Objective To investigate the effect of transcription factor specific protein5(Sp5)silencing on Wnt signaling pathway correlated factors and cell proliferation ability in mouse embryo palatal mesenchymal cells(mEPMCs).Methods mEPMCs of 14.5 d pregnant C57BL/6J mice were isolated and cultured in vitro.Cell source was identified by immunofluorescence staining.Lentivirus transfection technique was used to silence the expression of Sp5 gene in mEPMCs,and the transfection efficiency was verified by Western blot assay.Follow-up experiments were set up with the blank control group,the no-load virus group and the slience group(the Sp5-shRNA group).The protein and mRNA expression levels of β-catenin,GSK-3β,Wnt3a and CyclinD1 were detected by Western blot assay and RT-qPCR after transfection for 72 h in each group.Cell proliferation capacity was detected by CCK-8.The proliferation rate of 5-Ethynyl-2'-deoxyuridine(EdU)positive cells was detected by immunofluorescence assay.Cell cycle was detected by flow cytometry.Results mEPMCs were successfully isolated,and Sp5 expression was silenced.Western blot and RT-qPCR results showed that the protein and mRNA expressions of β-catenin,GSK-3β,Wnt3a and CyclinD1 were significantly higher in the Sp5-shRNA group than those in the blank control group and the no-loaded virus group(P<0.05).The proliferative ability and the proliferative rate of EdU positive cells were higher in the Sp5-shRNA group than those in the blank control group and the no-loaded virus group(P<0.05).The proportion of mEPMCs in S phase was higher in the Sp5-shRNA group than that in the blank control group and the no-loaded virus group(P<0.05).Conclusion Sp5 in silenced mEPMCs can participate in palate development and promote the proliferation of mEPMCs by regulating Wnt signaling pathway.

Objective:To evaluate and summarize the best evidence for exercise scheme after bariatric and metabolic surgery in obese patients at home and abroad.Methods:We used "obesity" " bariatric and metabolic surgery" "sleeve gastrectomy" "gastric bypass surgery" "banding surgery" "exercise" "physical activity" "exercise therapy" "guideline" "expert consensus" "systematic review" "Meta-analysis" and "evidence summary" as keywords, and searched databases such as UpToDate, Cochrane Library, PubMed, China National Knowledge Infrastructure (CNKI) , Wanfang Data, and the guide network and professional association platforms by computer. Literature retrieved included guidelines, expert consensus, best clinical practice, clinical decision-making, systematic reviews, and the search time limit was from the database establishment to July 18, 2020. Two researchers evaluated the quality of literature and extracted evidence, and the evidence was revised and perfected through expert consultation.Results:A total of 4 systematic reviews and Meta-analysis articles, 2 clinical decision-making articles, 4 guidelines, and 1 expert consensus were included. The evidence was collected from 7 aspects, namely the importance of exercise, pre-exercise evaluation, exercise style, exercise intensity and duration, exercise safety, exercise follow-up, exercise effect evaluation, and finally 33 best evidences were summed up.Conclusions:Evidence of exercise scheme after bariatric and metabolic surgery in obese patients is comprehensive. Medical institutions and clinical medical and nursing staff can combine the institutional environment to transform and apply the evidence.

