在络病理论指导下,将肺结节治疗窗口前移,充分发挥中医"治未病"的优势.肺结节早期起于肺气络,进展或恶化于肺血络,以气痰阻络、痰瘀阻络为基本病机,灵活运用行气通络、化痰通络、逐瘀通络3种治法通畅络脉,身心同调,积极干预肺结节的发生、发展过程,使结无所生,癌无所转,达到延缓结癌转化进程的目的.

目的 探究冷冻消融治疗对肺腺癌细胞凋亡的影响.方法 根据冷冻消融术后肿瘤组织局部变化,在细胞水平上建立肺癌冷冻消融模型.传代培养人肺癌H1299细胞株,将细胞分为4组:A组,未处理细胞,为对照组;B组,未处理细胞培养液中加入坏死液(将细胞悬液放入液氮罐中冷冻5 min,37℃复温后离心取上清液,得到坏死液);C组,亚致死细胞(细胞在-80℃环境中冷冻7 min,模拟亚致死状态);D组,亚致死细胞培养液中加入坏死液.24 h后用流式细胞术检查冷冻消融对肺癌细胞凋亡的影响,qRT-PCR和Western blot检测冷冻消融对凋亡相关分子B细胞淋巴瘤基因-2(Bcl-2)及Bcl-2相关x蛋白(Bax)表达的影响.采用Lewis肺腺癌细胞株建立C57BL/6小鼠皮下移植瘤模型,造模成功的小鼠随机分成2组,假手术组和冷冻消融组,每组4只,氩氦刀冷冻14 d后,取肿瘤组织,通过qRT-PCR和Western blot检测冷冻消融对凋亡相关分子Bax及Bcl-2表达的影响.结果 细胞冷冻模型中与对照组A组相比,B、C、D组均能促进细胞凋亡(P<0.05),且D组细胞凋亡率最高,高于其他组(P<0.05),体外和体内实验均显示冷冻消融能提高Bax mRNA和蛋白的表达(P<0.05),体内实验中Bcl-2 mRNA和蛋白的表达均下降(P<0.05),在体外细胞冷冻模型中差异无统计学意义.结论 冷冻消融通过细胞凋亡机制达到有效消融目的,其作用机制可能与降低Bcl-2/Bax相关.

Purpose: Yin-Huo-Tang (YHT) is a classic traditional Chinese prescription, used to prevent lung adenocarcinoma (LUAD) relapse by "nourishing yin and clearing heat". In this study, the mechanism of YHT in LUAD recurrence was investigated. Methods: Firstly, the bioactive compounds and targets of YHT, as well as related targets of LUAD recurrence, were collected from public databases. The protein-protein interaction network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to find the pivotal compounds, hub genes, functional annotation and main pathways. Subsequently, RNA sequencing of recurrent tumor tissues from Lewis lung carcinoma mice treated with YHT was used to explore the main pathways. At the same time, pathways screened by network pharmacology and RNA sequencing analysis were considered the most important pathways. Finally, liquid chromatography mass spectrometry was used to validate the pivotal active ingredients. Molecular docking technology was performed to validate the binding association between the hub genes and the pivotal active ingredients. PCR and WB analysis were used to validate the main pathways. Results: There were 128 active compounds and 419 targets interacting with YHT and LUAD recurrence. Network analysis identified 4 pivotal compounds, 28 hub genes and 30 main pathways. Sphingolipid signaling pathway was the common main pathway in network pharmacology and RNA sequencing results. The hub gene related to the sphingolipid signaling pathway was S1PR5. Qualitative phytochemical analysis confirmed the presence of 3 pivotal compounds, namely stigmasterol, nootkatone and ergotamine. The molecular docking verified that the pivotal compounds could good affinity with S1PR5. The PCR and WB analysis verified YHT suppressed Lewis lung cancer cells proliferation and migration by inhibiting the sphingolipid signaling pathway. Conclusion: The potential mechanism and therapeutic effect of YHT against the recurrence of LUAD may be ascribed to inhibition of the sphingolipid signaling pathway.

