针刀松解联合丹参注射液关节腔注射治疗骨性关节炎模型兔

文题释义： 针刀疗法：用一个完整的语言来概括应该是一种介于手术方法和非手术疗法之间的闭合性松解术。针刀疗法是将东方中医学的基本理论和西方医学的手术解剖基本理论融为一体，针刀疗法其操作的特点是在治疗部位刺入深部到病变处进行轻松的切割、剥离等不同的刺激，以达到止痛祛病的目的。 丹参注射液：其化学成分主要是水溶性酚酸类化合物，通过多种靶标起到促进血液循环和祛瘀的作用。动物研究表明，丹参注射液可通过抑制IκBα磷酸化来抑制NF-κB信号通路的激活。保护软骨下骨及软骨细胞，有效防治骨关节炎。 背景：丹参注射液与针刀松解术都是临床中治疗骨关节炎很常用的技术，目前缺乏对2种治疗方法联合使用的研究。 目的：对比单独使用针刀松解术、单独使用丹参注射液与两种方法联合使用治疗兔模型骨关节炎的效果。 方法：实验方案经黑龙江中医药大学动物实验伦理委员会批准。50只新西兰白兔分为5组：空白对照组；模型组；丹参注射液组；针刀组；针刀联合丹参注射液组。除空白对照组外，其他4组兔均制备膝关节骨关节炎模型。造模成功后，对针刀组兔内外侧支持带、内外侧膝眼，膝关节上方髌上囊、股四头肌各肌肌腹，膝关节内侧股薄肌肌腹及止点、收肌肌群肌腹及止点和胫骨平台附近部位进行针刀松解；空白对照组及模型组兔关节腔注射生理盐水0.3 mL；丹参注射液组兔关节腔每次注射0.3 mL丹参注射液；针刀联合丹参注射液组：每周进行1次针刀治疗同针刀组，每次针刀干预之后，关节腔注0.3 mL丹参注射液。上述干预每周1次，持续5周。对各组兔膝关节软骨进行大体观察及病理切片组织学观察，ELISA 检测关节液白细胞介素1、肿瘤坏死因子α水平。 结果与结论：①大体观察：模型组膝关节磨损较为严重，针刀组、丹参注射液组、针刀联合丹参注射液组膝关节轻度磨损；②病理切片评分：丹参注射液组评分略高于针刀组和针刀联合丹参注射液组差异无显著性意义；③ELISA 检测结果：针刀联合丹参注射液组白细胞介素1、肿瘤坏死因子α水平显著低于或针刀组或丹参注射液组(P < 0.05)；④结果说明，在兔膝关节骨关节炎模型中降低白细胞介素1、肿瘤坏死因子α水平方面，针刀松解术结合丹参注射液关节腔注射治优于单独使用针刀或单独使用丹参注射液关节腔注射。ORCID: 0000-0003-4119-633X(刘广宇) 中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程     

小檗碱对皮肤鳞状细胞癌裸鼠模型的抑制作用及其机制研究

【摘要】 目的 研究小檗碱对皮肤鳞状细胞癌（cSCC）-A431裸鼠移植瘤的体积、重量、细胞增殖及凋亡的影响，探索小檗碱抑制cSCC的可能机制。方法 培养A431细胞，于20只裸鼠背部皮下注射A431细胞悬液建立cSCC移植瘤裸鼠模型。接种第15天，将荷瘤裸鼠随机平均分为4组：低、中、高剂量组裸鼠腹腔分别注射10、20、25 mg/kg小檗碱溶液，对照组腹腔注射生理氯化钠溶液，每日1次，连续给药35 d。分别于给药前、给药第7、14、21、28、35天检测移植瘤体积。实验结束后，处死裸鼠并随即剥离瘤块称重，计算肿瘤生长抑制率。移植瘤行组织病理检查，免疫组化检测Ki67表达水平，TUNNEL染色检测移植瘤组织中凋亡细胞数，荧光定量PCR和Western印迹法分别检测凋亡相关蛋白Bax、Bcl-2、caspase-3和Ezrin mRNA和蛋白的表达。多组间比较采用单因素方差分析，各组与对照组比较采用Dunnett-t检验。结果 随小檗碱剂量升高和作用时间延长，肿瘤生长曲线逐渐变平缓，各小檗碱组肿瘤生长受到不同程度的抑制，其中高剂量组肿瘤生长抑制作用最明显。小檗碱低、中、高剂量组肿瘤生长抑制率分别为31.05%、66.68%、76.49%，瘤重均显著低于对照组（t = 4.07、6.33、7.26，均P < 0.01）。移植瘤组织病理检查显示，随小檗碱剂量的增加，肿瘤细胞坏死程度和范围增加。免疫组化显示，随小檗碱剂量的增加，Ki67阳性细胞逐渐减少。此外，低、中、高剂量组Ki67阳性细胞数均显著低于对照组（均P < 0.01），而凋亡细胞数均显著高于对照组（P < 0.05或 < 0.01）。4组Bax、Bcl-2、caspase-3、Ezrin mRNA及蛋白表达差异均有统计学意义（均P < 0.01）。其中，小檗碱低、中、高剂量组Bcl-2 mRNA的表达均显著低于对照组（均P < 0.01），中、高剂量组Bcl-2蛋白表达显著低于对照组（均P < 0.01）；高剂量组Bax mRNA及中、高剂量组caspase-3 mRNA的表达均显著高于对照组（P < 0.05或 < 0.01），而低、中、高剂量组Bax、caspase-3蛋白表达量均显著高于对照组（均P < 0.01）；仅高剂量组Ezrin mRNA表达显著高于对照组（均P < 0.01），而低、中、高剂量组Ezrin蛋白表达均显著低于对照组（均P < 0.01）。结论 小檗碱可抑制cSCC-A431裸鼠移植瘤细胞的增殖并促进凋亡，从而一定程度抑制cSCC-A431裸鼠移植瘤的生长，其机制可能与小檗碱上调Bax、caspase-3的表达，同时下调Bcl-2、Ezrin的表达有关。     

