Objective The BOIN12 design was improved based on conditional weighted likelihood method to solve the optimal dose exploration in the case of delayed toxicity and efficacy of drugs.Methods The conditional weighted likelihood method was used to estimate the toxicity rate and conditional efficacy rate.The improved BOIN12 design was compared with other phase Ⅰ-Ⅱ design through simulation to evaluate its performance.Results Simulation results show that the improved design still has excellent statistical performance in different scenarios and the trial duration is greatly shortened.Conclusion The improved design can addresses both toxicity and efficacy delays in phase Ⅰ-Ⅱ trials.

Objective Aiming at the problem of delayed therapeutic effect of tumor targeting agents and cellular immunotherapy,an innovative TITE(e)-U-Keyboard design is established based on the framework of phaseⅠ/Ⅱclinical trial design.Methods Approximated binomial likelihood method was used to incorporate the unobserved efficacy outcome information and construct approximated distribution to assist decision making.TITE(e)-U-Keyboard was compared with theⅠ/Ⅱ trial design method(U-BOIN、BOIN12)from multiple perspectives.Results Simulation results show that the accuracy of OBD selection and the number of patients allocated at optimal dose of the three methods were similar,but TITE(e)-U-Keyboard requires the shortest trial duration.Sensitivity analysis shows that the effectiveness evaluation window has an effect on the TITE(e)-U-Keyboard duration,which increases with the increase of effectiveness evaluation window.Conclusion TITE(e)-U-Keyboard significantly reduces the trial duration while maintaining good simulation performance and it can address the problem of delayed treatment effects in phase Ⅰ/Ⅱ clinical trials,thus accelerating the clinical trial process.

Objective:To examine the prognosis factors of postoperative cardiac complications in colorectal cancer patients co-morbidated with coronary artery disease.Methods:Clinical data of 449 patients colorectal cancer patients co-morbidated with coronary artery disease accepted redical surgery from April 2013 to April 2020 at Department of General Surgery, Peking Union Medical College Hospital were analyzed retrospectively. There were 306 males and 143 females, aging (68.7±8.9) years (range: 44 to 89 years). Postoperative acute coronary syndrome, new-onset arrhythmia and heart failure that causes clinical symptoms were recorded as cardiac complications. t test, χ 2 test and Fisher exact test were used for univariate analysis of prognosis factors of postoperative cardiac events. The variables with P<0.05 were included in the multivariate Logistic regression was used to determine the independent prognosis factors. Results:After surgery, 44 patients (9.8%) suffered from at least one cardiac event, including 30 patients with acute coronary syndrome, 19 patients with new-onset arrhythmia and 9 patients with heart failure. There were 3 deaths in the cohort within 30 days after surgery. Two patients died from cardiac-related complications, and one from septic shock due to postoperative anastomotic leaks. On Univariate analysis showed that cardiac complications were associated with age ≥80 years, co-morbidated diabetes, emergency surgery, re-operation, anastomotic leakage, intestinal flora disorder and elevation of preoperative neutrophil-lymphocyte ratio (χ 2: 4.308 to 12.219, all P<0.05). Multivariate Logistic regression analysis identified age ≥80 years ( OR=3.195, 95% CI: 1.379 to 7.407, P=0.007), co-morbidated diabetes ( OR=2.551, 95% CI: 1.294 to 5.025, P=0.007), emergency surgery ( OR=4.717, 95% CI: 1.052 to 20.833, P=0.043), and elevated preoperative neutrophil-lymphocyte ratio ( OR=1.114, 95% CI: 1.018 to 1.218, P=0.018) as independent prognosis factors for cardiac complications. Conclusions:Emergency surgery, advanced age, co-morbidated type 2 diabetes and elevated preoperative neutrophil-lymphocyte ratio may increase the risk of postoperative cardiac complications in colorectal cancer patients with coronary artery disease. Surgeons should strictly master surgical indications, pay attention to preoperative assessment, perioperative monitoring, and diagnosis and treatment of postoperative complications in order to reduce the risk of complications.

