Polyphyllin B inhibited STAT3/NCOA4 pathway and restored gut microbiota to ameliorate lung tissue injury in cigarette smoke-induced mice.

OBJECTIVE: Smoking was a major risk factor for chronic obstructive pulmonary disease (COPD). This study plan to explore the mechanism of Polyphyllin B in lung injury induced by cigarette smoke (CSE) in COPD. METHODS: Network pharmacology and molecular docking were applied to analyze the potential binding targets for Polyphyllin B and COPD. Commercial unfiltered CSE and LPS were used to construct BEAS-2B cell injury in vitro and COPD mouse models in vivo, respectively, which were treated with Polyphyllin B or fecal microbiota transplantation (FMT). CCK8, LDH and calcein-AM were used to detect the cell proliferation, LDH level and labile iron pool. Lung histopathology, Fe3+ deposition and mitochondrial morphology were observed by hematoxylin-eosin, Prussian blue staining and transmission electron microscope, respectively. ELISA was used to measure inflammation and oxidative stress levels in cells and lung tissues. Immunohistochemistry and immunofluorescence were applied to analyze the 4-HNE, LC3 and Ferritin expression. RT-qPCR was used to detect the expression of FcRn, pIgR, STAT3 and NCOA4. Western blot was used to detect the expression of Ferritin, p-STAT3/STAT3, NCOA4, GPX4, TLR2, TLR4 and P65 proteins. 16S rRNA gene sequencing was applied to detect the gut microbiota. RESULTS: Polyphyllin B had a good binding affinity with STAT3 protein, which as a target gene in COPD. Polyphyllin B inhibited CS-induced oxidative stress, inflammation, mitochondrial damage, and ferritinophagy in COPD mice. 16S rRNA sequencing and FMT confirmed that Akkermansia and Escherichia_Shigella might be the potential microbiota for Polyphyllin B and FMT to improve CSE and LPS-induced COPD, which were exhausted by the antibiotics in C + L and C + L + P mice. CSE and LPS induced the decrease of cell viability and the ferritin and LC3 expression, and the increase of NCOA4 and p-STAT3 expression in BEAS-2B cells, which were inhibited by Polyphyllin B. Polyphyllin B promoted ferritin and LC3II/I expression, and inhibited p-STAT3 and NCOA4 expression in CSE + LPS-induced BEAS-2B cells. CONCLUSION: Polyphyllin B improved gut microbiota disorder and inhibited STAT3/NCOA4 pathway to ameliorate lung tissue injury in CSE and LPS-induced mice.

Repeat-dose toxicity study of human umbilical cord mesenchymal stem cells in cynomolgus monkeys by intravenous and subcutaneous injection.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are proposed for the treatment of acute lung injury and atopic dermatitis. To advance hUC-MSC entry into clinical trials, the effects of hUC-MSCs on the general toxicity, immune perturbation and toxicokinetic study of hUC-MSCs in cynomolgus monkeys were assessed. hUC-MSCs were administered to cynomolgus monkeys by intravenous infusion of 3.0 × 106 or 3.0 × 107cells/kg or by subcutaneous injection of 3.0 × 107cells/kg twice a week for 3 weeks followed by withdrawal and observation for 6 weeks. Toxicity was assessed by clinical observation, clinical pathology, ophthalmology, immunotoxicology and histopathology. Moreover, toxicokinetic study was performed using a validated qPCR method after the first and last dose. After 3rd or 4th dosing, one or three the monkeys in the intravenous high-dose group exhibited transient coma, which was eliminated by slow-speed infusion after 5th or 6th dosing. In all dose groups, hUC-MSCs significantly increased NEUT levels and decreased LYMPH and CD3+ levels, which are related to the immunosuppressive effect of hUC-MSCs. Subcutaneous nodules and granulomatous foci were found at the site of administration in all monkeys in the subcutaneous injection group. Other than above abnormalities, no obvious systemic toxicity was observed in any group. The hUC-MSCs was detectable in blood only within 1 h after intravenous and subcutaneous administration. The present study declared the preliminary safety of hUC-MSCs, but close monitoring of hUC-MSCs for adverse effects, such as coma induced by intravenous infusion, is warranted in future clinical trials.

Physiological analysis of severe chlamydia psittaci pneumonia and clinical diagnosis after doxycycline-based treatment.

