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Background The E6 and E7 proteins in human papillomavirus 16 (HPV 16) are the main oncogenes in the occurrence of lung cancer. In recent studies, we found that E6 and E7 downregulated the expression of LKB1 in lung cancer cells. However, it is still unclear how E6 and E7 regulate LKB1 in lung cancer cells. Methods Double directional genetic manipulation and nuclear plasma separation technology were performed to explore the molecular mechanism of E6 and E7 inhibiting the antitumor activity of LKB1 in well-established lung cancer cell lines. Results E6 but not E7 significantly downregulated the expression of tumor suppressor KIF7 at protein level, and the inhibition of KIF7 further reduced the expression of LKB1 both in the nuclei and in the cytoplasm, whereas reduced the expression of p-LKB1 in the cytoplasm only. This suggested that HPV 16 E6 but not E7 downregulates the antitumor activity of LKB1 by downregulating the expression of p-LKB1 in the cytoplasm only. Conclusions Here, we demonstrated for the first time that E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by downregulating the expression of KIF7. Our findings provide new evidence to support the important role of KIF7 in the pathogenesis of lung cancer and suggests new therapeutic targets.

Background: HPV16 is the most common infection subtype, among which E6 and E7 proteins are the most common carcinogenic proteins. Our previous studies found that E6 and E7 proteins regulated the expression of GLUT1 through multiple molecular signaling pathways in lung cancer. However, whether they can regulate the glucose uptake of GLUT1 and the underlying molecular mechanism has not been identified. Methods: The modulating effects of E6 or E7, NDRG2, β-catenin, and GLUT1 were detected by double directional genetic manipulations in lung cancer cell lines; The immunofluorescence was used to detect the effect of NDRG2 on the nuclear translocation of β-catenin; The glucose uptake level of GLUT1 was observed under the confocal microscope.Results: We demonstrated for the first time that E6 and E7 had inhibitory effects of NDRG2 which further resulted in increased β-catenin expression and promoted β-catenin nuclear translocation, furthermore promoted the expression and glucose uptake of GLUT1. Therefore, we hypothesized both E6 and E7 in HPV16 promoted the expression and glucose uptake of GLUT1 through HPV-NDRG2- β-catenin-GLUT1 axis. Conclusion: Our findings confirmed the regulatory role of tumor suppressor NDRG2 in the pathogenesis of lung cancer, and we further demonstrate the detail relationships among E6 and E7, NDRG2, β-catenin, and GLUT1; which provided a novel therapeutic target for tumor treatment.

Chronic infection of HPV16 E6/E7 is frequently associated with lung cancers, especially in non-smokers and in Asians. In our previous studies, we found that HPV16 E6/E7 up-regulated HIF-1α at protein level and further up-regulated GLUT1 at both protein and mRNA levels in well-established lung cancer cell lines. In one of our further mechanism study, the results demonstrated that HPV16 E6/E7 up-regulated the expression of GLUT1 through HPV-LKB1-HIF-1α-GLUT1 axis. However, there are multiple pathways involved in HPV16 E6/E7 regulation of HIF-1α expression. In current study, using double directional genetic manipulation in well-established lung cancer cell lines, we showed that both E6 and E7 down-regulated the expression of RRAD at both protein and mRNA levels. Like LKB1, RRAD is one of the cancer suppressor genes. The loss of RRAD further activated NF-κB by promoted cytoplasmic p65 translocated to nucleus, and up-regulated the expression level of the p-p65 in nucleus. Furthermore, p-p65 up regulated HIF-1α and GLUT1 at both protein and mRNA levels. Thus, we proposed HPV16 E6/E7 up-regulated the expression of GLUT1 through HPV-RRAD-p65- HIF-1α- GLUT1 axis. In conclusion, we demonstrated for the first time that E6 and E7 promoted the expression of HIF-1α and GLUT1 by relieving the inhibitory effect of RRAD which resulted in the activation of NF-κB by promoting cytoplasmic p65 translocated to nucleus, and up-regulated the expression of the p-p65 in nucleus in lung cancer cells. Our findings provided new evidence to support the critical role of RRAD in the pathogenesis of HPV-related lung cancer, and suggested novel therapeutic targets.