Objective:To examine the prognosis factors of postoperative cardiac complications in colorectal cancer patients co-morbidated with coronary artery disease.Methods:Clinical data of 449 patients colorectal cancer patients co-morbidated with coronary artery disease accepted redical surgery from April 2013 to April 2020 at Department of General Surgery, Peking Union Medical College Hospital were analyzed retrospectively. There were 306 males and 143 females, aging (68.7±8.9) years (range: 44 to 89 years). Postoperative acute coronary syndrome, new-onset arrhythmia and heart failure that causes clinical symptoms were recorded as cardiac complications. t test, χ 2 test and Fisher exact test were used for univariate analysis of prognosis factors of postoperative cardiac events. The variables with P<0.05 were included in the multivariate Logistic regression was used to determine the independent prognosis factors. Results:After surgery, 44 patients (9.8%) suffered from at least one cardiac event, including 30 patients with acute coronary syndrome, 19 patients with new-onset arrhythmia and 9 patients with heart failure. There were 3 deaths in the cohort within 30 days after surgery. Two patients died from cardiac-related complications, and one from septic shock due to postoperative anastomotic leaks. On Univariate analysis showed that cardiac complications were associated with age ≥80 years, co-morbidated diabetes, emergency surgery, re-operation, anastomotic leakage, intestinal flora disorder and elevation of preoperative neutrophil-lymphocyte ratio (χ 2: 4.308 to 12.219, all P<0.05). Multivariate Logistic regression analysis identified age ≥80 years ( OR=3.195, 95% CI: 1.379 to 7.407, P=0.007), co-morbidated diabetes ( OR=2.551, 95% CI: 1.294 to 5.025, P=0.007), emergency surgery ( OR=4.717, 95% CI: 1.052 to 20.833, P=0.043), and elevated preoperative neutrophil-lymphocyte ratio ( OR=1.114, 95% CI: 1.018 to 1.218, P=0.018) as independent prognosis factors for cardiac complications. Conclusions:Emergency surgery, advanced age, co-morbidated type 2 diabetes and elevated preoperative neutrophil-lymphocyte ratio may increase the risk of postoperative cardiac complications in colorectal cancer patients with coronary artery disease. Surgeons should strictly master surgical indications, pay attention to preoperative assessment, perioperative monitoring, and diagnosis and treatment of postoperative complications in order to reduce the risk of complications.

Objective To define a parameter of autologous arteriovenous fistula stenosis that limits the fistula function for hemodialysis in our country.Methods Retrospectively study the doppler ultrasound of patients who accepted the percutaneous transluminal angioplasty (PTA) therapy due to autogenous arteriovenous fistula dysfunction;identify the least diameter of the fistula vein and compare it with the corresponding data of well-functioned fistula.Determine which absolute diameter constitutes a hemodynamically significant stenosis in a radioeephalic autologous arteriovenous fistula by receiver operating characteristic curve (ROC curve).Result Forty-two patients were enrolled in the study.The average age of those patients was 54.63±2.44 years old.Twenty-one patients were female.Twenty-six fistula located on the left arm.The minimal diameter of the dysfunction fistula averaged 1.57±0.07 mm,while the average forearm fistula vein diameter was 4.04±0.23 mm,significantly smaller than those in the compare group-an average minimal fistula vein diameter of 3.34±0.11 mm and a forearm vein diameter of 5.36(4.52,6.45) mm (P ＜ 0.05).The control group contained sixty-eight patients.The average age of those patients was 52.56±2.00 years old.Thirty-one patients were female.Forty-nine fistula located on the left arm.It was quiet appropriate in using minimal diameter of the fistula vein to indicate the dysfunction istula with an under-curve area of 0.979,95％C1 0.959-0.998.The under-curve area would be at the largest level when meeting the cutoff point at 2.40mm,in which it could achieve the area of 0.853.Conclusions The minimal diameter of the dysfunction wrist autogenous arteriovenous fistula was much smaller than the functioned ones.Minimal diameter of the fistula vein may serve as an effective parameter in detecting dysfunction fistula.