Objective: To describe the clinical spectrum of severe Chlamydia psittaci pneumonia in order to understand the disease better. Methods: Retrospective analysis was made on 31 patients with severe Chlamydia psittaci pneumonia diagnosed in ICU by next-generation sequencing of metagenome Metagenomic next-generation sequencing(mNGS) from January 2019-November 2022, including clinical characteristics, laboratory examination results, imaging characteristics, treatment, and prognosis. Results: We included 31 patients with severe Chlamydia psittaci pneumonia, 15 of whom had a history of virus exposure. There were 12 cases with multiple bacterial infections, and the common symptoms included fever (31/31,100%), dyspnea (31/31, 100%), cough (22/31, 71.0%), and myalgia (20/31, 64.5%). Laboratory data showed that white blood cells were average or slightly increased, but the levels of C-reactive protein and neutrophils were high. CT findings of the lung were consolidation (19/31, 61.3%) and pleural effusion (11/31, 35.5%). Only one lobe was involved in 11 patients (35.5%). Before diagnosis, 22 patients (71.0%) did not have atypical pathogens in their antimicrobial regimen. After diagnosis, 19 patients (61.3%) received single drug treatment, of which doxycycline or moxifloxacin were the most commonly used drugs. Among 31 patients, three died, nine improved, and nineteen were cured. Conclusion: The clinical manifestations of severe Chlamydia psittaci pneumonia are non-specific. The application of mNGS can improve the diagnostic accuracy of Chlamydia psittaci pneumonia, reduce the unnecessary use of antibiotics, and shorten the course of the disease. Doxycycline-based treatment is effective for severe chlamydia psittaci pneumonia, but it is necessary to understand the secondary bacterial infection and other complications in the course of the disease.

Preclinical Toxicity and Immunogenicity of a COVID-19 Vaccine (ZF2001) in Cynomolgus Monkeys.

Although the new coronavirus disease 2019 (COVID-19) outbreak occurred in late 2019, it is still endemic worldwide, and has become a global public health problem. Vaccination against SARS-CoV-2 is considered to be the most effective intervention to prevent the spread of COVID-19. ZF2001 is a recombinant protein vaccine based on SARS-CoV-2 receptor-binding domain (RBD) subunit which contains aluminum adjuvant. In order to advance our research on ZF2001 into clinical trial, we investigated the general toxicity and immunogenicity of ZF2001 in cynomolgus monkeys and assessed the possible target organs for vaccine-induced toxicity. In the present research, we observed no significant systemic toxicities and abnormal cardiovascular and respiratory events following four times injections of intramuscular ZF2001 in cynomolgus monkeys. Histological examination revealed recoverable inflammatory changes in quadricep muscle and adjacent lymph node at the vaccine injection site. As expected, the vaccine can produce a strongly specific binding antibody and neutralizing antibodies in cynomolgus monkeys after inoculation. Taken together, our regulatory toxicology research proves the safety and immunogenicity of the ZF2001 vaccine, supporting its entry into large scale clinical trials.

MiroRNA-31-3p Promotes the Invasion and Metastasis of Non-Small-Cell Lung Cancer Cells by Targeting Forkhead Box 1 (FOXO1).

OBJECTIVE: To explore the possibility of microRNA miR-31-3p as a biomarker for bone metastasis of non-small-cell lung cancer (NSCLC) and its molecular mechanism to the invasion and metastasis of NSCLC cells. METHODS: Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of miR-31-3p and forkhead box 1 (FOXO1) in NSCLC tissues, serum, and cells to analyze the correlation between the expression levels of miR-31-3p and the clinicopathology of NSCLC. After interference with or overexpressing miR-31-3p, NSCLC cell proliferation, apoptosis, invasion ability, and migration ability were detected by MTT, flow cytometry, Transwell, and scratch experiment, respectively. The interaction between miR-31-3p and FOXO1 was further verified by the dual-luciferase reporter experiment. Western blot was performed to detect the protein expression of FOXO1 in tissues and FOXO1, RhoA, p-RhoA, ROCK-2, and p-ROCK-2 in cells. RESULTS: In tissues, serum, and NSCLC cell line A549 of the NSCLC patients, the expression of FOXO1 was notably lower, and the miR-31-3p expression was significantly higher. Overexpression of miR-31-3p could distinctly improve the proliferation, invasion, and migration of A549 cells, meanwhile inhibit cell apoptosis, and activate the RhoA/ROCK-2 signaling pathway, while interfering with the expression of miR-31-3p has the opposite function. Besides, bioinformatics analysis and luciferase reporter assay confirmed that FOXO1 was a target gene of miR-31-3p. Overexpressing FOXO1 could inhibit the proliferation and metastasis of A549 cells, but overexpressing miR-31-3p reverses the results. CONCLUSION: This study confirmed that miR-31-3p promotes the proliferation, invasion, and migration of NSCLC cells and inhibits apoptosis through targeted regulating FOXO1 and be a potential therapeutic targets for the treatment of NSCLC.

