OBJECTIVES: To explore the role of oxidative stress and immune infiltration in rheumatoid arthritis (RA). METHODS: RA datasets GSE55235 (10 RA vs 10 normal samples) and GSE55457 (13 RA vs 10 normal samples) from the GEO database were merged as the test set to identify the differentially expressed genes (DEGs) in RA using R. The DEGs were intersected with oxidative stress-related genes to obtain oxidative stress-associated DEGs. KEGG and GO enrichment analyses of the DEGs were performed, and the RA-related pathways and biological processes were analyzed using GSEA. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape, and the top 10 key genes were obtained using the Degree algorithm. The validation dataset GSE1919 from GEO database was used for ROC analysis of the key genes to obtain the core genes, and their correlations with infiltrating immune cells were analyzed using CIBERSORT. The results were verified by RT-qPCR for detecting expression levels of the core genes in RA and normal joint samples. RESULTS: We identified 89 oxidative stress-associated DEGs. Enrichment analysis suggested that these DEGs were involved in the biological processes including oxidative stress, chemical stress response, reactive oxygen species response, and lipopolysaccharide response. ROC analysis showed that the 5 core genes (STAT1, MMP9, MYC, CCL5, and JUN) all had AUC values >0.7, indicating their high diagnostic sensitivity and specificity for RA. These genes were closely correlated with immune cells, particularly T cells. RT-qPCR confirmed significant differential expressions of the core genes between RA and normal samples. CONCLUSIONS Oxidative stress and diverse immune responses are features of RA, and the immune responses contribute to activation of oxidative stress. The identified core genes can potential serve as new diagnostic markers for RA.
Arthritis, Rheumatoid/genetics* ; Oxidative Stress/genetics* ; Humans ; Computational Biology ; Protein Interaction Maps ; Gene Expression Profiling ; Gene Regulatory Networks

Objective To observe the value of deep learning combine with radiomics based on MRI for evaluating H3 K27 status of midline gliomas.Methods Totally 127 patients with diffuse midline glioma H3 K27-altered(H3-DMG)and 127 patients with midline glioblastoma(GBM)without H3 K27 mutation were retrospectively enrolled.The patients were randomly divided into training set(n=204)and test set(n=50)at the ratio of 8:2.U-Net neural network visual and radiomics features of tumors were extracted based on MRI,and a deep learning radiomics model was established,its value for evaluating H3 K27 status was observed.Results Based on training set,0.500 was obtained as the security score partition value for the model classification task.In test set,the median safety score of the obtained deep learning radiomics model for evaluating H3 K27 status of H3-DMG and GBM was 0(0,0)and 0.999(0.616,1.000),respectively,for the former was lower than for the latter(Z=-5.114,P＜0.001).The sensitivity,specificity,accuracy and area under the curve of deep learning radiomics model for evaluating H3 K27 status in training set was 93.14％,81.37％,87.25％and 0.953(95％CI[0.923,0.976]),respectively,while was 88.00％,80.00％,84.00％and 0.922(95％CI[0.829,0.986])in test set,respectively.Conclusion Deep learning radiomics based on MRI could accurately evaluate H3 K27 status of midline gliomas.

Combining with advances in optogenetics and feedback control of physiological function, we have utilized self-made PPDP (preview, presentation, demonstration, promotion) teaching method to clarify how various physiological functions are regulated by the nervous system and carried out physiological innovation experiment activities. The innovative experiments aim to cultivate students' self-study capability, broaden their vision, enhance their interest in physiology, and finally promote the effect of physiological theory teaching. We herein summarize our practice of closed-loop control of innovative experimental teaching in optogenetics from the following four facets: education concept, students and teacher resources, teaching design, and teaching experience. This summary is trying to explore new experiences of promoting students' participation in teaching activities and improving the teaching quality of physiology.

