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.

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.

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

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 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 master the area scope and epidemic situation of Kaschin-Beck disease (KBD) in Harbin,and to accumulate data and information for the midterm examination and evaluation of the 12th Five-Year Plan of the National Endemic Disease Prevention and Control.Methods In the original 10 counties (districts,cities) of Harbin with KBD,2 surveys were carried out from 2011 to 2015,5 townships were extracted in each county (district,city),3 villages were extracted in each township,clinical investigation and X-ray examination of 7-12 years old children were carried out;according to the criteria for Diagnosis of Kaschin-Beck Disease,a clinical survey was conducted in 2013 in the 10 counties (districts,cities) with KBD.According to the KBD prevalence and X-ray examination results in each county (district,city),reference to Criteria for Control of Kaschin-Beck Disease Areas,Criteria for Delimitation and Classification of Kaschin-Beck Disease Area,Evaluation Methods for Endemic Diseases Control and Elimination,the types of the disease areas,control and eliminating situation were determined;organization and management of the control and prevention measures were evaluated.Results Currently,there were 10 counties (districts,cities),373 villages,6 969 patients with KBD in Harbin.According to the KBD area division and control standard,369 villages were light KBD areas (prevalence of clinical degrees Ⅰ and above patients or detection rate of 7-12 children by X-ray for local residents ≤ 10％) and 4 villages were medium KBD areas (prevalence of clinical degrees Ⅰ and above patients or detection rate of 7-12 children by Xray for local residents ＞ 10％-≤20％).Clinical census showed that the people under 20 years had no cases with degree Ⅰ and above in each village,X-ray detection rate was 0 in 7-12 years old children,in line with the standards of history KBD areas.There were no clinical KBD cases in 7-12 years old children in all villages of KBD areas,positive detection rate of children by X-ray was 0 in the sampling KBD area villages,in line with the standards of eliminate technical standards of KBD area village.The management index scores of KBD were from 85 to 95 points in every area county (district,city),getting to the eliminating requirement which was more than 85 points.Conclusion The KBD areas have narrowed down and prevalence has declined significantly in Harbin,which has reached the area eliminating standards and the index of basically eliminating KBD proposed by the 12th Five-Year Plan.

Objective In order to accumulate data for the final evaluation and acceptance of the Twelfth Five-Year Plan of National Endemic Disease Prevention and Control,we investigated the endemic scopes and basic situation of Keshan disease (KD) in Harbin.Methods According to the Criteria for Diagnosis of Keshan Disease (WS/T 210-2011),we conducted clinical survey of KD prevalence in 10 KD endemic counties in Harbin in 2013.2011-2015,we detected and searched for cases in 10 ward counties of Keshan disease.According to the Delimitation and Classification of Keshan Disease Areas and the Evaluation of Endemic Disease Control and Elimination,we determined the regional type,the situation of control and elimination of the disease,at the same time all KD patients were positioned by global positioning system (GPS).Results There were 2 KD endemic counties,12 endemic townships,and 37 KD patients in Harbin.All 12 townships were the light endemic regions of KD.Other townships were conformed to be the history regions with KD.The management index scores of KD reached the elimination requirements which were more than 85 points in every region county (city).Ten region counties got to technical standards for KD elimination.Harbin basically reached the index of KD elimination.The GPS satellite positioning of KD patients were concentrated in the 45.1-45.5 degrees north latitude,and 127.7-128.3 degrees east longitude.Conclusion The regions of KD endemic areas have narrowed down and the prevalence rate has declined significantly in Harbin,which have reached the basic elimination standards of KD by the 12th Five-Year Plan.

Objective:To investigate the effect of estrogen on the expression of P2X7 receptor ( P2X7R) in the cerebral cortex and neuroinflammation after subarachnoid hemorrhage ( SAH) in rats.Methods:The rat model of SAH was induced by modified mono-filament puncture method.Sixty male SD rats were divided randomly into three groups:sham group;SAH group and estrogen-treatment group.The local cerebral blood flow was detected with laser doppler blood flow meter.The content of tumor necrosis factor alpha ( TNF-α) and interleukin-6 (IL-6) were measured by ELISA analysis.The expression of P2X7R in the cerebral cortex was tested by immuno-histochemical and Western blot methods.Results:Compared with that in Sham group,cerebral blood flow was significantly decreased after SAH (P<0.05),the content of TNF-αand IL-6 in the cerebral cortex were significantly up-regulated at each time point after SAH (P<0.05),peaked at 24 h,and the expression of P2X7R significantly increased at 6 h,12 h and 24 h after SAH (P<0.05),peaked at 12 h.Compared with that in SAH group,cerebral blood flow was significantly increased in estrogen-treatment group (P<0.05),the levels of TNF-α,IL-6 and P2X7R were down-regulated in estrogen-treatment group ( P<0.05).Conclusion: Estrogen could attenuate neuroinflammation in the cerebral cortex after subarachnoid hemorrhage in rats, which may be associated with the down-regulation in P2X7R proteins.