The cytology of peritoneal washing fluids for gastric cancer is the most basic method for judging peritoneal micrometastasis. However, the clinical value of this method is not clear at present. A retrospective analysis was performed on 277 patients with pathologically proven and surgically treated gastric cancer. The peritoneal washing fluids were collected after opening the abdomen and before the operation, and were sent to the cytology laboratory for screening of occult cancer cells in the collected washing fluids. The number of cases diagnosed as cancer cells, reactive mesothelial cells, serosal balls, and traumatic mesothelial cells were 42, 18, 27, and 190, respectively. Typical adenocarcinoma cell nests were found in eight of 10 T4b samples, whereas 34 cases of cancer cells in T3 and T4a showed that these cell nests usually contained mesothelial cells, and the three-dimensional stereoscopic sense of the nests was not obvious. In the specific subcellular morphological changes of both reactive mesothelial cells and serosal balls, the changes of both the contour of nuclear membrane and the polarity of cell alignment were present only in stage T3 and T4a. The presence or absence of mesothelial cells in the nests of cancer cells and the changes of the contour of nuclear membrane and of the polarity of cell alignment in reactive mesothelial cells or serosal balls may help us to predict the depth of invasion of cancer cells.

Background: The cytological diagnosis of a malignant epithelial tumor, i.e., a cancer cell in the body fluid effusions is usually made by cytomorphological examination alone; however, diagnostic challenges can occur when the cancer cells are rare or cytological atypia is minimal. Morphological similarity between the cancer and the reactive mesothelial cell is the most common problem in establishing a clear diagnosis. The aim of this study is to investigate whether the cocktail acid phosphatases (ACP) special staining will be a useful tumor marker in differentiation of the reactive mesothelial cells from the cancer cells in the body fluid effusions. Methods: The cocktail ACP special staining was performed on 212 body fluid effusion samples, which included 128 pleural effusions, 69 ascites, and 15 pericardial effusions. Results: The mesothelial cells were cocktail ACP positive in 84 out of 84 benign effusion cases, and the sensitivity and the specificity were 100% for the benign effusions which including pleural effusions, ascites, and pericardial effusions. On the other hand, 122 out of 128 cancer cases were cocktail ACP negative, indicating that the sensitivity of using the cocktail ACP staining to rule out the malignant effusions was 95.3%. Thus, the cocktail ACP staining is an excellent marker with high sensitivity and specificity to distinguish the carcinoma from the reactive mesothelial cells in the body fluid effusions. Conclusions: Our finding provided a new tool for cytopathologists in diagnosing the body fluid effusion that could impact clinical decision making.

High-risk human papillomavirus (HPV) infection might play an important role in the development of lung cancer. We Our previously study showed that E6 and E7 in HPV16 could upregulated the expression of GLUT1 in lung cancer cells. However, whether they can promote the glucose uptake by GLUT1 and their underlying molecular mechanism have has not been identified. It has been reported that thioredoxin interacting protein (TXNIP) regulates both the expression of GLUT1 and its glucose uptake. We speculate that high risk HPV16 infection may be closely related to TXNIP expression. Therefore, we associate HPV16 with TXNIP to explore the potential molecular mechanism of their regulation of GLUT1 expression and glucose uptake. Using double directional genetic manipulation in lung cancer cells, we showed that HPV16 E6/E7 proteins downregulated the expression of p-PTEN in lung cancer cells, the knockdown of p-PTEN further inhibited the expression of TXNIP, the inhibition of TXNIP further promoted the accumulation of HIF-1α by inhibiting the translocation of nuclear HIF-1α to the cytoplasm, and subsequently upregulated the expression of GLUT1 at the protein and mRNA levels. More interestingly, we found for the first time that the knockdown of TXNIP played a decisive role to promote the glucose uptake by GLUT1. Together, these findings suggested that the PTEN-TXNIP-HIF-1α axis might be related to the E6/E7-mediated expression of GLUT1 and its glucose uptake.

Background: The E6 and E7 proteins in HPV16 are the main oncogenes in the occurrence of lung cancer. In recent studies, we had found that E6 and E7 downregulated the expression of LKB1 in lung cancer cells. However, it is not clear how E6 and E7 regulate LKB1 in lung cancer cells. Methods: The double directional genetic manipulation and Nuclear plasma separation technology were performed to explore the molecular mechanism of E6 and E7 inhibiting the antitumor activity of LKB1 in well-established lung cancer cell lines. Results: E6 but not E7 significantly downregulated the expression of tumor suppressor KIF7 at protein level, and the inhibition of KIF7 further reduced the expression of LKB1 both in the nuclei and in the cytoplasm, whereas reduced the expression of p-LKB1 in the cytoplasm only. Therefore, we suggested that HPV16 E6 but not E7 downregulates the antitumor activity of LKB1 by down regulating the expression of p-LKB1 in the cytoplasm only. Conclusion: We demonstrated for the first time that E6 but not E7 inhibits the antitumor activity of LKB1 in lung cancer cells by downregulating the expression of KIF7. Our findings provided new evidence to support the important role of KIF7 in the pathogenesis of lung cancer and suggested new therapeutic targets.

