Objective:To investigate whether F.nucleatum affects the chemotherapy resistance of colorectal cancer by regulating ABC subfamily G subtype 2 (ABCG2), in view of the fact that the correlation between the two has not been reported. Methods:Oxaliplatin was used to interfere with colorectal cancer cells and co-cultured with F.nucleatum to establish a chemotherapy-induced model of microbial infection. Calcein AM/PI cell staining, trypan blue staining, and cell counting kit 8 (CCK-8) method were used to detect cell activity. Real-time fluorescence quantitative polymerase chain reaction and western blot were used to detect ABCG2 mRNA and protein expression levels in colorectal cancer cells. The target gene was knocked down by constructing shRNA plasmids. The HCT-116 cell F.nucleatum infection model was constructed and transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses were performed to determine the differential gene expression enrichment pathways. Genistein (GST) was used as an E-cadherin blocker, and triclabendazole sulfoxide (TCBZSO) was used as an ABCG2 blocker. Immunofluorescence was used to detect E-cadherin and β-catenin protein expressions and intracellular localization levels. The subcutaneous xenograft model of nude mice was constructed in vivo, and the expression level of ABCG2 protein in tissues was detected by immunohistochemical staining. Results:CCK-8 results showed that F. nucleatum+oxaliplatin group [HT-29, (92.26±1.66)%; HCT-116, (82.13±1.84)%] cell relative survival rate was higher than that of oxaliplatin group [HT-29, (79.64±3.72)%; HCT-116, (67.56±2.96)%; P＜0.001]. The relative survival rate of oxaliplatin and F. nucleatum co-culture group with ABCG2-knockdown HCT-116 cells [(61.44±1.48)%] was lower than that of F. nucleatum and oxaliplatin co-cultured with HCT-116 cells [(69.29±4.45)%, P=0.015]. GO enrichment analysis showed that HCT-116 cells co-cultured with F.nucleatum were significantly enriched in "β-catenin binding", "cadherin binding" and "regulation of Wnt signaling pathway". RT-qPCR results showed that the relative expression of ABCG2 mRNA in F.nucleatum + genistein group was significantly lower than that in F.nucleatum group ( P＜0.001). The results in vivo showed that the tumor weight in the F.n+L-OHP+TCBZSO group [(0.12±0.02)g] was lower than that in the F.n+L-OHP group [(0.33±0.05)g, P＜0.001]. Immunohistochemistry suggested that the promotion of ABCG2 protein expression by F. nucleatum was blocked after TCBZSO intervention. Conclusion:F. nucleatum up-regulates ABCG2 expression through E-cadherin/β-catenin signaling pathway to promote colorectal cancer resistance to oxaliplatin.

