Objective To investigate the effect of silenced RBM8A gene on the biological behavior (proliferation, migration, and apoptosis) of human endometrial cancer HEC-1A cells and its possible mechanism. Methods The hairpin shRNA targeted by the RBM8A gene was designed, and the best shRNA silencing fragment was screened. The recombinant lentiviral interference vector carrying the target gene was constructed and used to infect HEC-1A cells. Cells with stable knockdown of RBM8A gene were screened by puromycin as the experimental group (shRBM8A), while the shRNA of nonsense sequence was designed as the control group (shControl). CCK-8 method was used to detect cell proliferation, and flow cytometry was used to detect cell apoptosis. Transwell assay was used to detect cell migration and invasion. Western blot was used to analyze the expression of apoptosis-related proteins and EMT signal transduction pathway related proteins. Results In comparison with the shControl group, after RBM8A knockdown, HEC-1A cell proliferation was reduced, apoptosis was increased, migration and invasion ability were significantly inhibited (P < 0.05), the expression of apoptosis-related proteins cleaved caspase 9 and caspase 3 increased, EMT-related protein E-cadherin expression increased, and Vimentin expression decreased. Conclusion RBM8A gene silencing can inhibit the proliferation, migration, and invasion and promote the apoptosis of endometrial cancer cells. The inhibition of EMT signal transduction pathway may be its mechanism.

Since 2016, Binzhou Medical University began to carry out the blended learning reform in the organ-systems based curriculum (OSBC) of the experimental class of clinical medicine. Based on the traditional face-to-face teaching method, the blended learning mode of the integrated course of endocrine system under OSBC has been carried out by using the small private online course (SPOC) of MOOC platform of China universities. Many teaching methods have been adopted and formed, including case-based learning (CBL), problem-based learning (PBL), professional bilingual teaching, scientific research teaching and virtual simulation experiment teaching. The evaluation system for the combination of formative and summary assessment has been also adopted in the whole process to assess the students' academic achievement, and the teaching effect as well. The blended learning mode of the integrated course of the endocrine system under OSBC is still in the exploratory stage. There are some limitations, such as too high requirements for teachers' quality, long preparation time for teaching, and great difficulty in supervising online learning. However, the practice of teaching reform that has been carried out shows that it is effective, feasible, and worth popularizing.

Background::Given that seizures may be triggered by vaccination, this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated against coronavirus disease 2019 (COVID-19).Methods::This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China. We divided the PWE into two groups as follows: (1) patients who developed seizures within 14 days of vaccination were assigned to the SAV (with seizures after vaccination) group; (2) patients who were seizure-free within 14 days of vaccination were assigned to the SFAV (seizure-free after vaccination) group. To identify potential risk factors for seizure reccurence, the binary logistic regression analysis was performed. Besides, 67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence, and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal.Results::The study included a total of 407 patients; of which, 48 (11.8%) developed seizures within 14 days after vaccination (SAV group), whereas 359 (88.2%) remained seizure-free (SFAV group). The binary logistic regression analysis revealed that duration of seizure freedom ( P < 0.001) and withdrawal from anti-seizure medications (ASMs) or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures (odds ratio= 7.384, 95% confidence interval = 1.732–31.488, P = 0.007). In addition, 32 of 33 patients (97.0%) who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination. A total of 92 (22.6%) patients experienced non-epileptic adverse reactions after vaccination. Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal ( P = 0.143). Conclusions::PWE need protection from the COVID-19 vaccine. PWE who are seizure-free for >3 months before vaccination should be vaccinated. Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19. Finally, PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.

