Objective:Explore the protective effect and mechanism of methyl badosolone (CDDO-Me) on rats with traumatic brain injury (TBI).Methods:A total of 72 SPF-grade SD rats aged 8 weeks were randomly (random number) divided into 4 groups ( n=18) using the random number table method: Sham, TBI, TBI+Vehicle, and TBI+CDDO-Me. The rat TBI model was established using the hydraulic impact head injury method. The TBI+CDDO-Me group was administered CDDO-Me (dissolved in 1% DMSO, at a dose of 10 mg/kg) via intraperitoneal injection 30 minutes after modeling, twice a day for a total of 3 days. On the third day after modeling, brain tissue was collected for pathological and water content detection after mNSS scoring. Immunofluorescence double staining was used to detect the expression of nuclear factor erythroid2 related factor 2 (Nrf2); immunohistochemical staining was used to detect the expression of ionized calcium binding adapter molecule-1(Iba-1); ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin (IL)-1β, and IL-18 in serum; kits were used to detect the levels of malondialdehyde (MDA) and reactive oxygen species (ROS); Western blot was used to detect the expression of the Nrf2 pathway, B-cell lymphoma-2 (BCL-2), and BCL-2 associated X protein (BAX). Results:(1) Compared with the Sham group, the mNSS scores and water content in the injured cortex of the TBI group rats were significantly increased (both P<0.05), and both significantly decreased after CDDO-Me intervention (both P<0.05). (2) Compared with the Sham group, the proportion of Nissl-stained injured neurons and apoptotic positive cells in the TBI group rats were significantly increased (both P<0.05), and both significantly decreased after CDDO-Me intervention (both P<0.05), accompanied by a decrease in BAX protein expression and upregulation of BCL-2 protein expression (both P<0.05). (3) Immunofluorescence and Western blot results showed that compared with the Sham group, the expression of total Nrf2, nuclear Nrf2, HO-1, and NQO1 proteins in the TBI group were all increased (all P<0.05), and the increase was more significant after CDDO-Me intervention (all P<0.05). (4) Immunohistochemistry and ELISA results showed that compared with the Sham group, the levels of MDA, ROS, Iba-1 in brain tissue and the levels of TNF-α, IL-1β, and IL-18 in serum in the TBI group rats were all significantly increased (all P<0.05), and all significantly decreased after CDDO-Me intervention (all P<0.05). Conclusion:CDDO-Me helps to reduce oxidative stress and inflammatory responses in TBI rats, and the mechanism may be related to the activation of the Nrf2/HO-1 antioxidant stress pathway.

Objective To establish a scientific training program that takes into account both anaerobic and aerobic training for pilots,and to explore the appropriate ratio of aerobic and anaerobic training.Methods According to the physical examination standards for pilots,a total of 16 healthy subjects aged 18-24 were selected from two batches.The two batches of subjects were trained with different aerobic and anaerobic ratios.Training period was 3 months.The changes in cardiopulmonary function of the subjects before and after training were evaluated using the cardiopulmonary function exercise testing system(CPET),and the changes in anaerobic capacity were evaluated using changes in strength as an indicator.Results After training,the weight load of the subjects in the two training programs,including barbell squats,leg flexion and hard pull,and barbell under 10RM and 3RM,was significantly increased(P<0.001),and there was no statistically significant difference in anaerobic strength growth between the two groups.The results of CPET showed that the maximum load,maximum heart rate,and respiratory quotient in the two groups were significantly increased after than before the training(P<0.01).The maximum load(Experiment group 1:29.12±19.69,Experiment group 2:72.00±46.24)and respiratory quotient(Experiment grouop 1:0.11±0.09,Experiment group 2:0.28±0.16)of the subjects in experiment group 2 before and after training were greater than those in experiment group 1.The difference was statistically significant(P<0.05).Conclusion The anaerobic and aerobic capacities of the subjects in the experiment group 2 are effectively improved,indicating that ratio of aerobic and anaerobic of the training scheme is better.

