胸腔积液中肺腺癌细胞EGFR突变状态与DNA含量的相关性

摘要 目的：探究胸腔积液中肺腺癌细胞表皮生长因子受体（epidermalgrowthfactorreceptor,EGFR）突变状态与DNA含量的相关性,以期探究EGFR突变状态是否同肿瘤的恶性程度存在一定关联。方法：选择2015年1月至2020年1月于我院接受EGFR基因检测以及基因定量分析的591例肺腺癌患者为研究对象,按照其是否出现EGFR基因突变将其分为突变组（335例）与非突变组（256例）,两组患者的胸腔积液均使用激光图像细胞仪开展DNA含量以及非整倍体峰检测,并开展组间差异性比较。结果：（1）将591例患者按照年龄、性别及是否吸烟等临床特征进行分组对比显示,性别（P=0.034）与吸烟（P=0.007）同肺腺癌患者胸腔积液细胞出现EGFR突变具有一定关联,而年龄因素与是否出现突变无明显相关性（P>0.05）;（2）突变组患者的最大DNA指数（DI）、大于5C细胞的平均DI以及大于9C细胞的平均DI均明显高于非突变组,组间差异明显（P<0.05）;（3）开展DNA非整倍体细胞峰比较显示突变组在单峰、双峰占比中明显高于非突变组,而无峰占比明显低于非突变组（P<0.05）,多峰占比方面两组差异不大（P>0.05）。结论：经研究显示,同未出现EGFR突变的肺腺癌患者相比较,发生EGFR突变的肺腺癌患者明显DI值更高,非整倍体细胞以及非整倍体峰值也呈现异常升高态,这提示EGFR发生突变的肺腺癌患者恶变洗吧的侵袭性更强。     

胸腹腔镜联合Ivor Lewis食管癌根治术对食管癌患者肺功能、红细胞免疫及应激反应的影响

目的:探讨胸腹腔镜联合Ivor Lewis食管癌根治术对食管癌患者红细胞免疫、肺功能及应激反应的影响。方法:选取2016年5月~2018年6月期间我院收治的食管癌患者150例。根据随机数字表法将患者分为A组(n=75)和B组(n=75),A组予以开胸Ivor Lewis食管癌根治术,B组予以胸腹腔镜联合Ivor Lewis食管癌根治术,比较两组围术期指标、肺功能、红细胞免疫、应激反应及并发症。结果:B组手术时间、住院时间短于A组,术中出血量少于A组(P<0.05);两组清扫淋巴结数目比较无差异(P>0.05)。两组术后1个月第1秒末用力呼气容积(FEV1)、用力呼吸肺活量(FVC)、FEV1/FVC均降低,但B组高于A组(P<0.05)。两组术后3d白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)均升高,但B组低于A组(P<0.05)。两组术后3d红细胞免疫复合物花环率(RBC-ICR)升高,但B组低于A组(P<0.05);红细胞C3b受体花环率(RBC-C3bRR)、肿瘤红细胞花环率(TRR)降低,但B组高于A组(P<0.05)。两组患者术后并发症发生率比较差异无统计学意义(P>0.05)。结论:胸腹腔镜联合Ivor Lewis食管癌根治术治疗食管癌患者,可有效改善围术期各项指标,减轻对机体肺功能、红细胞免疫及应激反应的影响,且不增加并发症发生率。     

圣乔治教堂诺卡菌引起的肺部感染1例

诺卡菌肺部感染可引起肺诺卡菌病,因其无特异性的临床表现,容易误诊、漏诊。因此,临床实验室的培养鉴定能力非常重要,若不能及时诊治,则会导致病死率较高。诺卡菌病临床较为少见,为引起临床实验室对诺卡菌的鉴定和药敏试验的重视,本文报道了上海市嘉定区中心医院2019年2月收治的1例由圣乔治教堂诺卡菌(Nocardia cyriacigeorgica)感染引起的肺诺卡菌病病例,针对其临床特征、实验室检测及治疗等进行分析,期望对临床诊治诺卡菌病有所帮助。     