Biopsy, brushing, and transbronchial needle aspiration (TBNA) are the most common methods for diagnosis of lung adenocarcinoma and are taken during the same diagnostic bronchoscopic procedure. However, it is not clear what the morphological diagnostic criteria of cytology by brushing or TBNA are. A retrospective analysis was performed on 136 patients who underwent video bronchoscopy examination for diagnostic purposes. All the subjects were performed brushing or TBNA and confirmed as lung adenocarcinoma by biopsy or postoperative pathology. An additional 140 randomly selected patients with benign lung diseases were included in the study and used as a control group. The benign cells usually confused with adenocarcinoma cells were ciliated columnar cells, mucous columnar cells, ciliated cuboid cells, and reactive ciliated cells, respectively. The number of cases diagnosed as adenocarcinoma cells, carcinoma cells, suspicious cancer cells, and atypical proliferative cells by cytology was 101, 11, 20, and 4, respectively. The main basis for the interpretation of adenocarcinoma cells is the enlargement of individual nucleus, the arrangements of multistage papillary, and the general enlargement of nuclei, while the main clue for the interpretation of suspicious cancer cells and dysplasia cells comes from escape cells. The results suggested that the degree of nuclear enlargement, multiple papillary arrangement, and escape cells or escape trend cells are important clues for the interpretation of lung adenocarcinoma cells, while the atypical proliferative cells were similar to escape cells or escape trend cells, which were essentially benign cells beside the cancer.

Biopsy, brushing, and transbronchial needle aspiration (TBNA) are the most common methods used for the diagnosis of small cell lung cancer during the same diagnostic bronchoscopic procedure. However, it is not clear which method provides better results.A retrospective analysis was performed of 140 patients who had undergone video bronchoscopy for diagnostic purposes. Bronchial brushings were obtained from all subjects. Biopsy specimens were also obtained from all subjects, except for 6 cases that could not be sampled; the TBNA method was used for some special lesions. The results were analyzed separately by histology and cytology.The diagnostic yield of cytology was significantly greater than that of histology (P .01) and that of conventional smear preparations in cytology was obviously greater than that of hematoxylin and eosin stains in histology (P .01). The false-negative results were significantly lower with cytology than with histology (P .01). Also, the cases of sampling site restriction with cytology were distinctly less than those with histology (P .05). Stretch deformation of the tissue structure and cell morphology was the main reason for the false-negative results in the histologic diagnosis. The use of TBNA resolved all 4 cases of hilar adenopathy and 2 cases of lesions outside the bronchus. Multiple brushings of the tissue adjacent to cancer tissue and liquid-based preparations of cancerous necrotic tissue can significantly reduce the false-negative results from biopsy.The diagnostic yield of cytologic examination of brushings and TBNA for small cell lung cancer was superior to that of histologic examination of hematoxylin and eosin stains and immunohistochemistry.

Liver kinase B1 (LKB1) is a critical tumor suppressor that is frequently mutated in human cancers. LKB1 has serine/threonine protein kinase activity, which regulates gene expression by phosphorylation of Yes-Associated protein (YAP). The phosphorylation-dependent YAP shuttling is critically important intracellular mechanism in the Hippo pathway. In our previous study, we found that the amplification of hTERC was significant higher in the bronchial brushing cells of patients with lung cancer, however, the underlying molecular mechanism is not clear. In this study, we showed that LKB1 overexpression could phosphorylate YAP and promoted its nuclear rejection. Silencing LKB1 could dephosphorylate YAP and promoted its entry into the nucleus. Here, we found that LKB1 inhibited the mRNA expression and the amplification of hTERC. YAP further up-regulated hTERC at mRNA and gene amplification levels. Therefore, we suggest that LKB1 may inhibit the expression and amplification of hTERC through the axis of LKB1-pYAP(YAP)-hTERC.

