Objective To compare the clinical outcomes of gefitinib and erlotinib treating non-small-cell lung cancer (NSCLC)with epidermal growth factor receptor (EGFR)mutation in either exon 19 or 21 . Methods A total of 242 patients diagnosed as NSCLC with EGFR mutation in either exon 19 or 21 from May 201 3 to December 2014 in our hospital were chosen in this study.According to age,sex,smoking history,eastern cooperative oncology group performance status and types of EGFR mutation,all the patients were matched to 121 pairs,and randomly divided into group A and B.Patients in group A received gefitinib treatment,and those in group B received erlotinib treatment.Based on the response evaluation criteria in solid tumors (RECIST),overall response rate (ORR),disease control rate (DCR),progression-free survival (PFS)were assessed.To assess the independent risk factors for PFS by univariate and multivariate Cox regression analysis.The subgroup analysis was performed for the 63 NSCLC patients using these two drugs as the first-line treatment.To evaluate the adverse drug reactions and quality of life between A and B groups.Results The median PFS of group A and B were 11 .6 months and 9.5 months,respectively,with no significant difference (HR =0.39,P >0.05).The ORR and DCR in the two groups were 76.9%,74.4% (χ2 =1 .03,P =0.58)and 90.1 %,86.8% (χ2 =1 .46,P =0.31 ). The independent risk factors of poor PFS were ECOG PS≥2 (HR =2.60,95%CI:1 .54 -4.43,P =0.001 )and non-adenocarcinoma (HR =3.61 ,95%CI:1 .54-8.66,P =0.003).For patients receiving these two drugs as the first-line treatment,there was no significant difference between two groups in overall response rates (76.6% vs. 90.2%,χ2 =0.83,P =0.12)and median PFS (11 .6 months vs.14.4 months,HR =0.59,P >0.05).The adverse drug reactions were significant differences in emotion function (F =10.27,P =0.03),diarrhea (F =10.24,P =0.03)and pain (F =9.02,P =0.04).After receiving drug treatment,the quality of life scores were improved,and most of the differences were statistically significant between A and B groups(P <0.05). Conclusion As for NSCLC with EGFR mutation in either exon 1 9 or 21 ,both gefitinib and erlotinib are well tolerated and have similar clinical effectiveness.

Child ; Child, Preschool ; Female ; Fluoroacetates ; poisoning ; Hemoperfusion ; Humans ; Infant ; Male

Traditional recombination technology of bacteria chromosome and its limitation were introduced. The definition of Red recombination technology is put forward: a method of homologous recombination between foreign linear DNA and the target gene in chromosomes mediated by ? phage Red system. The linear DNA referred here is general PCR product or oligonucleotide, which has a 36~50bp homologous sequence with the target gene in chromosome at both flanking. Red recombination technology leaves out the in vitro DNA restriction enzyme digestion and link process, which makes the knockout and alternation of target gene in bacteria chromosome relatively easier, and becomes an effective method to exploring genes and constructing new strains gradually. The gene inactivation and alternation method aiming at bacteria chromosome applied to Red recombination system was summarized by the structure element, action mechanism, and strategy of recombination, advantage and developing prospect. The Red system includes three genes: bet (aka?), exo and gam (aka ?). Exo is a 5′→3′ exonuclease, which degrades the 5′ ends of linear DNA molecules. Bet is a single-stranded DNA binding protein that binds to the single stranded 3′ ends generated by Exo and promotes annealing to complementary DNA. Gam binds to the host RecBCD complex and inhibits its exonuclease activity. Red recombination system may be constructed in such plasmids as pKD20 and pKD46 or in chromosome of bacteria. Most bacteria are not readily transformable with linear DNA because of the presence of intracellular exonucleases that degrade linear DNA. But when bacteria cells are transformed with pKD20 or pKD46 plasmid, or integrated with a detective ? prophage, Red recombination enzymes may be expressed in host cells, which make linear DNA with 36~50bp extensions that are homologous to both flanking of target genes transform E.coli readily and knock-out or alternate target gene. The Red recombination method is not only useful in chromosomal gene inactivation in E.coli, but also in other bacteria or virus, such as Salmonella, Shigella flexneri and virus HaSNPV. With the proceeding research, Red system will be applied for more and more purposes, and contribute a lot for gene improvement and gene function investigation in the coming Postgenome Era.

