辛伐他汀对烟雾吸入性肺损伤大鼠炎性因子及氧化应激反应的影响

目的:研究辛伐他汀对烟雾吸入性肺损伤大鼠炎性因子及氧化应激反应的影响。方法:选取60只清洁级SD大鼠,将其按照随机抽签法分成正常组、盐水组以及辛伐他汀组,每组各20只。盐水组与辛伐他汀组大鼠均制备发烟罐烟雾吸入性肺损伤模型,建模成功后30 min,辛伐他汀组大鼠予以50 mg/kg剂量的辛伐他汀灌胃,盐水组则予以等量的生理盐水灌胃,正常大鼠予以正常饲养处理。采用酶联免疫法检测血清、肺泡灌洗液中炎症因子[包括白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]及氧化应激反应指标[包括超氧化物歧化酶(SOD)、丙二醛(MDA)]水平。结果:盐水组、辛伐他汀组大鼠血清、肺泡灌洗液中IL-6、TNF-α水平均高于正常组,且辛伐他汀组大鼠上述各项指标低于盐水组(均P<0.05)。盐水组、辛伐他汀组大鼠血清、肺泡灌洗液中SOD水平低于正常组,辛伐他汀组明显高于盐水组(均P<0.05),盐水组、辛伐他汀组大鼠血清、肺泡灌洗液中MDA水平高于正常组,辛伐他汀组明显低于盐水组(均P<0.05)。结论:辛伐他汀对烟雾吸入性肺损伤大鼠的炎性因子具有明显的改善作用,且有利于减轻大鼠的氧化应激反应程度。     

脑缺血大鼠肺组织NGF/TrkA表达变化及其意义

目的:探讨大鼠脑缺血后肺组织神经生长因子(nerve growth factor,NGF)/酪氨酸蛋白激酶A(tropomyosin-related kinase A,TrkA)表达的变化。方法:成年雄性大鼠随机分为假手术组和脑缺血后6 h、24 h及48 h组,每组8只。建立大脑中动脉永久性局灶性缺血模型,术后于各时间点麻醉处死大鼠后,测定肺组织湿重/干重(W/D),光镜下观察HE染色肺组织病理学改变;Western blot法检测肺组织NGF、TrkA蛋白表达。结果:与假手术组相比,脑缺血后6 h肺组织W/D有增加,差异无统计学意义(P>0.05),而脑缺血后24 h及48 h肺组织W/D均有显著增高(P<0.05),其中以24 h组最明显(P<0.01);脑缺血后6 h肺组织出现轻度充血、水肿及炎性改变,24 h及48 h组肺泡结构破坏明显。病理学评分结果显示,脑缺血后24 h及48 h组大鼠肺组织病理评分较假手术组显著升高(P<0.05);Western blot法显示,脑缺血6 h肺组织中NGF表达增加(P<0.05),48 h时表达有下降趋势,但仍高于假手术组(P<0.05)。而肺组织中TrkA表达在脑缺血6h有下降(P>0.05),24 h下降明显(P<0.05),48 h时TrkA蛋白表达虽有上升,仍显著低于假手术组(P<0.05)。结论:大鼠肺组织NGF/TrkA的动态变化可能参与了脑缺血后肺损伤的病理生理过程。     

单孔、两孔及三孔胸腔镜下早期非小细胞肺癌根治术的效果比较研究

目的:通过比较不同胸腔镜手术方式治疗早期非小细胞肺癌根治术术后的相关临床指标,为临床手术方式提供经验。方法:收集我院2017年1月～2019年12月收治的行肺癌根治术的早期非小细胞肺癌病例共100例,分别采用单孔胸腔镜(40例),两孔胸腔镜(32例)及三孔胸腔镜(28例)手术方式,比较三组手术术中及术后的相关指标。结果:单孔胸腔镜组术中出血量、术后引流量明显少于两孔胸腔镜组和三孔胸腔镜组(P0.05),而两孔胸腔镜组明显少于三孔胸腔镜组(P0.05);单孔胸腔镜组术后胸管留置时间和术后住院时间均短于两孔胸腔镜组和三孔胸腔镜组(P0.05),而两孔胸腔镜组明显短于三孔胸腔镜组(P0.05)。三组组内疼痛评分术后24h低于术后12h,术后48h低于术后24h,差异均有统计学意义(P0.05)。三组组间不同时间点疼痛评分比较发现,单孔胸腔镜组疼痛评分低于两孔胸腔镜组和三孔胸腔镜组(P0.05),而两孔胸腔镜组低于三孔胸腔镜组(P0.05)。三组清扫淋巴结数目、淋巴结站数和术后并发症发生率差异均无统计学意义(P0.05)。结论:单孔胸腔镜早期非小细胞肺癌根治术与两孔、三孔胸腔镜手术相比优势明显,且不会显著增加术后并发症,可作为临床首选。     