Objective:To observe the effect of low-expression or over-expression of NUP88 gene on the proliferation and invasion ability of breast cancer cell line BT-20.Methods: NUP88 recombinant adenovirus expression vector and NUP88 RNAi adenovirus vector were transfected into breast cancer BT-20 cells to obtain BT-20 cells over-expressing NUP88 and BT-20 cells lower-expressing NUP88 and then detected the expression of NUP88 mRNA and NUP88 protein.After that,the apoptosis of BT-20 cells was detected by flow cytometry and the invasion and metastasis of BT-20 cells were detected by Transwell invasion assay.The expression of apoptosis protein and invasion and metastasis proteins were detected by Western blot.Results: BT-20 cell with the over expression levels of NUP88 mRNA and NUP88 protein and BT-20 cell with the low expression levels of NUP88 mRNA and NUP88 protein were structured.The over-expression of NUP88 gene led to proliferation rate and the number of invasive cells were significantly higher than BT-20 cells,apoptosis cells were significantly lower than BT-20 cells(P<0.05).However,the low-expression of NUP88 gene led to proliferation rate and the number of invasive cells were significantly lower than BT-20 cells,apoptosis cells was significantly higher than BT-20 cells(P<0.05).The over-expression of NUP88 gene led to Bcl-2 and β-catenin level were significantly higher than that of BT-20 cells,and Bax and E-cadherin level were significantly lower than that of BT-20 cells(P<0.05).However,the low-expression of NUP88 gene led to Bcl-2 and β-catenin level were significantly lower than that of BT-20 cells,and Bax and E-cadherin level were significantly higher than that of BT-20 cells(P<0.05).Conclusion: NUP88 gene regulates the proliferation and invasion and migration ability of breast cancer cells by regulating the expression of Bax,Bcl-2,E-cadherin and β-catenin.It has an important significance in the target treatment of breast cancer.

Objective To study the technical method of immunohistochemical staining in pathological tissue.Methods 80 cases of hospitalized patients in our hospital from May 2015 to May 2016 were selected, they were randomly divided into immunohistochemical staining group(immunohistochemistry group, n=40)and biopsy group(n=40)two groups, then the AFP(alpha-Fetoprotein), Glypican-3 positive situation of the the two groups and diagnostic Resultsof patients with different types of disease in the immunohistochemistry group were statistically analyzed.ResultsThe positive rate of AFP(a-Fetoprotein), Glypican-3 of the immunohistochemistry group 92.5%(37/40)was significantly higher than the biopsy group 50.0%(20/40)(P<0.05), Among the 37 cases of positive patients, metastatic tumors 19 cases, hepatocellular carcinoma 9 cases, intrahepatic bile duct carcinoma 7 cases, hemangioma 3 cases, the positive rates were 100.0%, 75.0%, 100.0%, 100.0%, 26 cases died, the mortality rate was 70.3%, of which metastatic tumors 13 cases, hepatocellular carcinoma 6 cases, intrahepatic bile duct carcinoma 5 cases, hemangioma 2 cases, the mortality rates were 72.2%, 66.7%, 71.4%, 66.7%.Conclusion Immunohistochemical staining technic in pathological tissue can promote positive rate, and standard operation procedures can reduce errors, which is worthy of clinical attention.

Objective To analyze the relationship between the least diameter of autogenous arteriovenous fistula and other parameters like flow rate and artery diameter. To identify an appropriate way in defining fistula stenosis. Methods Physical examination and Doppler ultrasound were used to examine the autogenous arteriovenous fistula of maintenance hemodialysis patients. Well?used wrist arteriovenous fistula was included. The least diameter of the fistula vein was found and marked by ultrasound, and the diameter and the distance between the point and the anastomotic stoma were measured. Diameters of different places along the cephalic vein of the fistula, including the forearm place, the place close to elbow and the upper arm place were measured by ultrasound. Meanwhile, diameter as well as flow velocity and flow rate of brachial artery, radial artery and ulnar artery were also measured. Result Sixty?eight patients were enrolled in the study. The average age of those patients was 52.56 ± 2.00 years old. Thirty?one patients were female. Forty?nine fistula were located on the left arm. The average diameter and flow rate of brachial artery were 5.72(5.34, 6.33) mm and 821.50 (540.50, 1075.00) ml/min, respectively. The average diameters of radial artery and ulnar artery were 3.95 ± 0.10mm and 3.17(2.73,3.75) mm, respectively. The least diameter of cephalic vein was 3.34 ± 0.11mm in average. The distance between the least place to the anastomotic stoma was 3.76±0.14cm in average. The diameter of forearm cephalic vein was averaged 5.36(4.52, 6.45) mm. Diameter of place close to elbow and the upper arm place in the cephalic vein were (5.57±0.12) mm and (5.80±0.14) mm, respectively. The least diameter of cephalic vein was positively and statistically associated with the diameter and flow rate of brachial artery as well as radial artery. The least diameter was also positively and statistically associated with the diameter of each place in the cephalic vein. Statistical inter?group difference was found when the division was based on the value of the least diameter. Conclusion sThe least diameter of the wrist autogenous arteriovenous fistula vein will indeed affect the whole diameter and flow rate of the fistula. The value of the least diameter is more closely associated with the fistula function rather than narrow rate.