Rationale Urinary bladder urothelial carcinoma is the most common malignant tumor in the urinary system, and noninvasive papillary urothelial carcinoma (NIPUC) comprises most bladder malignancies. NIPUC grading is important for therapeutic and clinical protocol selection. Here, we report a case of NIPUC with pathological features in between low (LG-NIPUC) and high (HG-NIPUC) grades NIPUC. Patient concerns A 72-year-old male, presenting with a 20-year history of hypertension and 5 months of hematuria. Diagnoses Computed tomography examination revealed a tumor in the urinary bladder neck. Microscopic investigation revealed that most tumor tissue samples had a branching papillary architecture, with well-developed fibrous-vascular cores. Tumor cells were slightly crowded, with somewhat altered cell polarity and cell adhesion. Immunohistochemistry showed positive Ki67 staining, mostly in the basal layer, while p53 staining was rarely positive. These samples were diagnosed as LG-NIPUC. However, a few tumor tissue samples presented mildly fused papillary architectures without cell polarity or adhesion. Most nuclei stained intensely and were pleomorphic. All epithelial tissue layers were ki67 positive, and the p53 positive rate was higher than that in the LG samples. Therefore, these were classified as HG-NIPUC. Interventions The tumor was completely resected during lithotomy postural surgery. Outcomes The patient is alive with a good recovery during 3 months after the surgery. Lessons We diagnosed this patient as having LG-NIPUC with local HG-NIPUC components. HG- and LG-HIPUC have different outcomes. This case is a new challenge for the pathological grading of NIPUC. An intermediate HIPUC grade might need to be added to the original NIPUC grading system.

Background and Objective: Small cell lung cancer (SCLC) is characterized by rapid growth, strong invasion, and early metastasis. However, the cause of its occurrence remains unclear. High-risk HPV infection is closely related to the occurrence of non-small cell lung cancer and cervical small cell neuroendocrine carcinoma. Methods: The expression levels of E6 mRNA and E7 mRNA in HPV16 were detected by qRT-PCR in the bronchial brushing and transbronchial needle aspiration (TBNA) of 310 patients with lung cancer and with benign lung diseases. To make the design of this experiment scientific and reasonable, the expression levels in lung squamous cell carcinoma were taken as positive controls, while those in benign cells were taken as negative controls. Results: The expression levels of E6 mRNA and E7 mRNA in SCLC group were significantly higher than those in benign cell group and slight higher than those in squamous cell carcinoma group. The expression levels of E6 mRNA and E7 mRNA in the central type of SCLC were significantly higher than those in the peripheral type of SCLC. Conclusions: We speculate that the occurrence of some small cell carcinoma is the same as that of some squamous cell carcinoma, which is closely related to HPV16 infection. The overexpression of E6 mRNA and E7 mRNA is in some benign lesion cells, which may be related to HPV transient infection.

Background TRAF2 and TRAF4, members of the tumor necrosis factor receptor- associated factor family of intracellular signal transduction proteins, are associated with breast cancer progression and metastasis. Methods We collected malignant serous effusion cells from the patients with breast cancer (n = 46). Cell blocks prepared from plural effusions (n = 46) and primary breast cancer (n = 50), lymph node metastases (n = 50), and normal breast tissue specimens (n = 30). The immunohistochemistry was performed for the detection of TRAF2 and TRAF4 expression with the correlation of their expression with clinicopathological parameters and survival rate analyzed. Results Compared with normal breast tissues, TRAF2 expression was upregulated, and nuclear TRAF4 expression was downregulated in malignant pleural effusion cells, primary tumors, and lymph node metastases (P

IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.

HPV 16 E6 upregulates hTERT expression in lung cancer cells. However, the underlying molecular mechanism is unclear. In this paper, E6, LKB1, SP1, and hTERT mRNA expression levels were detected in brushing cells of patients with lung cancer (n = 106) and with benign lung disease (n = 68) by qRT-PCR. The mRNA expression levels of E6, SP1, and hTERT were significantly increased in the malignant group compared with the benign group (P < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group (P < 0.01). Furthermore, the correlation between E6, Sp1, hTERT, and LKB1 was performed, our results indicated that E6, Sp1, and hTERT with positive, but LKB1 with negative correlation (P < 0.01). To investigate the potential relationship between these genes, using double directional genetic manipulation, we showed that overexpression of E6 in H1299 cells down-regulated LKB1 mRNA and protein expression but up-regulated SP1 and hTERT as well as the transcriptional activity of Sp1. In contrast, knockdown of E6 in A549 cells by short-interference RNAs (siRNAs) up-regulated LKB1 expression, but down-regulated SP1 and hTERT expression as well as Sp1 activity. LKB1 loss upregulated both SP1 and hTERT at the protein and mRNA level as well as SP1 activity. To verify that the role of E6 on hTERT was mediated by SP1, siRNA knockdown of SP1 was performed on both H1299 and A549 cell lines. Inhibition of SP1 downregulated hTERT expression. Our results indicate that HPV16 E6 indirectly upregulated the expression of hTERT by inhibition of LBK1 expression and upregulation of Sp1 expression, thus suggesting a HPV-LKB1-SP1-hTERT axis for the tumorigenesis of lung cancer. Our study also provides new evidence to support the critical role of SP1 and LKB1 in the pathogenesis of HPV-related lung cancer, and suggests novel therapeutic targets.

