Objective To establish a trimethyltin chloride (TMT) -induced learning and memory impairment model in rats, and to investigate the protective effects and potential mechanisms of ferulic acid. Methods Specific pathogen-free male SD rats were randomly divided into control group, TMT intoxication group, fluoxetine group and 25, 50, 100 mg/kg ferulic acid group. The rats in the last five groups were injected with a dose of 8 mg/kg body weight TMT solution, and the rats in control group were injected with the same volume of 0.9% sodium chloride solution. After 24 hours of TMT injection, the rats in fluoxetine group were treated 10 mg/kg body weight of fluoxetine, the rats in the three ferulic acid groups were treated with ferulic acid at doses of 25, 50, and 100 mg/kg body weight, respectively. The rats in the control group and TMT intoxication group were treated with the same volume of 0.9% sodium chloride solution, once per day for continuous gavage for 28 days. Morris water maze experiment and light-dark box test were used to assess the learning and memory abilities of the rats. The mRNA and protein expressions of nuclear transcription factor-κB (NF-κB), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the rat hippocampus were detected by real-time quantitative polymerase chain reaction and Western blot. The levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the rat hippocampus were detected by enzyme-linked immunosorbent assay. Results Compared with the control group, rats of TMT intoxication group on day four had prolonged escape latency (P<0.05), fewer platform crossing (P<0.05), shorter time spent in the target quadrant and shorter latency to enter the dark compartment (all P<0.05). The mRNA and protein relative expression of NF-κB, TNF-α and IL-1β increased (all P<0.05), ROS and MDA levels increased (all P<0.05), SOD and CAT activities decreased (all P<0.05) in the rat hippocampus of TMT intoxication group on day four compared with that of the control group. Except for the terms of escape latency and target quadrant period of the rats in the 25 mg/kg ferulic acid group, rats in three ferulic acid groups on day four had lower escape latency (all P<0.05), more platform crossing (all P<0.05), longer period in the target quadrant and longer latency to enter the dark compartment (all P<0.05), compared with TMT intoxication group. Except for the relative protein expression of TNF-α in the rats of 50 mg/kg ferulic acid group, the mRNA and protein expression of NF-κB, TNF-α and IL-1β decreased (all P<0.05), ROS and MDA levels were reduced (all P<0.05), and the activities of SOD and CAT increased (all P<0.05) in the hippocampus of rats of 50 and 100 mg/kg ferulic acid groups compared with TMT intoxication group. Conclusion Ferulic acid can reverse TMT-induced learning and memory impairment in rats, and its mechanism of action may be related to alleviating oxidative stress damage and excessive inflammatory response in rat hippocampus.

Objective To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia(AVNRT)and atrioventricular re-entrant tachycardia(AVRT)using 12-lead wearable electrocardiogram devices.Methods A total of 356 samples of 12-lead supraventricular tachycardia(SVT)electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model,and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October,2021 to March,2023 were selected as the testing set.The changes in electrocardiogram parameters before and during induced tachycardia were compared.Based on multiscale deep neural network,an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated.The 3-lead electrocardiogram signals from Ⅱ,Ⅲ,and V1 were extracted to build new classification models,whose diagnostic efficacy was compared with that of the 12-lead model.Results Of the 101 patients with SVT in the testing set,68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study.The pre-trained model achieved a high area under the precision-recall curve(0.9492)and F1 score(0.8195)for identifying AVNRT in the validation set.The total F1 scores of the lead Ⅱ,Ⅲ,V1,3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597,0.6061,0.3419,0.6003 and 0.6136,respectively.Compared with the 12-lead classification model,the lead-Ⅲ model had a net reclassification index improvement of-0.029(P=0.878)and an integrated discrimination index improvement of-0.005(P=0.965).Conclusion The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