食管癌三维适形放疗前后肺功能、生活质量的变化及放射性肺炎的影响因素分析

目的:探讨食管癌三维适形放疗前后肺功能、生活质量的变化及放射性肺炎的影响因素。方法:收集2017年11月~2019年11月在我院进行三维适形放疗的食管癌患者102例,对患者放疗前后的肺功能进行检测对比,并采用生活质量评价简表(QLQ-C30)对患者放疗前后的生活质量进行评估对比。统计患者放疗后放射性肺炎的发生率,根据患者放疗后是否发生放射性肺炎将患者分为放射性肺炎组和非放射性肺炎组,对两组患者的临床资料进行对比分析,采用单因素和多因素Logistic回归分析影响食管癌三维适形放疗后放射性肺炎发生的影响因素。结果:放疗前后患者肺活量(VC)占预计值的百分比、用力肺活量(FVC)占预计值的百分比、第一秒用力呼气容积(FEV1)占预计值的百分比、最大通气量(MVV)占预计值的百分比对比无统计学差异(P>0.05),放疗后患者一氧化碳弥散量(DLCO)占预计值的百分比低于放疗前(P<0.05)。放疗后患者的QLQ-C30各项评分均低于放疗前(P<0.05)。102例患者中放疗后出现放射性肺炎33例,发生率为32.35%。经单因素分析显示,两组患者在性别、体质量指数(BMI)、吸烟史、饮酒史、肿瘤大小、病理类型、肿瘤位置、合并化疗方面比较差异无统计学意义(P>0.05),而在年龄、合并肺基础疾病、全肺接受20Gy的体积(V20)、全肺照射平均剂量(MLD)方面比较差异有统计学意义(P<0.05)。经多因素Logistic回归分析显示,年龄≥60岁、合并肺基础疾病、V20≥30%、MLD≥1200cGy是食管癌三维适形放疗后出现放射性肺炎的危险因素(OR=1.309、1.193、1.416、1.309,P<0.05)。结论:食管癌三维适形放疗会对患者的肺部弥散功能、生活质量产生负面影响。部分患者放疗后会出现放射性肺炎,其主要受年龄、肺基础疾病、V20、MLD的影响。     

抗生素诱导的呼吸道菌群缺失对小鼠RSV感染的影响

目的探究抗生素雾化暴露引起的呼吸道菌群缺失对小鼠呼吸道合胞病毒(RSV)感染的影响,为临床合理使用抗生素提供指导意见。方法32只BALB/c小鼠分为2组:雾化ddH₂O对照组和雾化ABX组合抗生素组,处理6 d后,进行细菌16S rRNA基因PCR检测,构建呼吸道菌群缺失小鼠模型。上述2组组内再随机分为2小组,即PBS对照组(ddH₂O+PBS,ABX+PBS)和RSV感染组(ddH₂O+RSV,ABX+RSV),饲养至第14天。检测和分析各组小鼠支气管肺泡灌洗液(BALF)中的炎症细胞和相关细胞因子(TNF-α、IL-8、IL-10及MCP-1)的数量和水平,观察肺组织病理学状况及检测病毒载量。结果BALF中细菌DNA提取和16S rRNA基因PCR检测显示,雾化ABX组合抗生素处理能够有效地剔除呼吸道菌群。BALF中炎症细胞和相关细胞因子检测显示,ABX+RSV组炎症细胞总数明显增多(P<0.05),分类以巨噬细胞和淋巴细胞为主;且细胞因子TNF-α、IL-8、MCP-1及IL-10水平显著升高(均P<0.05)。肺部HE染色显示,感染RSV后ddH₂O+RSV组和ABX+RSV组小鼠肺部损伤明显加重(均P≤0.01),与ddH₂O+RSV组相比较,ABX+RSV组的病毒载量明显升高(t=2.7160,P=0.0217)。结论雾化ABX组合抗生素不仅能够有效地剔除呼吸道菌群,而且明显增加了小鼠感染RSV的风险,导致呼吸道炎症加重,以及病毒载量升高。     

Automatic lung segmentation in COVID-19 patients: Impact on quantitative computed tomography analysis