Background The cytologic assessment of pleural effusions to distinguish carcinoma cells from reactive mesothelial cells is particularly challenging. The aim of this study was to investigate the diagnostic value of monoclonal antibody (MOC-31) and calretinin in pleural fluid of patients with lung cancer to significantly improve the diagnostic accuracy. Methods The expressions of MOC-31 and calretinin were detected by means of S-P immunocytochemical technique in pleural effusions of patients with lung cancer (n = 92) and in patients with benign lung disease (n = 70). Results The positive rate of MOC-31 in pleural fluid was 90.2% (83/92) from patients with lung cancer and 2.9% (2/70) from patients with benign lung diseases, showing a significant difference (P < 0.01). Calretinin was expressed 87.1% (61/70) in benign lung diseases and 6.5% (6/92) in lung cancer, also showing a significant difference (P < 0.01). The optimal combination for assay was MOC-31 + calretinin: Sensitivity and specificity were 100 and 98.6%, respectively. Conclusion MOC-31 and calretinin are of important clinical value for diagnosing and differentially diagnosing the cancer cells in pleural fluid of patients with lung cancer. Diagn. Cytopathol. 2015;43:527–531. © 2014 Wiley Periodicals, Inc.

Background and objective Bronchial brushing is important for cytological diagnosis of lung carcinoma; however, cytological evaluation alone remains relatively insensitive. The aim of this study was to assess the diagnostic utility of vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) and specificity protein 1 (SP1) mRNA in bronchial brushings in patients with or without lung cancer. Methods VEGF mRNA and SP1 mRNA were measured in liquid-based cells from bronchial brushings in patients with verified lung cancer (n = 93) and with benign lung disease that included tuberculosis (n = 51). This was done using the reverse-transcription polymerase chain reaction. Results Both VEGF mRNA and SP1 mRNA were significantly more likely to be expressed in the cancer group than in the control (benign) group, whatever their cell type. It was also more often found in the tuberculosis group than in the inflammation group (P

Background: Optimizing basic techniques in diagnostic bronchoscopy is important for improving medical services in developing countries. In this study, the optimal sequence of bronchial brushing relative to bronchial biopsy for lung cancer diagnosis was evaluated. Methods: A total of 420 patients with visible endobronchial tumors were prospectively and randomly enrolled in two groups: a pre-biopsy brushing group, receiving two brushings before biopsy; two brushings which performed afterwards; were set as self-control and compared with the pre-biopsy brushings as the intra-group comparison; and a post-biopsy brushing group, only receiving two brushings after biopsy, which were compared with the pre-biopsy brushings as the inter-group comparison. Diagnostic yield of brushing was compared before and after biopsy, and as well as for different tumor pathologies and bronchoscopic morphologies. The occurrence of treated bleeding which defined as bleeding needed further intervention with argon plasma coagulation and/or anti-coagulation drugs in two groups was also compared. Results: Only patients with a definitive cytological or histological diagnosis of lung cancer based on bronchoscopy or other confirmatory techniques were included. Patients were excluded if they had submucosal lesions, extrinsic compressions, pulmonary metastasis of extrapulmonary malignancies or uncommon non-small cell lung carcinoma (NSCLC). A total of 362 patients who met the inclusion criteria were analyzed. Diagnostic yield for pre-biopsy brushing (49.2%, 88/179) was significantly higher than for post-biopsy brushing within the same pre-biopsy brushing group (31.8%, 57/179) (P=0.007) as the intra-group comparison, and significantly higher than for post-biopsy brushing in the post group (30.6%, 56/183) (P

