To investigate the modulation on the P-glycoprotein in the jejunum by combined use of Glycyrrhiza inflata and Kansui with ussing chamber and rt-pcr, Rhodamine 123 (R123), a P-gp substrate and fluorescein sodium (CF), a model drug of non-P-gp substrate transported by a passive diffusion were taken as investigational drugs. Because these two drugs can be easily assayed and widely used in various research fields. The permeability of R123 or CF via Wistar rat jejunum membranes was evaluated by in vitro ussing chamber after oral administration of four different decoctions of Glycyrrhiza inflata and Kansui for 1 week. And the concentration of R123 or CF was determined by the fluorospectrophotometry in the receiving solution. Meanwhile the expression of mdr1a in P-glycoprotein was detected by real-time fluorescent quantitative PCR. After oral administration of combined decoction of the single drug, the absorptive directed permeability of R123 increased significantly (P < 0.01). On the other hand, Kansui and combine decoction of the two drugs also decrease the permeability of secretory directed transport (P < 0.05). No action of Glycyrrhiza inflata was found on the secretory transport of R123 [Papp = (2.56 +/- 0.38) x 10(-5), cm x s(-1)] across the jejunum tissues, while Papp of control group was found [Papp = (2.35 +/- 0.27) x 10(-5), cm x s(-1)]. After oral administration of Kansui decoction for 1 week and 2 weeks, the levels of mdr1a expression in Wistar rats were lower than that of the control group, but there were no significant difference in the results. Meanwhile, Glycyrrhiza inflata had no effect on transport of CF across the jejunum tissues, though the other three groups could decrease the permeability of CF, as compared with control group. Kansui may slightly inhibit P-glycoprotein function in the intestinal membrane. For another, some compositions in Kansui inhibit P-glycoprotein function, and some others strengthen the tight junction between cells in the intestinal membrane to decrease permeability of CF. As the inhibitory action to P-glycoprotein was enhanced by combination of Glycyrrhiza inflata and Kansui, based on the results, it may be one of the mechanisms of creating toxicity once co-administration of Glycyrrhiza inflata and Kansui.

Objective · To explore the change of metabolomic profiling after erlotinib (anepithelial growth factor receptor tyrosine kinase inhibitor)resistance of lung adenocarcinoma cells (PC9-ER), and find the differential metabolome associated witherlotinib resistance. Methods · Metabolic profiling of PC9-ER cells and homologous parent PC9 cells was acquired by the ultraperformance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The data were analyzed by multi-dimensional statistical methods, such as partial least squares projection to latent structures-discriminant analysis (PLS-DA), to select and identify differential metabolites associated with erlotinib resistance. Results · A total of 14 differential metabolites were identified in PC9-ER cells. Seven up-regulated metabolites included N-acetylspermidine, phosphatidylethanolamine, AMP, pantothenic acid,proline, glutamate, and histidine, while seven down-regulated metabolites included citrulline, phosphorylcholine, glutathione, cysteinylglycine, glutathione oxidized, NAD, and S-adenosylmethionine, mainly participating in glutathione metabolism, glutamate metabolism, ammonia recycling, and protein biosynthesis. Conclusion · Metabolic profiling of erlotinib-resistant lung adenocarcinoma cells was changed. The information of differential metabolites associated with erlotinib resistance could provide clues for new resistance mechanisms and potential metabolism-related drug targets.

Objective:To explore the research hotspots and development trends of the transformation of virtual skill training to practical clinical ability in current medical simulation education, and to conduct visual bibliometric analysis.Methods:Taking 783 pieces of literature related to the transformation of simulation skill training to clinical competence collected from the Web of Science core collection database from 2006 to 2020 as data sources, CiteSpace V was used for visualization processing and analysis, so as to reveal the transformation effect and future research direction.Results:The number of published papers and citations increased exponentially with each year. The United States and Canada were the main research forces, the University of Toronto Medical Center contributed the largest number of research, and Professor McGaghie of Northwestern University was the author with the most published articles. According to the literature co-citation cluster analysis, it is found that the transformation of simulation skill training includes both operation and non-operation skills. High-frequency cited references reflect the knowledge base of this field and research to a certain extent. Research frontiers include the improvement of virtual reality simulators, clinical outcomes of simulated training in pediatrics, nursing, and emergency disciplines, and the design of randomized controlled clinical trials.Conclusion:The research on the clinical effect verification of simulation skill training is developing rapidly in the world. The research on medical skills' transformation represented by minimal invasive surgery such as endoscopy is a hot topic. Non-operational skills including communication skills, teamwork, pediatric emergency skills, and virtual reality technology simulation effects are the research frontiers. The number of researches on the effect of simulation training is small and the effect is unclear. In the future, more randomized controlled studies are still needed to determine the effectiveness of the transformation of simulation training to clinical competence.