Objective:To investigate the changes of circulating tumor DNA (ctDNA), circulating B cell-specific Moloney leukemia virus insertion site 1 mRNA (Bmi-1 mRNA) and microRNA-21 (miR-21) before and after treatment with epidermal growth factor receptor (EGFR) monoclonal antibody in advanced colorectal cancer, and analyze their association with treatment response.Methods:The clinical data of 98 patients with advanced colorectal cancer from March 2019 to March 2021 in Yantai Yuhuangding Hospital were retrospectively analyzed. After treatment with cetuximab, complete remission was in 4 cases, partial remission in 26 cases, stable disease in 39 cases, and progressive disease in 29 cases. The patients with complete remission and partial remission were classified as remission group (30 cases), the stable disease and progressive disease were classified as non-remission group (68 cases). Before treatment and after 2 cycles of treatment, the plasma level of ctDNA was detected by high-throughput sequencing; the levels of Bmi-1mRNA and miR-21 were detected by real-time fluorescence quantitative polymerase chain reaction. Spearman correlation was used to analyze the relationship between ctDNA, Bmi-1mRNA, miR-21 and treatment responsiveness after 2 cycles of treatment; multivariate Logistic regression was used to analyze the independent risk factors affecting treatment responsiveness; receiver operating characteristic (ROC) curve was drawn to evaluate the value of ctDNA, Bmi-1mRNA and miR-21 in predicting remission after 2 cycles of treatment.Results:There were no significant differences in ctDNA, Bmi-1mRNA and miR-21 before treatment between 2 groups ( P>0.05); the ctDNA, Bmi-1mRNA and miR-21 after 2 cycles of treatment in remission group were significantly lower than those in non-remission group: (10.03 ± 3.32) μg/L vs. (15.33 ± 5.14) μg/L, 0.13 ± 0.04 vs. 0.19 ± 0.05 and 0.81 ± 0.26 vs. 1.08 ± 0.24, and there were statistical differences ( P<0.01). Spearman correlation analysis result showed that ctDNA, Bmi-1mRNA and miR-21 were negatively correlated with treatment response ( r = -0.500, -0.506 and -0.531; P<0.01). Multivariate Logistic regression analysis result showed that, after controlling for the number of distant metastatic organs and clinical stage, ctDNA, Bmi-1mRNA and miR-21 were still independent risk factors for treatment response in patients with advanced colorectal cancer ( OR = 3.342, 2.725 and 1.838; 95% CI 3.116 to 3.584, 2.647 to 2.805 and 1.768 to 1.911; P<0.01). ROC curve analysis result showed that the area under the curve (AUC) of ctDNA, Bmi-1mRNA combined with miR-21 after 2 cycles of treatment to predict the treatment response was the largest with 0.922. Conclusions:The changes of ctDNA, Bmi-1mRNA and miR-21 in patients with advanced colorectal cancer before and after treatment with EGFR monoclonal antibody are related to the treatment response. Combined detection is helpful for screening patients sensitive to EGFR-targeted therapy, and can provide reference for new targets of molecular intervention.

OBJECTIVE：To prov ide effective improvement paths and policy suggestions for improving the innovation efficiency of TCM industrial enterprises. METHODS ：Based on the input and output data of innovation resources of 38 listed TCM industrial enterprises from 2014 to 2020，an evaluation index system was constructed from the perspective of all factors. First ，the deta envelopment analysis （DEA）model was used to measure the static efficiency of the sample enterprises ，and at the same time ， four patterns of innovative resource utilization were provided ；then the total factor Malmquist index method was used to analyze the decomposition of the changes in utilization efficiency of innovative resources according to different periods and micro-individuals. RESULTS & CONCLUSIONS ：The overall efficiency of innovative resource utilization of listed TCM industrial enterprises was too low，and the average overall efficiency was only 0.293. The input and output of innovation resources of 33 enterprises were unreasonable，and the reasons for the inefficiency are mostly due to insufficient pure technical efficiency. The average value of the all-factor Malmquist index was 0.818 for 38 sample enterprises ，and the overall efficiency was declining. The obstacles to technological progress were a more important reason for the decline in efficiency. It is recommended to improve TCM industrial enterprise’s ability to allocate innovation resources and adjust the proportion of R&D investment in conjunction with the return to scale；clarify the development principles with scientific and technological innovation as the core driving force ，and actively carry out basic research work ；implement the production and research platform of “TCM industrial enterprise-TCM research institution ” to promote the overall technological progress of the industry.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.

Objective To study the levels of antibodies against bordetella pertussis among pregnant women and neonates in Beijing. Method From December 2016 to March 2017, pregnant women and their newborns from three women and children′s hospitals in Beijing were enrolled in this study. 3 ml of venous blood from the mothers and 3 ml of umbilical cord blood from neonates were drawn.Pertussis bacillus IgG antibody (PER-IgG) and pertussis toxin IgG antibody (PT-IgG) were tested using enzyme-linked immunosorbent assay. χ2 test was used to compare the positive rate of pertussis IgG antibodies in maternal and cord blood in the three hospitals. Correlational analyses of the antibodies levels in each hospital were conducted. The demographic characteristics, history of cough during pregnancy and history of DTaP vaccination of the mothers were collected via questionnaires. Result A total of 612 pairs of venous blood and cord blood samples were collected, including 4 mothers delivered twins and 616 cases of cord blood sample were collected. No history of pertussis were found in the 612 mothers. Among the 616 cases of umbilical cord blood, positive rate of PER-IgG was 13.3％ (82/616), positive rate of PT-IgG was 0.5％ (3/616). Among 612 cases of venous blood from the mothers, positive rate of PER-IgG was 7.7％ (47/612), positive rate of PT-IgG was 0.3％ (2/612). Positive rates of PER-IgG and PT-IgG in the mothers′ venous blood were not correlated with their residences (P=0.676 and 0.544). Positive rates of PER-IgG (r=0.842, P<0.001) and PT-IgG (r=0.619, P<0.001) in the mothers′ blood were positively correlated with the positive rate in umbilical cord blood. Conclusion This study shows that the positive rate of PER-IgG is very low in the maternal and umbilical cord blood in Beijing. Positive correlations of PER-IgG and PT-IgG between mother and umbilical cord blood were existed. Most mothers and their newborns do not have enough protection against pertussis.

