BACKGROUND:The pathogenesis of autoimmune hepatitis has not been clearly elucidated.Circular RNA(CircRNA)is a research hotspot in the field of RNA and is involved in the pathogenesis of many autoimmune diseases.However,the role of CircRNA in autoimmune hepatitis remains unclear. OBJECTIVE:To investigate the relationship between CircRNA(CircRNA)and concanavalin A induced liver injury in mice with autoimmune hepatitis. METHODS:Bioinformatics analysis was performed on CircRNA profiles selected by previous microarray technology,including gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,so as to explore the potential biological functions of these differentially expressed genes.Twelve C57BL/6 mice were randomized into normal group and model group(n=6 per group).Autoimmune hepatitis model was established by tail vein injection of concanavalin A in the model group.Mice were killed at 12 hours after modeling to extract mouse liver and peripheral blood.The expression levels of CircRNAs were verified by qRT-PCR.Serum alanine aminotransferase and aspartate aminotransferase levels were detected by colorimetric method.The levels of oxidative stress indexes malondialdehyde and nitric oxide in mouse liver were detected by microplate method.The correlation between oxidative stress level and liver injury index was analyzed. RESULTS AND CONCLUSION:The results of GO analysis showed that the target genes with up-regulated CircRNAs expression were mainly involved in the biological processes of SNARE complex assembly regulation(P=0.004),their molecular functions were mainly metal ion binding(P=0.000 29),and the cell components were mainly enriched in CORVET complex(P=0.075).The biological processes involved in the down-regulated circRNAs target genes were mainly"negative regulation of pancreatic secretion"(P=0.000 42),the molecular functions were mainly"transcriptional activator activity"(P=0.025),and the cell components were mainly enriched in"extracellular components"(P=0.006).KEGG results showed that the target genes with up-regulated CircRNAs expression were mainly enriched in the"base excision-repair"signaling pathways(P=0.026).Compared with the normal group,serum alanine aminotransferase and aspartate aminotransferase levels and the levels of malondialdehyde and nitric oxide in mouse liver in the model group were significantly increased(P＜0.01).Compared with the normal group,the expression of two selected CircRNAs(mmu-circ-0001520 and mmu-circ-0001577)was increased in the model group(P＜0.05).Spearman correlation analysis showed that the expression of mmu-circ-0001520 and mmu-circ-0001577 was positively correlated with alanine aminotransferase,aspartate aminotransferase,malondialdehyde and nitric oxide.To conclude,the differential expression of CircRNAs is correlated with liver injury in autoimmune hepatitis mice.mmu-circ-0001520 and mmu-circ-0001577 are expected to be diagnostic biomarkers and therapeutic targets for autoimmune hepatitis.

Objectives:To investigate the outcomes of cochlear implantation in Mandarin-speaking cochlear implant (CI) users with single-sided deafness (SSD).Methods:This study was a single-center prospective cohort study. Eleven Mandarin-speaking adult SSD patients who underwent CI implantation at Capital Medical University Beijing Tongren Hospital from August 2020 to October 2021 were recruited, including 6 males and 5 females, with the age ranging from 24 to 50 years old. In a sound field with 7 loudspeakers distributed at 180°, we measured root-mean-square error(RMSE)in SSD patients at the preoperative, 1-month, 3-month, 6-month, and 12-month after switch-on to assess the improvement of sound source localization. The Mandarin Speech Perception (MSP) was used in the sound field to test the speech reception threshold (SRT) of SSD patients under different signal-to-noise locations in a steady-state noise under conditions of CI off and CI on, to reflect the head shadow effect(S SSDN NH), binaural summation effect(S 0N 0) and squelch effect(S 0N SSD). The Tinnitus Handicap Inventory (THI) and the Visual Analogue Scale (VAS) were used to assess changes in tinnitus severity and tinnitus loudness in SSD patients at each time point. The Speech, Spatial and Qualities of Hearing Scale(SSQ) and the Nijmegen Cochlear Implantation Scale (NCIQ) were used to assess the subjective benefits of spatial speech perception and quality of life in SSD patients after cochlear implantation. SPSS 19.0 software was used for statistical analysis. Results:SSD patients showed a significant improvement in the poorer ear in hearing thresholds with CI-on compared with CI-off; The ability to localize the sound source was significantly improved, with statistically significant differences in RMSE at each follow-up time compared with the preoperative period ( P<0.05). In the S SSDN NH condition, which reflects the head shadow effect, the SRT in binaural hearing was significantly improved by 6.5 dB compared with unaided condition, and the difference was statistically significant ( t=6.25, P=0.001). However, there was no significant improvement in SRT between the binaural hearing condition and unaided conditions in the S 0N 0 and S 0N SSD conditions ( P>0.05). The total score of THI and three dimensions were significant decreased ( P<0.05). Tinnitus VAS scores were significantly lower in binaural hearing compared to the unaided condition ( P<0.001). The total score of SSQ, and the scores of speech and spatial dimensions were significant improved in binaural hearing compared to the unaided condition ( P<0.001). There was no statistical difference in NCIQ questionnaire scores between preoperative and postoperative ( P>0.05), and only the self-efficacy subscore showed a significant increase( Z=-2.497, P=0.013). Conclusion:CI could help Mandarin-speaking SSD patients restore binaural hearing to some extent, improve sound localization and speech recognition in noise. In addition, CI in SSD patients could suppress tinnitus, reduce the loudness of tinnitus, and improve subjective perceptions of spatial hearing and quality of life.