Objective Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus is a rare morphological variant of endometrioid carcinoma.The biphasic morphological features may cause confusion with carcinosarcoma of the uterus,leading to misdiagnosis.The aim of this article is to elucidate the clinicopathological characteristics of such endometrial carcinoma to avoid misdiagnosis.Methods The clinical and pathological data of 5 cases of endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus were collected and analyzed.Results The age of the 5 patients ranged from 29 to 39 years,with a mean age of 33 years.Four patients underwent surgery of radical hysterectomy,the other dilation and curettage biopsy.Among the former,3 patients were at FIGO stage Ⅰ A,the other Ⅲ C1.Microscopically,all 5 tumors contained endometrioid carcinoma components,4 of which were FIGO grade Ⅰ,the remaining one was grade Ⅱ.Each tumor was of variable proportions of corded and hyalinized areas ranging from 10％ to 60％.The cells in the corded and hyalinized areas were epithelioid,fusiform and spindle in morphology,admixed with the endometrioid carcinoma component,resulting in a biphasic pattern.The corded and hyalinized component exhibited distinctively different immunophenotypical feature from that by the conventional endometrioid carcinoma component.The results of follow-up for 4 patients of 7 to 68 months (mean =26.5 months) revealed that all patients were alive without recurrence of the malignancy.Conclusions Endometrioid carcinoma with sex cord-like formations and hyalinization of the uterine corpus presents unique morphology,and the patients are usually young with relatively favorable prognosis.The definite mechanism for the pathogenesis of the sex cord-like formations and hyalinization needs further investigation.

Medical microbiology experiment is faced with many problems in online teaching. This study adopts the teaching mode of online live broadcast + operation video + virtual experiment, and make up the operation gap to some extent through operation video and virtual experiment. The mode of assessment is subjective thinking question (closely following the operation process) + experiment design + literature review (focusing on the key technology or new technology of clinical assessment that cannot be carried out due to the limitation of conditions in traditional experiments, such as mass spectrometry, fluorescence quantitative PCR, and G-test), and it is helpful to understand students' mastery of teaching objectives, and the ability of comprehensive application and innovative thinking. The student questionnaire shows that most students hold a positive attitude towards the online experimental teaching mode, and the quality of students' homework shows that most students have a good learning effect.

Background and purpose:Long non-coding RNA(lncRNA)LINC01410,with a length of 647 bp,participates in a variety of tumor biological processes.However,the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma(ESCC)remain unclear.This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion,to provide a potential prognostic indicator and therapeutic target for individuals with ESCC.Methods:Gene Expression Profiling Interactive Analysis 2(GEPIA2)databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas(TCGA).Gene Set Enrichment Analysis(GSEA)was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC.A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected.This project has been approved by the Hospital Ethics Committee(First Affiliated Hospital of Xinxiang Medical College,No.2018036;First People's Hospital of Pingdingshan City,No.2019-018).The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR).We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410.Stable transfected cells(EC109/NC,EC109/OE,EC9706/NC and EC9706/KD)were selected in primary cell culture medium containing puromycin.The expression of LINC01410 was detected by RTFQ-PCR.The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and colony formation assays.The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay.T cell factor/lymphoid enhancer factor 1(TCF/LEF1)luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway.The expressions of Wnt/β-catenin and epithelial-mesenchymal transition(EMT)signal pathway related proteins in ESCC cells were detected by Western blot.Results:By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2,we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues(P＜0.05),and high LINC01410 expression was associated with poorer overall survival(OS).RTFQ-PCR assay showed that expressions of LINC01410 were higher in esophageal cancer tissues and esophageal cancer cells(EC109 and EC9706)than in precancerous tissues and HEEC cells(P＜0.05).The expression level of LINC01410 was significantly correlated with invasion range,lymph node metastasis and TNM stage in ESCC patients(P＜0.01).LINC01410 expression was also upregulated in EC109/OE,however the expression of LINC01410 in EC9706/KD was decreased(P＜0.01).MTT assay showed overexpression of LINC01410 increased the viability of EC109 cells,while knockdown of LINC01410 decreased the viability of EC9706 cells(P＜0.01).Colony formation assay indicated that overexpression of LINC01410 enhanced the clonogenic ability of ESCC cells,while knockdown of LINC01410 reduced colony formation(P＜0.01).Transwell migration assay showed that LINC01410 overexpression drastically increased the number of migratory cells,while silencing of LINC01410 suppressed the migration in EC9706 cells(P＜0.01).GSEA revealed that Wnt/β-catenin and EMT pathways were significantly enriched in ESCC samples with a high level of LINC01410.TCF/LEF1 luciferase reporter assay showed higher levels of Wnt-dependent activities were observed in EC109/OE cells,whereas silenced LINC01410 in EC9706 cells led to contrary results(P＜0.01).Western blot analysis showed that overexpression of LINC01410 in EC109 cell significantly increased the expression levels of N-cadherin,β-catenin,cyclin D1,c-Myc and decreased E-cadherin expression,while knockdown LINC01410 resulted in opposite results.Conclusion:LINC01410 promotes proliferation and metastasis of ESCC,which might be caused by activation of Wnt/β-catenin and EMT signaling pathways.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.