载芬维A铵脂质体抑制A375黑素瘤细胞裸鼠皮下移植瘤的初步研究

目的 探讨载芬维A铵脂质体（4-HPR-L）对裸鼠皮下人恶性黑素瘤的抑制作用。方法 采用薄膜-超声分散法制备4-HPR-L。通过皮下接种黑素瘤A375细胞至BALB/c裸鼠右侧腋窝建立黑素瘤荷瘤裸鼠模型。取10只荷瘤裸鼠模型，随机等分为两组，分别给予尾静脉注射同浓度细胞膜近红外荧光探针（DiR）溶液和DiR脂质体（DiR-L），应用小动物活体成像仪观察给药后6、12、24 h药物在体内分布情况。取30只荷瘤裸鼠，随机等分为3组，即对照组、4-HPR组和4-HPR-L组，分别经尾静脉每次注射5%（质量分数）葡萄糖溶液0.2 ml、25 mg/kg 4-HPR和4-HPR-L溶液，于接种A375细胞后第8、10、12、14、16、18、20、22天给药，动态监测给药后各组裸鼠的体重和肿瘤体积，观察生存情况。于末次给药后第2天处死裸鼠，取心、肝、脾、肺、肾及肿瘤组织，HE染色和免疫组化染色观察黑素瘤体内转移情况，并用脱氧核糖核苷酸末端转移酶介导的缺口末端标记法检测肿瘤细胞凋亡情况。计量资料采用单因素方差分析和独立样本t检验进行分析。结果 小动物活体成像仪显示，DiR-L能较长时间滞留于肿瘤组织，给药24 h后在肿瘤部位仍可观察到较强荧光；定量分析显示，肿瘤组织中DiR-L荧光强度（22.85 ± 1.66）显著高于DiR（8.45 ± 0.97，t = 12.957，P < 0.01）。与对照组和4-HPR组相比，4-HPR-L组末次给药后第2天离体瘤重明显降低（F = 27.055，t值分别为4.768、6.640，均P < 0.05）。HE染色显示，4-HPR-L组2只裸鼠发生肝脏转移，而对照组、4-HPR组全部裸鼠发生肝脏转移。荷瘤鼠的生存期观察显示，4-HPR-L组裸鼠于接种后76 d内全部死亡，对照组和4-HPR组分别于接种后56 d和59 d内全部死亡。对照组凋亡指数为（12.14 ± 1.33）‰，4-HPR组为（67.17 ± 15.18）‰，4-HPR-L组为（152.73 ± 11.27）‰，3组间差异有统计学意义（F = 167.588，P < 0.05），4-HPR-L组与对照组和4-HPR组相比，t值分别为18.162、11.075，均P < 0.05。结论 4-HPR-L能够有效抑制裸鼠皮下黑素瘤体积增长和黑素瘤细胞转移，并延长裸鼠生存期。     

Sleep,brain development,and autism spectrum disorders: Insights from animal models