PurposeTo assess the impact of lung segmentation accuracy in an automatic pipeline for quantitative analysis of CT images.MethodsFour different platforms for automatic lung segmentation based on convolutional neural network (CNN), region-growing technique and atlas-based algorithm were considered. The platforms were tested using CT images of 55 COVID-19 patients with severe lung impairment. Four radiologists assessed the segmentations using a 5-point qualitative score (QS). For each CT series, a manually revised reference segmentation (RS) was obtained. Histogram-based quantitative metrics (QM) were calculated from CT histogram using lung segmentationsfrom all platforms and RS. Dice index (DI) and differences of QMs (ΔQMs) were calculated between RS and other segmentations.ResultsHighest QS and lower ΔQMs values were associated to the CNN algorithm. However, only 45% CNN segmentations were judged to need no or only minimal corrections, and in only 17 cases (31%), automatic segmentations provided RS without manual corrections. Median values of the DI for the four algorithms ranged from 0.993 to 0.904. Significant differences for all QMs calculated between automatic segmentations and RS were found both when data were pooled together and stratified according to QS, indicating a relationship between qualitative and quantitative measurements. The most unstable QM was the histogram 90th percentile, with median ΔQMs values ranging from 10HU and 158HU between different algorithms.ConclusionsNone of tested algorithms provided fully reliable segmentation. Segmentation accuracy impacts differently on different quantitative metrics, and each of them should be individually evaluated according to the purpose of subsequent analyses.     

Antiproliferative and antioxidant properties of nematocysts crude venom from jellyfish Acromitus flagellatus against human cancer cell lines

This study aimed to investigate the antiproliferative and antioxidant properties of crude venom from the nematocyst of Jellyfish Acromitus flagellates on human lung cancer (A549) and liver cancer (HepG2) cell lines. The prepared crude venom was subjected to analyses of the biochemical constituents, protein profiles, antioxidant and anticancer activities by standard methods. The extracted venom was pale-yellow in color and viscous/sticky. The biochemical composition such as, protein (1.547 mg/ml), lipid (0.039 mg/ml) and carbohydrate (0.028 mg/ml) was estimated. Protein profiles were determined by SDS PAGE, the result revealed that the molecular weight range from 205 ? 3.5 kDa. The free radical scavenging activity was analyzed by the reducing potential (56.36%), DPPH (72.47%), hydroxyl (68.50%), superoxide anion (65.75%), and nitric oxide (33.04%). The cell viability was observed by using different concentrations (20 to 100 µg/ml) of crude venom on A549 and HepG2 cancer cell lines and the IC₅₀ values were recorded in (60 μg/ml and 40 μg/ml) respectively, while it had none cytotoxic effects on Vero cell line up to the concentration of 90 μg/ml. These results suggest that crude venom from nematocyst of A. flagellatus possesses anti-cancer activity and able to develop novel drugs on marine-derived compounds.     

Differences in mRNA Expression,Protein Content,and Enzyme Activity of Superoxide Dismutases in Type II Pneumocytes of Acute and Chronic Lung Injury

The lung is protected against oxidative stress by a variety of antioxidants and type II pneumocytes seem to play an important role in antioxidant defense. Previous studies have shown that inhalation of NO₂ results in acute and chronic lung injury. How the expression and enzyme activity of antioxidant enzymes are influenced in type II cells of different inflammatory stages has yet not been studied. To elucidate this question, we exposed rats to 10 ppm NO₂ for 3 or 20 days to induce acute or chronic lung injury. From these and air-breathing rats, type II pneumocytes were isolated. The mRNA expression and protein content of CuZnSOD and MnSOD as well as total SOD-specific enzyme activity were determined. For the acute lung injury (3 d NO₂), the expression of CuZnSOD mRNA was significantly increased, while MnSOD expression was significantly reduced after 3 days of NO 2 exposure. For the chronic lung injury (20 d NO₂), CuZnSOD expression was still enhanced, while MnSOD expression was comparable to control. In parallel to CuZnSOD mRNA expression, the protein amount was significantly increased in acute and chronic lung injury however MnSOD protein content exhibited no intergroup differences. Total SOD enzyme activity showed a significant decrease after 3 days of NO₂ exposure and was similar to control after 20 days. We conclude that during acute and chronic lung injury in type II pneumocytes expression and protein synthesis of CuZnSOD and MnSOD are regulated differently.     