Human telomerase reverse transcriptase (hTERT) gene amplification was detected in pleural effusions of patients with lung cancer (n = 69) and in patients with benign lung disease (n = 46) when using a quantitative polymerase chain reaction (qPCR) technique.hTERT gene relative copy numbers were significantly higher in effusions from patients with malignant, adenocarcinoma and small-cell lung cancer than in effusions from patients with benign lung disease (P.01). By using a threshold value of 1.39, hTERT gene amplification was significantly more frequent in malignant effusions compared with benign effusions and more likely to be positive for malignant effusions, compared with cytology (P.01). The diagnostic performance of qPCR of hTERT gene amplification was significantly higher than that of cytology, in terms of sensitivity (91.3% vs. 56.5%), negative predictive value (87.8% vs. 60.5%), and accuracy (92.2% vs. 73.9%).Detecting hTERT gene amplification by qPCR appears suitable for distinguishing carcinoma cells from reactive mesothelial cells in pleural effusions. hTERT gene amplification was more sensitive than cytology and may be useful for diagnosing pleural micrometastases.

Background and objective: Transbronchial needle aspiration (TBNA) is a well-established diagnostic method that is underutilized due to the relatively high percentage of non-diagnostic samples and low success rates. This study was designed to evaluate the impact of liquid-based cytology test (LBC) on the diagnostic yield from TBNA. Methods: Ninety-seven consecutive patients who underwent TBNA due to significant mediastinal adenopathy were enrolled in the study. Each target site was aspirated four times, with the first and third aspirates being prepared for LBC and the second and fourth aspirates being reserved for conventional pick-and-smear (CPS) cytology. Results: Paired aspirates were obtained from 114 target sites, giving a total of 228 test samples from 97 consecutive patients. The overall diagnostic sensitivity of TBNA was 63.6% (56/88). The yields from small cell lung cancers were better than those from non-small cell lung cancers (P 20 mm on computed tomography were also associated with better yields than nodes with diameters of 10–20 mm (P = 0.001). The diagnostic sensitivity of TBNA was similar for each processing method—59.8% (61/102) for LBC and 64.7% (65/102) for CPS. Conclusions: LBC was not inferior to CPS with respect to diagnostic yields from TBNA, and enabled efficient pathological evaluation.

Objective. To evaluate diagnostic utility of Dishevelled-3 (DVL-3) mRNA andδ-catenin mRNA expression in pleural effusions of patients with lung cancer.Methods. DVL-3 mRNA andδ-catenin mRNA levels were assessed by performing RT-PCR on pleural effusion specimens from patients with lung cancer (n=75) and with lung benign disease (n=51).Results. The expressions of DVL-3 mRNA andδ-catenin mRNA were significantly higher in malignant than in benign lung disease (P<0.01) and were obviously higher than cytology in adenocarcinoma (P<0.01). In single use, DVL-3 mRNA had the highest specificity (94.1%) and PPV (95.7%), whereasδ-catenin mRNA had the highest sensitivity (92.0%) and NPV (88.5%). When combinations of markers were evaluated together, DVL-3 mRNA andδ-catenin mRNA gave a high-diagnostic performance: sensitivity of 100.0%, NPV of 100.0%, and accuracy of 96.0%, respectively.Conclusion. As molecular markers of detecting pleural micrometastasis, DVL-3 mRNA andδ-catenin mRNA are helpful to diagnose the cancer cells in pleural effusions of patients with lung cancer.

Background and objective: The aim of this study was to evaluate the diagnostic utility of lung-specific X protein (LUNX) mRNA expression in bronchial brushing specimens from patients with lung cancer. Methods: LUNX mRNA levels were assessed by performing RT-PCR on liquid-based cytology bronchial brushing specimens from patients with lung cancer (n = 104) or benign lung disease (n = 91). Results: LUNX mRNA expression was significantly more frequent in patients with all carcinomas, squamous cell carcinomas, adenocarcinomas, as well as patients with central, peripheral and diffuse carcinomas (P

Reliability of equipment has long been considered as an important quality characteristic. But the reliability assessment of multi-parameter system still remains a problem. Based on the multi-parameter degradation process of a certain diesel engine, the article proposes a reliability assessing method for multi-parameter degradation system. The method uses SVDD to convert multi-parameter into one single degradation measure which reveals the overall system degradation. Using degradation measure distribution, a reliability assessment model is built. Through experiments on vehicle, the method shows the degradation regular of vehicle diesel engine, builds the reliability curve, provides evidences for equipment maintenance.