Objective? To explore the changes of lipid metabolism in schizophrenics with long-term use of antipsychotics. Methods? The waist circumference, hip circumference, weight, years of using psychiatric drugs and blood lipid of 1 077 schizophrenic patients hospitalized in a Class Ⅲ Grade A psychiatric specialized hospital in Beijing from January to December 2017 were collected. Patients with normal blood lipid without taking lipid-lowering agents were assigned into N1 group (n=437). Patients with normal blood lipid taking lipid-lowering agents were assigned into N2 group (n=331). Patients with high blood lipid without taking lipid-lowering agents were assigned into N3 group (n=148). Patients with high blood lipid taking lipid-lowering agents were assigned into N4 group (n=161). The lipid metabolism was compared among the four groups. Results? There were significant differences in the years of taking antipsychotic drugs, waist circumference, hip circumference, weight, total cholesterol, triglyceride, high density lipoprotein and low density lipoprotein (P＜0.01). The results of pairwise comparison showed that between the two groups without taking lipid-lowering drugs, there was no statistical significance in the difference in apolipoprotein A (apoA) and apolipoprotein B (apoB) (P＞0.05), otherwise the differences in other indexes were statistically significant (P＜0.01). Between the two groups taking lipid-lowering agents, besides of other indexes (P＜0.01), there was no statistical significance in the differences in years of taking antipsychotic drugs, total cholesterol, apoA and apoB (P＞ 0.05). The further correlation analysis showed that the years of taking antipsychotic drugs was positively correlated with the waist circumference and apo A (P＜0.01). The waist circumference was positively related to the hips, weight, triglycerides (P＜0.01), and negatively related with high density lipoprotein and apolipoprotein A (P＜0.01). The hip circumference was positively correlated with weight, triglyceride, low density lipoprotein (P＜0.05), and negatively correlated with high density lipoprotein (P＜0.01). Weight was positively related with triglyceride (P＜0.05), and negatively correlated with high-density lipoprotein and apoA (P＜0.01). Conclusions? During the period of drug use, especially in the early period of drug use, the patients with schizophrenia must be monitored for blood lipid regularly. It is suggested to take the combined medication actively, guide the patients correctly, encourage more participation in recreational activities, help them improve the diet structure, control the weight, and prevent the occurrence of cardiovascular and cerebral blood tube diseases.

OBJECTIVE:To provide reference for exploring the strategy of promoting TCM formula granules.METHODS:The questionnaire was designed to investigate the cognition and attitude of TCM practitioners from different grades to TCM formula granules in our university,and the investigation data were analyzed statistically.RESULTS:A total of 312 questionnaires were collected and 306 questionnaires were collected with recovery rate of 98.08％.Among them,305 questionnaires were effective with effective rate of 99.67％.46.89％ of interviewed practitioners were found to know and understand about TCM formula granule,52.46％ knew but did not understand;the higher the grade,the higher the proportion of the known and the better understanding (P＜0.05);the cognitive channels included diagnosis and treatment course (69.64％),took by others (65.02％),took by oneself (51.49％).TCM formula granules were easy to take without decoction (95.71％) and easy to carry (87.13％),the advantage of which had high popularity,but there was not much knowledge about other advantages.7.54％ of interviewed practitioners fully appreciated TCM formula granules and 69.18％ recognized them;the higher the grade,the higher the degree of recognition (P＜ 0.05).89.51％ were willing to learn more about TCM formula granules.60.98％ said they would prescribed TCM formula granules in the furure.Among the influential factors for the attitude of the practitioners to TCM formula granules,the three factors with the highest influence were the influence of the teachers,the influence of the patients and their own practice.CONCLUSIONS:The practice of TCM practitioners in our university in Beijing is not ideal for the cognition of TCM formula granules.There is still a great room for improvement in the attitude to TCM formula granules.The teachers and patients are key influential factors for the attitude to TCM formula granules.