Objective To explore the influence of RNAi-mediated hypoxia-inducible factor 1? (HIF-1?) silencing on the growth and metastasis of colon cancer in nude mice.Methods A total of 30 6-week-old female nude mice were randomly divided into normal saline group (NS group),negative plasmid group and RNA interference group after injected with SW480 subcutaneously to form a colon carcinoma.shRNA-HIF-1? vector was constructed and injected (50 ?g/time,once per 2 d,for 7 times) into the tumor mass of nude mice of RNA interference group to induce RNAi.Normal saline or blank vector was injected into the corresponding nude mice.The changes of HIF-1? were detected with RT-PCR and Western blot analysis.The size of tumors,metastasis rate and the positive rate of lymphnode were compared among different groups.Results In 15 d after RNAi vector injection,the tumor volume of RNAi group [(273.9?14.7) mm3] was much smaller than those of NS group [(1 845.5?91.2) mm3] and negative plasmid group [(1 842.7?115.7) mm3] (P

Objective To explore the tobacco control project based health education curriculum reform's effect of improving medical students' tobacco control.Method Choosing the students of two classes of students in preventive medicine specialty of Harbin Medical University as the research object, investigating the students respectively with the questionnaire prepared uniformly by 7 schools before and after the course.All data were coded by Epidata 3.0, and SPSS 18.0 was used to carry out the relevant information for the chi square test and t test.Result The sample size of baseline survey was114 and after the intervention was 87.The knowledge pass rate of the girls before and after the intervention were 87.3％ (48/55) and 98.2％ (54/55) respectively (P=0.000).The boys' awareness rate of the secondhand smoke safety level were 13.6％ (8/59) and 21.9％ (7/32) respectively, and the girls were 13.0％ (7/55) and 31.5％ (17/55) (P=0.021).Students interested in tobacco increased from 79.8％ (91/114) before intervention to 90.8％ (79/87) after intervention (P=0.033).Students willing to work in the tobacco related increased from 52.2％(59/114) before intervention to 66.7％ (58/87)after intervention (P=0.044).The girl who replied after intervention I am not smoking now, but won't smoke either when working in the disease control in the future reached as high as 96.4％ (53/55), but the students were lack of confidence to help people to stop smoking.Conclusion The reform of social practice activity curriculum designed for tobacco control project is effective, and it is urgent to strengthen the training of preventive medical students' smoking cessation skills and enhance their confidence.

To explore influence of interventional closure on heart rate in patients with atrial septal defect . Methods : A total of 63 patients with atrial septal defect undergoing percutaneous interventional closure in our hospi‐tal were selected. Heart rate was compared before and after surgery ,and correlation among heart rate ,age ,occlude size and preoperative pulmonary artery pressure was analyzed .Results : Compared with before surgery ,there was significant reduction in heart rate [(75.22 ± 8.23) beats／min vs. (64.87 ± 10. 65) beats／min] after percutaneous in‐terventional closure of atrial septal defect , P＝0.001 ;Pearson correlation analysis indicated that postoperative heart rate change was not correlated with age ,occluder size and pulmonary artery systolic pressure (PASP ) ( r＝0.017－0.182 , P＞0.05 all) . Compared with patients without preoperative pulmonary artery hypertension ,there was sig‐nificant rise in postoperative reduction amplitude of heart rate [ (2.28 ± 9.81) beats／min vs. (11. 35 ± 10.73) beats／min] in those with preoperative elevated pulmonary systolic pressure (≥25mmHg) , P＝0.038 .Conclusion : After percutaneous interventional closure ,heart rate significantly decreases in patients with atrial septal defect .Presence of preoperative pulmonary artery hypertension can be regarded as a risk predictor for postoperative heart rate reduction .

