AIM:To investigate the effect of growth differentiation factor 11 ( GDF11 ) on the expansion of CD8 +memory stem T cells ( Tscm) and to further improve the effect of adoptive immunotherapy.METHODS:Healthy human peripheral blood mononuclear cells ( PBMCs) were isolated by density gradient centrifugation at first.Among the i-solated PBMCs, CD8 +T cells were further purified with MACS microbeads.The CD8 +T cells were then randomly divided into experimental groups and control group.The same volume of different concentrations of GDF11 were added into the ex-perimental groups, and the same volume of PBS solution was added into the control group.Finally, the expansion of Tscm in experimental groups and control group was measured by flow cytometry at several time points.RESULTS:GDF11 sig-nificantly increased the number of Tscm in CD8 +T cells in vitro expansion and also dramatically increased the ratio of Tscm in CD8 +T cells.Furthermore, 400 μg/L GDF11 treatment for 3 weeks was the optimal condition to induce CD8 +Tscm. CONCLUSION:GDF11 effectively increases the number and ratio of Tscm in the CD8 +T cells in cell culture growth, thereby creating a new strategy to further improve the efficiency of adoptive immunotherapy.

ObjectiveTo compare the efficacy of intravenous infusion of dexmedetomidine and midazolam for premedication in children.MethodsNinety-two ASA Ⅰ or Ⅱ children (46 cases aged 1-3 yr and 46 cases aged 4-6 yr) scheduled for elective general or urologic surgeries,were enrolled in this study.The children were randomly divided into 2 groups (n =46 each):midazolam group (group M) and dexmedetomidine group (group D).The children accompanied by their parents were admitted to the anesthesia preparation room at about 20 min before induction of anesthesia,and midazolam 0.1 mg/kg òr dexmedetomidine 1 μg/kg was infused intravenously over 10 min.Anesthesia was induced with proporol-rocuroniume-remifentanil,and maintained with sevoflurane-remifentanil-rocuroniume.Modified Yale Preoperative Anxiety Scale (mYPAS) score,sedation score,HR,mean arterial pressure (MAP),respiratory rate (RR) and SpO2 were recorded before premedication (T1),before separation from their parents (T2) and when entering the operating room (T3).The incidence of sleep (a sedation score of 4) was recorded at T2,3.The end-tidal concentration of sevoflurane,infusion rate of remifentanil,laryngeal air way removal time,emergence time,duration of stay at the recovery room,incidence of delirium during recovery period,the percentage of patients requiring rescue analgesic,and adverse effects were also retorded.ResultsCompared to that at T1,the mYPAS score was significantly decreased at T2,3,and the sedation score was significantly increased at T2,3 in both groups ( P ＜ 0.05),HR at T2 and MAP at T2,3 were significantly decreased in group D,and HR at T3 was significantly increased in group M ( P ＜ 0.05 ).Compared to group M,the sedation scores and the incidence of sleep were significantly increased at T2,3,and the HR was significantly decreased at T2 in group D ( P ＜ 0.05).There was no significant difference in the mYPAS score,RR,MAP,SpO2,end-tidal concentration of sevoflurane,infusion rate of remifentanil,laryngeal air way removal time,emergence time,duration of stay at the recovery room,incidence of delirium during recovery period,the percentage of patients requiting rescue analgesic,and incidence of adverse effects between D and M groups ( P ＞ 0.05).ConclusionThe sedative efficacy of iv dexmedetomidine is superior to that of iv midazolam when infused for premedication in children,but it exerts much influence on hemodynamics,and the changes in hemodynamics should be noted.

Objective To type Streptococcus pneumoniae(S.pneumoniae) isolated from children, and provide scientific basis for the correct selection of S.pneumoniae vaccine.Methods 182 strains of S.pneumoniae were collected from Children's Hospital of Hebei Province in 2014, species of strains were identified by polymerase chain reaction (PCR), types of strains were analyzed with multiplex PCR.Results PCR detection showed that cpsA gene amplification of 182 strains were all positive;multiplex PCR detection revealed that except 8 strains were not typed, the main types of the remaining 174 strains were 19 F (n=68, 37.36%), 19A(n=33, 18.13%), and 6A/6B (n=26,14.28%), the other types were 35B, 14, 6C/6D, 23F, 15B/15C, and so on.Conclusion The main types of 182 strains of S.pneumoniae are 19 F, 19A, and 6A/6B, which provide scientific basis for the correct selection of S.pneumoniae vaccine for this province.