Subjective strain of care experienced by pulmonary and critical care medical nurses when caring for patients with delirium: a cross-sectional study.

BACKGROUND: Delirium, a disorder of consciousness, often occurs for a period of time during hospitalisation. It is characterised by a disturbance of attention or awareness. Hyperactive delirium may lead to accidental removal of medical equipment, while hypoactive delirium may inhibit patients from participating in nursing interventions, medical treatment, and physical therapy. However, there are limited relevant studies of the strain of care of nurses in China when caring for patients with delirium. This study, thus, aimed to investigate the subjective level of the strain of care experienced by pulmonary and critical care nurses when caring for patients with delirium. METHODS: This was a descriptive, cross-sectional study. A survey was conducted with 100 nurses in the Chinese pulmonary and critical care medical (PCCM) department in 2018. The Strain of Care for Delirium Index (SCDI) was used to measure nurses' strain of care. Participants were instructed to rate the degree of perceived difficulty in managing patients who displayed the behaviours listed in the SCDI, on a scale from 1 (quite easy) to 4 (very difficult). The mean ± standard deviation (SD) scores of the ranked difficulty scores were calculated. RESULTS: In our sample, 47 % of the nurses had received delirium-related training previously. The three wards with the highest strain of care scores when caring for patients with delirium were the chronic obstructive pulmonary disease ward (3.29 ± 0.72), interstitial lung disease ward (3.11 ± 1.31), and respiratory intensive care unit (3.02 ± 0.78). The three types of patient behaviours associated with the highest degree of nursing strain of care were being uncooperative and difficult to manage (3.37 ± 0.84), pulling out tubes and tearing out dressings (3.33 ± 0.98), and irritability (3.22 ± 0.95). CONCLUSIONS: This study is the first to focus on nurses' subjective strain of care when caring for patients with delirium in PCCM departments in China. The findings suggest the need to pay more attention to the working status of Chinese nurses. Further trials with large samples assessing relevant outcomes of patients with delirium are warranted.

Protective effects of resveratrol and SR1001 on hypoxia-induced pulmonary hypertension in rats.

Hypoxic pulmonary hypertension (HPH) is a fatal disease with limited therapeutic strategies. Combination therapy is regarded as the standard of care in PH and becoming widely used in clinical practice. However, many PH patients treated with combinations of available clinical drugs still have a poor prognosis. Therefore, identifying innovative therapeutic strategies is essential for PH. This study is designed to examine the effects of combined prevention with resveratrol and SR1001 on HPH in rats. The effects of combined prevention with resveratrol and SR1001 and each mono-prevention on the development of HPH, Th17 cells differentiation, expression of guanine nucleotide exchange factor-H1 (GEF-H1), Ras homolog gene family member A (RhoA) and Phosphorylated myosin phosphatase target subunit (MYPT1) were examined. HPH and RV hypertrophy occurred in rats exposed to hypoxia. Compared with normoxia group, the hypoxia group showed significantly increased ratio of Th17 cells. After treatment with resveratrol, HPH rats showed an obvious reduction of Th17 cells. SR1001 significantly reduced the increased p-MYPY1, RhoA, and GEF-H1 expression in the hypoxic rats. The mono-prevention with resveratrol or SR1001 significantly inhibited the Th17 cells differentiation, p-STAT3, p-MYPY1, RhoA, and GEF-H1 protein expression, which was further inhibited by their combination prevention. The combination of resveratrol and SR1001 has a synergistic interaction, suggesting that combined use of these pharmacological targets may be an alternative to exert further beneficial effects on HPH.

Long non-coding RNA MALAT1 sponges miR-149 to promote inflammatory responses of LPS-induced acute lung injury by targeting MyD88.