Objective:To investigate whether F.nucleatum affects the chemotherapy resistance of colorectal cancer by regulating ABC subfamily G subtype 2 (ABCG2), in view of the fact that the correlation between the two has not been reported. Methods:Oxaliplatin was used to interfere with colorectal cancer cells and co-cultured with F.nucleatum to establish a chemotherapy-induced model of microbial infection. Calcein AM/PI cell staining, trypan blue staining, and cell counting kit 8 (CCK-8) method were used to detect cell activity. Real-time fluorescence quantitative polymerase chain reaction and western blot were used to detect ABCG2 mRNA and protein expression levels in colorectal cancer cells. The target gene was knocked down by constructing shRNA plasmids. The HCT-116 cell F.nucleatum infection model was constructed and transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analyses were performed to determine the differential gene expression enrichment pathways. Genistein (GST) was used as an E-cadherin blocker, and triclabendazole sulfoxide (TCBZSO) was used as an ABCG2 blocker. Immunofluorescence was used to detect E-cadherin and β-catenin protein expressions and intracellular localization levels. The subcutaneous xenograft model of nude mice was constructed in vivo, and the expression level of ABCG2 protein in tissues was detected by immunohistochemical staining. Results:CCK-8 results showed that F. nucleatum+oxaliplatin group [HT-29, (92.26±1.66)%; HCT-116, (82.13±1.84)%] cell relative survival rate was higher than that of oxaliplatin group [HT-29, (79.64±3.72)%; HCT-116, (67.56±2.96)%; P＜0.001]. The relative survival rate of oxaliplatin and F. nucleatum co-culture group with ABCG2-knockdown HCT-116 cells [(61.44±1.48)%] was lower than that of F. nucleatum and oxaliplatin co-cultured with HCT-116 cells [(69.29±4.45)%, P=0.015]. GO enrichment analysis showed that HCT-116 cells co-cultured with F.nucleatum were significantly enriched in "β-catenin binding", "cadherin binding" and "regulation of Wnt signaling pathway". RT-qPCR results showed that the relative expression of ABCG2 mRNA in F.nucleatum + genistein group was significantly lower than that in F.nucleatum group ( P＜0.001). The results in vivo showed that the tumor weight in the F.n+L-OHP+TCBZSO group [(0.12±0.02)g] was lower than that in the F.n+L-OHP group [(0.33±0.05)g, P＜0.001]. Immunohistochemistry suggested that the promotion of ABCG2 protein expression by F. nucleatum was blocked after TCBZSO intervention. Conclusion:F. nucleatum up-regulates ABCG2 expression through E-cadherin/β-catenin signaling pathway to promote colorectal cancer resistance to oxaliplatin.

Chongqing Medical University and University of Dundee have explored the "4+ 1" integration training mode combining undergraduate and postgraduate for biomedical engineering major in 2018, including mode of education, curriculum linkage and credit recognition, contract signing and publicity, process assessment and management, and degree awarding. After repeated communication and argument, Chongqing Medical University and University of Dundee signed the contract of the "4+ 1" integration training mode in 2019. One junior student participated in the "Summer Camp of University of Dundee" in the same year, and one senior student participated in this integration training mode program in 2020. According to the feedback of the first batch of students, the "4+ 1" integration training mode can guide students from different angles, which is conducive to broadening students' international vision and injecting strong power into the cultivation of biomedical engineering talents.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

Objective:To observe the clinical effect of Bairui grain combined with ambroxol atomization inhalation treating acute attack of chronic bronchitis (wind heat attact the lung symptom). Methods:A total of 150 patients with acute attack of chronic bronchitis who were admitted in our hospital from July 2015 to July 2018 were randomly divided into control and intervention groups (75 each group) by the random number table method. The control group received ambroxol atomization inhalatio based on the regular western medicine treatment; the intervention group took Bairui grain orally based on control group. Both of the two groups were treated for 2 weeks. Before and after the treatment, to score the clinical symptoms and wind-heat attact the lung symptom. Use pulmonary function meter to detect the ratio of FEV1 to estimated value (FEV1%) and FEV1/FVC; use ELISA to detect serum and sputum levels of TNF-α and IL-6. Record the extinction time of the symptoms (cough, wheezing, sputum, lung rumble) and evaluate the clinical efficacy. Results:The total efficacy rate of intervention group was 98.6% (72/73), which was significantly higher than control group 88.9% (64/73) ( χ2=4.354, P=0.037). The symptoms (cough, wheezing, sputum, lung rumble) extinction time of intervention group were significantly less than those of the control group ( t values 5.331, 5.590, 5.841, 6.305, respectively, all Ps<0.01). After the treatment, scores of clinical symptoms (cough, wheeze, cough, cough) and symptoms of wind-heat attacking lung (cough, wheezing, fever, dry mouth, stuffy nose, runny nose) of intervention group were significantly lower than those of the control group ( t values 4.990, 4.431, 5.221, 5.004, 5.652, 5.190, 5.311, 5.793, 5.643, respectively, all Ps<0.01). After treatment, the FEV1% (52.51% ± 5.63% vs. 47.30% ± 5.21%, t=8.931) and FEV1/FVC (61.57 ± 6.44 vs. 56.87 ±5.82, t=8.251) were significantly higher than the control group ( P<0.01). The serum level of TNF-α, IL-6 ( t values 5.331, 4.908) and the level of TNF-α, IL-6 ( t values 6.001, 4.803) in sputum were significantly lower than those of the control group ( P<0.01). Conclusions:The Bairui grain combined with ambroxol atomization inhalation can decrease the inflammotory cytokine levels of the acute attack patients with chronic bronchitis (syndrome of wind-heat attacking lung symptome), improve clinical symptoms and enhance efficacy.

