Objective To explore the effects of mitogen-activated protein kinase (MAPK) pathway by estradiol induced vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in endometrial cancer Ishikawa cells.Methods The experiments were divided into 4 groups:E2 group (Ishikawa cells treated with 1 p mol/L estradiol for 30 minutes); inhibitor group:including Ishikawa cells treated with 10 μmol/L Bibf1 120 (Bibf1 120 group),or treated with 2.5 μmol/L Ponatinib (Ponatinib group),or treated with 10 p mol/L U0126 (U0126 group) for 60 minutes; inhibitor + E2 group:including Ishikawa cells treated with 10 μmol/L Bibf1120 (Bibf1120 + E2 group),or treated with 2.5 μmol/L Ponatinib (Ponatinib + E2 group),or treated with 10 μmol/L U0126 (U0126+ E2 group) for 60 minutes following incubation with 1 μmol/L estradiol for 30 minutes; control group:only adding the culture medium without serum DMEM.(1) Western blot analysis was used to detect phosphorylation extracellular signal-regulated kinase 1/2(p-ERK 1/2) protein expression with stimulation in different concentrations of estradiol (0.01,0.1,1,10,100 μmol/L).(2) Quantitative fluorescent reverse transcription (qRT)-PCR and western blot analysis was used to test the level of mRNA and protein of VEGF,bFGF,MAPK kinase 1/2 (MEK1/2),extracellular signal-regulated kinase 1/2 (ERK1/2),p-ERK1/2 and phosphorylation MEK1/2 (p-MEK1/2).Flow cytometry were used to examine the cell cycle,and transwell chamber assay were used to detect the cell migration in different groups.Results The expression of the p-ERK1/2 protein at 0.01,0.1,1,10,100 μ mol/L were 0.16±0.03,0.10±0.03,0.41 ±0.04,0.19±0.03,0.19±0.03,there were significantly higher than that in control group(0.05±0.00,P＜0.05),and which was more obvious at the concentration of 1 μmol/L estradiol.The expression level of VEGF,bFGF mRNA and protein in E2 group were higher than those in the control group (P＜O.05).VEGF mRNA and protein in Bibf1120+E2 group were higher than those in E2 group.The expression of MEK1/2,ERK1/2 mRNA protein in E2 group were higher than those in control group (P＜0.05).The expression of MEK1/2,ERK1/2 mRNA or p-MEK1/2,p-ERK1/2 protein in Bibf1120 + E2 group,Ponatinib+E2 group or U0126+E2 group were lower than those in E2 group(all P＜0.05).Percentage of G1 phase [(53.6±3.2)％] and S phase[(29.2±4.2)％] in E2 group was significantly different with those in control group respectively(P＜0.05).Percentage of G1 phase[(66.8±2.6)％,(63.1±2.6)％ and (63.3±0.4)％] and S phase [(25.4±1.9)％,(25.0±3.8)％ and(23.8±0.5)％] in U0126+E2 group,Bibf1120+E2 group or Ponatinib +E2 group was also significantly different with those in control group (all P＜0.05); percentage of G1 phase and S phase in U0126+E2 group was significant difference with those in Bibf1120+E2 group or ponatinib+E2 group (P＜0.05).The number of cell colony in E2 group (110± 17) was more than those in control group (65±8) ;the number of cell colony in U0126+E2 group(28±4),Bibf1120+E2 group(38±5) or Ponatinib+E2group(42±6) were significant different with those in E2 group (P＜0.05),the number of cell colony in U0126+E2 group was significant difference with those in Bibf1 120+E2 group or Ponatinib+E2 group (all P＜0.05).The results shown that the abilities of proliferation and cell migration were significantly increased in cells after estradiol stimulation.Conclusion Estradiol inducing the production of VEGF and bFGF could activate MAPK pathway through ER-independent manner,further promote development.