Objective:To investigate the learning curve of laparoscopic transanal total mesorectal excision (taTME) for rectal cancer operated by one or two surgery teams.Methods:The retrospective cross-sectional study was conducted. Based on the concept of real-world research, the clinical data of 1 458 patients undergoing laparoscopic rectal cancer taTME from 44 medical centers who were registered in the Chinese taTME registry collaborative (CTRC) database from May 2010 to May 2020 were collected. The 1 458 patients were divided into cohorts with one surgery team or two surgery teams according to the operation method. Patients with one surgery team underwent taTME by transabdominal operation and then by transanal operation. Patients with two surgery teams underwent taTME by transabdominal and transanal operation simultaneously with duration of the simutaneous operation time ≥30 minutes. The entire surgical process of patients with two surgery teams is not required to be performed by two surgery teams simutaneously. The clinical data were collected from the medical centers with similar operation amount according to the operation time sequence to analyze the difference between different operation stages and explore the learning curve. The operation time was taken as the parameter to carry out cumulative sum analysis and draw the learning curve of laparoscopic rectal cancer taTME in each medical center. The clinicopathological characteristics of patients from two medical centers with the largest difference in learning curves were analyzed. Observation indicators: (1) screening results of clinical data; (2) clinical data collection of patients with one surgery team; (3) surgical situations of laparoscopic rectal cancer taTME from the one surgery team in different operation stages; (4) learning curve of the one surgery team; (5) clinical data collection of patients with two surgery teams; (6) surgical situations of laparoscopic rectal cancer taTME from the two surgery teams; (7) learning curve of the two surgery teams. The cumulative sum was calculated by the CUSUM=∑i=1nXi-U, where Xi represented the operation time of each taTME, U represented the average operation time of all cases, and n represented the operation number. Fitting process was conducted on scatter plot of learning curves. Taking the apex of learning curve as the boundary, the learning curve was divided into two stages. The abscissa corresponding to the apex of learning curve was the number of operations that needed to be performed to cross the learning curve. Measurement data with normal distribution were represented as Mean±SD. Comparison between two groups was conducted using the t test and comparison between multiple groups was conducted using the ANOVA. Measurement data with skewed distribution were represented as M( P25,P75), and comparison between groups was conducted using the Mann-Whitney U test. Comparison of ordinal data was analyzed using the rank sum test. Count data were analyzed using the chi-square test or Fisher exact probability. Results:(1) Screening results of clinical data:the clinical data of 661 patients from 7 medical centers with one surgery team and two surgery teams were collected. (2) Clinical data collection of patients with one surgery team: the clinical data of 312 patients undergoing laparoscopic rectal cancer taTME from 5 medical centers were collected including 42 cases in the number 2 medical center, 97 cases in the number 20 medical center, 82 cases in the number 33 medical center, 35 cases in the number 37 medical center and 56 cases in the number 39 medical center, respectively. (3) Surgical situations of laparoscopic rectal cancer taTME from the one surgery team in different operation stages: three medical centers including the number 2, number 37 and number 39 medical center with close operation volume provided the clinical data of cases distributed in five operation stages. Among the five operation stages, the proportion of high-quality operation of total mesorectal excision (TME) was ≥17/18, the incidence of postoperative complications was ≤13.3%(4/30) and the incidence of anastomotic leakage was ≤10.0%(3/30). There was no significant difference in the TME quality, postoperative complications or anastomotic leakage among the five operation stages ( P>0.05). There was no significant difference in the operation time among the five operation stages ( χ2=6.950, P>0.05). (4) Learning curve of the one surgery team: the number of operations corresponding to the turning point of learning curve in number 2 and number 20 medical center was 22 and 39, respectively. The number of operations corresponding to the turning points of learning curve in number 33 and number 37 medical center was 15, 66 and 10, 28, respectively. The number of operations corresponding to the turning point of learning curve in number 39 medical center was 20. The overall curve of number 20 medical center was in line with the trend of learning curve and 39 cases of operations was the minimum number needed