A method was developed for analyzing the stable carbon isotope ratio of five volatile components ( Ethanol, Glycerol, Acetic acid, Ethyl lactate, 2-methyl-butanol ) in wine using gas chromatography-combustion-isotope ratio mass spectrometer ( GC-C-IRMS ) . The sample injection volume was less than 0. 5 μL, and the analytical time of each run was less than 14 min. The precision of this method was 0. 08‰-0. 25‰ for analyzing standards, while 0. 09‰-0. 36‰ for wine samples. Compared to element analysis-isotope ratio mass spectrometry ( EA-IRMS) results, the deviations were lower than 0. 5‰. Fifty-four wine samples from France, Australia, America and China were considered. The δ13 C of five volatile components were measured using GC-C-IRMS. Discriminant analysis ( DA) was employed for analyzing the geographical origin traceability of selected wine. The result indicated that δ13 C of volatile components could be used to distinguish the origin of wines. The method was shown to be effective in improving detection of the origin traceability of wine.

Background and purpose:For patients with advanced lung adenocarcinoma harboring an activating EGFR gene mutation, the current standard of care is EGFR-TKI alone. This study aimed to compare efficacy and safety of gefitinib plus chemotherapy with gefitinib or chemotherapy alone for treating advanced lung adenocarcinoma with an activatingEGFR gene mutation.Methods:This study included 61 patients with lung adenocarcinoma harboring an acti-vatingEGFR gene mutation (19 exons deletion and exon 21 L858R mutations) whose ECOG performance status was 0 or 1. Patients were randomly divided into 3 groups. Group A (n=20) were given carboplatin/pemetrexed of a 4-week cycle, six cycles at most, plus gefitinib (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1; gefitinib 250 mg/d, d 5-21), and then re-ceived pemetrexed of a 4-week cycle plus gefitinib as maintenance therapy; Group B (n=20) were given carboplatin/peme-trexed of a 4-week cycle, six cycles at most (pemetrexed 500 mg/m2, d1; carboplatin AUC 5, d1), then received pemetrexed as maintenance therapy; Group C (n=21) were given gefitinib (gefitinib 250 mg/d). Patients continued to receive therapy until disease progression or unacceptable toxicity or death. The primary end point was middle PFS and 12 months PFS rate. The secondary end points included objective response rate and adverse events.Results:Groups A and C both lost 1 case during follow-up. Median PFS for patients was 20.1 months (95%CI:18.0-22.2) in group A, 5.5 months (95%CI:3.9-7.2) in group B, and 9.8 months (95%CI:6.8-12.8) in group C. PFS rates of 12 months for groups A, B and C were 78.9%, 15.0% and 40.0%, respectively. The overall objective response rates for groups A, B and C were 84.2%, 35.0% and 65.0%, respectively. Serious adverse events were reported by 36.8% for group A, 30.0% for group B, and 5.0% for group C. The most common grade 3/4 adverse events were neutropenia (3 cases in group A, 4 cases in group B), fatigue (2 cases in group A, 2 cases in group B) and liver function impairment (2 cases in group A, 1 case in group C).Conclusion:Among patients withEGFR mutant lung adenocarcinoma, combination of chemotherapy with gefitinib as first-line treatment demonstrates an improvement in PFS. Long-term survival results will be further followed up.

Background and purpose: Multidrug resistance (MDR) is the dominating obstacle to the chemotherapy. There is strong evidence that the phosphoinositide 3-kinases (PI3Ks) signaling pathway is involved in MDR phenotype, however, the mechanism of MDR occurrence is still unknown. This study tended to investigate the regulating effect of PI3K/Akt signaling pathway and its downstream target genes in P-glycoprotein (P-gp) (ABCB1 gene encoding)-mediated MDR in human colon carcinoma HCT-116/L-OHP cells. Methods:Pretreatment with PI3K selective inhibitor LY294002 (20μmol/L) for 2 h, the sensitivity of L-OHP was evaluated by the CCK-8 (cell counting kit-8) assay in HCT-116/L-OHP cells, and the expressions of P-gp, LRP, MRP-2, Akt, p-Akt, IκB and p-IκB were evaluated by Western blot. The activity of ABCB1 promoter was evaluated by chromatin immunoprecipitation analysis (CHIP). Results: After inhibiting the activity of PI3K/Akt signaling pathway, the IC50 value of L-OHP decreased from(157.48±16.73)μg/mL to (53.68±3.18)μg/mL in HCT-116/L-OHP cells, and the reversal index was 2.93 (P<0.01). The expressions of P-gp, p-Akt and p-IκB were down-regulation compared with the concrol group (P<0.01), but the expressions of LRP, MRP-2, Akt and IκB didn't change signiifcantly. CHIP result has conifrmed that NF-κB protein could bind to the region of ABCB1 gene promoter in HCT116/L-OHP cells. Conclusion:Blocking of PI3K/Akt/NF-kB signal pathway could increase the drug sensitivity to MDR cells, inhibit the phosphorylation of p-Akt and p-IκB, and reversing ABCB1/P-glycoprotein-mediated multidrug resistance in colon carcinoma cells.