食管癌调强放射治疗的初期疗效及急性放射性肺损伤的影响因素分析

摘要 目的：探讨食管癌调强放射治疗的初期疗效及急性放射性肺损伤的影响因素。方法：选取2015年1月-2019年1月在我院进行调强放射治疗的食管癌患者322例,评价食管癌调强放射治疗后一个月的疗效;按照是否发生急性放射性肺损伤（RILI）分为急性RILI组和无急性RILI组,采用多因素Logistic回归分析分析急性RILI的影响因素。结果：调强放射治疗的完全缓解和部分缓解的患者占98.45%;322例患者中90例（27.95%）出现急性RILI,其中36例（11.18%）出现2级及以上的急性RILI;急性RILI组和无急性RILI组间卡氏（KPS）评分、淋巴结转移、基础肺疾病、V5、V10、V20、V30和全肺平均剂量（MLD）差异有统计学意义（P<0.05）;多因素Logistic回归分析显示,KPS评分<80分、有淋巴结转移、有基础肺疾病,V5≥60%、V10≥40%、V20≥28%、V30≥20%和MLD≥10Gy是食管癌调强放射治疗后急性放射性肺损伤的危险因素（P<0.05）。结论：使用调强放射治疗技术治疗食管癌的初期疗效较好,治疗过程中,应充分考虑病患的临床特征,优化放疗方案和靶区,减少急性RILI的发生,提高食管癌患者放疗后的生存质量。     

RHCG基因在非小细胞肺癌中的表达及对细胞增殖的影响

为了探讨Rh type C glycoprotein (RHCG)对非小细胞肺癌(non-small cell lung cancer,NSCLC)细胞增殖的影响及可能的作用机制,本研究使用荧光定量PCR法检测12对NSCLC及癌旁组织样本中RHCG mRNA的表达水平及pcDNA3.1-RHCG质粒对A549细胞RHCG m RNA的表达;采用CCK-8法检测细胞增殖能力;运用PI染色法检测细胞周期;使用免疫印迹法检p-PI3K、PI3K、p-AKT以及AKT蛋白表达水平。本研究发现,与癌旁组织比较,NSCLC中RHCG m RNA表达水平明显降低。RHCG过表达能抑制NSCLC细胞系A549细胞增殖能力。此外,RHCG过表达使A549细胞周期G1/S期转化发生阻滞。本研究还发现,RHCG过表达可下调A549细胞p-PI3K/PI3K和p-AKT/AKT水平。本研究表明,RHCG抑制NSCLC细胞增殖的作用与其抑制PI3K/AKT信号通路有关。     

Intrinsically altered lung‐resident γδT cells control lung melanoma by producing interleukin‐17A in the elderly

Cancer is an age‐associated disease, potentially related to the altered immune system of elderly individuals. However, cancer has gradually decreased incidence in the eldest globally such as the most common lung cancer, the mechanisms of which remain to be elucidated. In this study, it was found that the number of lung‐resident γδT cells was significantly increased with altered gene expression in aged mice (20–24 months) versus young mice (10–16 weeks). Aged lung Vγ4⁺ and Vγ6⁺ γδT cells predominantly produced interleukin‐17A (IL‐17A), resulting in increased levels in the serum and lungs. Moreover, the aged mice exhibited smaller tumors and reduced numbers of tumor foci in the lungs after challenge with intravenous injection of B16/F10 melanoma cells compared with the young mice. Aged lung Vγ4⁺ and Vγ6⁺ γδT cells were highly cytotoxic to B16/F10 melanoma cells with higher expression levels of CD103. The markedly longer survival of the challenged aged mice was dependent on γδT17 cells, since neutralization of IL‐17A or depletion of indicated γδT cells significantly shortened the survival time. Consistently, supplementation of IL‐17A significantly enhanced the survival time of young mice with lung melanoma. Furthermore, the anti‐tumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota, as demonstrated through co‐housing of the aged and young mice. Intrinsically altered lung γδT17 cells underlying age‐dependent changes control lung melanoma, which will help to better understand the lung cancer progression in the elderly and the potential use of γδT17 cells in anti‐tumor immunotherapy.     

High-dose neoadjuvant chemoradiotherapy versus chemotherapy alone followed by surgery in potentially-resectable stage IIIA-N2 NSCLC. A multi-institutional retrospective study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society)

BackgroundThe optimal induction treatment in potentially-resectable stage IIIA-N2 NSCLC remains undefined.AimTo compare neoadjuvant high-dose chemoradiotherapy (CRT) to neoadjuvant chemotherapy (CHT) in patients with resectable, stage IIIA-N2 non-small-cell lung cancer (NSCLC).MethodsRetrospective, multicentre study of 99 patients diagnosed with stage cT1-T3N2M0 NSCLC who underwent neoadjuvant treatment (high-dose CRT or CHT) followed by surgery between January 2005 and December 2014.Results47 patients (47.5%) underwent CRT and 52 (52.5%) CHT, with a median follow-up of 41 months. Surgery consisted of lobectomy (87.2% and 82.7%, in the CRT and CHT groups, respectively) or pneumonectomy (12.8% vs. 17.3%). Nodal downstaging (to N1/N0) and Pathologic complete response (pCR; pT0pN0) rates were significantly higher in the CRT group (89.4% vs. 57.7% and 46.8% vs. 7.7%, respectively; p < 0.001)). Locoregional recurrence was significantly lower in the CRT group (8.5% vs. 13.5%; p = 0.047) but distant recurrence rates were similar in the two groups. Median PFS was 45 months (CHT) vs. “not reached” (CRT). Median OS was similar: 61 vs. 56 months (p = 0.803). No differences in grade ≥3 toxicity were observed. On the Cox regression analysis, advanced pT stage was associated with worse OS and PFS (p < 0.001) and persistent N2 disease (p = 0.002) was associated with worse PFS.ConclusionsCompared to neoadjuvant chemotherapy alone, a higher proportion of patients treated with preoperative CRT achieved nodal downstaging and pCR with better locoregional control. However, there were no differences in survival. More studies are needed to know the optimal treatment of these patients.     

