OBJECTIVETo study the excision repair capacity of human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) for 8-OH-dG and the oxidative DNA damage among workers exposed to nickel in stainless steel production environment.

METHODSA total of 231 workers exposed to nickel in a stainless steel production enterprise were recruited as nickel exposure group, and another 75 water pump workers in that enterprise were recruited as control group. The workplace occupational hazard factors were determined. Double-antigen sandwich ELISA was used to determine urinary 8-OH-dG level; RT-PCR was used to determine hOGG1 mRNA level. Pearson correlation was used to analyze the correlation between urinary 8-OH-dG level and hOGG1 mRNA level.

RESULTSLevel of 8-OH-dG was compared between different types of nickel-exposed workers and control workers; rolling mill workers showed no significant difference from the control group (P > 0.05), while steel making workers and steel slag disposing workers showed significant differences from the control group (P < 0.05). Level of 8-OH-dG was also compared between nickel-exposed workers with different working years and control workers; nickel-exposed workers with 0∼5 and 6∼10 working years showed no significant differences from the control group (P > 0.05), while other exposed workers showed significant differences from the control group (P < 0.05). Different types of nickel-exposed workers all showed significant differences from the control group in hOGG1 mRNA level (P < 0.05). Nickel-exposed workers with 0∼5 working years showed no significant difference from the control group in hOGG1 mRNA level (P > 0.05), while other exposed workers showed significant differences from the control group (P < 0.05). Pearson correlation analysis showed that urinary 8-OH-dG level was positively correlated with hOGG1 mRNA level (r = 0.993) in different types of nickel-exposed workers, and the correlation was significant at α = 0.01 (P < 0.05); urinary 8-OH-dG level also showed a positive correlation with hOGG1 mRNA level in nickel-exposed workers with different working years (r = 0.968), and the correlation was significant at α = 0.01 (P < 0.05).

CONCLUSIONExposure to nickel increases oxidative DNA damage among steel workers, and hOGG1 shows active excision repair capacity for 8-OH-dG.

Adult ; DNA Damage ; DNA Glycosylases ; metabolism ; DNA Repair ; Humans ; Male ; Metallurgy ; Middle Aged ; Nickel ; adverse effects ; Occupational Exposure ; adverse effects ; Stainless Steel ; Young Adult

OBJECTIVETo study the regulation trend of resveratrol on TNF-alpha, IL-1beta, IL-6 expressions in bronchoalveolar layage fluid (BALF) of RSV-infected BALB/c mice at different time points.

METHODRSV-induced BALB/c mice were orally administered with resveratrol. Their BALFs were collected at 24, 72 and 144 h after the first nasal drip with RSV to detect the level of TNF-alpha, IL-1P3, IL-6 by EILSA.

RESULTThe expression of TNF-alpha, IL-1Pf and IL-6 in BALF increased significantly compared with the normal group (P <0. 01) after 24 hours of RSV infection, while the expression of TNF-alpha (P < 0.01), IL-1beta (P < 0.05), IL-6 (P < 0.01) in the resveratrol group decreased notably compared with the model group. After 72 hours of infection with RSV, although the expression of TNF-alpha (P < 0.05), IL-1beta (P < 0.01) and IL-6 (P < 0.01) in BALF in model group were higher than those in the normal group, they were much more lower than at 24 h. The expression of IL-1beta and IL-6 (P < 0.05) in the resveratrol groups were down-regulated significantly, but no difference had been shown in TNF-alpha expression compared with the RSV infection group. After infection with RSV for 144 h, the expression of IL-1beta (P < 0.01) and IL-6 (P < 0.05) in BALF in the model group were higher than those in the normal group, but there was no difference in the secretion of TNF-alpha. The expression of TNF-alpha, IL-1beta and IL-6 showed also no remarkable difference between the resveratrol groups and the RSV infection group.

CONCLUSIONResveratrol can inhibit the over expression of inflammatory factors TNF-alpha, IL-1beta, IL-6 in bronchoalveolar lavage fluid of RSV-induced BALB/c mice and keep them at a low level with the passing of infection time.

Animals ; Bronchoalveolar Lavage Fluid ; immunology ; Female ; Interleukin-1beta ; analysis ; Interleukin-6 ; analysis ; Mice ; Mice, Inbred BALB C ; Respiratory Syncytial Virus Infections ; drug therapy ; immunology ; Stilbenes ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; analysis

