To characterize the prevalence of BRCA mutations and characteristics of BRCA carriers in China and to update the clinical recommendations for BRCA testing, we conducted a wide screen for BRCA ...mutations using next‐generation sequencing (NGS). A total of 4,034 Chinese subjects were screened for germline BRCA1/2 mutations, including 2,991 breast cancer patients and 1,043 healthy individuals from the community enrolled as controls. We developed an NGS‐based approach to perform BRCA1/2 screening. BRCA mutations were identified in 9.1% (232/2,560) of cases with at least one risk factor, in 3.5% (15/431) of sporadic patients and in 0.38% (4/1,043) of healthy controls. The mutation frequency ranged from 8.9 to 15.2% in cohorts with a single risk factor to 16.6–100% in groups with multiple risk factors. We identified 70 novel BRCA mutations. A high frequency of BRCA1 c.5470_5477del was detected, accounting for 13.9% (16/115) of the BRCA1 mutations detected in our study. Clinical characteristics such as family history, invasive carcinoma, negative human epidermal growth factor receptor 2 (HER2), high Ki67 index, lymph node status, and high tumour grade were closely related to BRCA mutations. BRCA2 carriers had poorer disease‐free survival among HER2‐ or hormone receptor‐positive patients (hazard ratio = 1.892; 95% confidence interval: 1.132–3.161; p = 0.013). This study shows that BRCA mutation carriers could be frequently identified among breast cancer patients with multiple risk factors. Importantly, we established an NGS‐based pipeline for BRCA1/2 testing in clinical practice and strongly suggest that breast cancer patients of premier‐ and moderate‐grade risks receive BRCA1/2 mutations testing in China.
What's new?
Chinese women carrying BRCA mutations are at lower risk of breast cancer compared with female carriers in other countries, a phenomenon that may explained by associations between ethnic background and specific BRCA variants. Little is known, however, about BRCA1/2 mutation prevalence and related clinical characteristics among Chinese women. Here, overall BRCA1/2 mutation frequency was found to be 9.1% in Chinese breast cancer patients, compared with 0.38% in healthy Chinese controls, based on next‐generation sequencing (NGS) analyses. BRCA mutations were closely associated with clinical characteristics, including family history and tumour grade. BRCA mutation carriers could be readily identified by NGS testing.
Water-reducible polyester resin (WRPE) for insulation varnish was prepared from waste polyethylene terephthalate (PET), glycerol (GL), and phthalic anhydride (PA)
via
depolymerization and ...condensation. PET was depolymerized
via
glycolysis at different molar ratios of PET/GL (PET repeating unit/GL molar ratios: 1.6, 1.3, and 1.0) with zinc acetate as a catalyst at 220-230 °C. The resulting glycolytic products (GPs) were reacted with PA at contents of 5, 7.5, 10, 12.5, and 15 wt%, based on the total weight. The prepared WRPEs were dissolved in phenol, neutralized with aqueous ammonia to pH = 7-7.5, and diluted in water. The WRPEs were cured with hexamethoxymethyl melamine resin (HMMM, WRPE : HMMM = 70 : 30, based on the dry mass) at 140 °C for 2 h. The formation of GPs, WRPE, and WRPE-HMMM was investigated using Fourier transformer infrared spectroscopy and proton nuclear magnetic resonance spectroscopy; the thermal properties were characterized using thermogravimetric analysis and differential scanning calorimetry. The electrical insulation strength and volume resistivity of the cured films with PA content were investigated. This strength and volume resistivity first increased with increasing PA content and then decreased above 10 wt%. The results show that WRPE with a PA content of 10 wt% exhibits optimal insulation properties.
Water-reducible polyester resin (WRPE) for insulation varnish was prepared from waste polyethylene terephthalate (PET), glycerol (GL), and phthalic anhydride (PA)
via
depolymerization and condensation.
Abstract
The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer ...in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that
NF2
loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer.
To explore whether there is a causal relationship between coffee consumption and primary open-angle glaucoma (POAG).
Two-sample Mendelian randomization (MR).