OBJECTIVE: To explore the effect of occupational aluminum exposure on the blood of male workers. METHODS: A total of 249 male workers were selected as the research subjects by cluster sampling method in the electrolytic workshop of an aluminum plant. Blood samples were collected for determination of the blood aluminum concentration and blood routine. The subjects were divided into low-, medium-, and high-aluminuml groups based on the tertile of blood aluminum level(P_(33) is 13.9 μg/L, P_(67) is 37.7 μg/L). RESULTS: The red blood cell(RBC) count and hemoglobin level in patients of the high-aluminum group were lower than that of the low-aluminum group(P<0.05). There was no significant difference of the RBC count and hemoglobin level of patients in middle-aluminum group compared with that of the low-and high-aluminum groups(P>0.05). There was no statistical significant difference in white blood cell count and platelet count among the three groups(P>0.05). The results of the generalized linear regression model showed that the higher the blood aluminum level, the lower the RBC count and hemoglobin level of workers(P<0.05) after eliminating confounding factors such as age, length of service, education level, smoking, and drinking. CONCLUSION: Occupational aluminum exposure can cause a decrease of RBC count and hemoglobin level with a dose-effect relationship in workers.

OBJECTIVE： To study the effects of ADRB2 （rs1042713） gene polymorphism on therapeutic efficacy of anticholinergic drug in the treatment for refractory asthma pediatric patients. METHODS： 171 children with refractory asthma were selected from outpatient department of Kunming Children’s Hospital during Nov. 2016 to Jul. 2019. The distribution of ADRB2 （rs1042713） genotype， the clinical efficacy [asthma control test （C-ACT） score， FEV1， FVC， PEF， maximal mid-expiratory flow （MMEF）] of anticholinergic drug were analyzed statistically； the response of different genotypes to the use of anticholinergic drug were also analyzed statistically. RESULTS： 148 of 171 refractory asthmatics pediatric patients were administered anticholinergic drug， among them 50 of the 71 AA genotype and 36 of the 77 GA genotype responded to anticholinergic drug treatment. Statistical analysis showed that 71 children with AA refractory asthma had improved C-ACT score， FEV1， FVC， PEF and MMEF， there was statistical significance， compared with GA genotype （P＜0.05）； the response rate of the AA genotype to anticholinergic drugs was 2.71 times that of the GA genotype [OR＝2.71， 95％CI （1.38， 5.34）， P＝0.005]. CONCLUSIONS： The detection of ADRB2 （rs1042713） gene polymorphism has some guiding significance in the treatment of refractory asthma with anticholinergic drugs， and the response of AA genotype is better.