Impact of lung density on isolated lung tumor dose in VMAT using inline MR-Linac

PurposeThis study investigated the impact of lung density on the isolated lung tumor dose for volumetric modulated arc therapy (VMAT) in an inline magnetic resonance linear accelerator (MR-Linac) using the Monte Carlo (MC) simulation.MethodsCT images of the thorax phantoms with lung tumors of 1, 2, and 3 cm diameters were converted into voxel-base phantoms with lung densities of 0.1, 0.2, and 0.3 g/cm³, respectively. The dose distributions were calculated for partial-arc VMAT. The dose distributions were compared using dose differences, dose volume histograms, and dose volume indices.ResultsIn all cases, the inline magnetic field significantly enhanced the lung tumor dose compared to that at 0 T. For the 1 cm lung tumor, the inline magnetic field of 1 T increased the minimum dose of 95% of the Planning target volume (PTV D₉₅) by 14.0% in 0.1 g/cm³ lung density as compared to that in 0.3 g/cm³ at 0 T. In contrast, at 0 and 0.5 T, the PTV D₉₅ in 0.3 g/cm³ lung density was larger than that in lung density of 0.1 g/cm³. For the 2 cm lung tumor, a similar tendency to 1 cm was observed, whereas the dose impact of lung density was smaller than that for 1 cm. For the 3 cm lung tumor, the lung tumor dose was independent of lung density at 0.5 T and 1.0 T.ConclusionThe inline MR-Linac with the magnetic field over 1 T can enhance the PTV D₉₅ for VMAT regardless of the lung density.     

Expression Analyses of MicroRNAs in Hamster Lung Tissues Infected by SARS-CoV-2

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an infectious disease with multiple severe symptoms, such as fever over 37.5°C, cough, dyspnea, and pneumonia. In our research, microRNAs (miRNAs) binding to the genome sequences of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory-related coronavirus (MERS-CoV), and SARS-CoV-2 were identified by bioinformatic tools. Five miRNAs (hsa-miR-15a-5p, hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-16-5p, and hsa-miR-196a-1-3p) were found to commonly bind to SARS-CoV, MERS-CoV, and SARS-CoV-2. We also identified miRNAs that bind to receptor proteins, such as ACE2, ADAM17, and TMPRSS2, which are important for understanding the infection mechanism of SARS-CoV-2. The expression patterns of those miRNAs were examined in hamster lung samples infected by SARS-CoV-2. Five miRNAs (hsa-miR-15b-5p, hsa-miR-195-5p, hsa-miR-221-3p, hsa-miR-140-3p, and hsa-miR-422a) showed differential expression patterns in lung tissues before and after infection. Especially, hsa-miR-15b-5p and hsa-miR-195-5p showed a large difference in expression, indicating that they may potentially be diagnostic biomarkers for SARS-CoV-2 infection.     

Circular RNA hsa_circ_0085131 is involved in cisplatin‐resistance of non‐small‐cell lung cancer cells by regulating autophagy

Non‐small‐cell lung carcinoma (NSCLC) continues to top the list of cancer mortalities worldwide. The role of circular RNAs (circRNAs) in tumorigenesis has been increasingly appreciated, although it is relatively unexplored in NSCLC. Herein, we reported the role of hsa_circ_0085131 in NSCLC. In the present study, NSCLC tumor specimens exhibited a higher hsa_circ_0085131 level in comparison to para‐tumor samples. And the higher level of hsa_circ_0085131 was associated with recurrence and poorer survival of NSCLC. Moreover, hsa_circ_0085131 promoted cell proliferation and cisplatin (DDP)‐resistance. Furthermore, hsa_circ_0085131 regulated cell DDP‐resistance by modulating autophagy. Hsa_circ_0085131 acted as a competing endogenous RNA of miR‐654‐5p to release autophagy‐associated factor ATG7 expression, thereby promoting cell chemoresistance. In conclusion, hsa_circ_0085131 enhances DDP‐resistance of NSCLC cells through sequestering miR‐654‐5p to upregulate ATG7, leading to cell autophagy. Therefore, these findings advocate targeting the hsa_circ_0085131/miR‐654‐5p/ATG7 axis as a potential therapeutic option for patients with NSCLC who are resistant to DDP.