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.     

基于HMGB1/TLR4/NF-κB信号通路研究木兰脂素对急性鼻窦炎大鼠的治疗作用及机制

目的： 观察木兰脂素对急性鼻窦炎(ARS)大鼠的治疗作用，并探讨其通过高迁移率家族蛋白1/ Toll样受体4/核因子-κB(HMGB1/TLR4/NF-κB)信号通路的调控机制方法： 49只大鼠，随机取9 只作为正常组，40只用鼻窦腔内接种金黄色葡萄球菌法制备ARS模型，36只建模成功大鼠随机分为模型组、木兰脂素低剂量组、木兰脂素高剂量组、阳性组，各9只。木兰脂素低剂量组、木兰脂素高剂量组分别灌胃20、80 mg·kg^-1体质量的木兰脂素，模型组和正常组灌胃等体质量溶媒，阳性组灌胃40 mg·kg^-1 体质量左氧氟沙星，连续7 d。给药前、末次给药后1 h评估各组鼻窦炎症状评分；测定给药后各组血白细胞(WBC)计数及中性粒细胞占比，观察鼻窦黏膜病理组织学变化，检测鼻腔灌洗液中肿瘤坏死因子-α(TNF-α)、白介素(IL)-6水平及鼻黏膜中HMGB1、TLR4、NF-κB mRNA和蛋白表达情况结果： 给药后，木兰脂素低剂量组、高剂量组、阳性组的急性鼻窦炎症状评分及血WBC计数均低于模型组，但仍高于正常组，且木兰脂素高剂量组及阳性组均低于木兰脂素低剂量组，差异均有统计学意义(P＜0.05)，而木兰脂素高剂量组与阳性组比较，差异无统计学意义(P＞0.05)。与给药前比较，给药后木兰脂素低剂量组、高剂量组及阳性组急性鼻窦炎症状评分均降低(P＜0.05)，正常组及模型组给药前后无明显差异(P＞0.05)。与模型组比较，木兰脂素低剂量组、木兰脂素高剂量组、阳性组中性粒细胞占比均降低，且木兰脂素高剂量组低于木兰脂素低剂量组，阳性组低于木兰脂素高剂量组，差异均有统计学意义(P＜0.05)，而阳性组与正常组比较，差异无统计学意义(P＞0.05)。HE染色显示，模型组大鼠纤毛脱落、缺失、排列紊乱，黏膜上皮破损、变性，黏膜内及黏膜下可见大量炎症细胞浸润； 木兰脂素低剂量组、木兰脂素高剂量组及阳性组上述病理变化均减轻，且木兰脂素高剂量组和阳性组炎症反应减轻更为明显。与模型组比较，木兰脂素低剂量组、木兰脂素高剂量组、阳性组鼻腔灌洗液中 TNF-α、IL-6水平及鼻黏膜中HMGB1、TLR4、NF-κB mRNA和蛋白相对表达量均降低，但仍高于正常组，且木兰脂素高剂量组及阳性组均低于木兰脂素低剂量组，差异均有统计学意义(P＜0.05)，而木兰脂素高剂量组及阳性组比较，差异无统计学意义(P＞0.05)结论： 木兰脂素治疗ARS效果显著，可能通过HMGB1/TLR4/NF-κB信号通路抑制鼻黏膜炎症反应。     

医院信息化平台住院陪护人员管理功能的开发与应用

目的 探讨医院信息系统中增加住院陪护管理功能的应用效果。方法 基于互联网医院、智慧医院等信息系统，开发信息化住院陪护管理功能，包括流行病学史调查、免费核酸申请、电子陪护证办理、体温监测登记及上报和统计查询。该功能与医院智慧护理链接后全院应用。比较功能应用前和应用后的遵医嘱一患一陪达标率、有效陪护证达标率、体温监测并登记日上报达标率和陪护证使用追溯率，评价护士和管理者疫情防控管理的人均耗时以及对该管理功能的满意度。结果 应用信息化陪护管理功能后，一患一陪达标率、有效陪护证达标率、体温监测并登记日上报达标率和陪护证使用追溯率显著高于应用前（均P＜0.05）；护士陪护管理人均耗时从（554.13±30.77）s降至（311.67±21.54）s（P＜0.05）；护士和管理者对该信息化陪护管理功能的满意度显著提高（均P＜0.05）。结论 信息化住院陪护管理功能的应用有效提升了疫情期间陪护的管理质量和管理效率，提高了一线护士和管理者的满意度。     