The single-nucleotide polymorphisms ...(SNPs) associated with coffee consumption (including phenotypes 1 and 2) were selected from a genome-wide association study (GWAS) involving 121 824 individuals of European descent. Coffee intake from the MRC-IEU UK Biobank was also used to identify instruments for coffee intake. Summary-level data for POAG were obtained from the largest publicly available meta-analyses involving 16 677 POAG cases and 199 580 controls of European descent.
The inverse variance-weighted (IVW) method was the main MR analysis, whereas weighted-median, weighted mode-based estimate (MBE), MR Pleiotropy RESidual Sum and Outlier (PRESSO) test, and MR-Egger regression were used for sensitivity analysis.
Diagnosis of POAG.
Three sets of instrumental variables were used to evaluate the causal association between coffee consumption and POAG risk. Results showed that genetically predicted higher coffee consumption phenotype 1 (cups/day) was significantly associated with higher risk of POAG (odds ratio OR, 1.241; 95% confidence interval CI, 1.041-1.480; P = 0.016). Genetically predicted higher coffee consumption phenotype 2 (high vs. no/low) was also significantly associated with higher risk of POAG (OR, 1.155; 95% CI, 1.038-1.284; P = 0.008, using the IVW method). Moreover, genetically predicted higher coffee intake from the MRC-IEU UK Biobank OpenGWAS was significantly associated with a higher risk of POAG (OR, 1.727; 95% CI, 1.230-2.425; P = 0.002, using the IVW method). Sensitivity analyses confirmed that the findings were robust to possible pleiotropy.
These findings provide the genetic evidence that higher coffee consumption is associated with a higher risk of POAG. Given that coffee is widely consumed, our findings provide new insights into potential strategies to prevent and manage POAG.
Acromioclavicular joint dislocation is a common shoulder injury, usually caused by direct violence on the shoulder. Optimal treatment of type III is still a hot discussion currently in orthopedic ...surgeons. With the advent of many flip-button techniques, Tightrope system and Endobutton system become popular techniques for reconstruction of coracoclavicular ligaments. The purpose of the study was to compare the clinical and radiological results between the two techniques. A retrospective case-control study was conducted in 60 patients with acute Rockwood III acromioclavicular joint dislocation. The two techniques conducted were open procedures using Twin Tail Tightrope system (Group A, n = 30) and Endobutton system (Group B, n = 30). 60 patients were followed up at least two years. Surgical parameters including incision length, operation time and operative blood loss were analyzed. Functional outcomes were evaluated using the Constant-Murley Score. Radiological results were assessed based on coracoclavicular distance preoperatively, one day postoperatively, and at the final follow-up. 60 patients were followed up for at least 24 months (range 24 to 32). The incision length and operation time were shorter in Group A than that in Group B. The blood loss of surgery was significantly less in the Group A. There were no significant differences between the two groups regarding the Constant-Murley Score at the final follow-up. No significant differences were found in the coracoclavicular distance preoperatively, immediately postoperatively, and at the final follow-up. Both techniques offered satisfying functional outcomes, however the Tightrope system provided better surgical parameters.
The 2019 novel coronavirus disease (COVID-19) has now swept through the continents and poses a global threat to public health. Several investigations have been conducted to identify whether COVID-19 ...can be transmitted through the ocular route, and the conclusion is that it is a potential route but remains uncertain. Due to the face-to-face communication with patients, frequent exposure to tears and ocular discharge, and the unavoidable use of equipment which requires close proximity, ophthalmologists carry a high risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Based on 33 articles published by Chinese scholars, guidelines and clinical practice experience in domestic hospitals, we have summarized the Chinese experience through the lens of ophthalmology, hoping to make a contribution to protecting ophthalmologists and patients around the world.