Objective To investigate the relationship between systemic immune-inflammation index (SII)and lower extremity vascular disease in patients with type 2 diabetes mellitus (T2DM).Methods A cross-sectional study was conducted on 390 T2DM patients admitted in our department from January 2013 to January 2024.According to the diagnostic criteria for lower extremity vascular disease in T2DM patients,they were divided into a lower extremity vascular disease group (n=158)and a control group (n=232).General data and results of laboratory tests were compared between the 2 groups.Spearman correlation analysis was used to identify the related factors for lower extremity vascular diseases in T2DM patients.The correlation between SII and lower extremity vascular diseases in T2DM patients was analyzed using the Row Mean Scores and Cochran-Armitage Trend analysis.Multivariate logistic regression analysis was applied to identify the risk factors for lower limb vascular lesions in T2DM patients.Receiver operating characteristic (ROC)curve was plotted to evaluate the diagnostic efficacy of SII for lower extremity vascular disease in the patients.Results Compared with T2DMpatients without lower extremity vascular disease,those with lower extremity vascular disease were older,had higher levels of total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),SII,larger proportion of carotid vascular lesions,and increased proportion of no-taking statins.The lower extremity vascular disease in T2DM patients was positively correlated with SII/100 (r=0.429,P<0.001),age (r=0.517,P<0.001),TC (r=0.161,P=0.001),LDL-C (r=0.117,P=0.021),carotid artery lesions (r=0.101,P=0.047),no-taking statins (r=0.266,P<0.001).Logistic regression analysis showed that SII,age,LDL-C,and no-taking statins were the risk factors for lower extremity vascular lesions in T2DM patients (P<0.01).The area under the curve (AUC)value of SII combined with age,LDL-C,and no-taking statins in predicting lower extremity vascular disease in T2DM patients was 0.896.Conclusion SII is not only a risk factor,but also a simple marker for lower extremity vascular disease in T2DM patients,suggesting that inflammatory response plays an important role in the occurrence and development of lower extremity vascular disease in T2DM.