AIM:To detect the changes of active status of bypass signaling pathways in EML4-ALK positive lung cancer cell line H3122 treated with alectinib, hepatocyte growth factor (HGF), epidermal growth factor (EGF) and transforming growth factor-α (TGF-α), and to explore the potential mechanisms.METHODS:EML4-ALK positive cell line H3122 was treated with increasing concentrations of alectinib or/and induced by HGF, EGF and TGF-α.The cell viability was measured by CCK-8 assay.The cell apoptosis was analyzed by flow cytometry.The protein levels and phosphorylation status of ALK, c-Met and EGFR, and the downstream molecules AKT, ERK, p-AKT and p-ERK were examined by Western blot.RESULTS:The viability of the H3122 cells was inhibited by alectinib in a dose-dependent manner after administrated for 72 h, and the IC50 value was 0.042 μmol/L.The concentration-growth curves of the H3122 cells shifted to the right after induced by HGF, EGF and TGF-α.After treatment with alectinib at 0.05 μmol/L for 48 h, the apoptotic rate of H3122 cells was (20.12±1.36)%, while the apoptotic rates of the cells in the groups of alectinib combined with HGF, EGF or TGF-α were (7.85±1.03)%, (5.60±0.79)% and (4.58±1.00)%, respectively.Those values were remarkably lower than those in alectinib single treatment group (P<0.05).Alectinib inhibited the protein levels of p-ALK and its downstream signaling pathway molecules, while HGF significantly up-regulated the protein levels of p-Met and its downstream p-AKT and p-ERK.Besides, EGF and TGF-α remarkablely up-regulated the protein levels of p-EGFR and its downstream p-AKT and p-ERK.Combined treatment with crizotinib and 17-DMAG successfully inhibited the viability of the H3122 cells even in the presence of the HGF and EGFR ligands, respectively.CONCLUSION:Bypass signaling pathways are activated by HGF, EGF and TGF-α in EML4-ALK positive lung cancer cell line H3122, which may be linked to alectinib resistance.

Objective To evaluate the efficacy and safety of consolidation chemotherapy after thoracic radical concurrent chemoradiotherapy for patients with oligometastatic non?small cell lung cancer ( NSCLC) . Methods Sixty?six NSCLC patients with more than five metastases from 2008 to 2013 were enrolled, and image?guided radiotherapy with conventionally fractionated or hypofractionated doses were performed for these patients. Platinum?based doublets chemotherapy was applied for both concurrent chemoradiotherapy and consolidation chemotherapy. Short?term outcome, adverse reactions, and survival rate were assessed for the patients after treatment. Results Sixty?four patients completed the treatment. The median biologically equivalent dose for planning target volume of thoracic primary tumor lesions was 72 Gy, with a median number of chemotherapy cycles of 4. The objective response rate for thoracic lesions was 70%. The follow?up rate was 97%. The 1?, 2?, and 3?year overall survival ( OS) rates were 72%, 53%, and 31%, respectively, with a median OS time of 25 months;the 1?, 2?, and 3?year progression?free survival ( PFS) rates were 56%, 26%, and 7%, respectively, with a median PFS time of 14 months. The incidence of grade 2?3 acute radiation pneumonitis and radiation esophagitis was 1% and 17%, respectively, and the incidence of grade 3?4 decreases in leukocytes, hemoglobin, and platelet count was 39%, 11%, and 16%, respectively. Conclusions Radical radiotherapy combined with concurrent and consolidation chemotherapy for oligometastatic NSCLC can achieve good short?term outcome and long?term survival, with tolerable adverse effects.

OBJECTIVEThe purpose of this study was to determine the incidence of temporary and permanent sensory disturbance of the inferior alveolar nerve (IAN) after bilateral sagittal split osteotomy (BSSO) of the mandible.

METHODS14 patients were selected for this study. Before BSSO and at 1 week, 1, 3, 6 and 12 months after BSSO, the sensibility of bilateral inferior alveolar nerves were examined using sharp-blunt testing, 2-point discrimination, electronic pain response test (ZGK-1 electrometer).

RESULTSWith conventional sharp-blunt and 2-point discrimination test, electronic pain response test, the incidence of temporary impairment of IAN after BSSO was 78% (22/28). Obvious sensory recovery of IAN was found 6 to 12 months postoperatively. Permanent sensory disturbance of unilateral inferior alveolar nerve occurred in 2 patients.

CONCLUSIONSSensory recovery of the inferior alveolar nerve after bilateral sagittal split osteotomy of the mandible would take 6 to 12 months. Serious injury of the IAN would cause permanent neurosensory deficits.

Adolescent ; Adult ; Female ; Humans ; Male ; Mandible ; surgery ; Mandibular Nerve ; physiopathology ; Oral Surgical Procedures ; adverse effects ; Osteotomy ; adverse effects ; methods ; Sensory Thresholds ; Trigeminal Nerve Injuries

Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P＜0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P ＜ 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .