OCT及OCTA在阿尔茨海默病诊断中的研究进展

阿尔茨海默病是一种进行性且不可逆转的神经系统疾病,由于视网膜和中枢神经系统有相似的胚胎起源和生理特征,眼科检查可提供简单无创的诊断方法。光学相干断层扫描技术(OCT)能够精确地测量视网膜各个组织层面的厚度,以评估视网膜的退行性改变,光学相干断层扫描血管成像(OCTA)可以提供高分辨率三维成像,从而更直观地检测视网膜血管的变化,间接地反映脑神经元和血管的病理特征。就OCT测量视网膜厚度及OCTA测量视网膜血流变化在阿尔茨海默病诊断中的研究进展进行综述。     

Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents.ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT.MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis.ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96).ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.     

A Proposal for an Alternative Approach to Particle Size Method Development During Early-Stage Small Molecule Pharmaceutical Development

Particle size analysis in the pharmaceutical industry has long been a source of debate regarding how best to define measurement accuracy; the degree to which the result of a measurement or calculation conforms to the true value. Defining a “true” value for the size of a particle can be challenging as the output of its measurement will differ because of variations in measurement approaches, instrumental differences and calculation methods. Consequently, for “real” particles, a universal “true” value does not exist and accuracy is therefore not a definable characteristic. Accordingly, precision is then a measure of the ability to reproducibly achieve a measurement of unknown relevance.This article proposes, in place of accuracy, a means to define the “appropriateness” of a measurement in line with the critical quality attributes (CQA) of the material being characterized. The decision as to whether the measurement is correct should involve a link to the CQA; that is, correlation should be demonstrated, without which the measured particle size cannot be defined as a critical material attribute.Correspondingly, methods should also be able to provide sufficient precision to demonstrate discrimination relating to variation in the CQA. The benefits and challenges of this approach are discussed.     

白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低的保护作用

目的探索白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低的影响。方法 30只12周雄性大鼠随机分为对照组、模型组和治疗组3组,每组10只。模型组和治疗组大鼠给予0.4 mL/100 g的20%乙醇溶液,每周3次。治疗组接受白藜芦醇40 mg/kg治疗,每日一次,治疗为期12周。治疗结束时收集血清和股骨对治疗结果进行评价。结果治疗12周后,治疗组的股骨骨密度较模型组显著升高,差异有统计学意义(P0.05);Mircro-CT显示治疗组大鼠股骨干骺端较模型组具有更多骨小梁以及更佳的骨微观参数,差异有统计学意义(P0.05);生物力学结果显示治疗组股骨的极限载荷和峰值负荷较模型组显著升高,差异有统计学意义(P0.05);而血清检测结果表明治疗组的碱性磷酸酶和骨钙素较模型组明显降低,差异有统计学意义(P0.05)。结论白藜芦醇对酒精诱导雄性大鼠骨量减少和骨强度降低有一定的保护作用。     

Deep learning with biopsy whole slide images for pretreatment prediction of pathological complete response to neoadjuvant chemotherapy in breast cancer：A multicenter study

IntroductionPredicting pathological complete response (pCR) for patients receiving neoadjuvant chemotherapy (NAC) is crucial in establishing individualized treatment. Whole-slide images (WSIs) of tumor tissues reflect the histopathologic information of the tumor, which is important for therapeutic response effectiveness. In this study, we aimed to investigate whether predictive information for pCR could be detected from WSIs.Materials and methodsWe retrospectively collected data from four cohorts of 874 patients diagnosed with biopsy-proven breast cancer. A deep learning pathological model (DLPM) was constructed to predict pCR using biopsy WSIs in the primary cohort, and it was then validated in three external cohorts. The DLPM could generate a deep learning pathological score (DLPs) for each patient; stromal tumor-infiltrating lymphocytes (TILs) were selected for comparison with DLPs.ResultsThe WSI feature-based DLPM showed good predictive performance with the highest area under the curve (AUC) of 0.72 among the cohorts. Alternatively, the combination of the DLPM and clinical characteristics offered a better prediction performance (AUC >0.70) in all cohorts. We also evaluated the performance of DLPM in three different breast subtypes with the best prediction for the triple-negative breast cancer (TNBC) subtype (AUC: 0.73). Moreover, DLPM combined with clinical characteristics and stromal TILs achieved the highest AUC in the primary cohort (AUC: 0.82) and validation cohort 1 (AUC: 0.80).ConclusionOur study suggested that WSIs integrated with deep learning could potentially predict pCR to NAC in breast cancer. The predictive performance will be improved by combining clinical characteristics. DLPs from DLPM can provide more information compared to stromal TILs for pCR prediction.