to cross the learning curve. The biggest difference in learning curve was shown between the number 20 and number 33 medical center. Cases with the gender of male or female, age, body mass index, cases classified as stage 1, stage 2, stage 3 or stage 4 of the American Society of Anesthesiologists (ASA) Classification, cases with neoadjuvant therapy, duration of postoperative hospital stay of the number 20 medical center were 77, 20, (60±10)years, 24 kg/m 2(22 kg/m 2, 26 kg/m 2), 1, 88, 8, 0, 8, 8, 11 days (9 days, 13 days), respectively, versus 51, 31, (64±11)years, 23 kg/m 2(21 kg/m 2, 26 kg/m 2), 0, 35, 43, 1, 31, 16 days (13 day, 21 day) of number 33 medical center, showing significant differences in the above indicators between the two medical centers ( χ2 =6.442, t=-2.265, Z=-2.032, -6.870, χ2 =22.120, Z=-8.408, P<0.05). (5) Clinical data collection of the two surgery teams: the clinical data of 259 patients undergoing laparoscopic rectal cancer taTME from 5 medical centers were collected, including 46 cases in the number 2 medical center, 47 cases in the number 8 medical center, 78 cases in the number 18 medical center, 43 cases in the number 33 medical center and 45 cases in the number 44 medical center, respectively. (6) Surgical situations of laparoscopic rectal cancer taTME from the two surgery teams: four medical centers including the number 2, number 8, number 33 and number 44 medical center with close operation volume provided the clinical data of cases distributed in four operation stages. Among the four operation stages, the proportion of high-quality operation of TME was ≥50.0%(13/26), the incidence of postoperative complications was ≤35.0%(14/40) and the incidence of anastomotic leakage was ≤22.5%(9/40). There was no significant difference in the TME quality, postoperative complications or operation time among the four operation stages ( χ2 =3.252, 4.733, 8.848, P>0.05). There was a significant difference in the incidence of anastomotic leakage among the four operation stages ( P<0.05). (7) Learning curve of the two surgery teams: the number of operations corresponding to the turning point of learning curve in number 2 and number 8 medical center was 28 and 16, respectively. The number of operations corresponding to the turning points of learning curve in number 18, number 33 and number 44 medical center was 12 and 58, 10 and 36, 14 and 36, respectively. The overall curve of number 2 medical center was in line with the trend of learning curve and 28 cases of operations was the minimum number needed to cross the learning curve. The biggest difference in learning curve was shown between the number 2 and number 33 medical center. The age and cases with tumor in stage T0 and (or) Tis, stage T1, stage T2, stage T3 or stage T4 of the T staging of the number 2 and number 33 medical center were (60±12)years, 3, 1, 9, 11, 20 and (65±10)years, 2, 3, 22, 15, 0, respectively, showing significant differences in the above indicators between the two medical centers ( t=-2.280, Z=-4.033, P<0.05). Conclusion:Thirty-nine cases of operations was the minimum number for the one surgery team to cross the learning curve of laparoscopic rectal cancer taTME and 28 cases of operations was the minimum number for the two surgery teams to cross the learning curve of laparoscopic rectal cancer taTME.

Objective To establish a stably overexpressing miR-31 transgenic mouse and detect the expression of miR-31 in the organs and tissues,and to provide qualified tool mice with overexpression of miR-31 in vivo. Methods The miR-31 overexpression vector was constructed by Gateway cloning technology. The vector was injected into fertilized ovum by DNA microinjection technology,then transferred to the pseudopregnant mice and waited for eutocia. Newborn mouse tail DNA was extracted and PCR and agarose gel electrophoresis were performed to identify the positive miR-31 transgenic mice. microRNA was extracted from the organs and tissues of miR-31 transgenic mice and the expression of miR-31 was de-tected by RT-PCR. The expression of Nestin and number of neural stem cells in the nervous system were compared in the positive and WT mice. Results The miR-31 transgenic mice were constructed successfully and bred more than 14 genera-tions in barrier environment. Expression of miR-31 was increased in major organs and tissues. The expression of Nestin and the number of neural stem cells in the positive mice were higher than those in the wild type mice. Conclusions MiR-31 overexpressing transgenic mice are constructed by Gateway cloning technology and the expression of miR-31 is stable in sub-sequent generations. The number of neural stem cells in the nervous system is higher than that in wild-type mice. The miR-31 overexpressing transgenic mice can be a good tool for experimental research of the function of overexpressed miR-31 in vivo and the treatment of nervous system diseases.

