基于网络药理学和实验验证研究柴胡疏肝散治疗慢性萎缩性胃炎的作用机制＊

目的 通过网络药理学的方法进行预测，再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制。方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点；通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点。将药物靶点与疾病靶点进行映射筛选出交集靶点，将得到的交集靶点构建PPI网络与活性成分-共同靶点网络，并对其进行GO和KEGG富集分析。最后利用Vina软件进行分子对接实验验证，并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响。结果 最终筛选得到柴胡疏肝散活性成分104个，潜在靶点238个，与慢性萎缩性胃炎的交集靶点52个；GO与KEGG富集分析分别得到2166条目和148条目，主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等；分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像；免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达。结论 通过网络药理学和实验验证，发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡，进而发挥着治疗慢性萎缩性胃炎的效果，为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法。     

Selective Laser Melting of Al-Based Matrix Composites with Al2O3 Reinforcement: Features and Advantages

Aluminum matrix composites (AMC) are of great interest and importance as high-performance materials with enhanced mechanical properties. Al₂O₃ is a commonly used reinforcement in AMCs fabricated by means of various technological methods, including casting and sintering. Selective laser melting (SLM) is a suitable modern method of the fabrication of net-shape fully dense parts from AMC with alumina. The main results, achievements, and difficulties of SLM applied to AMCs with alumina are discussed in this review and compared with conventional methods. It was shown that the initial powder preparation, namely the particle size distribution, sphericity, and thorough mixing, affected the final microstructure and properties of SLMed materials drastically. The distribution of reinforcing particles tends to consolidate the near-melting pool-edges process because of pushing by the liquid–solid interface during the solidification process that is a common problem of various fabrication methods. The achievement of an homogeneous distribution was shown to be possible through both the thorough mixing of the initial powders and the precise optimization of SLM parameters. The strength of the AMCs fabricated by the SLM method was relatively low compared with materials produced by conventional methods, while for superior relative densities of more than 99%, hardness and tribological properties were obtained, making SLM a promising method for the Al-based matrix composites with Al₂O₃.     

基于《金匮要略》头风摩散结合摩法治疗偏头痛思路探究

偏头痛是临床常见头面部疾病,现在医学多采用特异性治疗药物跟非特异性止痛药物治疗。长期服药造成一定的并发症及不良反应,中西医结合治疗偏头痛是临床研究的重点。张仲景《金匮要略.中风历节病脉证并治》篇中初次记录头风摩散,该外治方的主要功效是用来治疗头风病,同时开创了摩顶膏法的先河。 摩法是最古老、最常用的手法之一。记载摩法的古代文献颇多,可追溯至《素问.病能》曰；“摩之切之。” 《素问.至真要大论》曰：“摩之、浴之。”并由此演绎出一系列实用手法。本文旨在探究摩法结合头风摩散治疗偏头痛的操作应用及其原理,进一步考究摩法与头风摩散结合治疗偏头痛的协同作用,以期对临床有一定指导意义。     

《邵氏医案》从血辨治痛经浅析

[目的]分析总结浙江近代著名临床医家邵兰荪治疗痛经的经验,以期为临床治疗提供借鉴。[方法]通过研读裘吉生编《邵氏医案》,筛选出其中治疗痛经的医案十余则,并结合邵氏在妇科方面的学术思想,进一步分析其辨证立法遣方特色,从而总结邵氏治疗痛经的临证经验。[结果]邵氏治疗痛经多从血辨治,且分虚实两端,其中属虚者血虚内热用益母胜金丹养血清热、活血止痛,血虚肝风治以养血柔肝、息风止痛;属实者水结血瘀用五苓散利水散瘀、行气止痛,气阻血滞治从行气活血、调经止痛。[结论]在治疗妇人痛经方面,邵氏辨治遣方确有独特经验,这些经验可为中医药治疗此类疾病拓宽诊治思路,有助于提高临床疗效。     

Therapeutic landscape of metaplastic breast cancer

Metaplastic breast carcinomas (MPBC) are rare, aggressive and relatively chemorefractory tumors with a high unmet need. While most are “triple negative” and lack expression of estrogen, progesterone and HER2 receptors, MPBC are associated with worse outcomes compared to conventional triple negative invasive tumors. MPBCs are genetically heterogeneous and harbor somatic mutations, most frequently in TP53, PIK3CA and PTEN, with emerging studies suggesting a role for novel targeted therapies. These tumors have also been associated with overexpression of PD-L1 and tumor-infiltrating lymphocytes suggesting an endogenous immune response and therefore a rationale for treatment with immunotherapies. Here, we focus on therapeutic options for this difficult to treat breast cancer subtype and encourage physicians to consider targeted therapies/immunotherapies as part of ongoing clinical trials.     

Establishment of an Evaluation Method for Gene Silencing by Serial Pulmonary Administration of siRNA and pDNA Powders: Naked siRNA Inhalation Powder Suppresses Luciferase Gene Expression in the Lung

In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders.     