Background and purpose:Multiple primary lung cancers (MPLC) is a rare entity, but recently there has been a gradual increase in the number of patients diagnosed with MPLC. The aim of this study is to investigate the diagnosis, treatment and prognosis of MPLC through analyzing the clinical data.Methods:Forty-one patients were diagnosed MPLC by Martini-Melamed criteria. Their clinicopathological data were retrospectively reviewed. Results:There were 3 patients with triple primary lung cancer and 38 patients with double primary lung cancer. There were 13 patients with synchronous MPLC, 26 patients with metachronous MPLC, 2 patients with synchronous and metachronous MPLC. Of 85 lesions, the surgical procedures were mainly lobectomy (78.8%, 67/85). Lesions (41.2%, 35/85) were frequently in right upper lobe. Pathological type was mainly adenocarcinoma (70.6%, 60/85),followed by squamous cell carcinoma (17.6%, 15/85). Of 60 adenocarcinoma specimens, the papillary predominant subtype was more common (50%, 30/60). Eighty percent (68/85) of the lesions were stage I. As to the initial cancer and repeated cancer, patients who shared the same pathological type (68.3%, 28/41) were more than the different (31.7%, 13/41), of which adenocarcinoma-adenocarcinoma was most common(82.1%, 23/28). Lesions located in contralateral lobes were in 37 patients (90.2%), and located in ipsilateral different lobes were in 4 patients (9.8%). The 2-year overall survival (OS) of them was 87.8%. Survival analysis showed that the prognosis of patients with same pathological type was better than patients with different pathological type (P=0.037), the prognosis of patients with no lymph node metastasis was better than patients with N1,N2 metastasis (P=0.02).Conclusion:Lesions in patients with multiple primary lung cancers are more frequently in the right upper lobes. The pathology type is mainly adenocarcinoma, of which the papillary predominant subtype was most common. Early diagnosis improves continuously, active treatment with operation can achieve better prognosis.

