Natural siliceous dust and human health： Pathways, toxicity, and impact

Fine atmospheric dust includes mineral particles and aggregates, fibrous minerals and fibrous organic material. Generation, dislodgement and transport （deflation） of natural dust with the finer （〈4 microns） components suspended as silt-size aggregates, is widespread in and adjacent to the world＇s drylands, as well as deriving from volcanic vents. Silica is a highly fibrogenic agent in lung tissue. Long-term inhaling of siliceous dusts can lead to a number of fibrotic lung diseases, including natural （non-occupational） pneumoconioses （notably silicosis, but including asbestosis and others）. Different polymorphs of silica show different levels of toxicity in interaction with lung tissue. Particles with highly active surfaces may release radicals, causing cell damage. Some types of inhaled particulates are degraded by macrophages, but many are highly resistant and persist in the lungs, some stimulating fibroblastic cells to deposit collagen. Silicosis is an inflammation of the lung commonly caused by silicate mineral particles, leading to fibrosis. Three types are recognized： nodular pulmonary fibrosis （simple or chronic silicosis）, acute silicosis, and accelerated silicosis. Generally, finer particulates have greater oxidative capacity than the coarser fractions. They contain more reactive oxygen species, their greater bioreactivity making them more toxic to pulmonary tissue. Nevertheless, inhalation of large dust particles （〉 10μm） may constitute a health risk if the mineralogy is toxic, regardless of where the grains lodge in the respiratory system. Dust may absorb harmful gases, disease-generating bacteria and carcinogenic hydrocarbon compounds. Silica-related respiratory disease may also an exacerbate cardiac problem, and epidemiology suggests a link with tuberculosis. Quantification of dust loading and exposure requires study of spatial and temporal patterns, supported by meteorological analysis, airflow modeling and satellite-borne imagery. Some acute, short-term health impacts have been assessed using atmospheric and health records both before and after a dust storm or by comparison of populations within and outside such events. Analysis of the size, shape, mineralogy and geochemistry of ambient dust particulates provides information on natural dust sources, dust concentrations, and potential particulate toxicity, as well as providing a datum for assessment of human exposure levels.     

阿霉素性心肌病大鼠左心室肌纤维化程度与缝隙连接蛋白的变化

目的 探讨阿霉素性心肌病大鼠发生心律失常的发病机制。方法 健康wistar雄性大鼠20只,体重200g,适应周围环境1周后,随机将20只wistar雄性大鼠分为对照组（n=10）和阿霉素（ADR）组（n=10）。ADR组的大鼠在1周内进行3次腹腔注射ADR 2mg/kg;同时对照组则进行3次腹腔注射0.9%NaCl （2ml/kg）,停药后让两组大鼠自由饮食4周。7周后对两组大鼠行心脏彩超检测,左心室舒张末径（LVEDd）与左心室收缩末期内径（LVESd）及左心室射血分数（LVEF）,行VG染色观察各组大鼠心肌纤维化情况;扫描电镜染色观察左心室心肌细胞闰盘病理学变化;两组大鼠心肌结缔组织生长因子（CTGF）、转化生长因子β1（TGF-β1）、N型钙黏蛋白（N-cad）、桥粒芯糖蛋白（DSG2）表达应用ELISA法检测;采用Western blot法检测两组大鼠的心肌细胞Cx40 、Cx43、p-Cx43蛋白表达。结果 与对照组相比,阿霉素组大鼠明显出现心室重构,并易出现心律失常;电镜下观察ADR组大鼠心肌细胞闰盘破损严重,间隙增宽,VG染色显示ADR组大鼠病理积分明显高于对照组（P<0.05）;ADR组大鼠相较于对照组大鼠心室肌中CTGF、TGF-β1的表达升高显著,N-cad、DSG2、Cx40、Cx43及p-Cx43的表达明显减低（P<0.05）。结论 ADR组大鼠可能由于心室肌细胞纤维化、闰盘结构受损、缝隙连接重构等原因导致心律失常。     

冠状动脉结扎法致大鼠心肌纤维化模型的建立方法探讨

目的：探讨采用冠状动脉结扎法建立大鼠心肌纤维化（Myocardial Fibrosis，MF）模型的方法，以期为临床防治MF提供实验基础。方法：术前进行包括对实验动物、药物、仪器和器械的准备；手术操作过程按照麻醉、消毒、连接呼吸机、心电图监测、开胸、结扎、关胸、脱机、术后处理的步骤；手术过程要求无菌操作，保护实验动物肺脏，观察其呼吸及恢复自主呼吸时间，注意结扎手法，预防感染。造模是否成功可通过HE染色观察心脏组织病理学变化、Masson染色显微镜下进行左室心肌胶原容积分数检测、心脏组织HYP、TGF-β1含量检测来确定。结论：规范冠状动脉结扎法建立大鼠MF模型的步骤，完善每个细节，对提高实验大鼠存活率及造模成功率具有重要的意义。     

基于网络药理学探讨黄芪治疗肝纤维化的作用机制

目的：基于网络药理学方法探讨黄芪治疗肝纤维化的作用机制。方法：使用TCMSP、PubChem和Swiss Target Prediction数据库预测黄芪有效成分的靶点;通过GenCards数据库收集肝纤维化靶点,取交集得到黄芪对肝纤维化的作用靶点。运用Cytoscape 3.8.2构建黄芪-有效成分-靶点-肝纤维化网络,预测核心靶点,构建基于STRING平台的PPI网络。利用 Metascape平台进行基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析。结果：筛选得到黄芪有效成分20种,治疗肝纤维化的相关靶点90个,疗效明显的有效成分是山柰酚、华良姜素、异鼠李素、槲皮素等,核心靶点是白细胞介素-6（IL-6）、丝氨酸/苏氨酸激酶1（AKT1）、转录因子（JUN）、表皮生长因子受体（EGFR）、半胱氨酰天冬氨酸特异性蛋白酶3（CASP3）等。黄芪治疗肝纤维化途径主要包括癌症通路、EGFR酪氨酸激酶抑制剂抗通路、PI3K-Akt信号通路、乙型肝炎、丙型肝炎等信号通路。结论：通过网络药理学方法初步探讨黄芪治疗肝纤维化的作用机制,表明黄芪具有多成分、多靶点、多通路等作用特点,可为基础和临床研究提供参考依据。     

原发性骨髓纤维化中医辨治思路探析

从脏腑病位、邪实偏胜、疾病发展阶段三方面探析原发性骨髓纤维化的中医辨证治疗思路。临床辨治本病应定病位,辨脏腑盛衰,从肝、脾、肾三脏论治。明病机,辨邪实偏胜,从瘀血、气、痰、毒邪论治。分阶段,辨寒热虚实,即病之初期,肝郁热盛,治以疏肝清热为主;病之中期,正虚邪实,治以扶正祛邪为主;病之末期,正气大虚,治以扶正气为主,忌一味猛攻。     

周胜红运用中药结合揿针治疗肺间质纤维化经验

总结周胜红主任医师运用中药结合揿针治疗肺间质纤维化（PIF）的临床经验。周师认为本病病机以血瘀痰凝、肺脾肾三脏虚损为关键,治疗时应虚实兼顾,标本同治,治疗原则包括：明辨分期,慢病慢治;立足整体,内外同治;益气养阴,健脾益肾;化痰祛瘀,止咳平喘。其于临床采用中药结合揿针疗法,可以有效控制PIF的进展,改善患者的临床症状,提高其生活质量,达到带病长期生存的目的。