Objective To explore the related risk factors for neuropathic pain in diabetic rats.Methods Female Wistar rats of clean grade were divided into three groups :Non diabetic standard diet (NdStd) group (n=10) ,diabetic high fat diet and pain (DbHFP) group (n=10) ,and diabetic high fat diet and no pain (DbHFNP) group (n=10).Body weight ,blood glucose ,TG ,TC ,HDL‐C ,LDL‐C and 50%pain threshold were measured regularly to assess the relationship between blood lipids and pain. Results Non‐conditional logistic regression analysis showed that pain threshold was negatively correlated with TG , LDL‐C and blood glucose(P<0.05) ,and positively correlated with HDL‐C (P<0.05). And there was no association between TC and body weight (P> 0.05). Conclusion Pain threshold of diabetic rats was negatively correlated with TG ,LDL‐C and blood glucose ,and positively correlated with HDL‐C.

AIM: To evaluate the cytotoxicity of a novel anticholinergic drug penehyclidine hydrochloride (PHC) and its four optical isomers R-1, R-2, S-1, and S-2. METHODS: Two in vitro assays, MTT assay and neutral red uptake assay, were used to evaluate the cytotoxicity following PHC and its isomers exposure to HepG2 cells at different concentrations. RESULTS: PHC and its isomers induced decreases of viability of HepG2 cells in a concentration-dependent manner. Comparison of the cytotoxicity of the five anticholinergic agents with 50% inhibitory concentration (IC50) values indicated that the order of potency was PHC>R-2>R-1>S-2>S-1 for MTT assay, and R-2>PHC≈R-1>S-2>S-1 for neutral red uptake assay. CONCLUSION: With respect to the cytotoxicity of the four isomers on HepG2 cells, the R configuration was more potent than the S configuration, and R-2 was the most potent isomer whereas S-1 was the least potent isomer among the four optical isomers.

Objective To establish the normal reference ranges of clinical pathology for Beagle dogs in the Good Laboratory Practice ( GLP ) system.Method Sixteen biochemical indexes , seventeen hematological indexs and three coagulation function indexes of 117 Beagle dogs were detected , and the mean value of each index and the normal reference ranges were calculated and compared .Results Only alkaline phosphatase ( ALP ) from the biochemical items was significantly different between males and females (P<0.01),which was higher among males than among females .Three in-dexes of hematology were significantly different between males and females (P<0.01),with red blood cell(RBC), hemo-globin(HGB)and hematocrit(HCT)lower among males than among females.The coagulation function items were not signif-icantly different between the two sexes .Conclusion Some indexes of clinical pathology were significantly different between males and females , which should be considered during statistic analysis on toxicity .Our study has established the normal reference range of clinical pathology for Beagle dogs in the GLP system , which provides reference for toxicity tests .

Objective To investigate the clinical curative effect of ipratropium bromide in combination with ambroxol hydrochloride (mucosolvan) on ventilator-associated pneumonia (VAP) in elderly patients.Methods From Jan 2013 to Nov 2014,a total of 46 elderly patients with VAP in our hospital were treated with ipratropium bromide 0.5 mg diluted in 5 ml saline by inhalation with ventilator,and mucosolvan 30 mg by intravenous injection,3 times/d (treatment group,n=23),and treated with ipratropium bromide 0.5 mg diluted in 5 ml saline by inhalation with ventilator,3 times/d (control group,n=23).Total clinical effective rate,ventilating time,number of sputum suction by fibre bronchoscope and white cell count were compared between the two groups.Results The total clinical effective rate was higher in treatment group than in the control group [91 ％ (21/23) vs.74％(17/23),x2=11.310,P=0.002].The indicators of ventilating time,number of sputum suction by fibre bronchoscope and white cell count were improved in treatment group as compared with control group [(8.2±1.5) d vs.(13.7±3.1) d,(3.5±0.3) vs.(6.7±1.2),(9.5±2.3) × 109/L vs.(14.2±2.7) × 109/L,t=17.510,2.750,3.810,respectively,P=0.000,0.001,0.001].Conclusions Compared with single-drug treatment,ipratropium bromide in combination with ambroxol hydrochloride (mucosolvan) could improve airway humidification,promote cilium to clean secreta,shorten the ventilating time and increase the curative rate of YAP in elderly patients.