Objective To develop an intelligent model for differential diagnosis of atrioventricular nodal re-entrant tachycardia(AVNRT)and atrioventricular re-entrant tachycardia(AVRT)using 12-lead wearable electrocardiogram devices.Methods A total of 356 samples of 12-lead supraventricular tachycardia(SVT)electrocardiograms recorded by wearable devices were randomly divided into training and validation sets using 5-fold cross validation to establish the intelligent classification model,and 101 patients with the diagnosis of SVT undergoing electrophysiological studies and radiofrequency ablation from October,2021 to March,2023 were selected as the testing set.The changes in electrocardiogram parameters before and during induced tachycardia were compared.Based on multiscale deep neural network,an intelligent diagnosis model for classifying SVT mechanisms was constructed and validated.The 3-lead electrocardiogram signals from Ⅱ,Ⅲ,and V1 were extracted to build new classification models,whose diagnostic efficacy was compared with that of the 12-lead model.Results Of the 101 patients with SVT in the testing set,68 were diagnosed with AVNRT and 33 were diagnosed with AVRT by electrophysiological study.The pre-trained model achieved a high area under the precision-recall curve(0.9492)and F1 score(0.8195)for identifying AVNRT in the validation set.The total F1 scores of the lead Ⅱ,Ⅲ,V1,3-lead and 12-lead intelligent diagnostic models in the testing set were 0.5597,0.6061,0.3419,0.6003 and 0.6136,respectively.Compared with the 12-lead classification model,the lead-Ⅲ model had a net reclassification index improvement of-0.029(P=0.878)and an integrated discrimination index improvement of-0.005(P=0.965).Conclusion The intelligent diagnostic model based on multiscale deep neural network using wearable electrocardiogram devices has an acceptable accuracy for classifying SVT mechanisms.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

Objective:To investigate the effects of serum exosomes of patients with gastric cancer on cisplatin resistance, clonal formation, migration, invasion and apoptosis of the AGS gastric cancer cells, and the corresponding molecular mechanisms.Methods:The experimental study was conducted. The exosomes of patients with gastric cancer was separated from their serum, and the expression of lncRNA HOTTIP was analyzed using the quantitative real time polymerase chain reaction (qRT-PCR). Normal gastric epithelial cell line GES1, gastric cancer cell line AGS and human embryonic kidney cell 293T were cultured in vitro. AGS cells were incubated with exosomes (Exo),with phos-phate buffered saline (PBS) treatment as control, and transfected with si-NC or si-HOTTIP-3, named as Exo group, PBS group, si-NC+Exo group, and si-HOTTIP-3+Exo group. The AGS cells were trans-fected with si-NC, si-HOTTIP-1, si-HOTTIP-2, si-HOTTIP-3, oe-HOTTIP, vector, oe-HOTTIP+miR-138-5p mimic, oe-HOTTIP+mimic NC, miR-138-5p inhibitor, inhibitor NC, miR-138-5p inhibitor+si-TJP1 and miR-138-5p inhibitor+si-NC. They were recorded as si-NC group, si-HOTTIP-1 group, si-HOTTIP-2 group, si-HOTTIP-3 group, oe-HOTTIP group, vector group, oe-HOTTIP+miR-138-5p mimic group, oe-HOTTIP+mimic NC group, miR-138-5p inhibitor group, inhibitor NC group, miR-138-5p inhibitor+si-TJP1 group and miR-138-5p inhibitor+si-NC group. The 293T cells transfected with mimic NC+HOTTIP wt, miR-138-5p mimic+HOTTIP wt, mimic NC+HOTTIP mut, miR-138-5p mimic+HOTTIP mut, mimic NC+TJP1 3'UTR wt, miR-138-5p mimic+TJP1 3'UTR wt, mimic NC+TJP1 3'UTR mut, miR-138-5p mimic+TJP1 3'UTR mut were recorded as the mimic NC+HOTTIP wt group, miR-138-5p mimic+HOTTIP wt group, mimic NC+HOTTIP mut group, miR-138-5p mimic+HOTTIP mut group, mimic NC+TJP1 3'UTR wt group, miR-138-5p mimic+TJP1 3'UTR wt group, mimic NC+TJP1 3'UTR mut group, miR-138-5p mimic+TJP1 3'UTR mut group. The cell counting kit-8 (CCK8) was used to analyze the cisplatin sensitivity of gastric cancer cells. The colony formation experiment was used to analyze the colony formation of gastric cancer cells. The Transwell experiment was used to analyzed cell migration and invasion of gastric cancer cells. The flow cytometry experiment was used to analyze cell apoptosis of gastric cancer cells. The Western bolt assay was used to analyze the expression of exosome marker proteins, including the CD63 and CD81, and the protein of TJP1, the drug-resistance related proteins, including the P-gp and MCL-1. The dual-luciferase assay was used to analyze the targeted relationships among lncRNA HOTTIP, miR-138-5p and TJP1. Observation indicators: (1) expression of lncRNA HOTTIP; (2) resistance of gastric cancer cells to cisplatin regulated by exosome-mediated lncRNA HOTTIP; (3) regulation of cisplatin resistance in gastric cancer cells mediated by miR-138-5p through lncRNA HOTTIP overexpression; (4) targeting of TJP1 gene 3′-untranslated region (UTR) by miR-138-5p; (5) regulation of cisplatin resistance in gastric cancer cells by TJP1 through miR-138-5p inhibition. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. The one-way ANOVA was used for comparison for multiple groups and the Tukey′s test was used for further pairwise compari-son. Count data were described as absolute numbers, and the chi-square test was used for comparison. Correlation analysis was conducted using the Pearson′s test. Results:(1) Expression of lncRNA HOTTIP. The expression of lncRNA HOTTIP in the serum exosome of patients with gastric cancer was higher than that in healthy volunteers, showing a significant difference ( P<0.05). Results of transmi-ssion electron microscopy examination showed that the serum exosomes were circular or oval in shape. Results of Western bolt assay showed the expression of marker proteins of CD63 and CD81 in serum exosomes. (2) Resistance of gastric cancer cells to cisplatin regulated by exosome-mediated lncRNA HOTTIP. Compared with the PBS group, the biochemical half maximal inhibitory concentra-tion (IC50), the number of clone formation, the number of invasive cell, the number of migratory cell, expression of P-gp protein, expression of MCL-1 protein in the Exo group increased, while the cell apoptosis rate decreased, showing significant differences between them ( P<0.05). Compared with the si-NC+Exo group, the IC50, the number of clone formation, the number of invasive cell, the number of migratory cell, expression of P-gp protein, expression of MCL-1 protein in the si-HOTTIP-3+Exo group decreased, while the cell apoptosis rate increased, showing significant differences between them ( P<0.05). (3) Regulation of cisplatin resistance in gastric cancer cells mediated by miR-138-5p through lncRNA HOTTIP overexpression. Compared with the vector group, the IC50, the number of clone formation, the number of invasive cell, the number of migratory cell, expression of P-gp protein, expression of MCL-1 protein in the oe-HOTTIP group increased, while the cell apoptosis rate decreased, showing significant differences between them ( P<0.05). Compared with the oe-HOTTIP+mimic NC group, the IC50, the number of clone formation, the number of invasive cell, the number of migratory cell, expression of P-gp protein, expression of MCL-1 protein in the oe-HOTTIP+miR-138-5p mimic group increased, while the cell apoptosis rate decreased, showing significant differences between them ( P<0.05). (4) Targeting of TJP1 gene 3′-UTR by miR-138-5p. Results of dual-luciferase assay showed that the luciferase activity in 293T cells treatment with mimics of control+vectors of wild type of TJP1 gene 3′-UTR and 293T cells treatment with mimics of miR-138-5p+vectors of wild type of TJP1 gene 3′-UTR was 1.00±0.09 and 0.21±0.03, respectively, showing a significant difference between them ( t=15.02, P<0.05). (5) Regulation of cisplatin resistance in gastric cancer cells by TJP1 through miR-138-5p inhibition. Compared with the inhibitor group, the IC50, the number of clone formation, the number of invasive cell, the number of migratory cell, expression of P-gp protein, expression of MCL-1 protein in the miR-138-5p inhibitor group increased, while the cell apoptosis rate decreased, showing significant differences between them ( P<0.05). Compared with the miR-138-5p inhibitor+si-NC group, the IC50, the number of clone formation, the number of invasive cell, the number of migratory cell, expression of P-gp protein, expression of MCL-1 protein in the miR-138-5p inhibitor+si-TJP1 group decreased, while the cell apoptosis rate increased, showing significant differences between them ( P<0.05). Conclusion:Serum exosomes-mediated lncRNA HOTTIP can promote cisplatin resistance, clonal formation, migration, invasion and apoptosis of gastric cancer cells and inhibit cell apoptosis of gastric cancer cells through regulating the expression of miR-138-5p/TJP1.