Objective To evaluate the clinical effects of sitagliptin and sitagliptin combined with glimepiride in the treatment of type 2 diabetes (T2DM).Methods Ninety-two patients with T2DM were randomly divided into sitagliptin group (group J),glimepiride group (group G) and sitagliptin combined with glimepiride group (group U),group J took sitagliptin,group G took glimepiride,group U took sitagliptin and glimepiride.Before and after treatments,blood glucose and insulin were determined in the fasting and 2-hour blood samples after taking glucose (fasting blood-glucose (FPG),2-hour postprandial blood glucose (2hPG),insulin (FIns),2-hour postprandial insulin (2hIns),and glycosylation hemoglobin (HBA1 c) were also determined and homeostasis model assessment was applied to estimate the functions index of islet β cell(HOMA-β).Results The levels of blood glucose and HBA1C in three groups decreased after treatments(FPG,(before treatment:(9.2±3.0),(9.2±2.8),(9.3±3.2) mmol/L),(after treatment:(7.7 ± 3.0),(6.9 ± 2.6),(6.0 ± 2.5) mmol/L),and t values are 2.205,3.203,3.691,P ＜ 0.01,P ＜ 0.05 ;2 hPG (before treatment:(14.1 ± 5.7),(14.8 ±6.3),(15.0±6.8) mmol/L),(after treatment:(7.9 ±2.9),(9.0 ±3.1),(7.1 ±3.1) mmol/L),and t values are 3.881,3.159,4.189,P ＜ 0.01 ; HBA1c (before treatment:(8.52 ± 2.01)％,(8.48 ± 1.94)％,(8.56 ±2.27)％,(after treatment:(7.64 ± 1.92)％,(6.81 ± 1.55)％,(6.19 ± 1.84)％),t values are 2.292,2.184,3.269,P ＜ 0.01,P ＜ 0.05) ; HOMA-β in the three groups increased after treatment ((before treatment:1.42 ± 0.07,1.44 ± 0.06,1.41 ± 0.11),(after treatment:1.76 ± 0.14,1.68 ± 0.20,1.85 ±0.17),t values are 2.180,2.073,2.882,P ＜ 0.01,P ＜ 0.05);levels of HBA1c and blood glucose in group U were lower than those in group J and G(HBA1 c:t values are 2.785,2.138,P ＜ 0.05,P ＜ 0.01 ;FPG:t values are 2.252,2.346,P ＜0.05;2hPG:t values are 2.147,2.829,P ＜0.01,P ＜0.05),HOMA-β in which was higher than that of group G(t =2.153,P ＜ 0.05),but with no significant difference compared with group J (t =1.796,P ＞ 0.05),levels of HBA1C,FPG and HOMA-β in group J were higher than those of group G (t values are 2.108,2.202,2.121,P ＜ 0.05),level of 2hPG of group J was lower than that of group G(t =2.307,P ＜ 0.05).Conclusion Sitagliptin provides significant glycaemic control,together with glimepiride,clinical effect of treatment of type 2 diabetes will be enhanced.

10.3969/j.issn.1007-3969.2013.05.002

Objective:To analyze the drug sensitivity of human lung adenocarcinoma stem cells (LASC) to cisplatin (DDP) and carboplatin (CBP). Methods:Human lung adenocarcinomaic cells SPC-A1,AG,and CPA-Y2 were treated with DDP and CBP. The cell viability of cells was detected by CCK-8 assay. The phenotypic characteristics of drug surviving cells(DSCs)were determined by immunofluorescence staining. The LASC population was then separated by magnetic-activated cell sorting method. The LASC in DSCs was traced by using green fluorescence protein (GFP). The drug sensitivity of DSCs to DDP and CBP was analyzed.Results:The LASC exhibited the phenotypes of bronchioalveolar stem cells (BASC, OCT4~+CCSP~+SP-C~+). After mixture of CD221~+LASC with CD221~-lung adenocarcinoma differentiated cells, the DSC population showed OCT4~+BASC phenotypes. These DSCs were significantly resistant to DDP and CBP.Conclusion:LASC has a high resistance to DDP and CBP. This may be the reason for tumor recurrence after chemotherapy.

A method for the determination of seven kinds of thiocarbamate herbicides, molinate, pebulate, vernolate, triallate, thibencarb, eradicane and butylate in black tea and green tea has been developed. After homogenization, 2.0 g tea sample was soaked with 6 mL water for 1 h. 2.5 g NaCl was then added, and the sample was extracted twice by 20 mL acetonitrile. After concentration, the extract was put through HLB column and eluted by 3 mL acetonitrile. The eluate was then concentrated and dissolved with 2.0 mL hexane-acetone (7∶ 3, V/V) mixture. The preparation was cleaned by Envi-Carb column and eluted with 5 mL hexane-acetone. After concentration, the residue was dissolved by acetonitrile-water (5∶ 5, V/V) solution. Detection was achieved by electrospray ionization(ESI) in positive mode using multiple reaction monitoring. D_3-carbaryl was used as the internal standard, the linear range for the herbicides was 0-200 μg/L and the limit of detection were from 0.093 to 1.77 μg/L, with the correlation coefficients(r) varying from 0.9954 to 0.9988. The recoveries of all thiocarbamate herbicides were from 77.3% to 91.5% at the spiked levels of 5-20 μg/kg. The RSD of each compound was less than 15%. Black tea and green tea samples were successfully analyzed by the proposed method with satisfactory results.