OBJECTIVE: To explore the mechanism of ubiquitin-proteasome pathway(UPP) in the degradation of hyperphosphorylated tau protein in aluminum-induced mouse neuroblastoma N2 a cells. METHODS: N2 a cells in logarithmic growth period were randomly divided into control group and MG132 group. Cells in control group were exposed to concentrations of 0 or 1 mmol/L aluminum chloride for 24 hours. Cells in MG132 group were pretreated with MG132 at a concentration of 5 μmol/L for 6 hours, then exposed to concentrations of 0 or 1 mmol/L aluminum chloride for 24 hours. After exposure, the cells were collected. Western blotting was used to detect the relative expression of tau-5, P-tau181, P-tau231, P-tau262, P-tau396, heat shock protein 70(Hsp70) and carboxyl terminus of the Hsp70-interacting protein(CHIP). The ubiquitin relative expression was detected by enzyme-linked immunosorbent assay. RESULTS: The results of factorial analysis showed that the relative expression of tau-5, P-tau231, P-tau262, P-tau396, CHIP, Hsp70 and ubiquitin in N2 a cells were statistically significant in the main effect and interaction effect of aluminum chloride and MG132 treatment(P<0.05). Both in the control group and MG132 group, the relative expression of tau-5, P-tau231, P-tau262, P-tau396, CHIP, Hsp70 and ubiquitin in N2 a cells exposed to 1 mmol/L aluminum chloride increased(P<0.05) when compared with the N2 a cells without exposed to aluminum chloride. No matter aluminum chloride exposed or not, the relative expression of tau-5, P-tau231, P-tau262, P-tau396, CHIP, Hsp70 and ubiquitin in N2 a cells of MG132 group was higher than that of control group(P<0.05). CONCLUSION: UPP is involved in the regulation of hyperphosphorylated tau protein by proteasome degradation in aluminum-induced N2 a cells. UPP mainly regulates P-tau231, P-tau262, and P-tau396 sites. CHIP and Hsp70 played an important role in the UPP pathway.

OBJECTIVE: To study the value of ADRB2, GLCCI1, FCER2 gene detection in individualized medication of children with refractory asthma.METHODS: Clinical pharmacists participated in therapy for 2 cases of refractory asthma, and comprehensively analyzed risk factors as its pathogenic factors (allergens and pathogens of respiratory infections), lung function indexes and family history. It was suggested to conduct anti-asthmatic drugs gene [p2-adrenergic receptor (ADRB2), glucocorticoid induced transcriptional 1 gene (GLCCI1), low affinity IgE receptor (FCER2)] testing. According to detection results, the suggestions were put forward such as increasing the dose of Glucocorticoid for inhalation, stopping β2 receptor agonist, additionally using anticholinergic drug. RESULTS: The clinical physicians adopted the suggestions of clinical pharmacists. After optimizing refractory asthma therapy plan according to the results of gene testing and clinical factors, 2 patients were stable and the number of seizures decreased significanthy. CONCLUSIONS: Gene test can provide evidence for the formulation of individualized therapy in asthma children.

Objective To observe the changes of serum sphingosine-1-phosphate (S1P) level in acute attack of adult bronchial asthma (simplified as asthma) and explore its clinical significance in the pathogenesis of the disease.Methods Forty-five patients of outpatient and hospitalized admitted to the Department of Respiratory Medicine in First Affiliated Hospital of Jiamusi University from November 2015 to July 2016 were arranged to an asthma group;in thc samc period,25 healthy peoples in our hospital having passed physical examination were chosen and assigned in a healthy control group.Serum S1P levels were determined by enzyme-linked immunosorbent assay (ELISA) in the subjects,the differences of pulmonary function indexes,the percentage of 1 second forced expiratory volume (FEV1)in predicted FEV1 value,FEV1/forced vital capacity (FVC) ratio were compared between the two groups,and the correlations between FEV1％,FEV1/FVC and S1P level were analyzed by Pearson analysis.Results The level of S1P in serum of asthma group was significantly higher than that of the healthy control group (μmol/L:1.90 ± 0.32 vs.0.89 ± 0.17,P ＜ 0.01),the levels of FEV1％,FEV1/FVC were significantly lower in the asthma group than those in healthy control group [FEV1％:(68.26 ±22.83)％ vs.(97.46 ± 10.44)％,FEV1/FVC:0.69 ±0.13 vs.0.82 ±0.05,both P ＜ 0.01].In the asthma group,the levels of FEV1％,FEV1/FVC were negatively correlated to the serum S1P level (r =-0.801 and -0.648,both P ＜ 0.01).While the levels of FEV1％,FEV1/FVC were not correlated to the serum S1P level in the healthy control group (r =-0.048 and 0.183,P ＞ 0.05).Conclusion The serum S1P is increased significantly in patients with asthma,and it being an important inflammatory mediator may play a crucial role in the pathogenesis of asthma.