ObjectiveTo investigate the changes and potential effects of differentially expressed microRNAs (miRNAs) in the development and progression of liver injury in a mouse model of autoimmune hepatitis (AIH) induced by concanavalin A (ConA). MethodsEight healthy male specific pathogen-free C57BL/6 mice were randomly divided into model group and control group, with four mice in each group. The mice in the model group were given tail vein injection of ConA 15 mg/kg, and those in the control group were given an equal volume of normal saline. All mice were sacrificed after 8 hours of modeling, Total RNA in liver tissue was extracted, gene microarray was used to screen out differentially expressed miRNAs, and target prediction and function analysis were performed for upregulated and downregulated miRNAs. The independent samples t-test was used for comparison of differentially expressed miRNAs between two groups. ResultsThe principal component analysis showed that the inter-group difference of the data extracted by gene microarray met the conditions for further analysis. Compared with the control group, the model group had 31 upregulated miRNAs and 18 downregulated miRNAs in mouse liver, which had a regulatory relationship with 959 target genes (601 upregulated genes and 358 downregulated genes). GO analysis showed that in the model group, the target genes of the upregulated miRNAs mainly had the molecular functions such as “DNA binding” (P=1.47×10-6), participated in the biological processes such as “transcription, DNA-templated” (P=2.36×10-7), and were mainly enriched in the cellular components such as “neuronal cell body” (P=5.99×10-6), while the target genes of the downregulated miRNAs had the molecular functions such as “RNA polymerase II proximal promoter sequence-specific DNA binding” (P=2.49×10-6), participated in the biological processes such as “regulation of transcription, DNA-templated” (P=1.64×10-11), and were mainly enriched in the cellular components such as “nucleoplasm” (P=4.30×10-10). KEGG pathway enrichment analysis showed that the target genes of the upregulated miRNAs were mainly enriched in “Endocytosis” (P=0.000 4), while the target genes of the downregulated miRNAs were mainly enriched in the “Hippo signaling pathway” (P=0.004), and the above functional analysis results were statistically significant (P＜0.05). ConclusionThere are differentially expressed miRNAs in the pathogenesis of AIH, and these differentially expressed miRNAs can provide new targets for the clinical treatment of AIH.

Wheat quiescin sulfhydryl oxidase was expressed in Escherichia coli for developing a new biological flour improver. The synthesized wqsox gene was constructed into the vector pMAL-c5x and expressed in E. coli, then the expression conditions of recombinant protein was optimized. The MBP fusion label in recombinant protein was removed by protease digestion after affinity purification. Moreover, enzymatic properties of the purified wQSOX and its effect on bread quality were investigated. The synthesized wqsox gene contained 1 359 bp and encoded 453 amino acids with a deduced molecular weight of 51 kDa. The constructed recombinant vector pMAL-c5x-wqsox could successfully express soluble recombinant protein MBP-wQSOX in E. coli Rosetta gamiB(DE3), and the optimal induced expression conditions for recombinant protein were 25 °C, 0.3 mmol/L IPTG and 6 h. MBP fusion tag was cut out by factor Xa protease and wQSOX was prepared after affinity purification. wQSOX could catalyze the oxidation of DTT, GSH and Cys, accompanying the production of H2O2, and exhibited the highest substrate specificity for DTT. Furthermore, enzymatic properties results demonstrated that the optimal temperature and pH for wQSOX catalyzing oxidation of DTT was 50 °C and 10.0, respectively, and wQSOX presented a good stability under high temperature and alkaline environment. The addition of wQSOX with 1.1 U/g flour significantly (P<0.05) increased 26.4% specific volume of the bread, and reduced 20.5% hardness and 24.8% chewiness of bread crumb compared to the control, indicating a remarkable ability to improve the quality of bread.
Bread ; Escherichia coli/genetics* ; Hydrogen Peroxide ; Oxidoreductases ; Triticum

