-two to one hundred and sixty-eight hours after inoculation. We suggest that these two antioxidant enzymes contribute to aphid resistance of these chrysanthemum cultivars. All three cultivars showed quick responses to aphid infestation by increasing polyphenol oxidase and phenylalanine ammonia lyase activities during the early period after inoculation. Activities of these two defense enzymes were higher in the two resistant cultivars after 72
h after inoculation, suggesting involvement of these two enzymes in aphid resistance.
A newly-developed platform, the Illumina TruSeq Methyl Capture EPIC library prep (TruSeq EPIC), builds on the content of the Infinium MethylationEPIC Beadchip Microarray (EPIC-array) and leverages ...the power of next-generation sequencing for targeted bisulphite sequencing. We empirically examined the performance of TruSeq EPIC and EPIC-array in assessing genome-wide DNA methylation in breast tissue samples. TruSeq EPIC provided data with a much higher density in the regions when compared to EPIC-array (~2.74 million CpGs with at least 10X coverage vs ~752 K CpGs, respectively). Approximately 398 K CpGs were common and measured across the two platforms in every sample. Overall, there was high concordance in methylation levels between the two platforms (Pearson correlation r = 0.98, P < 0.0001). However, we observed that TruSeq EPIC measurements provided a wider dynamic range and likely a higher quantitative sensitivity for CpGs that were either hypo- or hyper-methylated (β close to 0 or 1, respectively). In addition, when comparing different breast tissue types TruSeq EPIC identified more differentially methylated CpGs than EPIC-array, not only out of additional sites interrogated by TruSeq EPIC alone, but also out of common sites interrogated by both platforms. Our results suggest that both platforms show high reproducibility and reliability in genome-wide DNA methylation profiling, while TruSeq EPIC had a significant improvement over EPIC-array regarding genomic resolution and coverage. The wider dynamic range and likely higher precision of the estimates by the TruSeq EPIC may lead to the identification of novel differentially methylated markers that are associated with disease risk.
There is a complex relationship between social anxiety and sleep quality. However, network analysis studies of associations between social anxiety and sleep quality are lacking, particularly among ...patients with breast cancer. The current study aimed to extend this research to a sample of patients with breast cancer and to examine symptom-level associations between social anxiety and sleep quality using network analysis.
Network analysis was conducted to explore their associations and identify bridge items of social anxiety and sleep quality.
The network structure revealed 9 important edges between social anxiety and sleep quality. "Subjective sleep quality" had the highest EI value in the network. "Working difficulty under watching" and "Sleep disorders" had the highest BEI values in their own communities.
There are complex pathological correlation pathways between social anxiety and sleep quality in breast cancer patients. "Subjective sleep quality", "Working difficulty under watching" and "Sleep disorders" have the potential to be intervention targets for sleep disorder-social anxiety comorbidity. Medical staff can take corresponding interventions according to the the centrality indices and bridge centrality indicators identified in this study, which is likely to effectively reduce the comorbidity of sleep disorders and social anxiety.
The governments of most countries are striving to coordinate residents’ housing demands with the supply of land to achieve high-quality urbanization and improve residents’ welfare. Based on the panel ...data of all Chinese provinces from 2010 to 2017, this study obtains 248 observations. It uses the coupling coordination degree, the Mann–Kendall trend test, and spatial autocorrelation methods to analyze the temporal and spatial variation of the coordination degree of population urbanization and affordable housing land supply. The study aims to clarify the temporal trend further and identify the spatial mismatch of affordable housing land resource allocation and apply a panel fixed model to determine its driving factors. The regional differentiation of the coordinated development level of population urbanization and affordable housing land in China’s provinces is apparent. The overall spatial distribution characteristics of coordination are opposite to the development of its economic level. The Mann–Kendall trend test indicated that the coupling coordination degree had a significant upward trend nationwide. Moreover, the coupling coordination degree shows a strong positive global spatial correlation. The local spatial agglomeration characteristics of the coordination are significant and primarily manifested in high–high and low–low agglomeration. A negative correlation exists between the degree of coupling coordination and the dependence of local governments on land finance and housing prices.