环状RNA ciRS-7在三阴性乳腺癌中的表达及其对细胞侵袭和迁移的影响

 目的 探讨环状RNA ciRS-7在三阴性乳腺癌（TNBC）中的表达及其对细胞侵袭和迁移的影响。方法 通过qRT-PCR法检测乳腺癌组织和细胞中ciRS-7的表达水平，分析其与乳腺癌患者临床病理指标之间的关系。用划痕实验和Transwell实验检测沉默ciRS-7后MDA-MB-231和BT-549细胞的迁移和侵袭能力的变化。利用动物实验在体内进行验证。结果 TNBC组织中ciRS-7的相对表达量为（6.52±0.38），显著高于Luminal型（1.56±0.17）（P<0.001）和HER2过表达型乳腺癌组织（2.27±0.66）（P<0.001）以及癌旁正常组织（0.83±0.09）（P<0.001）。ciRS-7表达与分子分型、肿瘤浸润和淋巴结转移明显相关（均P<0.05）；而与患者年龄、肿瘤直径和病理分级无关（均P>0.05）。沉默ciRS-7后，MDA-MB-231和BT-549细胞的迁移和侵袭明显减弱（均P<0.05）。ciRS-7敲低组肺转移瘤数明显减少（P<0.05）。结论 ciRS-7在TNBC中高表达，并可能增强TNBC细胞的侵袭和迁移。     

双歧杆菌四联活菌片联合四联疗法对HP阳性胃溃疡患者血清TGF-β1、G17、PGI的影响

目的探讨双歧杆菌四联活菌片联合四联疗法对幽门螺旋杆菌(HP)阳性胃溃疡患者血清转化生长因子-β1(TGF-β1)、胃泌素17(G17)、胃蛋白酶原I(PGI)的影响。 方法选取HP阳性胃溃疡患者98例,随机均分为对照组和联合组。对照组采用四联疗法,联合组采用双歧杆菌四联活菌片联合四联疗法治疗。比较两组临床疗效、胃黏膜组织学评分、血清TGF-β1、PGI、G17、胃动素(MTL)、不良反应等情况。 结果联合组治疗总有效率高于对照组(P＜0.05)。与治疗前比较,治疗后两组胃黏膜组织学各项评分、TGF-β1、G17、PGI均降低,MTL升高,且联合组较对照组更为显著(P＜0.05)。联合组不良反应总发生率低于对照组(P＜0.05)。 结论双歧杆菌四联活菌片联合四联疗法治疗HP阳性胃溃疡患者疗效满意,可调节胃肠激素水平,安全性良好,具有临床应用价值。     

消风散合凉血五根汤联合西药治疗成人过敏性紫癜性肾炎临床疗效及对患者血表皮生长因子、血小板活化因子乙酰水解酶的影响

目的观察消风散合凉血五根汤联合西药治疗成人过敏性紫癜性肾炎(HSPN)的临床疗效及对患者血表皮生长因子(EGF)、血小板活化因子乙酰水解酶(PAF-AH)的影响。方法将90例成人HSPN患者按照随机数字表法分为2组。对照组45例予常规西医治疗;治疗组45例在对照组基础上加服消风散合凉血五根汤治疗。2组均治疗8周。比较2组治疗前后中医证候评分、血肌酐(Cr)、尿素氮(BUN)、24 h尿蛋白定量、尿红细胞计数(U-RBC)、尿微量白蛋白尿肌酐比值(UACR)、估算肾小球滤过率(e GFR)、血EGF、PAF-AH水平,并统计2组临床疗效及不良反应情况。结果治疗组总有效率88.89%,对照组总有效率68.89%,治疗组疗效优于对照组(P<0.05)。治疗后2组各项中医证候评分及总分均降低(P<0.05),治疗组治疗后各项中医证候评分及总分均低于对照组(P<0.05)。治疗后2组Cr、BUN、24 h尿蛋白定量、U-RBC、UACR均降低(P<0.05),e GFR升高(P<0.05);治疗组治疗后Cr、BUN、24 h尿蛋白定量、U-RBC、UACR均低于对照组(P<0.05),e GFR高于对照组(P<0.05)。治疗后2组血EGF、PAF-AH水平均降低(P<0.05),治疗组治疗后血EGF、PAF-AH水平均低于对照组(P<0.05)。治疗组不良反应率(11.11%)低于对照组(26.67%,P<0.05)。结论成人HSPN在西医治疗基础上,加用消风散合凉血五根汤可提高临床疗效,不仅可改善临床症状,还能改善肾功能,降低糖皮质激素不良反应,其机制之一可能与其下调血EGF、PAF-AH水平有关。     

蛇伤散外敷联合艾灸治疗五步蛇咬伤的临床观察与护理

目的 探讨蛇伤散外敷联合艾灸治疗五步蛇咬伤的临床效果。方法 选取本院2018年3月～2019年9月门诊患者117例,随机分为观察组59例和对照组58例。对照组给予抗五步蛇毒血清、抗破伤风、糖皮质激素、对症处理、局部处理等西医常规治疗,并给予护理配合;观察组在常规西医治疗与护理配合基础上,咬伤局部给予蛇伤散外敷,并施以八风、八邪灸疗。治疗结束后,进行疗效评价,并观察其他指标,包括消肿时间、止痛时间、臂围差值及住院时间。结果 观察组、对照组治愈率分别为76.3%、56.9%,两组总体疗效经秩和检验,差异有统计学意义(P0.05)。观察组、对照组止痛时间分别为(6.3±1.4) h、(11.8±2.9) h,与对照组比较,观察组明显缩短(P0.05);观察组、对照组消肿时间分别为(97.3±5.8)h、(152.5±37.2) h,与对照组比较,观察组明显缩短(P0.05);观察组治疗前后臂围差值为(5.9±1.1)cm,对照组为(2.5±0.6)cm,与对照组比较,观察组臂围明显减小(P0.05);观察组、对照组住院时间分别为(3.9±0.9)d、(5.5±1.2)d,与对照组比较,观察组时间明显缩短(P0.05)。结论 蛇伤散外敷联合艾灸治疗五步蛇咬伤在临床疗效、消肿止痛等方面均有效,值得进一步推广应用。