Objective:To explore the clinical significance of multi-sample next-generation sequencing (NGS) in detecting gene mutations in non-small cell lung cancer (NSCLC), so as to provide a basis for individualized targeted treatment.Methods:The data of 51 patients with NSCLC in the First Affiliated Hospital of Zhejiang University Medical College from June 2016 to February 2019 was retrospectively analyzed. The patients' age, gender, smoking status, pathological type, tumor staging, pleural invasion status and meningeal invasion status were collected, and the tissues, cerebrospinal fluid, pleural effusion and plasma samples were detected by NGS. The correlations between the driver gene mutations [epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)] and the clinicopathological features of patients were analyzed by χ 2 test or Fisher exact probability method. Cohen Kappa coefficient analysis was used to compare the consistency of NGS detection results in different samples. Results:Among the 51 patients, 3 different types of specimens were examined in 7 patients. Of which, the driver gene mutations were all positive in 3 cerebrospinal fluid samples and double gene mutations were found in 2 hydrothorax samples. Driver gene mutations were more common in female [90.48% (19/21) vs. 50.00% (15/30), χ 2 = 9.107, P = 0.003], non-smokers [80.00% (24/30) vs. 47.62 (10/21), χ 2 = 5.829, P = 0.016], adenocarcinoma patients [72.34% (34/47) vs. 0, P = 0.017] and patients with malignant pleural effusion [92.86% (13/14) vs. 56.76% (21/37), χ 2 = 4.443, P = 0.035], and the differences were statistically significant. However, there was no statistically significant difference in mutations of driver gene among patients with different age or tumor stages (both P > 0.05). The consistency rate of genetic test results of the driver gene mutations in 37 plasma samples and matched tissue samples was 70.27% (26/37), κ value was 0.430, which suggested a good consistency between them. Conclusions:In patients with advanced NSCLC, gene detection of cerebrospinal fluid is of high application value for patients with meningeal metastasis; for patients with pleural invasion, gene detection of pleural effusion is an effective means to screen targeted therapy drugs. NGS detection of multiple specimens can better reflect the status of gene mutations and guide the individualized targeted therapy of lung cancer patients.

Lung cancer is the most common malignancy and is a major public health problem worldwide. Programmed cell death receptor 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors provide a new treatment strategy for non-small cell lung cancer (NSCLC). The existing biomarkers all have advantages and defects in selecting patients who benefit from immunotherapy. The multiplex immunohistochemistry/immunofluorescence (mIHC/IF) provides multiplex staining, allows comprehensive studies of cellular composition, cellular functions and cell-cell interactions. A number of studies have used mIHC/IF to explore specific immune cells in tumor immune microenvironment (TIME) and found that it is helpful for clinical prognosis and efficacy prediction in patients with lung cancer. In the era of immunotherapy for lung cancer, this technique has a bright future in translational research and clinical practice. The research progress of mIHC/IF detection in lung cancer immunotherapy is summarized in this review.
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A 54-year-old, non-smoking woman was diagnosed as stage ⅣB adenocarcinoma with widespread bone metastasis (cT4N2M1c) in the First Affiliated Hospital, Zhejiang University School of Medicine. Immunohistochemistry result showed the presence of anaplastic lymphoma kinase (ALK) gene rearrangement; next-generation sequencing (NGS) indicated EML4-ALK fusion (E6:A20) with concurrent CCDC148-ALK (C1:A20), PKDCC-ALK (Pintergenic:A20)and VIT-ALK (V15:A20) fusions. After 32 weeks of alectinib treatment, the patient complained cough and exertional chest distress but had no sign of infection. Computed tomography (CT) showed bilateral diffuse ground glass opacities, suggesting a diagnosis of alectinib-related interstitial lung disease (ILD). Following corticosteroid treatment and discontinuation of alectinib, clinical presentations and CT scan gradually improved, but the primary lung lesions enlarged during the regular follow-up. The administration of crizotinib was then initiated and the disease was stable for 25 months without recurrence of primary lung lesions and ILD.
Female ; Humans ; Middle Aged ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Crizotinib/therapeutic use* ; Lung Neoplasms/drug therapy* ; Anaplastic Lymphoma Kinase/therapeutic use* ; Lung Diseases, Interstitial/diagnosis*

Lung cancer is the most common malignancy in the world and the leading cause of cancer death. Human epidermal growth factor receptor 2 (HER2) positive non-small cell lung cancer (NSCLC) refers to the NSCLC caused by mutation, amplification or overexpression of the HER2 gene, resulting in its dysfunction. HER2 is the most active receptor in the HER family and can combine with other members to form dimers, which can activate multiple signaling pathways and regulate cell proliferation, differentiation, migration and apoptosis. In NSCLC, HER2 positivity is usually considered a poor prognostic marker. At present, the diagnosis and treatment of HER2-positive NSCLC are not mature. Immunohistochemistry (IHC), next generation sequencing (NGS) and other technologies are often used to detect the positive status of HER2 mutation, amplification or overexpression. In previous studies, antitumor drugs did not show ideal therapeutic effects in HER2-positive NSCLC. However, in recent years, related researches have shown that antibody-drug conjugates (ADCs) and new tyrosine kinase inhibitors (TKIs) in targeted therapy show good antitumor activity against HER2 positive NSCLC. This article summarized the progress in diagnosis and treatment of HER2-positive NSCLC, so as to provide reference for subsequent researches.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Receptor, ErbB-2/genetics* ; Mutation ; Antineoplastic Agents/pharmacology* ; Signal Transduction ; Protein Kinase Inhibitors/therapeutic use*