Eyelid tumor is a serious eye disease that leads to vision loss or even blindness.The similarity between benign and malignant characteristics makes it difficult for ophthalmologists lacking clinical experience to distinguish between them.To address the problem,a method(ResNet101_CBAM)based on two-stage target localization using fully convolutional one-stage object detection(FCOS)and residual network incorporating a dual attention mechanism is proposed to realize the automatic diagnosis of benign and malignant eyelid tumors.FCOS is used to automatically localize the overall contour of the orbit,removing the background and surrounding noise,and then finely localize the tumor lesion inside the orbit.The obtained lesion region is input into ResNet101_CBAM for the automatic diagnosis of benign and malignant eyelid tumors.The experimental results show that the average precision of the target localization algorithm for tumor lesion is 0.821,and that compared with ResNet101,ResNet101_CBAM improves the sensitivity and accuracy in eyelid tumor classification by 4.7%and 3.0%,respectively,indicating that the proposed model has superior performances in the automatic diagnosis of benign and malignant eyelid tumors.

{L-End}Objective To establish the norm of Core Occupational Stress Scale (COSS) for electronic manufacturing industry workers in China. {L-End}Methods A total of 3 049 workers from five electronic manufacturing enterprises in four prefecture-level cities concentrated distribution of the electronics manufacturing industry in China were selected as research subjects using a stratified sampling method. COSS was used to investigate occupational stress levels, and the mean norm, percentile norm and threshold norms were established. {L-End}Results The average score of COSS for the electronic manufacturing industry workers in China was (43.5±7.4) points, and the average scores of social support, organization and reward, demand and effort, and autonomy dimensions were (9.5±3.1), (15.1±3.9), (13.1±3.0), and (5.7±2.0) points, respectively. A total score of 0.0-<47.0 points was determined as no occupational stress, 47.0-<51.0 points as mild occupational stress, 51.0-≤54.0 points as moderate occupational stress, and >54.0 points as severe occupational stress. {L-End}Conclusion The norm of COSS for workers in China's electronics manufacturing industry has been established, which can provide a reference for the evaluation and intervention of their occupational stress levels.

BACKGROUND: Acquired and primary resistance to epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is still the bottleneck of clinical treatment of advanced non-small cell lung cancer (NSCLC). STE029 is a novel anticancer drug which consists of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMGCR) inhibitor and novel cancer cell membrane targeting molecular. This study aimed to investigate the reversal mechanism of EGFR-TKI resistance by STE029 in lung adenocarcinoma. METHODS: CCK8 test was used to test the cell viability and survival rate of EGFR mutated PC9 cell (Gefitinib sensitive), PC9/BB4 cell (acquired Gefitinib resistant), and EGFR wild type A549 cell after treatment of STE029, Gefitinib or combination of both. EdU test was applied to detect changes in cell cycle and Hoechst 33258 was applied to detect apoptosis rate in overcoming the EGFR-TKI resistance. The activity of EGFR/PI3K/Akt, cell cycle and apoptosis signal pathways were examined. In vivo, nude mice were exposed to STE029, Gefitinib and STE029+Gefitinib for 5 wk. And the the tumor volume was measured and tumor weight was obtained on the last day. RESULTS: (1) PC9 cells was highly sensitive to Gefitinib, while PC9/BB4 and A549 cell showed significant resistance to Gefitinib treatment; (2) STE029+Gefitinib treatment could significantly decrease the 50% inhibitory concentrarion (IC₅₀) of Gefitinib in PC9, PC9/BB4 and A549 cells (P<0.05, respectively); (3) In PC9 and PC9/BB4 cells, STE029+Gefitinib can block cell cycle and inhibit cell proliferation (P<0.001), while there was no significant difference in apoptosis rate among three drug intervention groups (P>0.05); However, apoptosis rate was increased in STE029+Gefitinib group in A549 cell (P<0.01), while no significance detected in cell proliferation (P>0.05). (4) In PC9 and PC9/BB4 cells, the combination of STE029 and Gefitinib could downregulate p-EGFR, p-Akt, p-Cyclin D1 and Cyclin D1 (P<0.001), and upregulate the expression of GSK-3β (P<0.001), and the expression of cleaved caspase-8, caspase-8 cleaved caspase-9, caspase-9 showed no difference among groups (P>0.05). In A549 cells, the combination of STE029 and Gefitinib could downregulate p-Akt (P<0.001) and upregulate cleaved caspase-8 and cleaved caspase-9 (P<0.001); (5)In vivo, the combination of STE029 and Gefitinib effectively inhibited tumor development and progression compared to STE029 alone or Gefitinib alone, with significant difference (P<0.05) in PC9 and PC9/BB4 xenografted tumor. CONCLUSIONS STE029 could sensitize Gefitinib by inhibiting EGFR/PI3K/Akt pathway, blocking the tumor cell cycle and proliferation and inducing apoptosis through caspase-8 and caspase-9 dependent pathway. STE029 deserves further investigations in overcoming EGFR-TKI resistance in lung cancer.