Acute lung injury (ALI) caused by sepsis occurs early and the condition is severe, and is also an important reason for accelerating the death of patients. Increasing evidence has identified long non-coding RNA (lncRNA) metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) as a regulator of ALI. However, the potential mechanism underlying MALAT1 on ALI still needs further identification. To explore the mechanisms of gene regulation expression mediated by MALAT1 through miR-149/MyD88 in lung injury inflammation, we constructed a lung injury inflammatory model using the lipopolysaccharides (LPS)-induced method and quantificated the cytokines and signaling cascade molecules as well as miR-149. The MALAT1, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 levels were significantly increased, and the nuclear factor-κB (NF-κB) pathway was activated, but the miR-149 level was decreased in the LPS-induced ALI model. miR-149 directly targeted both lncRNA MALAT1 and the MyD88 gene. Knockdown of MALAT1 down-regulated the levels of MyD88, TNF-α, IL-1ß, and IL-6, and inhibited the NF-κB pathway. However, MALAT1 knockdown up-regulated the expression of miR-149. Overexpression of miR-149 down-regulated MyD88, TNF-α, IL-1ß, and IL-6 levels, and inhibited the NF-κB pathway. MALAT1 acts as a pro-inflammatory factor in ALI via the miR-149/MyD88/NF-κB axis and is therefore a potential novel therapeutic target for ALI treatment.

[Nontuberculous mycobacteria pulmonary disease: A retrospective analysis].

OBJECTIVE: To analyze the clinical characteristics and drug resistance in patients with non-tuberculous mycobacteria (NTM) pulmonary disease in Changsha Central Hospital of Hunan Province in recent three years.
 Methods: The clinical data of 153 patients with NTM pulmonary disease, who were diagnosed in Changsha Central Hospital of Hunan Province from February 2014 to May 2017, were retrospectively analyzed. According to the concentration of drug sensitivity test, the patients were divided into a low concentration group and a high concentration group. The status of drug sensitivity and drug resistance were examined.
 Results: Among 153 patients, 79 patients (51.63%) were male, 74 patients (48.37%) were female. The mean ages were (60.27±19.46) years. The NTM pulmonary disease mainly occurred in the individuals with bronchiectasis, and the course of disease was long (mean 7.8 years). The clinical symptoms were not specific and mostly misdiagnosed as pulmonary tuberculosis (92.81%). Mycobacterium avium-intracellulare (56.21%) and mycobacterium chelonae-abscess (20.92%) were the majority. The drug-resistance rate of the first-line and second-line anti-tuberculosis drugs was high. The majority was resistant to more than eight drugs, 38.56% patients in the low concentration group were resistant to total drugs, and 25.49% patients in the high concentration group were resistant to total drugs.
 Conclusion: The NTM pulmonary disease is easily misdiagnosed, and the drug resistance rate is high. Identification of mycobacterium species and detection of drug sensitivity play an important role in clinical diagnosis and treatment.

Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Lung Cancer Cells and Inhibits Regulating Epithelial-to-Mesenchymal Transition.

In order to improve therapeutic efficacy, it is a current emergency to better know the mechanisms underlying cisplatin resistance in lung cancer cells. In this study, we aim to investigate the role of Krüppel-like factor 4 (KLF4) in cisplatin-resistant lung cancer cells. We developed cisplatin-resistant lung cancer cell line A549/DDP, and then a battery of experiments was used to analyze the effects of KLF4 in cisplatin resistance of lung cancer. We found that KLF4 was significantly downregulated in cisplatin-resistant A549 cells and forced KLF4 expression inhibited cell growth and induced apoptosis. Further, we found that overexpression of KLF4 was able to inhibit cell migration and invasion, to inhibit the expression of Slug, Twist, and vimentin, and to increase the expression of E-cadherin and subsequent inhibition of the EMT process. Thus, overexpression of KLF4 may be a potential strategy for lung cancer treatment, especially for cisplatin-resistant cases.

[Clinical efficacy of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy].

