Objective:To investigate high mobility group protein 1(HMGB1), tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels and their clinical significance in elderly patients with viral pneumonia.Methods:One hundred and sixty elderly patients with viral pneumonia admitted to the Sixth Hospital Affiliated to Anhui Medical University were enrolled as research subjects.In addition, 40 elderly people who underwent regular physical examination were considered as the control group.Patients with viral pneumonia were divided into the low-risk group, middle-risk group and high-risk group according to CURB-65 scores and pneumonia severity index(PSI)scores.HMGB1, TNF-α and IL-6 levels were compared between different groups.The correlations of CURB-65 scores and PSI scores with HMGB1, TNF-α, IL-6 levels were analyzed.Multivariate Logistic regression analysis was used to examine influencing factors for the severity of viral pneumonia in elderly patients.Results:HMGB1, TNF-α and IL-6 levels were higher in research subjects than in the control group.As the severity of viral pneumonia increased, so did HMGB1, TNF-α and IL-6 levels(all P<0.05). HMGB1, TNF-α and IL-6 levels in the severe viral pneumonia group were significantly higher than those in the non-severe viral pneumonia group( P<0.05). HMGB1, TNF-α and IL-6 levels were positively correlated with CURB-65 scores and PSI scores(CURB-65 score: r=0.463, 0.392 and 0.497, P=0.015, 0.003 and 0.025; PSI score: r=0.596, 0.515 and 0.381, P=0.007, 0.011 and 0.009). HMGB1, TNF-α and IL-6 levels were influencing factors for the severity of viral pneumonia in elderly patients( OR=1.344, 1.422 and 1.351, P=0.006, 0.015 and 0.009). Conclusions:HMGB1, TNF-α and IL-6 levels are closely correlated with the severity of viral pneumonia and are helpful for early assessment of viral pneumonia.

OBJECTIVE： To explore the ways to improve the efficiency and quality of ethical review in multi-center clinical trial. METHODS： After issuing the policy of Opinions on Deepening the Reform of Approval System and Encouraging the Innovation of Pharmaceutical Medical Devices and Measures for the Administration of Drug Registration （Revised Version）， combined with the practice of our center， the methods to improve the efficiency and quality of ethical review， the possible problems of complete filling system and the way to improve the efficiency and quality of ethical review in multi-center clinical trial were analyzed in our center. RESULTS & CONCLUSIONS： Our center adopted a variety of review methods （conference review， rapid review， filing system， etc.）， implemented hierarchical management and differential review process for research projects， and formulated defined rules of filling system operation and other ways to improve the efficiency and quality of review， doubled the review efficiency， increased the number of follow-up review and field visit. In the process of exploration， the ethics committee of our center believes that the complete implementation of the filing system will lead to problems such as the difficulty to evaluate the quality of the ethical review of the leader unit， different research qualifications and conditions of each center， etc. In order to improve the efficiency and quality of the ethical review of multi-center clinical research， the measures are can be adopted， such as improving the quality of the ethical review of the center， strengthening the communication and mutual recognition of the ethics committees of each center， and establishing the preliminary review system of the secretary of the ethics committee， so as to realize the balance of efficiency and quality.

BACKGROUNDΔNp73 is an isoform of the p53 homologue p73, which lacks an NH₂-terminal transactivation domain and antagonizes the induction of gene expression by p53 and p73. The aim of this study is to investigate the expression of ΔNp73 mRNA in non-small cell lung cancer (NSCLC) and to analyse its relations with clinicopathologic factors and prognosis.

METHODSSemiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of ΔNp73 mRNA in 40 resected NSCLC specimens with the neighboring noncancerous tissue. The significance of ΔNp73 mRNA expression was analyzed statistically.

RESULTSΔNp73 mRNA was highly expressed in lung cancer tissues (62.7%, 32/51) while negative in neighboring noncancerous tissue. The expression of ΔNp73 mRNA was associated with pathological TNM stage (P=0.046), but not associated with age, gender, histological type and differentiation status. Survival of patients with high ΔNp73 mRNA was significantly poorer than those with low ΔNp73 mRNA levels (P < 0.001). Multivariate analysis revealed that ΔNp73 mRNA levels were a significant prognostic factor, independent of the other conventional prognostic factors.

CONCLUSIONSNSCLC has overexpression of ΔNp73 mRNA, which is closely related to TNM stages and prognosis of patients with NSCLC. These results suggest that measurement of ΔNp73 mRNA levels in tumor tissues might be useful as a promising predictor for the prognosis of patients with NSCLC.

BACKGROUNDLocally advanced lung cancer includes IIIA and IIIB lung cancer that tumors are localized within the chest and with no clinic and pathologic distal metastasis. In this study the results of extended resection of a portion of heart or great vessels with cardiopulmonary bypass was summarized in the treatment of locally advanced lung cancer.

