基于调控肠道菌群探讨中药防治脑卒中

肠道菌群是一个独特的生态系统,被称为人体"被遗忘的器官",被誉为人类的"第二基因组"。肠道菌群失调与许多中枢神经系统疾病相关,例如帕金森病、阿尔茨海默症、精神分裂症及多发性硬化等。脑卒中具有高的发病率、复发率、死亡率和致残率的特点。肠道菌群在脑卒中的发生、发展中起着关键的作用,可通过影响机体的吸收、代谢、血压、血糖、血脂及动脉粥样斑块等因素,进一步影响脑卒中的发病。中医认为脾胃气血流注失度、阴阳盛衰失衡,机体生理功能失调,化生"风、火、痰、虚、瘀"等病理产物,可致中风的发生。脾胃主腐熟运化水谷,肠道菌群影响饮食的消化吸收,现代研究的肠道菌群功能与中医之脾胃功能失调相关。因此,调整肠道菌群的稳态,可作为一个潜在的干预靶点预防和治疗缺血性脑卒中。中药干预脑卒中已经取得了很好的疗效,是否与调节肠道菌群有关,值得未来做进一步的研究。同时对中药有效成分(小檗碱、黄芩苷、白藜芦醇等),中药单方(丹参、红景天等)和中药组方(补阳还五汤、脑心通胶囊、补中益气汤等)防治脑缺血的研究进展进行综述,为缺血性脑卒中的预防和开发提供新的途径和思路。     

Hyodeoxycholic acid protects the neurovascular unit against oxygen-glucose deprivation and reoxygenation-induced injury in vitro

Calculus bovis is commonly used for the treatment of stroke in traditional Chinese medicine. Hyodeoxycholic acid(HDCA) is a bioactive compound extracted from calculus bovis. When combined with cholic acid, baicalin and jas-minoidin, HDCA prevents hypoxia-reoxygenation-induced brain injury by suppressing endoplasmic reticulum stress-mediated apoptotic signaling. However, the effects of HDCA in ischemic stroke injury have not yet been studied. Neurovascular unit(NVU) dysfunction occurs in ischemic stroke. Therefore, in this study, we investigated the effects of HDCA on the NVU under ischemic conditions in vitro. We co-cultured primary brain microvascular endothelial cells, neurons and astrocytes using a transwell chamber co-culture system. The NVU was pre-treated with 10.16 or 2.54 μg/mL HDCA for 24 hours before exposure to oxygen-glucose deprivation for 1 hour. The cell counting kit-8 assay was used to detect cell activity. Flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling were used to assess apoptosis. Enzyme-linked immunosorbent assay was used to measure the expression levels of inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor-α, and neurotrophic factors, including brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. Oxidative stress-related factors, such as superoxide dismutase, nitric oxide, malondialdehyde and γ-glutamyltransferase, were measured using kits. Pretreatment with HDCA significantly decreased blood-brain barrier permeability and neuronal apoptosis, significantly increased transendothelial electrical resistance and γ-glutamyltransferase activity, attenuated oxidative stress damage and the release of inflammatory cytokines, and increased brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression. Our findings suggest that HDCA maintains NVU morphological integrity and function by modulating inflammation, oxidation stress, apoptosis, and the expression of neurotrophic factors. Therefore, HDCA may have therapeutic potential in the clinical management of ischemic stroke. This study was approved by the Ethics Committee of Experimental Animals of Beijing University of Chinese Medicine(approval No. BUCM-3-2016040201-2003) in April 2016.     

《针灸大成》关于气海穴临床应用的文献研究

目的:通过检索《针灸大成》中与气海穴治疗作用相关的文献条文,总结气海穴在治疗各系统疾病中运用频次较高的疾病及其配穴规律,为临床针灸对气海穴的使用提供理论支持。方法:以《中华医典》(第五版)中《针灸大成》作为文献检索来源,将气海穴及气海穴的别称“脖胦”“下肓”“丹田”“肓之原”“肓原”“下言”和“气泽”为检索词,用计算机检索工具及人工检索相结合的方法检索符合要求的文献条文,通过建立本研究的数据库,频次分析、条形统计图比较分析等方法,总结出气海穴在治疗各系统疾病中的运用频次及其配穴规律。结果:在《针灸大成》所涉及的条文中,气海穴尤善治疗内科疾病,在治疗内科疾病中排名前3位的是脾胃系病症、气血津液疾病、肾系病症和妇科疾病,气海穴配穴习惯为上下配穴法,同名经配穴法,以及前后配穴法,其中主要为前后配穴法和同名经配穴法。结论:气海穴《针灸大成》中单穴应用占比最高,而在气海穴众多配穴中,运用了本经配穴法、上下配穴法、前后配穴法,配穴归经主要来自任脉和足太阳膀胱经。同名经配穴法,同气相求,可增加疗效;与气海穴配伍较多的足太阳膀胱经以背腧穴为主,此为前后配穴法,亦称腹背阴阳配穴法,腹部为阴,腰背为阳,前后配穴法可起到“从阳引阴”亦可“从阴引阳”的作用,以达到调节阴阳,调和脏法,调畅经络的目的。     