This study is to investigate the therapeutic effect and mechanism of indole-3-carbinol (I3C) on pig serum-induced liver fibrosis of rats. The liver fibrotic model of rats was induced by pig serum. After models were successfully established, rats in the treatment groups were administered with I3C through intraperitoneal injection or curcumin by intragastric administration, daily for 17 days. Hepatic hydroxyproline (Hyp) content was measured. The liver histology and immunohistochemistry with a-smooth muscle actin (alpha-SMA) were assayed. Hepatic stellate cells line, HSC-T6 was incubated with different concentrations of I3C (25, 50, and 100 micromol x L(-1)) for 24 h. The effect of I3C on cell apoptosis was identified by FITC-Annexin V/PI double labeled assay. And the mRNA expressions of Bax and Bcl-2 were measured by real time RT-PCR. The results showed that hepatic content of Hyp decreased by I3C treatment, as compared with the fibrotic model control. Histopathological changes, such as steatosis, necrosis, deposition of collagenous fiber reduced remarkably and the expression of alpha-SMA was significantly down-regulated in the I3C-treated groups (P < 0.01). Apoptosis analysis showed that I3C significantly increased HSC-T6 apoptosis rate and the expressional ratio of Bax to Bcl-2. The results indicated that I3C could effectively cure pig serum-induced liver fibrosis in vivo by inducing HSC apoptosis and promoting ECM degradation.

Objective To investigate the relationship between carotid intima media thickness (IMT) and pulse pressure index (PPI) in elderly hypertensive patients.PPI was defined as 24 h mean pulse pressure(PP)/24 h mean SBP.Methods One hundred and three elderly hypertensive patients were categorized by PPI level:group A (PPI

OBJECTIVETo observe the inhibitory effect of gefitineb on the proliferation and its inducing effect on the apoptosis of mouse I-10 Leydig testicular cancer cells in vitro.

METHODSWe treated I-10 Leydig testicular cancer cells of mice with gefitineb at 0, 1.25, 2.5, 5, 10, 20, and 40 µmol/L. Then we determined the inhibitory effect of gefitineb on the growth of the cells by MTT, detected their early and late apoptosis by Annexin V-FITC/propidium iodide double staining and Hoechst 33258 nuclear staining, respectively, and observed the expressions of apoptosis-related proteins Bcl-2, Bax and caspase 3/9 by Western blot.

RESULTSCompared with the blank control group, gefitineb significantly inhibited the proliferation of the I-10 cells at 10 and 20 µmol/L (P < 0.05). The survival rate of the cells was (32.4 ± 2.8)% (P < 0.01) and their early and late apoptosis rates were (26.7 ± 4.2)% and (59.33 ± 10.2)% in the 40 µmol/L group, significantly different from those in the control (P < 0.05 and P <0.01). In comparison with the blank control group, gefitineb at 10, 20, and 40 µmol/L increased the expression of pro-apoptotic protein Bax by (41.9 ± 7.1), (60.1 ± 9.8), and (69.0 ± 11.3)% (all P < 0.05), decreased that of apoptosis-inhibitory protein Bcl-2 by (50.3 ± 8.9), (63.9 ± 6.9), and (88.7 ± 13.9)% (all P < 0.05), and elevated that of the cleft proteins caspase-3 by (69.0 ± 6.9)% (P < 0.05), (71.5 ± 8.1)% (P < 0.05), and (110.9 ± 14.2)% (P < 0.01) and caspase-9 by (51.8 ± 4.9), (54.7 ± 6.7), and (43.8 ± 11.8)% (all P < 0.05).

CONCLUSIONGefitineb can increase the cytotoxicity of I-10 Leydig testicular cancer cells of mice and induce their apoptosis via the mitochondria-mediated apoptosis signaling pathway.

Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Apoptosis Regulatory Proteins ; metabolism ; Caspase 3 ; metabolism ; Caspase 9 ; metabolism ; Cell Proliferation ; drug effects ; Cell Survival ; Leydig Cell Tumor ; drug therapy ; metabolism ; pathology ; Male ; Mice ; Neoplasm Proteins ; metabolism ; Neoplasms, Germ Cell and Embryonal ; drug therapy ; metabolism ; pathology ; Quinazolines ; pharmacology ; Testicular Neoplasms ; drug therapy ; metabolism ; pathology ; bcl-2-Associated X Protein ; metabolism

OBJECTIVETo summarize our experiences in anesthetic management for the resection of tracheal masses.