METHODSLobectomy or pneumonectomy combined with extended partial excision of the heart or great vessels were carried out in 10 patients with locally advanced lung cancer. The operations included aortic resection and reconstruction with left heart bypass in 2 cases, extended resection of left atrium with normal cardiopulmonary bypass in 5 cases, and resection and reconstruction of superior vena cava in 3 cases respectively.

RESULTSThe patients had no operative complication except for one haemothorax, which was controlled by re-exploration. One patient died of brain metastasis 6 months after operation and another one died of multiple metastasis 26 months after operation. The others were alive.

CONCLUSIONSCPB is a safe and effective anesthetic procedure during extended resection of locally advanced lung cancer although it is controversial for aggravating operative trauma, complex technique and higher cost.

BACKGROUND: The role of p53 gene in human lung cancer has been confirmed. Since the discovery of p63 gene as the homologue of p53, its role and possible mechanism-have aroused the attention of investigators all over the world. But the principle concerning transcription and expression of p63 in small-cell lung carcinoma (SCLC) remains unclear.OBJECTIVE: To investigate the level of the expression of p63 gene in SCLC and lung adenocarcinoma tumor tissues, peri-carcinoma tissues and normal tissues, and observe the expression of p63 protein in these tissues so as to understand the principle and clinical significance concerning p63gene expression in SCLC and lung adenocarcinoma.DESIGN: Controlled experiment.SETTING: Department of Thoracic and Cardiovascular Surgery, Research Institute of Field Surgery of Daping Hospital of Third Military Medical University of Chinese PLA.PARTICIPANTS: Six SCLC specimens dissected during the surgical operation in Daping Hospital, Third Military Medical Univers ity of Chinese PLA, between October 2000 and September 2002 , were recruited. There were 4 male and 2 female patients aged 42 to 67 years (mean age of 50.7years); 15 specimens of lung adenocarcinoma were also collected at the same time. Tumor tissues, peri-carcinoma tissues and normal tissues were chosen in each specimen.METHODS: Reverse transcriptase polymerase chain reaction (RT-PCR)was used to detect and compare the transcription expression of two subtypes of p63 gene (TAP63 and △NP63)in the tumor tissues of 6 cases of SCLC and 15 cases of lung adenocarcinoma. At the same time, immunohistochemical staining technique was used to detect the expression of p63protein in the above tissues.MAIN OUTCOME MEASURES: ① Expression of p63 protein detected by RT-PCR in tissue specimens. ② Expression of p63 protein detected in tissue specimens detected by immunohistochemical staining technique.RESULTS: ① Expression of p63 protein detected by RT-PCR in tissue specimens: The positive expression of △Np63 gene could be found in 5cases (83%, 5/6) of SCLC cancer tissues and 1 case of SCLC peri-carcinoma tissues (17%, 1/6), and the expression of TAp63 was not observed in all of the tumor, peri-carcinoma and normal tissues of SCLC. There was no expression of △Np63 or TAp63 in tumor, peri-carcinoma and normal tissues of lung adenocarcinoma. ② Expression of p63 protein detected by immunohistochemical staining in tissue specimens: The positive expression rate of p63 protein in SCLC tumor tissues was significantly higher than that in lung adenocarcinoma tissues [83% (5/6), 17% (1/6), P ＜ 0.01].CONCLUSION: p63 gene shows positive expression in SCLC, among which the expression level of △NP63 is increased while the expression level of p63 protein is obviously higher in SCLC than in adenocarcinoma tissues, which may be related to its regulatory role in the occurrence and development of SCLC. It is presumed that△NP63 gene has high transcription expression level in SCLC, which might inhibit cellular apoptosis, promote the proliferation of tumors, play the role as an oncogene. It suggests that p63 may be one of the factors influencing the prognosis of SCLC.

BACKGROUNDTo study the effect of overexpression of p73 gene on cell growth curve and vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) mRNA expression in lung adenocarcinoma cell, and to explore its effect on angiogenesis in lung adenocarcinoma.

METHODSp73α and p73β were transferred into A549 cell and H1299 cell by liposome, the positive cell clones were chosen by G418. The cell growth curves were drawn by cell counting. The expressions of VEGF and bFGF mRNA were detected by RT-PCR.

RESULTSOverexpression of p73 gene could inhibit the growth of A549 cell and H1299 cell. VEGF and bFGF mRNA expressions in A549 cell and H1299 cell were decreased after transfer of p73 gene (P < 0.05), VEGF mRNA was decreased more obviously after transfer of p73β (P < 0.01).

CONCLUSIONSOverexpression of p73 gene can inhibit the growth of lung adenocarcinoma cell, decrease VEGF and bFGF mRNA expression. The results suggest that overexpression of p73 gene might be involved in the regulation of VEGF and bFGF gene expression in lung adenocarcinoma and act as an antioncogene.