2019年重庆市30岁及以上人群归因于被动吸烟的肺癌疾病负担研究

目的 分析重庆市肺癌发病死亡和疾病负担归因于被动吸烟的情况,为开展肺癌防治提供建议。 方法 肺癌死亡个案数据来源于2019年重庆市肿瘤登记报告系统,被动吸烟率来自2013年重庆市慢性病及危险因素监测。计算人群归因危险度百分比(population attributable risk percent, PAR%)、被动吸烟导致的肺癌发病、死亡和疾病负担。采用Excel 2010与SPSS 25.0进行统计分析,率的比较采用χ²检验。 结果 2013年30岁及以上成年人被动吸烟率为52.37%。2019年重庆市30岁及以上人群肺癌发病率与标化发病率分别为118.44/10万与80.83/10万,死亡率与标化死亡率分别为96.51/10万、63.58/10万。肺癌发病率和死亡率归因于被动吸烟的PAR%分别为19.76和19.04,归因发病率与归因标化发病率分别为23.41/10万和16.34/10万,归因死亡率与归因标化死亡率分别为18.38/10万和12.40/10万。2019年重庆市30岁及以上肺癌早死所致寿命损失年率(years of life lost,YLL)、残疾所致寿命损失年率(years lived with disability,YLD)、调整伤残寿命损失年率(disability adjusted life year,DALY)分别为21.16‰、0.31‰、21.47‰,YLL率、YLD率、DALY率归因于被动吸烟的PAR%分别为21.16、19.76和20.49,归因YLL率为4.34‰,归因YLD率为0.06‰,归因DALY率为4.40‰。 结论 2019年重庆市30岁及以上人群肺癌发病率、死亡率、YLL率、DALY率高,被动吸烟率高,肺癌归因于被动吸烟的疾病负担重,应加强落实控烟工作。     

浅谈口腔医学硕士研究生科研作图能力的培养

科研作图是展示研究数据的主要形式,也是科研素养的重要体现。口腔医学硕士研究生是接触科学研究的第一站,然而目前的研究生教育环节对科研作图能力缺乏系统性培养,许多研究生在科研作图中存在许多不规范的问题,本文针对这一问题进行初步探讨。本文分析比较了常用作图工具Microsoft Excel、Origin和Graphpad Prism的特点;以学校口腔医学硕士的培养过程为参考,分析目前硕士研究生科研作图方面存在的主要问题及应对策略。发现不同作图软件具有不同的风格特点,当前硕士研究生作图存在风格不统一、拼图不规范、图注不规范等问题,应当根据自身需求合理选择作图工具,提升作图能力。科研作图是科研能力的重要方面,应当加强口腔医学硕士研究生作图能力的培养。     

慢性心力衰竭护理结局分类评价表的构建研究

目的本研究以护理结局分类(NOC)为基础,筛选符合慢性心力衰竭患者的相关护理结局,由此构建具有专科专病特点的慢性心力衰竭患者护理结局评价表。方法成立研究核心小组,应用文献回顾法、专家函询法确定护理结局分类指标,并进行统计学分析,最终建立慢性心力衰竭护理结局分类评价表。结果通过研究,确定慢性心力衰竭护理结局中包含4个领域、8个一级指标、68个二级指标。4个领域分别是生理健康、功能健康、健康知识和行为、心理社会健康。一级指标中包含心脏泵血功能、活动耐力、社会支持、抑郁水平等。二级指标中包含心脏指数、血压、呼吸困难、情绪波动大、步行距离、步行速度等68个指标。统计学分析中:第一、二轮函询专家的积极系数分别为90%、100%,专家权威系数为0.895,专家意见协调程度(P<0.05)。结论本研究成功建立慢性心力衰竭护理结局分类评价表,有助于临床护士用于评价护理措施的有效性,也使其成为一种标准化语言,便于应用到护理电子信息系统中进行绩效测算等。但是本研究不足之处是未能将该研究进行临床实证,未能进一步确认其有效性。     