Objective To compare the efficacy of closed-loop infusion of propofol for surgery in pe-diatric patients of different ages. Methods Forty-five pediatric patients of both sexes, weighing 10-63 kg, of American Society of Anesthesiologists physical statusⅠ or Ⅱ, scheduled for elective urologic sur-gery under general anesthesia, were divided into 3 groups(n=15 each)according to the age: infant group (1-3 yr), pre-school group(4-6 yr)and school-age group(7-12 yr). The bispectral index(BIS)moni-tor was connected to the closed-loop anesthesia delivery system, and the system automatically regulated the target plasma concentration of propofol to achieve a target BIS value of 45-55 during maintenance of anes-thesia. Remifentanil was given by target-controlled infusion at a target plasma concentration and rocuronium was intravenously injected when necessary during surgery. BIS40-60time percentage(percentage of time of BIS value maintaining at 40-60 in time of closed-loop infusion), median performance error(MDPE), me-dian absolute performance error(MDAPE), wobble and global score were recorded. The consumption of propofol, mean target plasma concentration and regulating frequency and consumption of remifentanil and rocuronium were recorded during surgery. Extubation time or laryngeal mask airway removal time, time to eye-opening and time of regaining consciousness were recorded. Results The BIS40-60time percentage was significantly higher, MDPE, MDAPE, wobble and global score were lower in pre-school and school-age groups than in infant group(P<005). Compared with pre-school group, the consumption of remifentanil was significantly decreased(P<005), and no significant change was found in BIS40-60time percentage, MDPE, MDAPE, wobble or global score in school-age group(P>005). There was no significant differ-ence in the consumption of propofol, mean target plasma concentration, regulating frequency, consumption of rocuronium, extubation time or laryngeal mask airway removal time, time to eye-opening or time of regai-ning consciousness among the 3 groups(P>005). Conclusion Closed-loop infusion of propofol produces better stability for surgery in pre-school and school-age children than in infants.

OBJECTIVE:To investigate off-label drug use of Ambroxol hydrochloride injection,and to provide reference for further evidence-based evaluation on rationality and standardized management of off-label drug use. METHODS:All medical orders for inpatients receiving Ambroxol hydrochloride injection were selected from 10 hospitals of Guangdong province during Apr. 2014 to Mar. 2015. Situation of drug use in different categories of departments was summarized,the incidence of off-label administation route and off-label dosage were analyzed;according to drug package inserts,prescription daily dose(PDD)and drug utilization in-dex(DUI)were calculated for each category of department,and the degree of off-label dosage was evaluated. RESULTS:A total of 761 821 person·day who used Ambroxol hydrochloride injection was included. Off-label drug use occurred in each category of departments,and the incidence of off-label drug use was 62.10%. The incidence of off-label administration route was 40.51%, mainly atomization inhalation;the incidence of it was the high-est in gynecology and obstetrics department(92.70%).The in-cidence of off-label dosage was 36.30%,and the incidence of it was the highest in cardiothoracic surgery department (85.36%). Departments whose PDDs were higher than the drug package inserts were cardiothoracic surgery department,ICU,surgical department,cardiovascular medicine department,emer-gency department,department of internal medicine and pediatrics department.CONCLUSIONS:Off-label drug use of Ambroxol hy-drochloride injection is common,and the effectiveness,safety and necessity remain controversial,which need to be proved by multi-center randomized controlled prospective trial.

Objective:This study aims to explore the survival advantages of different maintenance strategies for MCL.Methods:Clinical data of 693 newly diagnosed MCL patients in multi-centers admitted from April 1999 to December 2019 were collected. 309 cases received maintenance treatment. The characteristics of patients in different maintenance treatment groups were summarized and Kaplan-Meier survival and prognosis analysis were conducted.Results:The overall 3-year and 5-year progression-free survival (PFS) rates were (73.5±2.9) % and (53.6±4.3) %, respectively. The 3-year and 5-year overall survival (OS) rates were (94.2±1.5) % and (82.7±3.2) %, respectively. The clinical features of different maintenance treatment groups were generally consistent. The 3-year PFS rates of rituximab maintenance, lenalidomide maintenance, BTK inhibitor maintenance and dual-drug maintenance were (70.4±4.1) %, (69.1±7.6) %, (86.9±5.0) %, and (80.4±5.1) %, respectively. Corresponding 3-year OS rates were (92.9±2.4) %, (97.3±2.7) %, (97.9±2.1) %, and (95.3±2.7) %, respectively. There were no significant difference in different groups ( P=0.632, 0.313). Survival analysis identified the MCL International Prognostic Index (MIPI) high-risk group and achieving complete remission before maintenance treatment as independent risk factors for PFS. The MIPI high-risk group, high-dose cytarabine application, treatment lines, and early disease progression (POD24) emerged as independent risk factors for OS. Conclusion:Comparing the different maintenance strategies of MCL, the result showed that BTK inhibitors (BTKi) maintenance demonstrated preliminary advantages in survival. Meanwhile, high-risk group according to MIPI and incomplete remission before maintenance treatment were significant factors related to disease progression.