Objective:To investigate the value of conbercept in experimental corneal nevascularization (CNV) and lymphangiogenesis in rabbit model.Methods:Forty-four adult New Zealand rabbits were randomly divided into a conbercept injected group (9 rabbits), a ranibizumab injected group (9 rabbits), a normal saline control group (9 rabbits), a model control group (9 rabbits) and a normal control group (8 rabbits) by random number table method, take the left eyes as the experimental eye.Whatman filter papers (8 mm in diameter) were soaked in 1 mol/L NaOH solution and then applied on the middle surface of the cornea for 30 seconds.On day 1st after alkali burning, the eyes in the conbercept injected group were treated with 0.1 ml/1 mg of conbercept, the eyes in the ranibizumab injected group were treated with 0.1 ml/1 mg of ranibizumab, the eyes in the normal saline control group were treated with 0.1 ml 0.9% NaCl, the eyes in the model control group just received alkali burning, and the eyes in the normal control group received neither alkali burns nor subconjunctival injection any drugs.All rabbits were monitored daily after alkali burning.Digital pictures were taken on day 4th, 7th, 14th and 21th after modeling.Image analysis was performed on the area of neovascularization, a ascertain number of rabbits were killed respectively.Aqueous humor was collected for the concentration of vascular endothelial growth factor (VEGF) assay.Corneal specimens were analyzed by histopathologically and immunohistochemical staining of lymphatic endothelial cells hyaluronic acid receptor 1(LYVE-1). The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology (ARVO).Results:On the 4th day after alkali burning, the neovascularization buds grew into the edge of the cornea in the conbercept injected group, the ranibizumab injected group, the normal saline control group and the model control group, and the corneal edema decreased.On day 7th, the neovascularization of the conbercept injected group and the ranibizumab injected group was less than that of the normal saline control group and the model control group; On day 4th after alkali burning, corneal epithelial cells were increased, vacuoles were found in the epithelium, a large number of inflammatory cells were found in the matrix, and small vascular lumens were seen below the epithelium.On day 7th after modeling, neovascularization infiltrated the shallow matrix with a large number of inflammatory cells.Surface areas of induced CNV in conbercept injected group were (15.20±9.16)mm 2, which were significantly less than those in ranibizumab injected group ([28.21±5.17]mm 2) on day 14th ( P<0.05). The concentration of VEGF in the conbercept injected group was (7.75±6.56)pg/ml, which was significantly lower than that in the ranibizumab injected group ([16.98±2.17]pg/ml on day 14th ( P<0.05). The normal control group had no lymphatic growth in the corneal tissue and no LYVE-1 positive particles.On day 4th after the alkil burning, corneal lymphatic vessels appeared in the corneal tissue of the conbercept injected group, the ranibizumab injected group, the normal saline control group and the model control group, which grew in parallel with the neovascularization.Lymphatic vessels counting in the conbercept injected group and ranibizumab injected group were 4.33±0.58 and 4.67±0.58 on day 7th and 14th, which were reduced significantly compared with normal saline control group (10.67±0.58) and the model control group (12.33±0.58) (all at P<0.05). Conclusions:Early subconjunctival administration of conbercept may successfully inhibit alkali-induced corneal neovascularization and corneal lymphangiogenesis in alkali burning animal model.The inhibit effect is related with the reduces of VEGF levels.

Objective:To explore the prognostic factors of patients with gallbladder cancer in different anatomical locations.Methods:A retrospective analysis of the clinical data of 140 patients with gallbladder cancer who were surgically treated in the 904 Hospital of the Joint Logistics Support Force from January 2015 to December 2015. Among them, 49 were males and 91 were females, with a median age of 64.0 years. According to the location of gallbladder cancer, they were divided into the neck of the gallbladder and the bottom of the gallbladder. The clinical data of the two groups were compared. The Kaplan-Meier method was used for univariate analysis, and Cox multivariate regression analysis was used to analyze the significant factors of univariate survival to determine the independent risk factors that affect the prognosis of patients with gallbladder cancer. Use Pearson correlation to analyze the correlation between clinicopathological characteristics.Results:Patients in the neck of the gallbladder group had higher levels of preoperative total bilirubin, preoperative albumin, carcinoembryonic antigen, carbohydrate antigen 19-9, extrahepatic bile duct resection (biliary-enteric anastomosis), radical resection, breakthrough of the liver/serous membrane invasion, lymph node metastasis, TNM staging, local recurrence in the operation area in the surgical area were statistically significant ( P<0.05). Univariate analysis suggested that preoperative jaundice, Glasgow prognostic score (GPS), C-reactive protein, carcinoembryonic antigen, carbohydrate antigen 19-9, accidental gallbladder cancer, surgical method, tumor pathological type, tumor differentiation degree, tumor growth location (neck than the bottom of the body) are related to the prognosis (all P<0.05). Cox regression analysis indicated that GPS ( RR=3.272, 95 CI: 1.987-5.388), surgical method ( RR=4.149, 95 CI: 2.561-6.723), tumor location ( RR=0.316, 95 CI: 0.209-0.478), distant metastasis ( RR=1.695, 95 CI: 1.036-2.775) and TNM staging ( RR=3.686, 95 CI: 2.222-6.115) are independent risk factors affecting the prognosis of gallbladder cancer. Correlation analysis suggests that neck tumors are related to later staging, liver bile duct invasion, lymph node metastasis, high inflammation levels, and low radical cure rates. Conclusions:Gallbladder cancer that occurs in the neck of the gallbladder is an independent factor influencing the poor prognosis of patients with surgical treatment. In addition, TNM staging, distant metastasis and Glasgow score are important predictors of survival in patients with gallbladder cancer.