OBJECTIVE: To analyze the clinical efficacy and toxicity of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy. METHODS: Two hundred and eighty-three patients with stage 3/4 lung adenocarcinoma treated at our hospital from August 2010 to August 2013 were included in this study. The lung adenocarcinomas in all the 283 patients were confirmed by pathology or cytology, all were EGFR-negative, and all patients received pemetrexed second line chemotherapy. The 283 patients were randomly divided into two groups: the improved treatment group (142 cases) and the conventional treatment group (141 cases). The patients of conventional treatment group received 400 µg folic acid per os daily for 7 days before the first dose of pemetrexed, and continued until 21 days after the last dose of pemetrexed. Besides, they received 1000 µg vitamin B12 injection at 7 days before the first dose of pemetrexed, and once per cycle of pemetrexed for 3 cycles after the last dose of pemetrexed. The patients of the improved treatment group took 400 µg folic acid daily per os from the day before the first dose to 21 days after the last dose of pemetrexed. They also received 500 µg vitamin B12 by injection one day before the first dose, and one day before each therapy cycle of pemetrexed therapy. RESULTS: The mean number of cycles of pemetrexed chemotherapy was 4 in both groups. In the 142 patients of improved treatment group, complete response (CR) was observed in two cases, partial remission (PR) in 28, stable disease (SD) in 21, and progressive disease (PD) in 91 cases, with a total effective rate of 21.1%. While in the conventional treatment group, CR was observed in one case, PR in 27 cases, SD in 23 cases, and PD in 90 cases, with a total effective rate of 19.9%. The median progression-free survival (PFS) was 3.8 months in the improved treatment group and 4.2 months in the conventional treatment group (P=0.143). The toxicity of chemotherapy was mild in both groups, with no significant difference between the two groups (P>0.05). The most common side effects of hematological system were leukopenia and neutropenia, and the most common side effects of non-blood system were nausea and vomiting. The most common grade 3-4 toxic reaction in both groups was leukopenia and neutropenia, with no significant difference between the two groups (P>0.05). Multivariate analysis showed that the age of patients was an independent factor of grade 3-4 chemotherapy toxic reaction (P<0.05), while gender, the baseline level of PS score or blood system had no significant effect on the grade 3-4 chemotherapy toxic reaction (P>0.05). CONCLUSIONS: Compared with the conventional treatment scheme, the improved treatment scheme has similar therapeutic effects and could be used more conveniently, while the toxic effects of chemotherapy are not increased at the same time. Our results indicate that pemetrexed-based chemotherapy does not need to delay the chemotherapy because of vitamin support treatment.

[The diagnostic value of flexible bronchoscopy in tracheobronchopathia osteochondroplastica].

OBJECTIVE: To enhance the knowledge of tracheobronchopathia osteochondroplastica (TO), and to describe the value of flexible bronchoscopic diagnosis and treatment for the disease. METHODS: The clinical data, bronchoscopic findings, histological results and the methods and effect of bronchoscopic treatment in 10 patients with TO admitted to Xiangya Hospital between June 2006 and July 2007 were retrospectively analyzed. RESULTS: There were 8 males and 2 females (mean age 46 +/- 16, range 33-76 years). The bronchoscopic appearance of TO was multiple whitish, hard nodules projecting into the tracheal lumen (mostly from the anterior and less from the lateral walls). The lesions were found most frequently in the trachea and major bronchi, and lobar and segmental bronchi were involved less frequently. Nodules were restricted to the anterolateral walls in 7 cases. The distribution of the lesions was diffuse in 5, confluent in 2 and scattered in 3 cases. Six patients received bronchoscopic management, including radiofrequency treatment for 2 patients and argon ion laser treatment for the other 4. The lesions in the airways were reduced and clinical symptoms improved to some extent after treatment. No severe complications occurred during and after the procedures. CONCLUSIONS: The diagnosis of TO can be easily underdiagnosed or misdiagnosed. Flexible bronchoscopy with histological examination is the main method for the diagnosis of TO. Radiofrequency and argon ion laser treatment are safe and effective.

[Bronchoscopic argon plasma coagulation therapy for bronchial carcinoma].

OBJECTIVE: To evaluate the effect of bronchoscopic argon plasma coagulation therapy on bronchial carcinoma. METHODS: Thirty-one bronchial carcinoma patients were diagnosed by bronchoscope and pathological tests, with or without atelectasis or obstructive pneumonia on chest X-ray or chest CT. Argon plasma coagulation therapy was performed through bronchoscope. The location of the airway lesions, the degree of obstruction, dyspnea index, and complications were evaluated. RESULTS: The patients with bronchial carcinoma were treated 1-4 times by bronchoscopic argon plasma coagulation therapy. Full effectiveness was achieved in 15 patients (48.4 %), partial in 12 (38.7 %), and mild in the other 4 (12.9 %). The overall effective rate was 100%. CONCLUSION: Bronchoscopic argon plasma coagulation therapy for bronchial carcinoma can remarkably reduce the tumor size, relieve clinical symptoms, and alleviate the obstruction caused by bronchial neoplasm. Bronchoscopic argon plasma coagulation therapy is an effective and safe method for patients with bronchial carcinoma.