AIM:This study is aimed to investigate the impact of 3,5,6,7,8,3',4'-heptamethoxyflavone(HMF)on the proliferation,invasion,and migration of human colorectal cancer(CRC)cell lines(SW480 and HCT116)and preliminarily explore the underlying molecular mechanisms.METHODS:Human colorectal cancer cells(SW480 and HCT116)cultured in vitro were subjected to various concentrations of HMF(0,12.5,25 and 50 μmol/L)for 48 h.Proliferation levels were assessed using the CCK-8 assay,invasion abilities were examined via the Transwell assay,migra-tion rates were measured using the scratch assay,and oxidative stress levels were determined by the DCF-DA reactive oxy-genation assay.The mRNA expression levels of heme oxygenase-1(HO-1)mRNA and NAD(P)H:quinone oxidoreduc-tase-1(NQO-1)were quantified using RT-qPCR.RESULTS:Treatment with varying concentrations of HMF resulted in a significant reduction in the proliferative capacity of SW480 and HCT116 cancer cells,as was indicated by CCK-8 experi-ments(P<0.05).Transwell assays demonstrated a pronounced attenuation in the invasive potential of SW480 and HCT116 following HMF treatment(P<0.05).Scratch assays highlighted a notable constraint on the migratory capabilities of SW480 and HCT116 after HMF treatment(P<0.05).DCF-DA staining revealed a substantial increase in reactive oxy-gen species(ROS)levels within SW480 and HCT116 cells after HMF treatment(P<0.05).Furthermore,RT-qPCR ex-periments elucidated that HMF markedly suppressed the mRNA expression of antioxidant genes HO-1 and NQO-1.CON-CLUSION:HMF induces oxidative stress response in SW480 and HCT116 cells,consequently inhibiting their prolifera-tion,invasion and migration.

Objective To investigate the effects of video-assisted thoracoscopic surgery (VATS) teaching in clinical education of the five-year undergraduates.Methods 50 undergraduate clinical interns were divided randomly into the experimental group and control group.The experimental group was applied with traditional method combined with VATS,and the interns studied the radical operation of lung cancer under thoracoscopy,while the control group was applied with traditional method.After the course,all students accepted theory and clinical examination,and a questionnaire survey was conducted.SPSS 18.0 was used for statistical analysis,and t-test was adopted for theoretical and clinical examination results.Questionnaire survey was conducted by chi-square test.Results ①Theory test:compared with control group,the scores of case analysis [(38.92 ± 2.50) vs.(34.56 ± 3.10)] and total scores [(79.92 ± 4.04) vs.(74.64 ± 4.82)] were improved (P＜0.05).②Clinical test:compared with control group,the scores of experimental group [(82.86 ± 4.46) vs.(76.04± 4.78)] were improved (P＜0.05).③Questionnairesurvey:there was statistical difference between the two groups in promoting the interest in learning,improving the comprehension of knowledge and approving of the teaching method used (P＜0.05).Conclusion VATS teaching method has positive effect on clinical education of the five-year undergraduates,and it should be worthy of extending.