腹腔镜与开腹手术治疗长径5~10 cm中危原发性胃间质瘤的安全性和有效性比较

目的　比较腹腔镜和开腹手术治疗长径5~10 cm的中危胃间质瘤的安全性和有效性，并评估患者术后使用伊马替尼辅助治疗是否有明显益处。方法　回顾性分析2010年1月—2020年7月在南京大学医学院附属鼓楼医院接受手术治疗的72例长径在5~10 cm的中危胃间质瘤患者资料。其中腹腔镜手术组28例，开腹手术组44例。比较两组患者基本资料、病理特征、围手术期结果、住院总费用。对比术后使用和不使用伊马替尼辅助治疗的生存率。结果　开腹组和腹腔镜组临床病理特征差异无统计学意义（P>0.05）。腹腔镜组术后并发症发生率为32.1%（9/28），开腹组为52.3%（23/44），两组比较差异无统计学意义（P=0.094）。与开腹组相比，腹腔镜组总住院时间明显缩短［（12.5±3.2） d比（15.0±3.5） d，P=0.004］；术后中位住院天数明显缩短（7.5 d 比 9.0 d，P=0.006）；首次排气时间明显缩短（P=0.003）。中位随访时间58个月（13~129个月），期间未出现与肿瘤相关的死亡病例。开腹组有2例死亡，分别因乳腺癌和心脏病；腹腔镜组有1例死亡，死亡原因与胃间质瘤无关。72例患者中，40例术后接受伊马替尼辅助治疗，开腹组22例（50.0%），腹腔镜组18例（64.3%），两组接受伊马替尼辅助治疗的患者例数占比差异无统计学意义（χ2=1.414，P=0.234）。术后使用伊马替尼辅助治疗组总体生存率与未使用伊马替尼辅助治疗组相比差异有统计学意义 （P=0.015）。结论　与开腹手术相比，腹腔镜治疗长径在5~10 cm的中危胃间质瘤是一种安全有效的方法。实现R0切除的长径在5~10 cm的中危胃间质瘤患者术后使用伊马替尼辅助治疗未增加生存率，且未使用伊马替尼者未出现与肿瘤相关的死亡、复发及转移。     

Epstein–Barr-virus-associated hepatitis with aplastic anemia: A case report

ABSTRACT BACKGROUND Hepatitis-associated aplastic anemia (HAAA) is a rare condition. Patients with HAAA usually present with acute hepatitis, jaundice and significantly increased transaminase. After 1–2 mo, hepatitis gradually improves, but progressive hemocytopenia, bone marrow hematopoietic failure, and severe or extremely severe aplastic anemia are manifest. Most cases of HAAA are fulminant and usually lethal if left untreated. The literature on Epstein–Barr virus (EBV)-associated HAAA is sparse. CASE SUMMARY We report a 30-year-old man who was admitted to our hospital because of pale yellow urine and skin with a simultaneous decrease in peripheral blood ternary cells. We made a diagnosis of EBV-associated HAAA. The treatment strategy for this patient included eltrombopag, an immunosuppressive regimen of rabbit anti-human thymocyte immunoglobulin, cyclosporine, and supportive care. The patient was discharged in normal physical condition after five months. A hemogram performed on follow-up revealed that he had achieved a complete response. CONCLUSION Eltrombopag plus anti-thymocyte globubin and cyclosporine may be a therapeutic option for EBV-associated HAAA.Larger studies are warranted to confirm.     

Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

核医学学科新增医疗服务项目定价方法研究

目的：基于以价值为基础的定价方法，计算核医学学科新增医疗服务项目镭[²²³ Ra]骨转移瘤治疗的医疗服务价格。为相关新增医疗服务项目的申报和定价打下循证基础，为合理补偿医务人员劳动价值、提升患者服务项目可及性提供依据。方法：采集2021年3—12月使用“镭核素[²²³ Ra]骨转移瘤治疗资源投入及费用数据采集表”相关数据，开展专家访谈进行系数赋值和基线对照项目确定，得到镭[²²³ Ra]骨转移瘤治疗服务各个环节的成本和新增服务的价值。结果：镭[²²³ Ra]骨转移瘤治疗服务按服务特点分为注射前评估、治疗计划、给药、给药后监测、废弃物处理与监测等环节，各环节3地平均人力耗时分别为104分钟、39分钟、25分钟、72分钟和56分钟，中位物耗成本为48.20元，3地总成本(平均人力成本+中位物耗成本)为763.68元。结合系数赋值结果和基线对比项目，得到新增项目的价值为810.19元。结论：运用基于技术难度和风险程度的价值定价理论，计算镭[²²³ Ra]骨转移瘤治疗新增医疗服务项目的服务价值，建议以价值作为服务定价依据。该定价公式和研究方法不仅可用于其他核医学学科新增服务项目的定价，还适用于现行医疗服务项目的价格动态调整，为未来学科价格工作提供方法学参考。