METHODSThe clinical data of 15 patients with tracheal masses in Peking Union Medical College Hospital from 2002 to 2012 were analyzed retrospectively. Remarkable dyspnea and tracheal stenosis were observed in 12 patients. Standard orotracheal intubation was carried out in patients with less than 50% of tracheal lumen obstructed. The location of masses was critical for those with severe tracheal stenosis. Local anesthetics were applied and tracheostomy were performed in patients with masses located at the upper part of the trachea. Intubation above the masses was established in patients with masses located at the lower part of the trachea. Percutaneous cardiopulmonary support was introduced before anesthetic induction in a patient with severe respiratory distress and hypercapnea,then an endotracheal tube successfully passed the stenosis guided by a fiberoptic bronchoscope. General anesthesia was induced intravenously and muscle relaxants were applied in all patients. Succinylcholine was administrated in 5 of 6 difficult patients.

RESULTSAirway management and anesthesia were performed successfully in all the 15 patients. After the operations,patients were extubated and discharged from the hospital without difficulty in respiration.

CONCLUSIONSThe successful airway management of tracheal masses depends on the degree and location of stenosis and the severity of dyspnea. Extracorporeal circulation is an optimal choice for those with critical airway occlusion and adequate oxygenation can not be accomplished with conventional anesthesia.

Adolescent ; Adult ; Aged ; Airway Management ; methods ; Anesthesia ; Extracorporeal Circulation ; Female ; Humans ; Intubation, Intratracheal ; Male ; Middle Aged ; Retrospective Studies ; Tracheal Stenosis ; surgery ; Tracheostomy ; Young Adult

OBJECTIVETo evaluate the feasibility and outcomes of chimeric deep circumflex iliac artery perforator flap (DCIAPF) applied in the simultaneous reconstruction of the oromandibular defect.

METHODSSix patients underwent simultaneous oromandibular reconstruction using DCIAPF following segmental mandibulectomy in Xiangya Hospital from March 2014 to July 2014. The skin paddle was designed to be centered on the pre-operative perforator mapping. Retrograde dissection was performed through the underlying abdominal wall to raise the skin paddle. The pedicle was isolated from the groin, and the iliac crest was cut. The deep iliac circumflex vessels were dissected until the skin paddle was reached. Finally, the donor site was strictly sutured layer by layer to avoid ventral hernia.

RESULTSThe skin paddles ranged from 3.5 cmx5.0 cm to 7.0 cmx 10.0 cm. The length of the bone components was 5.0 cm to 11.0 cm. All donor sites closed primarily without skin grafting. DCIAPF was harvested successfully in five patients, except for one patient whose perforator originated from the superficial iliac circumflex vessels. An additional pair of anastomoses was performed. All iliac flaps survived. However, slight skin-edge necrosis and exfoliation caused by flap thinning occurred in one patient and healed after pruning and dressing change. The heights of all alveolar ridges were significantly restored, and no serious donorsite complication was observed during the three to six months' follow-up.

CONCLUSIONDCIAPF is a reconstructive option for mandibular defects because of its adequate bone tissue and rich blood supply. Satisfactory alveolar ridge restoration greatly facilitates future denture retention. DCIAPF also has a great degree of mobility between the skin paddle and the bone component when appliedin composite oromandibular defect reconstruction.

Humans ; Iliac Artery ; Ilium ; Mandible ; surgery ; Maxillofacial Abnormalities ; surgery ; Perforator Flap ; Reconstructive Surgical Procedures ; methods ; Skin