Objective:To conduct periodic revalidation of the 15 items and 43 terms autoverification rules of blood analysis after 1 year of application, analyze the application suitability and make the rules improved.Methods:Track the results of 528 010 blood analysis samples of our hospital from August 1, 2019 to January 31, 2020, and analyze the pass rate and interception rate of autoverification; 600 specimens in total were selected randomly for microscope examination, including 300 specimens which touched autoverification rules (1 012 items of autoverification rules) and were intercepted by autoverification and 300 specimens which untouched autoverification rules and were released by autoverification. The abnormal characteristics and unacceptable Delta check of the specimens also need to be concerned at the same time.The false negative rate and false positive rate, true negative rate, true positive rate and pass correct rate of autoverification were verified and compared with the rate of the second phase verification when the autoverification rule was established. The false negative rate, false positive rate, true negative rate and true positive rate of the Delta check rule which 54 716 specimens touched were calculated and compared with the second phase verification rate when the autoverification rule was established.The results of microscopic examination were used as the gold standard for the calculation of the rates, and P<0.05 was considered as a significant difference. The false positive and true positive of 1 012 autoverification rules were analyzed item by item.The false positive and true positive of 108 specimens which touched blast cell autoverification rule were analyzed terms by terms. The mean TAT and median TAT of 528 010 specimens and 193 750 outpatient specimens were calculated respectively, and the report percentages of 528 010 samples that TAT<30, 30-60　and>60 min were calculated respectively. Analyze and evaluate the application suitability of autoverification rules to juge whether they meet the needs of doctors and laboratory. The design process and the rules and application process of autoverification were optimized and improved.Results:The autoverification pass rate was 63.06% (332 971/528 010), the interception rate was 36.94% (195 039/528 010). The false negative rate was 1.00% (1/600), the false positive rate was 12.67% (76/600), the true negative rate was 49% (294/600), the true positive rate was 37.33% (224/600), and the correct rate was 98% (294/300). The pass rate, true negative rate, true positive rate and correct rate of the periodic reverification group were higher than the second phase verification group, the false negative rate and false positive rate were lower than that the second phase verification group. The false negative rate and true positive rate of the Delta check of periodic verification group were lower than that the second phase verification group, the false positive rate and true negative rate were higher than the second phase verification group, there were significant differences in the comparition results. The mean TAT of 528 010 specimens was25 min, and the median TAT was 22 min. The mean TAT of 193 750 outpatient specimens was 23 min, and the median TAT was 20 min. The report percentages of 528 010 samples that TAT<30 min, 30 min-60 min and>60 min were 83.30% (439 819/528 010), 8.00% (42 250/528 010) and 8.70% (45 941/528 010), respectively.Conclusion:The results of periodic revalidation of autoverification after 1 years application show that the 15 items and 43 terms autoverification rules of blood analysis could meet requirements about the accuracy and efficiency of the laboratory, and have a good suitability for application.

Objective:To establish a set of artificial intelligence (AI) verification rules for blood routine analysis.Methods:Blood routine analysis data of 18 474 hospitalized patients from the First Hospital of Jilin University during August 1st to 31st, 2019, were collected as training group for establishment of the AI verification rules,and the corresponding patient age, microscopic examination results, and clinical diagnosis information were collected. 92 laboratory parameters, including blood analysis report parameters, research parameters and alarm information, were used as candidate conditions for AI audit rules; manual verification combining microscopy was considered as standard, marked whether it was passed or blocked. Using decision tree algorithm, AI audit rules are initially established through high-intensity, multi-round and five-fold cross-validation and AI verification rules were optimized by setting important mandatory cases. The performance of AI verification rules was evaluated by comparing the false negative rate, precision rate, recall rate, F1 score, and pass rate with that of the current autoverification rules using Chi-square test. Another cohort of blood routine analysis data of 12 475 hospitalized patients in the First Hospital of Jilin University during November 1sr to 31st, 2023, were collected as validation group for validation of AI verification rules, which underwent simulated verification via the preliminary AI rules, thus performance of AI rules were analyzed by the above indicators. Results:AI verification rules consist of 15 rules and 17 parameters and do distinguish numeric and morphological abnormalities. Compared with auto-verification rules, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score of AI rules in training group were 22.7%, 1.6%, 74.5%, 1.3%, 75.7%, 97.2%, 93.5%, 94.7%, 94.1, respectively.All of them were better than auto-verification rules, and the difference was statistically significant ( P<0.001), and with no important case missed. In validation group, the true positive rate, the false positive rate, the true negative rate, the false negative rate, the pass rate, the accuracy, the precision rate, the recall rate and F1 score were 19.2%, 8.2%, 70.1%, 2.5%, 72.6%, 89.2%, 70.0%, 88.3%, 78.1, respectively, Compared with the auto-verification rules, The false negative rate was lower, the false positive rate and the recall rate were slightly higher, and the difference was statistically significant ( P<0.001). Conclusion:A set of the AI verification rules are established and verified by using decision tree algorithm of machine learning, which can identify, intercept and prompt abnormal results stably, and is moresimple, highly efficient and more accurate in the report of blood analysis test results compared with auto-vefication.