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1.
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.  相似文献   
2.
目的 探索贵州省男性主要少数民族骨量异常的影响因素,为骨量异常的防控提供参考依据。 方法 基于中国多民族队列,采用多阶段分层整群抽样方法调查贵州省苗族、布依族、侗族男性共5 727名。采用随机森林算法、非条件logistic回归和限制性立方样条回归探讨骨量异常的影响因素。结果 骨量异常重要的前5名的因素依次是职业、午睡时长、年龄、BMI、静态行为。布依族(OR=1.223,95%CI:1.065~1.405)、年龄≥50岁(OR=1.254,95%CI:1.038~1.515)、吸烟(OR=1.191,95%CI:1.060~1.338)、有关节炎(OR=1.259,95%CI:1.001~1.583)和有骨折史(OR=1.528,95%CI:1.227~1.902)可能是骨量异常的危险因素。而农林牧渔劳动者(OR=0.787,95%CI:0.626~0.990)、午睡时长≥90分钟(OR=0.725,95%CI:0.612~0.858)、中水平体力活动(OR=0.818,95%CI:0.708~0.946)和高水平体力活动(OR=0.824,95%CI:0.696~0.975)可能是贵州省主要男性少数民族骨量异常的保护因素。BMI与骨量异常的患病关联强度呈非线性关系,业余静态行为时长与骨量异常的患病关联强度呈线性关系。结论 影响贵州省男性主要少数民族骨量异常的因素包括多方面,包括非可控因素和可控因素,建议加强对可控因素的管理以预防骨量异常的发生。  相似文献   
3.
《Pancreatology》2022,22(8):1175-1180
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.  相似文献   
4.
目的 探索人工智能骨髓细胞识别系统Morphogo应用于多发性骨髓瘤微小残留病(minimal residual disease,MRD)检测的临床价值及面临问题。方法 收集已经由流式细胞术(multiparameter flow cytometry,MFC)检查后明确微小残留病结果的病例65例,调取其留存的骨髓瑞氏染色涂片,通过基于人工智能(artificial intelligence,AI)平台的分析系统Morphogo对所有骨髓涂片进行全自动扫描及细胞分类。AI及细胞形态学多发性骨髓瘤MRD阳性阈值设为浆细胞比例大于4.4%。按AI自动识别细胞数量将病例分为I 500组、I 1000组、I 2000组,每组病例的人工智能微小残留病(AI-MRD)、细胞形态学(morphology)微小残留病(M-MRD)和流式细胞术微小残留病(MFC-MRD)结果两两行Kappa一致性检验,并计算各组敏感度、特异度、准确度。分别以MFC-MRD和M-MRD结果为金标准绘制AI-MRD的受试者工作特征(receiver operating characteristic,ROC)曲线并计算其曲线下面积(area under the curve,AUC)。结果 分组后AI-MRD vs. MFC-MRD 和AI-MRD vs. M-MRD的Kappa值、敏感度、特异度、准确度、AUC均随识别细胞数量的增加而增高,其中I 2000组AI-MRD vs. MFC-MRD的Kappa一致性检验结果为Kappa=0.500(P=0.013),敏感度为71%,特异度为80%,准确度为75%;AI-MRD vs. M-MRD的Kappa一致性检验结果为Kappa=0.667(P=0.001),敏感度为100%,特异度为75%,准确度为83%。以MFC-MRD结果为标准,I 2000组AI-MRD的ROC AUC=0.800(P=0.002,95%CI=0.588~0.934),M-MRD的ROC AUC=0.779(P=0.005,95%CI=0.564~0.921)。结论 人工智能骨髓细胞识别系统Morphogo检测多发性骨髓瘤MRD具有细胞识别准确度高、速度快、成本低等特点,后续开发中应加入细胞组化染色、细胞免疫等技术提高人工智能多发性骨髓瘤微小残留病诊断的准确率。  相似文献   
5.
目的分析同型半胱氨酸(Hcy)、溶血磷脂酸(LPA)及转化生长因子-β1(TGF-β1)在创伤性骨折下肢静脉栓塞中的预测价值。方法选取2019年3月至2020年2月商丘市第一人民医院收治的104例创伤性骨折者(观察组),根据有无DVT:有DVT组33例,无DVT组71例;根据创伤严重程度:轻度组61例,重度组43例。另选取本院同期92例健康体检者设为对照组。比较不同人群、不同病情程度以及有无DVT者血浆Hcy、LPA及血清TGF-β1水平,分析Hcy、LPA及TGF-β1对DVT的预测价值。结果观察组Hcy、LPA及TGF-β1表达水平均明显高于对照组,差异均有统计学意义(P<0.05)。重度组Hcy、LPA及TGF-β1表达水平明显高于轻度组,差异均有统计学意义(P<0.05)。有DVT组者Hcy、LPA及TGF-β1表达水平明显高于无DVT组,差异均有统计学意义(P<0.05)。依据ROC曲线分析可知,Hcy+LPA+TGF-β1三者联合预测创伤性骨折后发生DVT敏感度和特异度分别为88.90%、8130%,明显高于三者单独检测(P<0.05)。结论Hcy、LPA及TGF-β1在创伤性骨折发生下肢静脉栓塞时水平均明显升高,三者联合检测对下肢静脉栓塞早期诊断有重要的临床价值。  相似文献   
6.
