基于系统药理学分析野生真菌硬皮马勃治疗肿瘤多层次作用机制＊

目的 鉴定当地民间应用普遍的野生药用真菌，并探讨其治疗肿瘤的作用机制。方法 采用形态学和分子生物学方法对一株采自定陶仿山野生药用真菌进行鉴定，确定为硬皮马勃。通过文献检索收集硬皮马勃化学成分，利用PubChem软件和TCMSP、GCS数据库得到化学成分结构信息及其药用动力学参数和相关靶点分析，通过SysDT和WES系统鉴定潜在化学成分靶点，利用CTD数据库获得靶点功能，将潜在化合物和肿瘤相关靶点导入Cytoscape3.8.0软件构建分子-靶标网络。应用DAVID数据库对肿瘤相关靶点进行GO和KEGG富集分析，揭示有关活性成分靶点所涉及的生物学过程和通路，将肿瘤相关靶点和通路导入Cytoscape3.8.0软件构建靶点-通路网络。结果 从文献中获得硬皮马勃的化学成分59个，通过ADME计算系统筛选出5个潜在活性的化合物即活性成分，预测到38个靶点，其中与肿瘤相关靶点16个。这些活性成分主要通过Toll-like receptor、PI3K-AKT、MAPK和NF-kappa B等通路参与免疫应答，抑制肿瘤细胞生长、增殖，促进其凋亡。结论 表明硬皮马勃治疗肿瘤具有多靶点、多途径协同作用的特点，并通过多层次效应达到治疗肿瘤的效果。本研究为更好理解硬皮马勃作用肿瘤的机制和肿瘤药物开发提供理论依据。     

Study on the Value of Ultrasound Elastography Combined with Plasma miRNA Expression in the Early Detection of Breast Cancer

Background: Breast cancer (BC) is the most common malignant tumor in women, and its morbidity and mortality are increasing each year, due to the lack of specific clinical symptoms in the early stage of BC, and the lack of diagnostic methods for early breast cancer. Therefore, identifying an effective diagnostic method for early BC has become urgent. Materials and Methods: Breast lesions with a histological diagnosis that were examined by ultrasonic elastography (UE) in our department from June 2020 to December 2021 were reviewed. qRT-PCR was performed to measure the expression levels of miR-144-5p and miR-26b-5p in the plasma of patients with BC. The receiver operating characteristics (ROC) curve and area under the curve (AUC) were used to investigate the potential diagnostic value of miR- 144-5p, miR-26b-5p and the elastographic score in BC. Results: The ultrasonic elastography score(UES) was found to be significantly upregulated in BC compared with that in benign breast lesions, and the AUC, sensitivity and specificity were 0.809, 0.717 and 0.806 for distinguishing BC from benign breast lesions, respectively. miR-144-5p and miR-26b- 5p were found to be upregulated in the plasma of BC patients, and miR-144-5p+miR-26b-5p had 0.781 sensitivity and 0.780 specificity for the diagnosis of BC. Furthermore, we found that the diagnostic performance of miR-144-5p and miR-26b-5p combined with UES for BC had 0.913 sensitivity and 0.890 specificity. Conclusions: The combination of plasma miR-144-5p, miR-26b-5p and UES has a very high clinical application value for the early detection of BC.     

寰枢椎后路柔性固定的生物力学研究

目的分析细棒、PEEK棒固定对寰枢关节稳定性的影响。方法采用6具新鲜成人枕骨(occipital bone,Oc)~颈椎C4节段进行测试,模拟以下手术及固定状态:①完整状态;②损伤状态:枢椎齿状突II型骨折;③坚强固定:寰枢椎均采用普通椎弓根螺钉固定,直径3.5 mm钛棒连接;④PEEK棒:直径3.5 mm的PEEK棒连接;⑤细棒:直径2.0 mm钛棒连接。采用重复测量实验设计,在完整、损伤和不同的固定状态下,通过脊柱试验机对标本分别施加1.5 N·m的前屈/后伸、左/右侧弯和左/右轴向旋转的纯力偶矩。采用Optotrak三维运动测量系统连续采集标本运动,分析寰枢椎之间角度运动范围和中性区。结果采用直径3.5 mm的钛棒,2.0 mm的细棒以及3.5 mm的PEEK棒固定后,在前屈、后伸、侧弯和旋转方向上均显著减小了固定节段的运动范围(P<0.05)。直径3.5 mm和2.0 mm的棒固定后的运动范围,在各个方向上无显著性差异。PEEK棒固定的运动范围仅在侧弯方向上大于坚强固定(P=0.005),其他方向无显著性差异。3种固定方式在屈伸、侧弯和旋转方向上均显著减小了固定节段的中性区(P<0.05)。各种固定方式之间相比较,无显著性差异(P>0.05)。结论在寰枢关节采用直径2.0 mm的细棒固定,与坚强固定的稳定性相当。采用直径3.5 mm的PEEK棒固定,在前屈、后伸、旋转方向上与坚强固定的稳定性相当,在侧弯方向上弱于坚强固定。     

信息化技术应用于静脉血栓栓塞症护理的研究进展

综述信息化技术在静脉血栓栓塞症护理领域中风险预测、警报接收与上报、抗凝防治管理、医护人员相关继续医学教育、患者疾病预后管理的应用现状，总结其应用阻碍因素，旨在为我国静脉血栓栓塞症护理信息化建设提供参考。     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

厦门市社区老年慢性病共病与不良生活方式共存现状研究

目的 调查社区老年人常见的14种慢性病共病情况及不良生活方式共存现象。 方法 采用方便抽样的方法抽取厦门市社区906例老年人群为研究对象,使用自设问卷调查研究对象的慢病共存及不良方式共存现象,使用检验和多因素logistic回归方法进行分析。结果 共纳入906例老年人,慢性病患病率为79.5%,老年人慢性病共病患病率为58.9%。主要的不良生活方式是BMI异常(46.8%)、饮酒(40.5%)、睡眠时间少(37.9%)、缺乏锻炼(35.2%)、吸烟(32.8%)等。多因素logistic回归分析显示,女性(OR=2.232,95%CI:1.474～3.380,P＜0.001)、高龄(OR=2.038,95%CI:1.234～3.365,P=0.001)、有慢性病家族史(OR=2.854,95%CI:1.943～4.194,P＜0.001)、肥胖(OR=2.571,95%CI:1.096～6.033,P=0.030)、饮酒(OR=3.582,95%CI:2.531～5.071,P＜0.001)、吸烟(OR=1.789,95%CI:1.172～2.732,P=0.007)、嗜盐(OR=1.818,95%CI:1.170～2.823,P=0.008)、嗜油(OR=2.023,95%CI:1.153～3.550,P=0.010)、睡眠质量差(OR=2.091,95%CI:1.360～3.215,P=0.001)的老年人,慢性病共病的比例高。 结论 厦门市社区老年人慢性病共病和不良生活方式共存现象严重。肥胖、饮酒、吸烟、嗜盐、嗜油、睡眠质量差等行为生活方式是慢性病重要的可干预因素,社区工作者应提高社区居民对健康生活方式重要性的认识,促使其主动改变不良生活方式并长期坚持健康的生活方式,以降低其慢性病的发病风险,减少其伤残程度,提高生活质量。