This paper presents a reliability assessment method for the system with multiple degradation parameters based on SVDD and SVR. The method transforms different performance parameters of the system to a distance measure by SVDD, uses SVR to analyze and predict the distribution parameters of SVDD distance, then create the overall system performance degradation assessment model. Through vehicle tracking experiment, collecting different degradation parameters of the diesel engine, a reliability curve stands for the whole system degradation is achieved. Compared to traditional reliability assessment method, the new method combines the various parameters so that more effectively describes the diesel engine performance degradation, and is more instructive for the maintenance of the vehicle.

M. Lv, Y.-B. Fan, Y.-J. Zhao, T.-Y. Wang and G.-P. Wu Expression and clinical significance of glucose transporter 1 mRNA in bronchial brushing liquid-based cytology specimens from patients with and without lung cancer Objective: The aim of this study was to evaluate the diagnostic utility of glucose transporter 1 (GLUT1) mRNA expression in bronchial brushing specimens from patients with lung cancer. Methods: GLUT1 mRNA levels were detected by reverse transcription–polymerase chain reaction (RT-PCR) in SurePathTM liquid-based cytology bronchial brushing specimens from patients with lung cancer (n = 76) and benign lung disease (n = 154). Results: Compared with patients with benign disease and compared with cytology, GLUT1 mRNA was found significantly more frequently in patients with all carcinomas, squamous cell carcinomas, adenocarcinomas and small cell carcinomas, as well as central, peripheral and diffuse carcinomas (P

Reliability of equipment has long been considered as an important quality characteristic. Traditional methods of equipment reliability assessment are based on lifetime data. With equipment being much more reliable and the growing need for developing new equipments within shorter period and at lower cost, we can hardly get enough lifetime data in many cases. Performance degradation data can also be used for reliability assessment. This paper is mainly researched on reliability of a certain diesel engine. Through analyzing the failure mode and failure mechanism, performance degradation parameters of the diesel engine is selected as compression pressure in a cylinder while driven by an electrical motor. Based on a long time accumulation on performance degradation data, two methods of degradation path fitting and degradation value distribution are tried in this paper to evaluate reliability of the diesel engine. Besides, the regulation of the reliability variation is given by the results of the assessment.

In the process of computed order tracking, traditional method is based on the given analyzed order requirements, and also assumed that the highest order component is known. But in practice, the order component in signal is usually unknown. With regards to this issue, the paper proposed a method using filter to limit frequency and order. A principle on how to choose filter cut-off frequency and angular domain resampling order are deduced in this paper, then the relationship is analyzed between filter cut-off frequency and resampling frequency in time domain. Simulated signals are tried on the method, the results show that it can solve order aliasing problem successfully, and also effectively reduce resampling order.

The aim of this study was to analyze the amplification of the human telomerase gene (TERC) in cervical specimens by fluorescence in situ hybridization (FISH), and FISH findings were compared with cytologic and histologic diagnoses. Slides prepared from 123 liquid-based preparations from cervical specimens with cytologic diagnoses of negative for squamous intraepithelial lesion or malignancy (n=20), atypical squamous cells of undetermined significance (n=22), low-grade squamous intraepithelial lesion (n = 55), high-grade squamous intraepithelial lesion (n = 21), or invasive cervical carcinomas (n = 5) were analyzed for the amplification of TERC using a 2-color FISH probe. The results of the cytologic analysis and those of concurrent or subsequent biopsies were compared with the FISH findings. Results showed that amplification of TERC was significantly associated with both cytologic and histologic diagnoses (P

The SurePath liquid-based Pap test (LPT) is successfully and widely used to assess sputum cytology. This study aimed to compare the cytological findings and diagnostic sensitivity of LPT with those of the conventional Pap smear (CPS) method for diagnosing lung cancer. Bronchial brushing specimens from 204 patients diagnosed with lung cancer were studied. LPT slides showed decreased areas of cell monolayers, a clearer background and distinct, stereoscopic cytological features. The LPT had a significantly higher diagnostic sensitivity for lung cancer (71.6%) than the CPS method (57.8%, p 2 cm lesions (p 2 cm lesions (81.4%) compared with the CPS method alone (p