Objective:To investigate the expression and clinical significance of Golgi phosphoprotein 3 (GOLPH3) and NOD-like receptor protein 3 (NLRP3) in gallbladder carcinoma (GBC).Methods:Surgical specimens and clinical data were collected from 63 patients with GBC who underwent radical cholecystectomy in the 904th Hospital of Joint Logistic Support Force of PLA from January 2014 to January 2019. In the GBC group, there were 21 males and 42 females, with an average age of 62.5 years. For 30 patients with mild to moderate atypical hyperplasia of gallbladder during the same period were included in the precancerous lesion group, including 9 males and 21 females, with an average age of 62.4 years. Normal gallbladder specimens from 20 patients who underwent surgical resection due to liver trauma or giant hepatic hemangioma were collected and included in the normal group, including 7 males and 13 females, with an average age of 61.9 years. The expressions of GOLPH3, NLRP3, Ki-67 were detected by immunohistochemistry. Log-rank test and Cox regression were adopted to analyze the GOLPH3 and NLRP3 expression and survival prognosis of gallbladder cancer patients.Results:Expression of GOLPH3 and NLRP3 in the tumor group, precancerous lesion group and normal group was decreased separately. In GBC tissues, the level of GOLPH3 and NLRP3 was positively correlated with the Ki-67 expression ( r=0.972 and r=0.969, both P<0.05). Multivariate analysis showed that high level of GOLPH3 ( HR=4.891, 95% CI: 1.776-13.470) and NLRP3 ( HR=3.006, 95% CI: 1.273-7.099) was an independent risk factor for predicting the postoperative survival of patients with GBC (both P<0.05). Conclusion:GOLPH3 and NLRP3 are highly expressed in GBC tissues, and high expression of GOLPH3 and NLRP3 is an independent risk factor for postoperative survival in patients with GBC.

Objective:To investigate the improved superantigen activity of SEC2(T20L/G22E) compared with recombinant staphylococcal enterotoxins C 2 ( rSEC2 ).Methods: The proliferation of spleen lymphocytes and T-cell subpopulations induced by rSEC2 and SEC2(T20L/G22E) were examined by WST-1 and flow cytometry separately,and the gene expression of cytokines and Vβspecificities were quantified by real-time PCR.Results: WST-1 and Flow cytometry assays showed that the superantigen activity of SEC2(T20L/G22E) was improved due to enhanced T-cell stimulating potency,resulting in massive activation of T-cells,particularly CD4+and CD8+T-cells.Quantitative real-time PCR assay showed that despite similar Vβspecificities induced by rSEC 2 and SEC2 (T20L/G22E),the quantities of activated T-cells bearing specific Vβwere different,and SEC2(T20L/G22E) could stimulate more gene expression of associated cytokines simultaneously.Conclusion: The results strongly suggested that the increased SEC 2 ( T20L/G22 E)-TCR-binding affinity contributed to more T-cells activation and cytokine release ,which elicit powerful immune activition.

A management window model for patients with atrial fibrillation (AF) was established in Tilanqiao Community Health Service Center cooperated with tertiary hospitals.Patients were screened and treated in the community health service center,and a comprehensive management plan was conducted and patients were followed-up.A total of 105 patients with atrial fibrillation (97.2％) were effectively managed with an average follow-up of 10.6 months.The CHADS2 score ≥ 2 in 78 cases,including 11 cases with administration of warfarin (14.1％) and 26 cases with paroxysmal AF without transition to persistent atrial fibrillation.Compared to the data before management,the rate of taking aspirin and warfarin in managed patients was increased (all P ＜ 0.05),the international normalized ratio (INR) of patients receiving warfarin was improved (P ＜ 0.05) ; the ratio of receiving comprehensive treatment program,standardized treatment and health education were significantly increased (P ＜ 0.05) ; the awareness of the disease,treatment compliance and satisfaction of patients were improved significantly (all P ＜ 0.05).The results suggest that the management widow model is feasible and effective for management of patients with atrial fibrillation in community health service centers.