The purpose of risk assessment is to evaluate the permissible exposure level under specific risk factors.To extrapolate the human acceptable daily intake (ADI) and/or reference dose (RfD), the traditional method uses the no-observed-adverse-effect level ( NOAEL ) to quantify toxicity after being divided by uncertainty factor.There are many limitations with NOAEL method in safety evaluation,for it relies too much on experimental design.Benchmark dose ( BMD) approach is a more reliable method with many advantages.BMD approach and its analysis software, the advantages of BMD over NOAEL, the application and methodological perfection in risk assessment of long-team exposure toxicity are presented in this review.

Objective To investigate the expression of Aire,Foxp3,AchR and other immune factors in human thymoma tissue and plasma and explore their role in myasthenia gravis with thymoma.Methods T lymphocyte subsets,immunoglobulin and other immune factors in plasma were compared,and the Expression of Aire,Foxp3 and AchR were examined in thymoma by reverse transcriptional polymerase chain reaction and immunohistochemical staining,and the results were analyzed by SPSS statistics software.Results The ratio of CD4 + to CD8 + T lymphocyte was much higher in plasma,while the expressions of Aire,Foxp3 and AchR at mRNA and protein level were much lower in thymoma patients with myasthenia gravis,and related to Ossermann subtype,WHO subgroup and Masaoka stage.The differences were statistically significant (P ＜ 0.05).Conclusion The ratio of CD4 + to CD8 + T lymphocyte and the abnormal expressions of Aire and Foxp3could used as an indicator of immune state in thymoma patient with myasthenia gravis and play an important role in the development of thymoma with myasthenia gravis,but the mechanism is indefinite.

BACKGROUNDThe extent of pulmonary resection is decided by the location and extent of the tumor and the patient's physiologic ability to tolerate resection. Bronchoplastic and pulmonary arterioplastic procedures have become increasingly popular in recent years as an alternative to pneumonectomy. In this article our experience with arterioplastic and bronchoplastic procedures in the treatment of central-type bronchogenic carcinoma was reviewed.

METHODSFrom October 1999 to October 2005, 12 pulmonary arterioplasties and 14 combined broncho-angioplasties were performed for bronchogenic carcinoma and meanwhile two replacement of vena cava were done.

RESULTSOf the 26 patients, 18 were in stage II and 8 were in stage III. No fatal surgical complications occured. Atelectasis occurred in 2 patients (7.7%), postoperative pneumonitis in 2 (7.7%), and reperfusion lung injury in one (3.8%). The 1-and 3-year survival rates for the entire group were 100.0% and 69.2% respectively.

CONCLUSIONSPulmonary arterioplastic and broncho-angioplastic procedures can be performed safely. Angioplastic and combined broncho-angioplastic procedures offer patients with bronchogenic carcinoma similar a long-term result as radical lung resection, especially in patients who cannot tolerate pneumonectomy due to poor cardiopulmonary reserve.