Development of a rat model by 3,4-benzopyrene intra-pulmonary injection and evaluation of the effect of green tea drinking on p53 and bcl-2 expression in lung carcinoma.

BACKGROUND: A convenient animal model of primary lung cancer is compelling for investigation into the disease mechanisms and for development of therapeutic strategies. This study aims to develop a reproducible rat model for lung carcinoma by intra-pulmonary injection of 3,4-benzopyrene, and to evaluate the preventive effect of green tea on the formation of lung carcinoma. METHODS: Sprague-Dawley rats of the same ages were randomly assigned into three groups treated differently. Rats in group one were given green tea in drinking water (tea concentration: 1.2%; tea polyphenols in the tea solution: 0.3%); rats in the groups two and three were given blank drinking water. Rats in the groups one and two were injected intra-pulmonarily with 3,4-benzopyrene dissolved in corn oil (2 mg/0.2 mL/injection, fortnightly, 4 times in all); rats in the group three were injected with the vehicle corn oil as the control for injection. All the rats were sacrificed one year after the first intra-pulmonary injection. Tumors developed in rats and lung tissues were collected for carcinoma diagnosis and for p53 and bcl-2 expression. RESULTS: Intra-pulmonary injection of 3,4-benzopyrene steady induced lung carcinoma at a success rate of 75%. Administration with green tea drinking significantly reduced the incidence of lung carcinoma to 30%. Green tea up-regulated p53 expression in lung carcinoma, but significantly down-regulated bcl-2 expression. CONCLUSIONS: Intra-pulmonary injection of 3,4-benzopyrene can steady induce lung carcinoma in rats, and green tea has preventive effect against lung cancer possibly by regulating expression of some critical genes such as p53 and bcl-2.

[Analysis of bronchoscopy characteristics for 729 female patients with lung cancer.].

BACKGROUND: The aim of this article is to study features of the bronchoscopy signs in female lung cancer patients. METHODS: The bronchoscopy data of 729 female lung cancer patients enrolled between January 1994 and June 2007 was analyzed, retrospectively. RESULTS: Most of the patients were middle-aged female (57.0%), then were the elderly (28.5%), and the youth composed much lower (14.0%). The most common histopathology was adenocarcinoma (42.8%), followed by squamous cell carcinoma (23.9%) and small cell carcinoma (19.2%), and all of them increased in the past few years. The female lung cancers were more in the right lung (P <0.05), and the upper lobes (P <0.05). Among 729 female lung cancer patients, 92.0% had apparent signs. Most of adenocarcinoma had infiltrative changes (P <0.05), but most of squamous cell carcinoma and small cell carcinoma had proliferative changes (P <0.05). The most common sing of bronchoscopy in patients with atelectasis was proliferative changes (P <0.05), but the most common sings of bronchoscopy in patients with pleural effusion was infiltrative changes (P <0.05). CONCLUSIONS: This study suggests brochoscopy is an important approach in diagnosis of female lung cancer. Paying more attention to the lung cancer of female patients and examining with bronchoscopy would be helpful for earlier diagnosis.

[Prevention of chinese green tea on 3,4-benzopyrene-induced lung cancer and its mechanism in animal mode.].

BACKGROUND: Chinese green tea is one of the daily consumption beverages in the world and is considered a promising cancer chemopreventive agent. In the present study, we investigate the role of lung cancer prevention by green tea and its mechanism. METHODS: Three groups of female SD rats were kept with the same feed. Rats in group A were administrated with 1% green tea drinking, while in group B and group C with water only. Animals in group A and group B were given 3,4-benzopyrene-corn oil mixture pulmonary injection fortnightly for 4 times, while in group C corn oil only. Rats were sacrificed 1 year after the first injection under narcotism. Lung tumors and lung tissues were performed H&E staining for cancer identification. Each case of lung cancer was examined for expression of p53 and Bcl-2 with in situ hybridization analysis and immunohistochemistry staining. RESULTS: No cancer was found in rats in group C. However, in group B, 15 out of 20 rats were found generating lung cancer, and in group A, 6 out of 20 rats inducing lung cancer were recorded. The rate of lung carcinogenesis in rats was decreased from 75% to 30% by 1% chinese green tea oral administration (Chi-Square=8.12, P <0.01). Higher level of p53 expression in lung cancer tissues of group A was observed under microscope than that of group B, but the difference has no statistic significance (P >0.05). However, significantly lower level of Bcl-2 expression was found in lung cancer tissues of group A than that of group B (P <0.05). CONCLUSIONS: The results indicate that chinese green tea inhibits lung carcinogenesis. Chinese green tea can slightly upregulate expression of p53, but significantly downregulate expression of Bcl-2 in lung cancer, and this may be related to the mechanism of lung cancer prevention.