Case of lung carcinoma revealed by vulvar metastasis associated with systemic scleroderma and literature review

Metastatic carcinoma to the vulva is rare, where the incidence is believed to be between 5% and 8%.However, malignant tumors have been described in 3–11% of systemic scleroderma (SSc) cases.We report the case of one patient, a 66-year-old postmenopausal woman, whose medical history was marked with rheumatic vascular disease (systemic scleroderma) since 1993 without muscular, renal, cardiac lesions or HTA (arterial hypertension) and without tobacco history.The woman presented with a new vulvar mass of the right labia in December 2011 that had progressively enlarged in size.CT scan of the abdominopelvic region demonstrated a lobular mass of the right labia with central necrosis, 7 cm on the wide axis, and the rectum and the vaginal wall were normal. No inguinal or iliac lymphadenopathy was noted.An outpatient excisional biopsy revealed a poorly differentiated malignant tumor suggestive of carcinoma.IHC: CK7+/CK20−, estrogen receptors−, AE 1 AE 3+, vimentine+, S100−, Desmina−, CD34−, KI 67: 20%.The thoracic scan revealed a large mass of 4 cm × 3 cm in the right lung base with right paratracheal lymphadenopathy 3 cm × 2 cm.A bronchoscopy revealed discrete stenosis of the mediastinal portion of the right bronchial tree.The bronchial biopsy also revealed poorly differentiated lung carcinoma, non-small cell, which was identical with the vulvar tumor.

Conclusion

The presence of the single lung lesion with only one lymphadenopathy paratracheal with pathological and immunohistochemical (IHC) profile similar to the vulvar lesion, and a particular IHC profile with CK7+ and CK20− was detected – that is more specific to the primitive pulmonary cancer, and the presence of only one sarcoma marker vementine+, desmine and actine−. Also the presence of KI 67: 20%, predicted the proliferative and great metastatic power of the lung tumor was observed.Additionally, lung cancer was the most frequent type and may develop in scleroderma as reported in most studies.This allows to conclude for primitive lung carcinoma revealed with vulvar metastasis after elimination of the possibility of vulvar sarcoma.The patient was treated by chemotherapy (Taxol/Platin) with partial response from the lung after 3 cycles and palliative radiotherapy in the vulva with a good response.This case described primary lung carcinoma associated with scleroderma, revealed by a vulvar metastasis, which may be related to the aggressiveness of lung cancer when the lung fibrosis follow-up is not performed well to detect early the development of lung tumors in the patient with systemic scleroderma.     

CYP1A1 genetic polymorphisms,tobacco smoking and lung cancer risk in a French Caucasian population

The CYP1A1 gene encoding for an enzyme involved in the metabolic activation of important tobacco carcinogens could be implicated in smoking-induced lung cancer. Given the strong association between tobacco smoking and lung cancer, the effect of tobacco smoke exposure has to be taken into account when studying the potential association between lung cancer and CYP1A1 genotypes. The effect of two CYP1A1 genetic polymorphisms (Mspl and IIe-Val) on lung cancer risk were evaluated using peripheral blood DNA from 150 lung cancer patients and 171 controls. The Mspl sitepresent allele was found among 19.3% of both cases and controls and the variant allele Val among 6.7% of cases and 8.8% of controls. Lung cancer risks associated with the Mspl site-present allele (OR= 0.9; 95%Cl: 0.5-1.8) or with the Val allele (OR= 0.8; 95%Cl: 0.3-1.9) were not increased after adjustment for tobacco and asbestos exposures. These results persisted when analyses were stratified on smoking status, daily consumption of tobacco or duration of smoking. Similar findings were obtained when squamous cell or small cell carcinomas were studied separately. This study thus suggests a minor role for the known CYP1A1 gene polymorphisms in predisposition to lung cancer among Caucasian populations.