Objective:To explore the influence on inflammation cytokines for anti-IL-1βand TNF-αIgY intranasal treatment in guinea pigs with allergic rhinitis.Methods:The allergic rhinitis model in guinea pigs was established using ovalbumin(OVA).Hartley guinea pigs were randomly divided into the control group(group C,n=17),the allergic rhinitis model group(group M,n=27),the 0.1%anti-IL-1βand TNF-αIgY treatment group(group Z1,n=21)and the fluticasone propionate treatment group(group Z2,n=21). At 2 h,4 h and 8 h after the last treatment,blood was got by heart puncture,as well as nose was lavaged using 0.9% saline and the nasal lavage fluid( NLF) was collected.The level of cytokines was examined using ELISA kits.Results: In the peripheral blood, the levels of IL-1β,IL-5,IL-9,IL-13,IL-18,IL-33 and TGF-β1 from 2 h to 8 h;TNF-αand OVA-specific IgE from 2 h to 4 h;and IL-22 from 4 h to 8 h were significantly decreased in the 0.1%anti-IL-1βand TNF-αIgY treatment group compared with the allergic rhinitis model group(P<0.05).In the NLF,the levels of IL-1β,IL-5,IL-9,IL-13,IL-22,IL-33,TNF-α,TGF-β1 and OVA-specific IgE from 2 h to 8 h;and IL-18 at 2 h were significantly decreased in the 0.1% anti-IL-1βand TNF-αIgY treatment group compared with the allergic rhinitis model group ( P<0.05 ) .Conclusion: Anti-IL-1βand TNF-αIgY intranasal treatment can significantly reduce inflammation cytokine levels in allergic rhinitis guinea pigs.

Objective:To investigate the current situation of basic knowledge and diagnosis and treatment behavior for chronic obstructive pulmonary disease (COPD) among physicians of South Henan area .Methods:Questionnaire was designed for a research ,which was conducted among physicians from 15 hospitals located in 9 counties ,and the data were analyzed by using SAS 6 .12 software .Results:A total of 135 valid questionnaires were collected .And 80 .7% (109/135)of the physicians understood the epidemiology of COPD ,while 31 .8% (43/135) of them understood the disease characteristics .The proportion of physicians who understood the disease characteristics in respiratory professional group was 44 .4% (20/45) ,which was significantly higher than that (25 .5% ,23/90) in non‐respiratory professional group (P<0 .05) .Furthermore ,66 .6% (90/135) of the physicians diagnosed disease by clinical symptoms ,while 33 .3% (45/135) of them diagnosed disease by clinical symptoms and pulmonary function .The proportion of physicians who diagnoses disease by clinical symptoms and pulmonary function in respiratory professional group was 60 .0% (27/45) ,which is significantly higher than that 20 .0% (18/90) in non‐respiratory professional group (P< 0 .05) .Therapy for acute exacerbation of COPD was nearly conformed to the treatment guidelines ,however ,50 .3% (68/135)of physicians did not completely understand mechanical ventilation .For therapy of stable COPD ,57 .7% (78/135) of physicians recommended inhaled glucocorticosteroids combined with beta‐2‐receptor agonist .The proportion of physicians who recommended inhaled glucocorticosteroids combined with beta‐2‐receptor agonist in respiratory professional group was 88 .8% (40/45) ,which was significantly higher than that 42 .2% (38/90) in non‐respiratory professional group (P<0 .05) .Non‐respiratory professional group were lack of knowledge of home oxygen therapy ,respiratory exercises , and nutritional support .Only 11 .1% (10/90) physicians in the non‐respiratory professional group understood the knowledge comprehensively .Conclusions:It is key to enhance the education of COPD and popularize the treatment guideline among the physicians ,especially non‐respiratory physicians ,in South Henan area .