The aim of this study was to investigate the frequency of amplification of the human telomerase gene (TERC), as measured by fluorescence in situ hybridization (FISH), in routine liquid-based cytological preparations from bronchial brushing specimens, and to assess the associations between TERC amplification, cytological diagnosis, and cytological morphology, in order to obtain further insight into these associations. Bronchial brushings from 102 patients with lung carcinoma (52 squamous-cell carcinomas, 22 adenocarcinomas, 28 small cell lung carcinomas) and 40 patients with nonmalignant disease were used. Amplification of TERC was performed using a commercially available two-color FISH probe, and slides were prepared for the SurePath liquid-based Pap test (LPT) using the same samples. Amplification of TERC was significantly associated with histological diagnoses (P0.05). Patients with lung cancer, and especially those with nonsmall cell lung cancer, had significantly higher percentages of cells with amplification of TERC than did patients with nonmalignant disease (P0.05). Comparing the FISH and LPT results, there was no significant difference in diagnostic sensitivity between the two methods (P0.05). However the difference in diagnostic sensitivity of the two methods for squamous-cell carcinoma was significant (P0.01). FISH can be performed on bronchial brushing specimens to detect amplification of TERC. This test may be an adjunct to cytology screening, especially in squamous-cell carcinoma, and may provide an indication of the potential of individual lesions to progress.

Objective To evaluate the individual and combined diagnostic utility of MOC-31, HBME-1 and MOC-31mRNA in the differentiation of adenocarcinoma cells from reactive mesothelial cells in pleural effusions. Study Design To subject the cells from 293 pleural effusions to immunocytochemical staining for MOC-31 and HBME-1 and reverse transcriptase polymerase chain reaction for the expression of MOC-31. Results MOC-31 and MOC-31mRNA expression were significantly higher in the cancer cell group and in 3 subgrouped as adenocarcinoma, squamous cell carcinoma and small cell lung carcinoma than in the mesothelial cell group, whereas HBME-1 expression was obviously lower in those (p < 0.01). In single use, MOC-31mRNA had the highest sensitivity (90.8%) and accuracy (91.5%), whereas MOC-31 had the highest specificity (100%). When combinations of markers were evaluated together, MOC-31mRNA and HBME-1 gave a high diagnostic performance: sensitivity of 96.7% and accuracy of 95.2%, respectively. Conclusion The detection of MOC-31, HBME-1 and MOC-31-mRNA is helpful in distinguishing between cancer and reactive mesothelial cells in pleural effusions. MOC-31mRNA could be useful to the diagnosis of pleural micrometastasis.

Objective: The aim of this study was to evaluate the individual and combined diagnostic utility of carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CK19) and HBME-1 in pleural effusions of patients with lung cancer. Study design: CEA, CK19 and HBME-1 were detected by immunocytochemistry in pleural effusions from patients with lung cancer (86 cases) and without lung cancer (40 cases). Results: CEA and CK19 expression were significantly higher in the carcinoma cell group and in three subgrouped as adenocarcinoma (AC), squamous cell carcinoma (SCC) and small cell lung cancer than in the mesothelial cell group, whereas HBME-1 expression was lower in the former group (P

Sepsis is a global major health problem in great need for more effective therapy. For thousands of years, Rhubarb had been used for various diseases including severe infection. Pharmacological studies and trials reported that Rhubarb may be effective in treating sepsis, but the efficacy and the quality of evidence remain unclear since there is no systematic review on Rhubarb for sepsis. The present study is the first systematic review of Rhubarb used for the treatment of experimental sepsis in both English and Chinese literatures by identifying 27 studies from 7 databases. It showed that Rhubarb might be effective in reducing injuries in gastrointestinal tract, lung, and liver induced by sepsis, and its potential mechanisms might include reducing oxidative stress and inflammation, ameliorating microcirculatory disturbance, and maintaining immune balance. Yet the positive findings should be interpreted with caution due to poor methodological quality. In a word, Rhubarb might be a promising candidate that is worth further clinical and experimental trials for sepsis therapy.

High-risk human papillomavirus (HPV) infection may play an important role in non-small cell lung carcinoma (NSCLC) development. However, some recent studies have proved that it was not directly associated with lung cancer. The aim of this study was to evaluate the underlying molecular mechanism that HPV16 regulate the expression of GLUT1 and may promote the development of lung cancer. HPV16, HIF-1α, and GLUT1 were detected in pleural effusions of patients with lung cancer (n = 95) and with benign lung disease (n = 55) by immunocytochemistry. Western blotting and qRT-PCR were used to detect the expression chances of HPV16 E6/E7, HIF-1α, and GLUT1 in lung cancer cells. HPV16, HIF-1α, and GLUT1 were significantly more likely to be expressed in the malignant group than in the benign group as detected by immunocytochemistry (ICC), and HIF-1α was significantly correlated with HPV16 or GLUT1 in the malignant group (P