Objective: To study the regulatory effect of cryoablation on MAPK/ERK signaling pathway in mice with lung adenocarcinoma. Methods: Lewis mouse lung adenocarcinoma cell line was used to establish subcutaneous transplanted tumor model in C57BL / 6 mice. Ten mice were randomly divided into two groups: sham operation group and cryoablation group, with 5 mice in each group. The cryoablation group was treated with double circulation-rewarming ablation, and the sham operation group was treated with incision and suture at the transplanted tumor. The tumor tissues were taken 14 days after operation. Detect the effect of cryoablation on MAPK/ERK pathway related proteins by Western blot, such as KRAS, RAF1, MEK1, ERK1/2, P-RAF1, P-MEK1, P-ERK1/2. The expression of KRAS gene was further verified by qRt-PCR. Results: Compared with the sham operation group, the phosphorylated proteins P-RAF1, P-MEK1 and P-ERK1/2 in tumor tissue after cryoablation were decreased (P< 0.05 ), and the key molecule KRAS in MAPK/ERK pathway was decreased in protein and gene expression (P< 0.05 ). Conclusion: Cryoablation can negatively regulate MAPK / ERK signaling pathway by down-regulating KRas expression.

BackgroundHOXA cluster antisense RNA 2 (lncRNA HOXA-AS2) is a long noncoding RNA (lncRNA) that aberrantly expressed in various cancers and is closely associated with cancer progression. To overcome the limitation of small sample sizes that are inherent to single studies, a meta-analysis was conducted to explore the relationship between the expression level of HOXA-AS2 and cancer prognosis.MethodsCorrelational studies were retrieved by searching the databases of PubMed, Embase and Web of Science (up to August 10, 2022). The survival and prognosis data included overall survival (OS), and clinical parameters were gathered and analyzed.ResultsEighteen publications with 1181 patients who were diagnosed with solid tumors were ultimately included. The results showed that, compared with patients with low HOXA-AS2 expression, patients with high HOXA-AS2 expression tended to have poorer overall survival (OS) (HR= 2.52, 95% CI 1.87-3.38, P < 0.01) and shorter disease-free survival (DFS) (HR=7.19, 95% CI 3.20-16.17, P < 0.01). In addition, elevated HOXA-AS2 expression indicated a larger tumor size (OR =2.43, 95% CI 1.53–3.88,P < 0.01), more advanced TNM stage (OR=3.85, 95% CI 2.79-5.31, P < 0.01), earlier lymph node metastasis (LNM) (OR = 4.41, 95% CI 3.05-6.39, P < 0.01) and distant metastasis (DM) (OR= 2.96, 95% CI 1.87-4.7, P < 0.01). Furthermore, HOXA-AS2 expression was notassociated with age (OR=1.15, 95% CI 0.90-1.47), gender (OR=1.16, 95% CI 0.89-1.53), or tumor differentiation (OR=1.21, 95% CI 0.56-2.63). Moreover, aberrant HOXA-AS2 expression was related to drug sensitivity in various types of cancers.ConclusionThe overexpression of HOXA-AS2 predicted poor cancer prognosis in the Chinese population, including poor OS, DFS, TNM, LNM, and DM. HOXA-AS2 could serve as a promising prognostic biomarker and therapeutic target.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022352604.

目的 探讨阻塞性睡眠呼吸暂停(OSA)与新发恶性肿瘤的相关性.方法 制定检索策略,检索中国知网、万方、维普、PubM ed、EM base、Cochrane Library数据库,检索时间截至2020年6月.根据纳入、排除标准对文献进行筛选,提取相关资料,并对纳入文献进行质量评价,使用Stata 15.0软件进行meta分析.结果 本研究共纳入10篇文献,均为高质量文献;研究发现OSA患者恶性肿瘤发生率较非OSA患者高52％(OR=1.52,95％CI:1.13～2.06,P=0.006);排除混杂因素的影响后,OSA患者恶性肿瘤风险是非OSA患者的1.65倍(HR=1.65,95％CI:1.24～2.20,P=0.001);未观察到不同程度OSA与恶性肿瘤风险的相关性(P>0.05).结论 OSA患者的恶性肿瘤发生率不仅较非OSA患者明显增高,OSA更可能是独立的致癌因素,但结论的适用范围仍需更多大样本研究的支持.