Objective: To compare the efficacy and treatment-related toxicity of high dose versus standard dose radiotherapy in concurrent chemoradiotherapy (CCRT) for patients with esophageal squamous cell carcinoma (ESCC). Methods: From 2005 to 2012, 183 pairs of patients with esophageal squamous cell carcinoma in the Fourth Hospital of Hebei Medical University were enrolled, all had undergone CCRT based on three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). A propensity score was constructed to match the cohort. The overall survival (OS), local control (LC) probability, as well as the acute and late toxicities between standard-dose and high-dose groups were compared. Results: Patients in the high-dose group had significantly better OS and LC probability compared with those in the standard-dose group: the 3-, 5- and 10-year LC rate were 60.9%, 57.6%, 52.3% versus 50.8%, 46.4%, 30.8%, respectively (P=0.032). The 3-, 5- and 10-year OS were 44.3%, 36.9% and 24.5% for high-dose group, and 31.7%, 20.6% and 14.1% for the standard-dose group, respectively(P=0.002). The incidence of acute radiation esophagitis (especially in grade 2 and 3) was 63.9% in high-dose group, which was significantly higher than that in the standard-dose group (59.6%). Severe (≥ grade 3) late-onset esophagitis was observed in neither group. The grade 4 acute esophagitis was rare. There was no significant difference in the incidence of radiation pneumonitis, gastrointestinal reactions or hematological toxicities between the two groups. Six patients in high-dose group and two patients in standard-dose group experienced ≥ grade 4 leukocytopenia, while no one experienced > grade 3 thrombocytopenia and anemia in both group. Conclusions 60 Gy was the preferred dosage of CCRT in patients with ESCC. Compared with standard-dose, the high-dose CCRT yielded slightly increased mild to moderate acute radiation esophagitis, while life-threatening toxicities were not increased.

Objective To evaluate the efficacy of early controlled cold atomization inhalation of budesonide in the treatment of post-operative sore throat (POST) after double-lumen endotracheal intubation. Methods A total of 105 ASAⅠ~Ⅲpatients having POST after thoracic surgery with double-lumen endotracheal intubation were randomly divided into three groups(n = 35 each). The patients in the control group were treated with atomization inhalation of 12 mL 20℃saline(Group C)and those in the observation groups were treated with 10 mL 20℃saline plus 2 mL(1 mg)budesonide(Group R)or 10 mL 0℃saline plus 2 mL(1 mg)budesonide (Group L)for 15 minutes immediately after extubation. The 4-score scale was used to evaluate sore throat,dry throat,hoarseness and swallowing difficulty 1,2,6 and 24 h after the extubation and QoR-40 scale to assess post-operative recovery at 24 h. Results The scores of sore throat and dry throat were significant lower in group L than those in group C(P < 0.05)at 1,2 and 24 h and the score of swallowing difficulty(dysphagia)was also signifi-cant relieved at 1,6 and 24 h after the extubation in group L. Furthermore,the score of sore throat was significant lower in group L than that in group R(P<0.05)at 1 h. There were no significant differences of hoarseness in three groups(P > 0.05). The total score of QoR-40 scale was the significantly highest in group L than that in group C and group R(P<0.05)24 h postoperatively. Conclusion Cold atomization inhalation of budesonide immediately after the extubation of double-lumen endotracheal can alleviate POST and bring more benefits to patients which help to enhance the recovery after throracic surgery.

Objective To determine the efficacy of primary tumor of esophageal cancer,according to the result of magnetic resonance imaging before and after chemoradiotherapy of esophageal cancer,combined with clinical efficacy evaluation,and to verify the reliable evaluation of the short-term curative effect of magnetic resonance on esophageal cancer,combined with the original CT and esophagogram evaluation criteria.Methods From May 2010 to March 2014,totally 83 patients with esophageal carcinoma treated with 3D-CRT or IMRT were enrolled.The prescribed doses were ranged from 50-64 Gy with median dose of 60 Gy and 1.8-2.0 Gy per fraction,of which 34 of the patients received concurrent chemotherapy of FP or TP.All the patients performed the examinations of DWI,CT scan and esophagogram before and after radiotherapy.The treatment efficacy was evaluated by short-term therapeutic effect evaluation criterion of versions 1989 and 2013 and the hyperintense expression on DWI sequence.Results According to the short-term therapeutic effect evaluation criterion of versions 1989 and 2013 based on the examination of esophagogram and CT scan,45 patients achieved complete remission (CR) after treatment(54.2％) and 38 achieved partly remission(PR) (45.8％) version 1989,while 35 patients achieved CR (42.2％) and 48 achieved PR (57.8％) version vesion 2013.In the two differentcriterions,the local control rate and survival rate of the complete remission group in 1 to 5 years were better than those in the partial remission group.According to the examination of DWI,48 patients' hyperintense disappeared completely at the end of treatment (which was defined to CR),25 patients had a slightly hyperintense expression and 10 patients still had hyperintense expression on DWI sequence (which two defined to PR),the local control and survival rates of the former group were superior to the latter groups (x2 =6.125,11.652,P ＜0.05).The TE results evaluated by DWI and TE evaluation criterion of version 2013 were compared according to Kappa test,as a result,the Kappa coefficient 0.478.According to the examination of esophagogram,CT scan and DW1,25 patients achieved CR and 58 achieved PR in all exams,and the local control and survival rates of the former group were superior to the latter group (x2 =5.559,10.014,P ＜0.05).Conclusions The esophagogram and CT based TE evaluation criterion could well indicate local control status of esophageal cancer,and the examination of DWI could afford visualized and quantifying reference information about the TE of esophageal cancer.The expression of hyperintense at the end of treatment may indicate a high risk of recurrence and metastasis.The therapeutic effect evaluated by esophagogram,CT scan and DWI maybe more objective and more accurate.