Objective To explore the effects of under-expression of large tumor suppressor 1 (LATS1) on activation of Hippo signaling pathway and differentiation, proliferation, migration of bone marrow mesenchymal stem cells (mMSCs) of micein vitro.Methods mMSCs of C57BL/6 mice were divided into normal control (MSC) group, empty vector control (MSC-GFP) group, LATS1-over-expressing (MSC-LATS1) group, empty vector without LATS1 shRNA control (MSC-shControl) group and LATS1-under-expressing (MSC-shLATS1) group. Lentiviral vectors with activated,inactivated LATS1 (the key molecule of Hippo signaling pathway) modifications and empty vectors were constructed and were used to infect mMSCsin vitro. The transduction efficiencies mediated by the lentiviral vectors were evaluated by fluorescence microscopy and flow cytometry. The mRNA expression of LATS1 was quantified by quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expressions of LATS1, YAP (p-YAP), 14-3-3 were quantified by Western Blot to evaluate the activation of Hippo signaling pathway. Osteogenic and adipogenic differentiation of mMSCs were evaluated through measurement of Runx2, OSX and C/EBPα, PPAR-γ mRNA by qRT-PCR, as well as Alizarin Red S and Oil red O staining. Proliferation of mMSCs was evaluated using methy thiazdyl tetrazolium (MTT) assay. The scratch test and Transwell chamber test were used to analyze the horizontal and vertical migration ability of mMSCs.Results The transduction efficiencies mediated by the lentiviral vectors were 94.74%-96.10%. Compared with MSC-GFP group, the activation of Hippo signaling pathway was promoted in MSC-LATS1 group [LATS1 mRNA (2-ΔΔCT): 4.37±0.21 vs. 1.20±0.04, LATS1 protein (gray value): 2.21±0.06 vs. 1.09±0.10, p-YAP/YAP protein (gray value): 1.51±0.13 vs. 0.98±0.05, 14-3-3 protein (gray value): 1.92±0.18 vs. 1.10±0.09, allP < 0.05], osteogenic and adipogenic differentiation of mMSCs were decreased in MSC-LATS1 group [mineralization (A value):0.13±0.02 vs. 0.40±0.03, Runx2 mRNA (2-ΔΔCT): 0.51±0.02 vs. 0.98±0.09, OSX mRNA (2-ΔΔCT): 0.41±0.04 vs. 1.04±0.09, lipid accumulation (A value): 0.10±0.02 vs. 0.25±0.03, C/EBPα mRNA (2-ΔΔCT): 0.33±0.03 vs. 1.11±0.09, PPAR-γ mRNA (2-ΔΔCT): 0.29±0.02 vs. 1.04±0.10, allP < 0.05], the proliferation rate of mMSCs at 4-7 days was decreased in MSC-LATS1 group and so were the horizontal and vertical migration of mMSCs [wound healing rate: (18.65±3.53)% vs. (40.29±1.87)%, migrated cells (cells/MP): 35.99±6.18 vs. 103.67±17.77, bothP <0.05]. Compared with MSC-shControl group, the activation of Hippo signaling pathway was inhibited in MSC-shLATS1 group [LATS1 mRNA (2-ΔΔCT): 0.16±0.01 vs. 0.98±0.03, LATS1 protein (gray value): 0.38±0.03 vs. 1.04±0.07, p-YAP/YAP protein (gray value): 0.58±0.04 vs. 1.05±0.06, 14-3-3 protein (gray value): 0.14±0.02 vs. 1.02±0.09, allP < 0.05], osteogenic and adipogenic differentiation of mMSCs were increased in MSC-shLATS1 group [mineralization (A value): 0.93±0.13 vs. 0.44±0.05, Runx2 mRNA (2-ΔΔCT): 1.44±0.12 vs. 0.95±0.04, OSX mRNA (2-ΔΔCT):1.67±0.06 vs. 1.10±0.11, lipid accumulation (A value): 0.47±0.06 vs. 0.28±0.04, C/EBPα mRNA (2-ΔΔCT):3.98±0.61 vs. 0.99±0.10, PPAR-γ mRNA (2-ΔΔCT): 3.05±0.36 vs. 0.98±0.14, allP < 0.05], the proliferation rate of mMSCs at 3-7 days was increased in MSC-shLATS1 group and so were the horizontal and vertical migration of mMSCs [wound healing rate: (80.18±6.98)% vs. (46.18±1.01)%, migrated cells (cells/MP): 212.69±41.21 vs. 115.87±35.15, bothP < 0.05].Conclusions Under-expression of LATS1 promotes the differentiation, proliferation, migration of mMSCs by inhibition of Hippo signaling pathwayin vitro.

Objective To observe the molecular weight distribution of soybean peptides prepared by complex enzyme hydrolysation and tumor inhibitory effect in vivo or in vitro. Method The soybean protein was enzymolyzed to soybean peptides by Flavourzyme, Alealase and neutral protease, at(50-55)℃, followed by separation, absorption,affination, ultra centrifuge and spray drying. The soybean peptides were passed Sephadex G25 column at 0.5ml/min with 0.1mol/L Tris-HCl buffer. The fragment of fluid collected was determined by UV at 280nm and HPLC. Then the molecular weight distribution was calculated. The inhibitory effect on ansplant glioma (G422) at dose 1.25, 2.5 and 5g/kg bw (ig daily for 11 d) was tested in mice and in Hep-2 in vitro. Results The peptides contents in three batches were 54.6%, 51.9%, 51.8% respeclively. The molecular weight