Natural killer (NK) cells are the first lymphocytes to recover after allogeneic stem cell transplantation (SCT) and can exert powerful graft-versus-leukemia (GVL) effects determining transplant ...outcome. Conditions governing NK cell alloreactivity and the role of NK recovery in sibling SCT are not well defined. NK cells on day 30 post-transplant (NK30) were measured in 54 SCT recipients with leukemia and donor and recipient killer immunoglobulin-like receptor (KIR) genotype determined. In univariate analysis, donor KIR genes 2DL5A, 2DS1, 3DS1 (positive in 46%) and higher numbers of inhibitory donor KIR correlated with higher NK30 counts and were associated with improved transplant outcome. NK30 counts also correlated directly with the transplant CD34 cell dose and inversely with the CD3+ cell dose. In multivariate analysis, the NK30 emerged as the single independent determinant of transplant outcome. Patients with NK30 >150/microl had less relapse (HR 18.3, P=0.039), acute graft-versus-host disease (HR 3.2, P=0.03), non-relapse mortality (HR 10.7, P=0.028) and improved survival (HR 11.4, P=0.03). Results suggest that T cell-depleted SCT might be improved and the GVL effect enhanced by selecting donors with favorable KIR genotype, and by optimizing CD34 and CD3 doses.
High-altitude polycythemia (HAPC) is a clinical syndrome that occurs in native inhabitants or long-term residents living at altitude. The kidney is one of the most affected organs. However, the ...clinical and kidney histopathological profiles of HAPC-related kidney disease have rarely been reported. Here, we report kidney biopsy-based clinicopathological study on this disease. HAPC was defined as excessive erythrocytosis females, hemoglobin 190 g/L or more; males, 210 g/L or more in patients living above an altitude of 2500 m for more than ten years. A total of 416 Tibetan patients underwent kidney biopsy between January 1, 2016, and November 31, 2020. Of these patients 17 met the diagnostic criteria for HAPC-related kidney disease. Clinically, these patients had a median urinary protein level of 2.5 g/24-hour (range 1.81–6.85). Twelve patients had hyperuricemia, nine had hypertension, and three had kidney insufficiency. On histopathology, glomerular hypertrophy, glomerular basement membrane thickening, podocyte foot process effacement, segmental glomerulosclerosis and global glomerulosclerosis were the main features. Extraglomerular arterial/arteriolar lesions were common, presenting as intimal fibrosis, hyalinosis and endothelial cell swelling/subintimal edema. Expansion of the arterial/arteriolar medial wall area characterized by smooth muscle cell proliferation was clearly observed, potentially indicating vascular remodeling. Hypoxia-inducible factor 2α was expressed in the kidney tissues of these patients. Thus, the pathological changes of HAPC-related kidney disease encompassed both glomerular and extraglomerular vascular lesions, suggesting a key role of both chronic hypoxia itself and secondary hemodynamic changes in the pathogenesis of this disease.
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This study was conducted to determine the effect of different forms of yeasts Saccharomyces cerevisiae supplementation on serum antioxidant capacity, mucosal secretory immunoglobulin A（s Ig A） ...secretions and gut microbial populations in weaned piglets. A total of 96 piglets weaned at 14 d of age were randomly allotted to 4 dietary treatments：（1） basal diet without yeast（Control）;（2） basal diet supplemented with 3.00 g kg–1 live yeast（LY）;（3） basal diet supplemented with 2.66 g kg–1 heat-killed whole yeast（HKY）; and（4） basal diet supplemented with 3.00 g kg–1 superfine yeast powders（SFY）. Each treatment had 4 replicates（pens）, with 6 piglets per replicate. The experiment lasted for 3 wk. At d 7 and 21 of the experiment, the samples of serum, mucosa and mesenteric lymph node（MLN） from jejunum, and digesta from the ileum and cecum were collected for determinations. Compared with the Control, dietary SFY supplementation increased serum superoxide dismutase（SOD） activity and lysozyme levels at d 7, and jejunum mucosal s Ig A secretions at d 21 of the experiment（P〈0.05）. Dietary LY supplementation increased serum SOD activity and jejunum mucosal s Ig A secretions, but decreased serum malondialdehyde（MDA） concentration at d 7 and 21（P〈0.05）. Piglets fed diets supplemented with LY and SFY had lower p H values and decreased numbers of Escherichia coli in the ileum and cecum contents at d 21 compared with the Control（P〈0.05）. Moreover, the ratio of Lactobacilli to E. coli in the ileum and cecum contents was increased by dietary LY and SFY supplementations（P〈0.05）. Collectively, different forms of yeasts, especially LY and SFY, may modulate body antioxidant capacity and enhance the intestinal immunity by regulation of secretions of mucosal s Ig A and reduction of pathogenic bacteria colonization, thus improving intestinal health of weaned piglets.
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