Objective To explore the predictive value of serum uric acid on new-onset cholelithiasis.Methods The retrospective cohort study was conducted.The data of 97 469 subjects who participated health examination at the Kailuan General Hospital Affiliated to the North China University of Science and Technology,Kailuan Linxi Hospital,Kailuan Zhaogezhuang Hospital,Kailuan Tangjiazhuang Hospital,Kailuan Fan'gezhuang Hospital,Kailuan Lyujiatuo Hospital,Kailuan Jinggezhuang Hospital,Kailuan Linnancang Hospital,Kailuan Qianjiaying Hospital,Kailuan Majiagou Hospital and Kailuan Branch Hospital from June 2006 to December 2015 were collected.Epidemiological investigation,anthropometric parameters and biochemical indicators were collected.All the subjects were allocated into 4 groups according to squartiles of serum uric acid:24 140 with serum uric acid ＜232 μmol/L in the Q1 group,24 473 with 232 μmol/L≤ serum uric acid ＜282 μmol/L in the Q2 group,24 382 with 282 μmol/L≤ serum uric acid ＜338 μmol/L in the Q3 group and 24 474 with serum uric acid ≥ 338 μmol/L in the Q4 group.Observation indicators:(1) comparisons of clinical characteristics among the 4 groups;(2) incidence of cholelithiasis in the 4 groups;(3) effects of serum uric acid on the new-onset cholelithiasis:① the dose-response relationship between serum uric acid and the risk of cholelithiasis,② comparisons of the fitting degree of serum uric acid on the cholelithiasis model,③ effects of different serum uric acid levels on incidence of cholelithiasis after stratification by sex,④ serum uric acid of different gender on the boxplots,⑤ effects of different serum uric acid levels on the incidence of cholelithiasis after stratification by age.Measurement data with normal distribution were expressed as (x)±s,and comparisons among groups were analyzed using the one-way ANOVA.Measurement data with skewed distribution is expressed by M (Q),and comparisons among groups were analyzed using the nonparametric Krustal-willis test.Count data were represented by percentage,and comparisons among groups were analyzed using chi-square test.The incidences of cholethiasis in 4 groups of different serum uric acid were calculated by person-year incidence.Restrictive cubic spline regression was used to calculate the dose-response relation between the continuous variable and the risks of new-onset cholelithiasis and 95％ confidence interval (CI).COX regression model was used to analyze the hazard ratio (HR) and 95％ CI of different serum uric acid levels on new-onset cholelithiasis.Likelihood ratio test and akaike information criterion (AIC) were used to calculate the fitting degree of serum uric acid on new-onset cholelithiasis model.Boxplots were used to describe serum uric acid in different genders.Results (1) comparisons of clinical characteristics among the 4 groups:sex (male),age,body mass index (BMI),systolic pressure,diastolic pressure,fasting plasma glucose (FPG),total cholesterol (TC),triglyceride (TG),high sensitive C-reactive protein,diabetes,hypertension,smoking,drinking and physical exercise were 15 162,(50± 11) years,(24±3)kg/m2,(123±21)mmHg (1 mmHg=0.133 kPa),(82± 12)mmHg,(5.6±2.0) mmol/L,(4.8±1.2) mmol/L,1.14 mmol/L (range,0.81-1.63 mmol/L),0.70 mmol/L (range,0.23-2.23 mmol/L),2 537,9 415,4575,2380,2 649 in the Q1 group,19 079,(51±12) years,(25±3)kg/m2,(130±21)mmHg,(83±12) mmHg,(5.5 ± 1.7) mmol/L,(4.9 ± 1.2) mmol/L,1.20 mmol/L (range,0.86-1.76 mmol/L),0.71 mmol/L (range,0.28-1.98 mmol/L),2 287,10 124,6 918,3 649,3 288 in the Q2 group,21 132,(52±13)years,(25±3)kg/m2,(132±21)mmHg,(84±12)mmHg,(5.5±1.6)mmol/L,(5.0±1.2) mmol/L,1.29 mmol/L (range,0.91-1.94 mmol/L),0.80 mmol/L (range,0.30-2.06 mmol/L),2 027,10 755,8 259,4 730,3 958 in the Q3 group,22 651,(53± 14) years,(26± 3) kg/m2,(134± 21) mmHg,(85±12)mmHg,(5.4±1.5)mmol/L,(5.1±1.2)mmol/L,1.54 mmol/L (range,1.05-2.35 mmol/L),1.02 mmol/L (range,0.43-2.50 mmol/L),1 981,12 082,9 562,6 209,4 758 in the Q4 group,respectively,with statistically significant differences among the 4 groups (x2 =7 624.63,F=279.93,961.91,330.84,271.40,38.25,353.18,H =3 406.30,912.23,x2 =108.15,590.49,2567.07,2 209.21,760.15,P＜0.05).(2)Incidence of cholelithiasis in the 4 groups:97 469 participants were followed up for 592 922 person-year,4 270 participants had new-onset cholelithiasis,with a total person-year incidence of 7.20 thousand person / year.The person-year incidence were respectively 6.34 (971/153 205 * 1 000),6.91 (1 034/149 686 * 1 000),7.44 (1 090/146 549 * 1 000),8.19 (1 175/143 482 * 1 000) thousand person / year in Q1,Q2,Q3 and Q4 group.(3) Effects of serum uric acid on the new-onset cholelithiasis.① The dose-response relationship between serum uric acid and the risk of cholelithiasis:restricted cubic spline regression showed a linear relationship between continuous serum uric acid,logarithmic transformated serum uric acid and the risk of cholelithiasis (x2 =11.74,8.01,P＜0.05).