Animals ; Mice ; Humans ; Gefitinib/pharmacology* ; Caspase 9 ; Caspase 8 ; Cyclin D1 ; Carcinoma, Non-Small-Cell Lung ; Glycogen Synthase Kinase 3 beta ; Mice, Nude ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/drug therapy* ; Protein Kinase Inhibitors/pharmacology* ; ErbB Receptors/genetics*

Medical microbiology is one of the compulsory courses of basic medical sciences, which lays an important theoretical foundation for the follow-up study of infectious diseases, contagions, tumors, and so on. The course of medical microbiology in our college adhered to the concept of student-centered, diversified teaching, scientific evaluation, and continuous improvement. Teaching design was a cross-link of general theories, specific chapters, clinical cases, theory and practice, and the ideological and political education throughout the curriculum. Lectures adopted the mode of offline teaching (such as flipped classroom, case analysis, and comprehensive experimental design), online assistance (such as classroom test, stage test, extracurricular homework, and questionnaire survey), and combined process evaluation. This teaching mode also reflected the deep integration of information technology and classroom teaching. With the development and construction in these years, medical microbiology has completed the renewal of curriculum resources, the construction of online question bank, the construction and design of ideological and political case bank, and process evaluation (10 points of usual score + 10 points of case study + 10 points of experimental performance + 100 points of final examination multiplied by 70%). There was no significant difference in the results of qustionnaire survey in terms of the improvement of independent learning ability, curriculum evaluation system and satisfaction feedback. Students in Batch 2019 were most satisfied with the teaching of keeping pace with the times and the guidance of positive outlook on life and values.

Objective:To investigate the effect of CIRc_0000267 on proliferation, migration, invasion and apoptosis of gastric cancer cells in vitro.Methods:Gastric cancer cell lines with circ_0000267 knockdown and miR-661 overexpression were constructed in vitro, and the expressions of circ_0000267, miR-661 and NGAL mRNA in gastric cancer tissues and cells were detected by qRT-PCR. Cell proliferation, migration, invasion and apoptosis were detected by clonogenesis, Transwell chamber and flow cytometry, and related protein expression was detected by Western blot. Online prediction combined with double luciferase assay and RNA pull down assay was used to verify the targeting relationship between circ_0000267, miR-661 and NGAL. Tumogenesis assay in nude mice was used to observe the effect of circ_0000267 knockout on the growth of gastric cancer cells in vivo. Results:Circ_0000267 was highly expressed in gastric cancer tissues and cells. Knockdown circ_0000267 inhibited the proliferation, migration and invasion of gastric cancer cells and promote apoptosis. Circ_0000267 targeted miR-661, and inhibition of miR-661 partially reversed the effect of circ_0000267 on gastric cancer cells. NGAL was the target gene of miR-661, and overexpression of miR-661 regulated the proliferation, migration, invasion and apoptosis of gastric cancer cells by inhibiting NGAL. Knockdown circ_0000267 targeting miR-661 inhibited NGAL expression in gastric cancer cells; Knockdown circ_0000267 inhibited the growth of gastric cancer cells in vivo.Conclusions:Circ_0000267 may regulate the proliferation, migration, invasion and apoptosis of gastric cancer cells and inhibit the growth of tumors in vivo by regulating the expression of miR-661/NGAL.