The use of Trichomonas vaginalis purine nucleoside phosphorylase to activate fludarabine in the treatment of solid tumors

Treatment with fludarabine phosphate (9-β-D-arabinofuranosyl-2-F-adenine 5′-phosphate, F-araAMP) leads to regressions and cures of human tumor xenografts that express Escherichia coli purine nucleoside phosphorylase (EcPNP). This occurs despite the fact that fludarabine (F-araA) is a relatively poor substrate for EcPNP, and is cleaved to liberate 2-fluoroadenine at a rate only 0.3% that of the natural E. coli PNP substrate, adenosine. In this study, we investigated a panel of naturally occurring PNPs to identify more efficient enzymes that may be suitable for metabolizing F-araA as part of experimental cancer therapy. We show that Trichomonas vaginalis PNP (TvPNP) cleaves F-araA with a catalytic efficiency 25-fold greater than the prototypic E. coli enzyme. Cellular extracts from human glioma cells (D54) transduced with lentivirus stably expressing TvPNP (D54/TvPNP) were found to cleave F-araA at a rate similar to extracts from D54 cells expressing EcPNP, although much less enzyme was expressed per cell in the TvPNP transduced condition. As a test of safety and efficacy using TvPNP, human head and neck squamous cell carcinoma (FaDu) xenografts expressing TvPNP were studied in nude mice and shown to exhibit robust tumor regressions, albeit with partial weight loss that resolved post-therapy. F-araAMP was also a very effective treatment for mice bearing D54/TvPNP xenografts in which approximately 10% of tumor cells expressed the enzyme, indicating pronounced ability to kill non-transduced tumor cells (high bystander activity). Moreover, F-araAMP demonstrated activity against D54 tumors injected with an E1, E3 deleted adenoviral vector encoding TvPNP. In that setting, despite higher F-araA cleavage activity using TvPNP, tumor responses were similar to those obtained with EcPNP, indicating factors other than F-Ade production may limit regressions of the D54 murine xenograft model. Our results establish that TvPNP is a favorable enzyme for activating F-araA, and support further studies in combination with F-araAMP for difficult-to-treat human cancers.     

磁共振弥散加权成像结合三维乳腺数字化断层摄影钙化分数在乳腺良恶性钙化病变鉴别中的诊断价值

  目的  评估磁共振弥散加权成像（DWI）结合三维乳腺数字化断层摄影（DBT）钙化分数对于钙化征象在乳腺良恶性病变诊断的应用价值。  方法  回顾性分析我院118例行乳腺DWI检查和DBT检查的患者，DBT检查发现有钙化征象，其中乳腺癌患者51例，病理类型包括:浸润性导管癌、浸润性导管癌、导管原位癌、髓样癌、浸润性小叶癌、黏液腺癌；乳腺良性病变67例，病理类型包括:纤维腺瘤、腺病、导管内乳头状瘤。对所有患者DBT图像的钙化征象进行钙化评分并且测量相应病变区域的表观扩散系数（ADC）值，分析ADC值、钙化分数及二者联合在乳腺含钙化病变的诊断效能。  结果  乳腺癌组ADC值低于乳腺良性病变组，差异有统计学意义（P < 0.05）；钙化分数高于良性病变组，差异有统计学意义（P < 0.05）。ADC值对诊断乳腺良恶性病变的曲线下面积（AUC）为0.853，钙化分数对诊断乳腺良恶性病变的AUC值为0.855，采用Delong检验得出两种方法对诊断乳腺含钙化病变的良恶性诊断效能一致，差异无统计学意义（P=0.625）。两种方法（钙化分数+ADC值）的Logistic回归分析显示，两种方法相结合的AUC值为0.903，具有很高的诊断效能。将ROC曲线（钙化分数、ADC值、两种方法结合的预测概率）经两两Delong检验结果显示，两种方法结合的ROC与单一ROC的差异有统计学意义（P=0.041、0.022）。  结论  DWI与DBT钙化分数对于钙化征象在乳腺良恶性病变的鉴别诊断效能无差别，两种方法相结合的诊断效能显著高于单一方法，为乳腺含钙化病灶的诊断与鉴别诊断中提供了更加可靠的依据。