Objective To explore the effect on metabolism of glucose and lipids, potential toxicity mechanism and possible biomarker candidates by analyzing urine metabonome changes of rats after oral administration of polychlorinated biphenyl congeners( PCBs) and high fat diet alone or in combination.Methods Male SD rats were divided randomly into control group,high fat diet group, PCBs group and combination group of PCBs and high fat diet.Urine samples were collected after 6-week treatment, 1 H NMR spectra were performed and analyzed by principal component analysis ( PCA) . Results The PCA scores plot of urine 1 H NMR data showed that the combined group could be easily distinguished from the other three groups, suggesting great difference in metabolism.The loading plot of the PCA revealed significant increase in the levels of lactate, glucose, creatine, 2-hydroxy-isovaleric acid and reduction in the levels of citrate, succinate, taurine, hippurate and trimethylamine oxide ( TMAO) in the combined exposure group after six-week exposure.Conclusion The altered levels of metabolites induced by combined exposure of PCBs and high fat diet may be related to the injury to mitochondrial function, reduction of energy metabolism in tricarboxylic acid cycle (TAC).These effects possibly lead to perturbations in the metabolism of glucose, lipid and amino acids.The altered metabolites may be considered biomarker candidates of toxicity induced by exposure to PCBs and high fat diet.

Objective To observe toxic symptoms and signs , toxic damage extents and reversibility in rats after oral administration of Tangwang Mingmu granules .Methods Four dose groups with 40 rats in each group were designed in this study, including control group fed with distilled water and three groups at different dosages of the test drug .Tangwang Mingmu granules were orally administered to SD rats at the dosage of 8.4, 4.2 and 2.1 g/kg for 3 weeks and 14.0, 8.4 and 4.2 g/kg for 23 weeks, for 26 consecutive weeks .The general state of the rats was observed every day , while body mass and food consumption were calculated once a week .Halfway through and at the end of the administration (13 and 26 weeks) and after four weeks of recovery, parameters of body mass, hematology, hematological biochemistry, organ/body mass ratio and histopathology were measured .Results Compared with the control group at the same time-point, body mass of male rats in the other three groups was slightly reduced .Food consumption in high and medium dose groups was reduced (P<0.05), MCHC, ALT, TBIL and Na +in high dose group were decreased (P<0.05), TP, ALB and D-BIL were increased (P<0.05), the mean body mass and relative organ weight of thymus in medium dose male rats were decreased (P<0.05), relative organ weight of the liver and kidney in high dose male rats was increased (P<0.05), and focal chronic inflammation to different extent was observed in the liver , kidney and prostate gland .No dose-effect relationship was found in these perturbations that were all within the normal range of animals .No significant drug-related pathological changes were found.Conclusion The NOAEL of Tangwang Mingmu granules is considered to be 14.0 g/kg body mass/day (equal to 50 times the proposed clinical adult dosage ) for the 26-week repeated dose oral toxicity study in male andfemale rats.

BACKGROUNDThere is important significance of micrometastasis for the individual treatment and prognosis of non-small cell lung cancer (NSCLC). LUNX is a lung-specific gene found recently. The aim of this study is to detect LUNX mRNA expression in NSCLC patients in order to discuss the possibility of indicating lung cancer micrometastasis by LUNX.

METHODSFluorescence quantitative reverse transcription-polymerase chain reaction (FQ-RT-PCR) and ordinary RT-PCR were used to detect LUNX mRNA in cancer tissues, bone marrow and peripheral blood from 62 patients with NSCLC. Lung tissue, bone marrow and peripheral blood from 10 patients with pulmonary benign diseases and peripheral blood from 10 healthy volunteers were served as controls.

RESULTSLUNX mRNA was expressed in all the lung tissues, either malignant or benign. No bone marrow and peripheral blood sample was positive for LUNX mRNA in controls. The positive detection rate of LUNX mRNA for NSCLC was 38.7% (24/62) in bone marrow, 29.0% (18/62) in peripheral blood, and 45.2% (28/62) in either. The positive rate of LUNX mRNA for NSCLC in bone marrow increased according to the stage of disease and there was a statistical significance (P=0.02), aod there was a correlation between bone marrow and peripheral blood expression in NSCLC (P < 0.001).

CONCLUSIONSLUNX mRNA is an efficient indicating factor on sensitivity and specificity to detect early haematogenous dissemination of cancer cells for patients with NSCLC. This method may lead to an earlier diagnosis of metastasis for lung cancer and help to evaluate the cancer more correctly and make the best treatment plan.