② Comparisons of the fitting degree of serum uric acid on the cholelithiasis model:adjusted for sex,age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risks of new-onset cholelithiasis increased in Q3 and Q4 groups compared with Q1 group (HR=1.10,1.12,95％CI:1.01-1.20,1.03-1.23,P＜0.05).The-2Log L and AIC value of multivariate model,serum uric acid+multivariate model were 92 532.39,92 550.39 and 92 525.35,92 549.35,respectively,with a statistically significant difference (x2=7.04,P ＜ 0.05).③ Effects of different serum uric acid levels on incidence of cholelithiasis after stratification by sex:in female participants,adjusted for age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in Q1 group was not statistically significant different from that in Q2,Q3,Q4 group (HR=1.06,1.15,1.09,95％CI:0.88-1.28,0.93-1.34,0.91-1.31,P＞0.05).In male participants,adjusted for age,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risks of new-onset cholelithiasis in Q2,Q3 and Q4 groups were increased compared with Q1 group (HR=1.17,1.24,1.30,95％CI:1.06-1.30,1.12-1.37,1.18-1.44,P＜0.05).④ Serum uric acid of different gender on the boxplots:in female participants,the level of serum uric acid was (249 ± 61) μmol/L,(235±50)μmol/L,(231±56) μmol/L,(250±66) μmol/L,(266±75) μmol/L,(281±81) μmol/L,(298±76) μmol/L,(379±86)μmol/L respectively in the group of 18-27 years old,28-37 years old,38-47 years old,48-57 years old,58-67 years old,68-77 years old,78-87 years old,88-97 years old after stratified by 10 years old.In male participants,the level of serum uric acid was respectively (310±76)μmol/L,(298 ±75) μmol/L,(298±74) μmol/L,(294±74) μmol/L,(302±78) μmol/L,(311 ±80) μmol/L,(322±80) μmol/Land (330±75)μmol/L after participants stratified by 10 years old.⑤ Effects of different serum uric acid levels on the incidence of cholelithiasis after stratification by age:in participants with age ≤ 60 years old,adjusted for sex,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in the Q2 and Q3 groups were not increased compared with Q1 group (HR=1.05,1.10,95％CI:0.94-1.17,0.99-1.23,P＞0.05),however,risk of new-onset cholelithiasis was increased in the Q4 group (HR =1.15,95％CI:1.02-1.28,P＜0.05).In participants with age ＞ 60 years old,adjusted for sex,BMI,TC,TG,diabetes,hypertension,smoking,drinking and physical exercise,risk of new-onset cholelithiasis in the Q2 groups was not increased compared with Q1 group (HR=1.16,95％CI:0.99-1.36,P＞0.05),however,risks of new-onset cholelithiasis were increased in the Q3 and Q4 groups (HR =1.19,1.21,95％CI:1.02-1.40,1.04-1.41,P＜ 0.05).Conclusion Elevated serum uric acid is an independent risk factor for the new-onset cholelithiasis.

Objective:To use the resting state functional network connectivity (FNC) method based on independent component analysis (ICA) to analyze the characteristics of FNC changes in patients with basal ganglia aphasia (BGA) after stroke, and to explore its occurrence and recovery mechanism under the intervention of acupuncture combined with language rehabilitation training.Methods:Using a prospective observational research method, 16 right-handed BGA patients who were treated at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from July 2021 to December 2022, as well as 14 healthy subjects matched in age, gender, education level, and handedness, were included. The resting state functional magnetic resonance imaging, demographic information, and Western Aphasia Examination data of healthy subjects and BGA patients before and after intervention were collected. The GIFT toolbox based on MATLAB platform was applied for ICA and resting state brain network FNC analysis. The FNC differences between BGA patients and healthy subjects were compared horizontally, and the FNC changes in BGA patients before and after intervention were compared vertically.Results:Compared with healthy subjects, post-stroke BGA patients showed decreased connectivity between the basal ganglia network, default network, and visual network before intervention, while increased connectivity between the auditory network, right frontoparietal network, and anterior cuneiform network; After the intervention of acupuncture combined with language rehabilitation training, the connectivity between the basal ganglia network, visual network, and anterior cuneiform network decreased, while the connectivity between the anterior convex network and bilateral frontoparietal network decreased, while the connectivity between the default network, auditory network, right frontoparietal network, and visual network increased. The BGA patient group showed enhanced connectivity between the basal ganglia network and the left frontoparietal network before and after intervention.Conclusions:The FNC changes between the basal ganglia network and other brain networks are key to reflecting the mechanism of BGA occurrence and language function recovery. Acupuncture combined with language rehabilitation training may improve language function by enhancing the connectivity between the basal ganglia network and the left frontoparietal network, and the redistribution of attention resources may also be one of the reasons for promoting language function recovery in BGA patients.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.