[Effect of ginsenoside Rh2 on immunocompetence of alveolar macrophages in patients with non-small cell lung cancer].

OBJECTIVE: To explore the effect of ginsenoside Rh2 (G-Rh2) on the excretion of cytotoxin-effecting molecule of alveolar macrophages (AM) in patients with non-small cell lung cancer (NSCLC). METHODS: The concentration of tumor necrosis factor (TNF-alpha) and NO in the bronchoalveolar lavage fluid (BALF) and the cultured supernatants of AM in 35 patients with NSCLC were measured by ELISA and enzyme method,and levels of TNF-alpha and NO in the cultured supernatants of AM after being cultivated with IFN-alpha, G-Rh2, and IFN-alpha+G-Rh2 were measured by the same method. RESULTS: AM in all the non-small cell lung cancer patients produced TNF-alpha and NO. The activity of TNF-alpha and NO was lower in the BALF and in the cultured supernatants of AM of the tumor-bearing lungs than that of the non-tumor-bearing lungs. The concentrations of TNF-alpha and NO in the cultured supernatants of AM cultivated with G-Rh2 were higher than those in the control (P<0.05), but there were no significant differences between the G-Rh2 group and IFN-alpha group (P>0.05). The concentrations of TNF-alpha and NO in the cultured supernatants of AM cultivated with both G-Rh2 and IFNalpha were obviously higher than those stimulated with IFNalpha or G-Rh2 (P<0.01) alone. CONCLUSION: G-Rh2 can enhance the excretion of cytotoxin-effecting molecules of AM in patients with NSCLC. The changes are more distinctive when G-Rh2 and IFNalpha have coordinated action.

[Study on the relationship between the polymorphism of p53 gene intron 7 and non-small cell lung cancer (NSCLC) and p53 mutation in NSCLC tissues].

OBJECTIVE: To investigate the relationship between p53 gene intron 7 polymorphism and non-small cell lung cancer (NSCLC). METHODS: One hundred and five patients with NSCLC and 100 controls were selected with case-control analysis. Polymerase chain reaction (PCR), Apa I restriction enzyme digestion and agarose gel electrophoretic separation were used to identify genotypes of p53 intron 7 in peripheral blood. Then, NSCLC biopsy tissues (n=64) and NSCLC paraffin-embedded tissues (n=40) were selected for mutation analysis. PCR products of p53 exons 5-8 were sequenced on an automated sequencer following the identification of intron 7 genotypes as previously described. RESULTS: In NSCLC patients, the homozygote positive for ApaI site in p53 intron 7 was 23.8%, the homozygote negative was 12.34%, and the heterozygote was 63.8%. Whereas in control group, the homozygote positive, the homozygote negative and the heterozygote were 44.0%, 11.0% and 45.0%, respectively (P<0.01). In the second part, mutation rate of p53 exons 5-8 was 20.0%, 50.0% and 52.9% in samples with ApaI positive, negative and heterozygotes, respectively (P<0.05). CONCLUSION: p53 intron 7 ApaI polymorphism may be associated with human NSCLC.

[Medical thoracoscopy in the diagnosis of complicate pleural effusion].

OBJECTIVE: To evaluate the role of medical thoracoscopy in the diagnosis of the pleural effusion of unknown etiology. METHODS: The results of 36 patients with the pleural disease of unknown etiology diagnosed by medical thoracoscopy were retrospectively analyzed, including the pathologic results and the complications. RESULTS: Among the 36 patients, 35 were determined with positive rate of 97.2%, and no serious complications was found. CONCLUSION: Medical thoracoscopy is an important method of diagnosing complicate pleural effusion, and has high positive rate. It is a simple operation, with no serious complication, and fast recovery.