Objective To explore and improve the feasibility and prognostic value of barium radiography and computed tomography (CT)-based evaluation criteria in evaluation of the short-term efficacy of radiotherapy for esophageal cancer,and to provide a basis for clinical application.Methods The short-term treatment outcomes of 529 patients with esophageal carcinoma receiving three-dimensional radiotherapy from 2004 to 2015 were evaluated by the 2013 version of barium radiography and CT-based evaluation criteria.The local control (LC) and survival rates were calculated using the Kaplan-Meier method.The log-rank test was used for data analysis and univariate prognostic analysis.The agreement between two evaluation criteria was measured by the Kappa coefficient.Results According to the results of the survival analysis in all the patients using the evaluation criteria for short-term treatment outcomes,the 3-,5-,7-,and 9-year LC rates were 78.6％,69.8％,69.8％,and 63.4％ in the complete response (CR) group (n=52),and 56.4％,47.9％,46.2％,and 42.4％ in the partial response (PR) group (n=409),respectively;the 3-,5-,7-,and 9-year overall survival (OS) rates were 62.7％,49.1％,39.8％,and 39.8％ in the CR group,and 29.5％,21.6％,20.6％,and 19.5％ in the PR group,respectively;the median OS time was 50,17,and 5 months in the CR group,PR group,and non-response group (n=12),respectively (P=0.000).According to CT measurements,the short diameter of residual metastatic lymph node after radiotherapy was between 0.37-3.40 cm (median value=0.82 em).All patients were divided into groups based on the short diameter of residual metastatic lymph node after radiotherapy with a gradient of 0.5 cm.Patients with short diameters of residual metastatic lymph node of ≤ 1.00 cm had a significantly higher OS rate than those with short diameters of residual metastatic lymph node of＞ 1.00 cm (P =0.000).The lymph node volume of 1.00 cm3 in the original criteria was replaced by the short diameter of residual metastatic lymph node of 1.00 cm after radiotherapy and treatment outcomes were re-evaluated using the new criteria.The CR group still had significantly higher LC and OS rates than the PR group (P=0.000).There was a good agreement between the two evaluation criteria (Kappa =0.863).Conclusions The barium radiography and CT-based evaluation criteria for short-term treatment outcomes can accurately evaluate the short-term outcomes and predict prognosis in patients with esophageal carcinoma.Replacing the volume in the original criteria with the short diameter of residual metastatic lymph node after radiotherapy achieves similar results in prognostic prediction.