Sleep is an evolutionarily conserved and powerful drive, although its complete functions are still unknown. One possible function of sleep is that it promotes brain development. The amount of sleep is greatest during ages when the brain is rapidly developing, and sleep has been shown to influence critical period plasticity. This supports a role for sleep in brain development and suggests that abnormal sleep in early life may lead to abnormal development. Autism spectrum disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States. It is estimated that insomnia affects 44%–86% of the ASD population, predicting the severity of ASD core symptoms and associated behavioral problems. Sleep problems impact the quality of life of both ASD individuals and their caregivers, thus it is important to understand why they are so prevalent. In this review, we explore the role of sleep in early life as a causal factor in ASD. First, we review fundamental steps in mammalian sleep ontogeny and regulation and how sleep influences brain development. Next, we summarize current knowledge gained from studying sleep in animal models of ASD. Ultimately, our goal is to highlight the importance of understanding the role of sleep in brain development and the use of animal models to provide mechanistic insight into the origin of sleep problems in ASD.     

三种智慧放疗计划预测模型的性能评价

目的比较三种智慧放疗计划预测模型的精度与泛化鲁棒性,为模型选择提供依据。方法收集45例前列腺癌和25例鼻咽癌临床放疗计划,运用Z、L、S模型预测前列腺癌中膀胱和直肠、鼻咽癌中左右腮腺的剂量体积直方图(DVH)。应用预测DVH与临床DVH曲线下面积的差别(|DVH预测-DVH临床|)评价预测误差,误差越小则预测精度越高。在单个危及器官(OAR)上比较3种预测模型的精度,并在不同OAR中计算各模型预测精度的标准差以评价和比较模型的泛化鲁棒性。结果对于膀胱和直肠,L模型的预测误差(0.114和0.163)显著大于Z和S模型(≤0.071,P<0.05);对于左腮腺,S模型的预测误差(0.033)与Z和L模型相近(≤0.025,P>0.05);对于右腮腺,S模型的预测误差(0.033)显著大于Z和L模型(≤0.028,P<0.05)。在不同OAR上,S模型的预测精度标准差比Z、L模型小(分别为0.016、0.018和0.060)。结论在前列腺癌膀胱和直肠的DVH预测中Z和S模型的精度较高,而在鼻咽癌左右腮腺中Z和L模型较高,在不同OAR上S模型的泛化鲁棒性相对较好。     

At the intersection of science and theory: How the Nurse Role Integration Model reconciles the conflict

As more nurses embrace precision science, there is a tendency to utilize theoretical frameworks from other disciplines thus, placing nursing at risk of losing its autonomy and independence. The discipline has fallen prey to internal binary opposition, eliminating opportunities to engage in civil discourse. To explore how the roles nurses select might fit together in a theoretical framework and help nurses understand how the roles they choose to support their identity as nurses, this paper introduced a model of nursing that includes the bench scientists, the policy activists, and bedside nurses, using the Neuman Systems Model (NSM). The Nurse Role Integration Model (NRIM) espouses the basic tenets of NSM: prevention counteracts stressors from penetrating the client’s lines of defense thus, reducing stress response. Primary prevention reflects the work of the nurse bench scientists, investigating the underlying mechanisms behind pathophysiology; secondary prevention is applied nurse scientists who build upon nurse researchers’ work, identifying and testing potential interventions; tertiary prevention is nurse policy activists, the fulcrum, who leverage primary and secondary findings to argue policy change at all levels. Once policy change is adopted, bedside nurses are educated and implement the change. This lens provides an opportunity to create greater solidarity, strengthening the unity and autonomy of the discipline.     

Genomic data in prognostic models—what is lost in translation? The case of deletion 17p and mutant TP53 in chronic lymphocytic leukaemia

Genomic technologies are revolutionizing the practice of haematology-oncology, leading to improved disease detection, more accurate prognostication and targeted treatment decisions. These advances, however, have also introduced new clinical challenges, which include problems of prognostic underdetermination and its attendant risks of over- and undertreatment. Genomic data is generated from different technologies, from cytogenetics to next-generation sequencing, which are often interpreted interchangeably and in a binary fashion—as the presence or absence of a given chromosomal deletion or mutation—an oversimplification which may lead to mistaken prognosis. We discuss the clinical use of one such prognostic marker, represented by sequence and copy number alterations in TP53, located on chromosome 17p. Mutations in TP53 are strongly linked to poor prognosis in a variety of haematological malignancies, including chronic lymphocytic leukaemia (CLL). We review studies in CLL which utilize the 17p deletion or TP53 mutations for prognostic stratification with specific focus on the technologies used for detection, the thresholds established for clinical significance, and the clinical contexts in which these alterations are identified. The case of CLL illustrates issues arising from simplistic, binary interpretation of genetic testing and highlights the need to apply a critical lens when incorporating genomics into prognostic models.