特纳综合征(TS)是女性常见的性染色体异常疾病,与多种疾病共存。越来越多的证据表明TS患者有较高的骨质疏松患病率,本文就近年来TS中骨质疏松的危险因素及管理治疗的相关研究进展做一综述。  相似文献   
7.
目的研究2型糖尿病(T2DM)患者发生慢性肾脏病(CKD)的危险因素,并着重分析肥胖与CKD发生的关系。方法纳入2009年1月至2019年6月在南京鼓楼医院就诊的18至75岁诊断为T2DM的患者,收集一般资料包括性别、年龄、体重指数(BMI)、收缩压、舒张压、糖尿病病程以及实验室指标包括血红蛋白(Hb)、白蛋白、丙氨酸转氨酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)、尿酸、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、尿白蛋白/肌酐比值和估算的肾小球滤过率。肥胖定义为BMI≥28 kg/m2,超重定义为24 kg/m2≤BMI<28 kg/m2。根据是否合并CKD,将研究对象分为合并CKD组和不合并CKD组。在不合并CKD的T2DM患者中,选取至少随访一次,随访时间超过12个月且随访数据完整的患者,按是否发生CKD分为发生CKD组和未发生CKD组。两组间各指标的比较采用t检验、非参数检验以及χ2检验。采用单因素及多因素logistic回归分析法分析T2DM患者发生CKD的危险因素,采用Cox比例风险模型分析随访的T2DM患者CKD发生的危险因素。采用限制性立方样条(RCS)拟合Cox回归模型来评估不同的BMI截点与CKD的关系。结果共纳入3194例T2DM患者,其中合并CKD组620例,不合并CKD组2574例。与不合并CKD组相比,合并CKD组T2DM患者BMI明显增高(P=0.005)。单因素logistic回归分析结果显示,性别、肥胖、收缩压、舒张压、Hb、白蛋白、TG、TC、FPG及HbA1c为T2DM患者发生CKD的影响因素(均P<0.05),将上述指标作为自变量,进行多因素logistic回归分析,结果显示,肥胖(OR=1.058,95%CI 1.079~2.018),收缩压增高(OR=1.027,95%CI 1.018~1.035),TG增加(OR=1.087,95%CI 1.008~1.171),FPG增高(OR=1.042,95%CI 1.003~1.083)是T2DM患者发生CKD的影响因素(均P<0.05)。不合并CKD组中随访时间超过12个月且随访数据完整的T2DM患者共753例,其中,发生CKD组182例,未发生CKD组571例。Cox比例风险模型分析结果显示,在校正年龄、糖尿病病程、收缩压、AST、TG及FPG后,超重为发生CKD的危险因素(OR=1.95,95%CI 1.05~3.61)。RCS拟合Cox回归模型结果显示,T2DM患者BMI与CKD发生风险呈非线性关系,BMI在28~31 kg/m2的T2DM患者CKD的发生风险增加(均P<0.05)。结论T2DM患者肥胖与CKD密切相关,肥胖的T2DM患者,特别是BMI在28~31 kg/m2,容易发展为CKD。  相似文献   
8.
《Vaccine》2022,40(30):4038-4045
PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.  相似文献   
9.
10.
Tsukamurella species are obligate aerobic, gram-positive, weak acid-fast, nonmotile bacilli. They are found in various environments, such as soil, water, sludge, and petroleum reservoir wastewater, and belong to the order Actinomycetales. In 2016, there was a reclassification of species within the genus Tsukamurella, merging the species Tsukamurella tyrosinosolvens (T. tyrosinosolvens) and Tsukamurella carboxydivorans. Tsukamurella species are clinically considered to be a rare opportunistic pathogen, because most reported cases have been related to bacteremia and intravascular prosthetic devices and immunosuppression. To date, it has been isolated only from human specimens, and has always been associated with clinical disease; human infections are very rare. Reported infections have included pneumonia, brain abscesses, catheter-related bloodstream infections, ocular infections, bacteremia, and sepsis presenting with septic pulmonary emboli in patients who are immunocompromised. To date, there is no commercially available test for identification. On the other hand, sequence-based identification, including matrix-assisted laser desorption ionization time-of-flight mass spectrometry, is an alternative method for identifying clinical isolates that are either slow growers or difficult to identify through biochemical profiling. The golden standards for diagnosis and optimal management still remain to be determined. However, newer molecular biological techniques can provide accurate identification, and contribute to the appropriate selection of definitive therapy for infections caused by this organism. Combinations of several antimicrobial agents have been proposed for treatment, though the length of treatment for infections has yet to be determined, and should be individualized according to clinical response. Immunocompromised patients often experience severe cases due to infection, and life-threatening T. tyrosinosolvens events associated with dissemination and/or failure of source control have occurred. Favorable prognoses can be achieved through earlier identification of the cause of infection, as well as successful management, including appropriate antibiotic therapy together with source control. Further analyses of similar cases are required to establish the most adequate diagnostic methods and treatment regimens for infections.  相似文献   
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