Objective To investigate the survival benefits of simultaneous integrated boost intensity-modulated radiotherapy ( SIB-IMRT ) in the treatment of esophageal squamous cell carcinoma ( ESCC ) . Methods From July 2003 to March 2014,1748 patients with ESCC received 3DCRT or IMRT in a single institution were enrolled in this retrospective study. Among them, 809 patients received conventional fractionated radiotherapy with the standard prescription dose and 110 patients received SIB-IMRT ( SIB-IMRT group).Survival analysis was performed and propensity score matching (PSM 1vs1) was conducted to evaluate and compare the survival benefits between SIB-IMRT and conventional fractionated radiotherapy. Results The baseline characteristics significantly differed between two groups. In the SIB group,the age was significantly younger ( 64 years vs. 66 years, P=0. 001 ) , the percentage of patients with cervical/upper thoracic tumors was considerably higher (53. 6％ vs. 31. 0％,P=0. 000) and the proportion of N2 patients was significantly higher ( 21. 8％ vs. 13. 7％,P=0. 027) compared with those in the other group. Accordingto the PSM of 1:1, 218 patients were successfully matched. After matching, the clinical data did not significantly differ between two groups. Prior to matching,the median survival time in the standard dose and SIB-IMRT groups were 23 and 21 months (P=0. 638).After matching,the median survival time in the SIB-IMRT group was 22 months,significantly longer than 18 months in the standard dose group (P=0. 000). Subgroup analysis demonstrated that patients with large tumors ( GTV volume>40 cm3 ) and middle/lower thoracic tumors obtained more survival benefits from SIB-IMRT. The median survival time of patients in the standard dose group was 14 months, significantly shorter than 21 months in the SIB-IMRT group ( P=0. 001).The median survival time of patients with middle/lower thoracic tumors in the SIB-IMRT group was 17 months,significantly longer than 9 months in the standard dose group (P=0. 000).Multivariate analysis using Cox regression model indicated that age, tumor site and radiotherapy modality were the independent prognostic factors. The HR of SIB-IMRT was 0. 551(P=0. 000),which was a factor for survival benefits. Conclusions SIB-IMRT possesses potential survival benefits for ESCC compared with conventional fractionated radiotherapy. Patients with large tumors and middle/lower thoracic tumors are more prone to obtaining benefits from SIB-IMRT than their counterparts.

Objective To observe the long?term survival and adverse reactions in patients with stage T4 N (+) Ⅲ middle and lower thoracic esophageal carcinoma undergoing intensity?modulated radiotherapy ( IMRT) . Methods From 2004 to 2010, 300 patients with stage T4 N (+) Ⅲ middle and lower thoracic esophageal carcinoma, consisting of 202 treated with three?dimensional conformal radiotherapy ( 3DCRT ) and 98 treated with IMRT, were enrolled as subjects. All patients received conventionally fractionated radiotherapy with a prescribed dose of 60 Gy. The long?term survival and adverse reactions were compared between patients treated with the two different radiotherapy regimens. The survival rates were calculated by the Kaplan?Meier method and analyzed by the log?rank test. Results The 5?and 7?year sample sizes were 239 and 120, respectively. The 3DCRT group had significantly lower 1?, 3?, 5?, and 7?year local control (LC) and overall survival (OS) rates than the IMRT group (64. 4% vs. 68. 3%, 40. 6% vs. 55. 3%, 38. 3% vs. 51. 9%, 34. 2% vs. 51. 9%, P=0. 048;54. 5% vs. 63. 3%, 19. 8% vs. 34. 7%, 14. 7% vs. 24. 4%, 10. 9% vs. 20. 3%, P=0. 013) . The stratified analysis showed that for patients older than 65 years, with the length of esophageal lesion>8. 0 cm before radiotherapy, the largest diameter of esophageal lesion in computed tomography image>4. 6 cm, gross tumor volume ( GTV)>60 cm3 , metastases to adjacent tissues or organs, stage N2 , and without chemotherapy, the IMRT group had a significantly higher OS rate than the 3DCRT group (P=0. 022,0. 003,0. 022,0. 034,0. 016,0. 044,0. 047). The GTV Dmin and GTVD100 were significantly higher in the IMRT group than in the 3DCRT group ( P=0. 000,0. 000) , while the Dmax of the spinal cord was significantly lower in the IMRT group than in the 3DCRT group ( P=0. 000) . Compared with the 3DCRT group, the IMRT group had a significantly higher incidence of acute radiation?induced esophagitis, particularly grade 1?2 esophagitis (P=0. 000). The mortality rate caused by local tumor was significantly higher in the 3DCRT group than in the IMRT group ( P= 0. 039 ) . Conclusions In the treatment of locally advanced middle and lower thoracic esophageal carcinoma, IMRT is safe and effective;it significantly improves the LC rate and long?term survival without severe toxicity to normal tissues. The results of this retrospective study need to be confirmed by prospective randomized controlled studies.