BACKGROUNDTo explore the sequential variation of pulmonary flow spectrum and its value on evaluation of risk for pulmonary resection in perioperative patients with lung cancer.

METHODSForty-nine patients with lung cancer who underwent pneumonectomy (12 cases) and lobectomy (37 cases) were observed for the values of Doppler pulmonary flow spectrum before operation, on the 3-5 days and 8-10 days postoperatively. Moreover the patients were divided into different groups according to the different operative procedures and with or without postoperative cardiac arrhythmia.

RESULTSDoppler pulmonary flow spectrum changed in all cases who underwent pneumonectomy and lobectomy from 3 to 5 days postoperatively. These changs included prolonged preejection period (PEP), shortened acceleration time (ACT), increased PEP/ACT ratio, increased pulmonary artery mean pressure (PAMP), and increased pulmonary vascular resistance (PVR). There were significant differences comparing with those before operation ( P < 0.01). The patients who underwent lobectomy recovered to the same level of pre operation on the 8th to 10th postoperative days. However, the changes of pulmonary flow spectrum continuously existed in the patients who underwent pneumonectomy on the 8th to 10th postoperative days. There were significant differences of pulmonary flow spectrum between patients with postoperative arrhythmia and without postoperative arrhythmia before operation.

CONCLUSIONSPulmonary hemodynamic obviously changes after pulmonary resection in the patients with lung cancer and the changes last longer in pneumonectomy patients. Patients with postoperative cardiac arrhythmia have marked pulmonary hemodynamic changes before operation. Doppler pulmonary flow spectrum can not only be used to analyse the pulmonary hemodynamic changes for those cases undergoing pulmonary resection after operation, but also to evaluate the risk of pulmonary resection before operation.

BACKGROUNDTo assess the effects of exogenous p73 gene on chemosensitivity of wild-type p53 human lung adenocarcinoma cell A549 to cisplatin (DDP) and adriamycin (ADM).

METHODSRecombinant eukaryotic expression vector pcDNA3 containing full-length human wild-type p73α cDNA or p53 cDNA was transfected into A549 cells which had wtp53 by lipofectamine-mediated gene transfection. The chemosensitivity of tumor cells to DDP and ADM was observed before and after transfection.

RESULTSA549-p73α could stably express P73α protein. The P73α protein expression was significantly increased in A549-p73α than that in A549 and A549-pcDNA3. The growth and colony formation of A549-p73α were significantly inhibited compared with A549, A549-pcDNA3 and A549-wtp53. Flow cytometry and DNA fragmentation analysis showed apoptosis of A549-p73α cells was significantly increased. The IC₅₀ values for DDP and ADM were reduced to approximate 1/6 and 1/70 in A549-p73α cells compared with A549 cells respectively..

CONCLUSIONSExogenous p73 gene is capable of enhancing the sensitivity of wild-type p53 human lung adenocarcinoma cell A549 to chemotherapeutic drugs. It is probably for p73 to be used in the treatment of p53-resistant tumors.

BACKGROUNDTo investigate the expression of p63 gene and its significance in non-small cell lung cancer (NSCLC) and pulmonary benign disease tissues.

METHODSp63 gene mRNA expression (TAp63 and ΔNp63) was detected in 40 NSCLC and 10 pulmonary benign disease tissues by RT-PCR (reverse transcriptase-PCR) technique, and immunohistochemical method was used to observe p63 protein expression in the above tissues.

RESULTSΔNp63 mRNA overexpression was observed in 18 squamous cell carcinoma (18/23), 1 bronchioloalveolar carcinoma (1/6) and 2 paracancerous tissues of squamous cell carcinoma (2/23). There was no expression of TAp63 both in NSCLC and benign disease tissues of the lung. Immunochemistry showed that the positive rate and intensity of p63 protein expression were significantly higher in squamous cell carcinoma than those in adenocarcinoma and benign disease tissues of the lung ( P < 0.01).

CONCLUSIONSp63 gene is mainly amplified in squamous cell carcinoma of the lung. It may act as an oncogene in the carcinogenesis and development of squamous cell carcinoma.

Objective　To study the expression of p73 in human non-small cell lung cancer (NSCLC) and the relationship between p73 expression and clinico-pathological parameters. Methods　Expression of p7 3 gene was detected by RT-PCR in 32 human NSCLC tissues, tissues adjacent to ca ncer and non-cancer lung tissues. Results　p73 gene expression up-regulated substantially and detected in 87.5%(28/32) of human NSCLC tissues while expressed at low level in tissues adjacent to cancer and non-cancer lung tissues. Conclusion　Marked up-regulation of p73 gene expres sion is found in human NSCLC.