Objective To examine the prediction value of diffusion-weighted magnetic resonance imaging (DWI) on radiotherapy response in esophageal cancer.Methods A total of 24 subcutaneous esophageal cancer xenograft models were randomly divided into experimental group (n =14,received a single dose of 15 Gy radiotherapy) and control group (n =10,without any treatment).MRI were required before and after radiotherapy at different check time points (1,6,13 days) of T1WI,T2WI,and DWI measurements.Apparent diffusion coefficient (ADCX) and volume (VX) of each xenograft were measured,and both △ADCX and △VX were calculated.Results The ADC values of both group were decreased at the first day,however,the decrease in experimental group were more obviously with an increase at 6 and 13 d gradually.However,the ADC values of the control group showed a persistent decline.There was no significant difference in the ADC values between the two different groups before radiotherapy (P ＞ 0.05),while significant difference was found in the ADC values (F =6.178,16.181,58.733,P ＜ 0.05) and △ADC after radiotherapy (F =9.038,12.360,35.140,P ＜ 0.05).The xenografts volume in the experimental group showed a significant growth delay.There was no significant difference in volume between the two groups (P ＞ 0.05) before radiotherapy.Significant difference in V between the two groups only began to exist at 5 d after radiotherapy (F =28.587,P ＜ 0.05).The ADC0,ADC1 of transplanted tumor in control group had linear correlation relationships with its volume of later period.After radiotherapy,the trend of r values gradually increased from-0.118 to 0.896.Conclusions ADC values may change significantly at the early stage after radiotherapy,and initial and early ADC value may have close relationship with xenograft volumes of later period,which indicates that DWI has huge potential in the prediction of radiotherapy response.

Objective To investigate the predictive value of symmetrical ambulatory arterial stiffness index (S-AASI) in detecting early renal impairment of patients with essential hypertension.Methods Totally 245 consecutive out-patients were confirmed with essential hypertension,and were divided into group A (56 cases),group B (64 cases),group C (72 cases),and group D (53 cases) according to the quartile of S-AASI.The combination testing of serum cystatin C,serum β2-microglobulin as well as urine microalbumin to creatinine ratio were implemented as laboratory diagnosis index of renal impairment in early stage and 109 essential hypertension patients were diagnosed with early renal impairment.The parameters were compared among 4 groups.Pearson correlation analysis and partial correlation analysis were performed to confirm the relationship between the markers of early renal impairment and S-AASI.The predictive value of S-AASI to detect early renal injury was evaluated by analyzing Receiver Operating Characteristic (ROC) curve.Results With the rising of S-AASI,age as well as 24 hours mean systolic blood pressure (24 h SBP),serum cystatin C,serum β2-microglobulin,urine microalbumin to creatinine ratio and the incidence rate of early renal injury went notably higher while estimated glomerular filtration rate (eGFR) decreased significantly.After controlling for age,correlation test showed S-AASI was positively correlated with24hSBP,serum cystatin C,serumβ2-microglobulin,urine microalbumin to creatinine ratio(r =0.392,0.627,0.514 and 0.643 respectively,P ＜ 0.05) and negatively correlated with eGFR(r =-0.312,P ＜ 0.05).The 24 hours mean diastolic blood pressure (24 h DBP) was uncorrelated with S-AASI.Area under ROC curve of S-AASI for diagnosis of hypertensive renal impairment was 0.885.The critical value of S-AA-SI was 0.17,the sensitivity,specificity,positive predictive value,and negative predictive value were 92.7％,65.2％,68.5％,and 91.7％,respectively.Conclusions When S-AASI was detected above 0.17,patients with hypertension had a higher risk of renal impairment.Higher S-AASI was correlated with worse early renal impairment laboratory indexes.The predictive accuracy of S-AASI for early hypertensive renal impairment was medium.