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult

Objective: To investigate the use of conventional MR imaging to guide treatment in patients with cholecystolithiasis and diffuse inflammatory thickening of gallbladder wall. Methods: The clinical data of patients who were treated in the Ningbo Huamei Hospital, University of the Chinese Academy of Sciences between January 2017 and January 2018 were analyzed. These patients were divided into two groups: patients with acute cholecystitis (n=139) and patients with viral hepatitis combined with cholecystolithiasis (n=67). Differences in the imaging signs in standardized upper abdominal contrast enhanced MRI examinations were retrospectively analyzed. Results: The imaging signs, including stone location, continuity of gallbladder mucosa, exudation in peri-gallbladder space, edema of intrahepatic portal area showed significant differences between the two groups (all P<0.05). On stratification analysis, the type of thickened gallbladder wall, background of liver parenchyma and extent of edema in intrahepatic catchment area also showed significant differences (all P<0.05). The imaging signs, including non-gallbladder neck ductal stones, concentric thickening of gallbladder wall, continuous mucous membrane in gallbladder and no peri-gallbladder space exudation but diffuse edema of intrahepatic catchment area supported the diagnosis of viral hepatitis combined with gallstones. The imaging signs, including discontinuity of gallbladder mucosa, exudation of peri-gallbladder space, diffuse edema of gallbladder wall without a cirrhotic background and edema in intrahepatic portal area supported the diagnosis of acute calculous cholecystitis of gallbladder. Conclusions Routine upper abdominal contrast enhanced MRI plays an important role in demonstrating the underlying cause of gallbladder wall diffuse edema thickening in patients with gallstones. It provides an important reference for the choice of clinical treatment pathway.

Objective To evaluate the efficacy of high performance liquid chromatography (HPLC) for simultaneous determination of propofol and remifentanil concentrations in human plasma.Methods Methods Eighteen healthy volunteers of both sexes,aged 18-45 yr,weighing 52-81 kg,were enrolled in the study.Venous blood samples were collected,and the concentrations of propofol and remifentanil in human plasma were detected simultaneously by HPLC.The internal standard was thymol.Potassium dihydrogen phosphate 0.1 mol/L was added to the plasma and then the plasma samples were extracted with extract liquor (ethyl acetate ∶ hexane =4 ∶ 1,V/V).The analytical column was ZORBAX Eclipse XDB-C18 (4.6 mm×250 mm,5 μm).The mobile phase was methano ∶ 0.02 mol/L NaH2PO4 ∶ acetonitrile,the flow rate was 1.0 ml/min,the detection wavelength was 210 nm within 1-7 min,and 266 nm within 7-16 min,and the sample size was 20 μl.Linear regression analysis was performed by using the least-squares method.The specimens of the blood with the final concentration of remifentanil 1.00,5.00 and 20.00 ng/ml and propofol 0.50,2.00 and 10.00 μg/ml were obtained to determine the recovery,precision and stability.Results Linear regression equation of remifentanil was C=12.853 5Ai/As+0.084 8 (R2 =0.999 4),and this system showed a good linear relationship with the concentration of remifentanil ranged 0.5-40.0 ng/ml.Linear regression equation of propofol was C=8.554 3 Ai/As+0.029 1 (R2=0.998 6),and this system showed a good linear relationship with the concentration of propofol ranged 0.2-20.0 μg/ml.For both propofol and remifentanil concentrations,the relative recovery was within the range of 85％-115％,the absolute recovery was larger than 75％,and the relative standard deviation of intra-and inter-day precision and stability was less than 5％.The method was proved to meet the requirements of biological sample analysis.Conclusion For HPLC method established in this trial,the determination is sensitive,reproducible,rapid and simple,and it can be used for simultaneous determination of propofol and remifentanil concentrations in human plasma and for clinical pharmacokinetic research.

Objective To investigate the impact of desmoglein 3 (Dsg3) on the proliferation of peripheral T lymphocytes from patients with pemphigus vulgaris (PV).Methods Peripheral blood mononuclear cells (PBMCs) were obtained from 12 patients with PV and 22 normal human controls,cultured with or without the presence of Dsg3 or phytohemagglutinin for 3 days.Flow cytometry was performed to detect the changes of T-lymphocyte subsets in PBMCs stimulated with Dsg3 and proliferation of T-lymphocytes.Results In patients with PV,the percentage of Th2 and Th1 cells was 12.17%±5.32% and 4.08%±1.50%,respectively in Dsg3stimulated PBMCs,9.84%±5.41% and 3.91%±1.38%,respectively in non-stimulated PBMCs.Increased percentage of Th2 cells was observed in Dsg3-stimulated and non-stimulated PBMCs from patients with PV compared with those from normal human controls (both P<0.05).After stimulation with Dsg3,there was a significant proliferation of T cells from patients,and the proliferation rate of CD4+T cells was 4.65%±3.28%,which was significantly higher than that from normal controls(P<0.05).Conclusion Dsg3 can induce the specific proliferation of CD4+T cells,especially Th2 type CD+4 T cells,from patients with PV.

Objective To investigate The Th1/Th2 and Tc1/Tc2 polarization in the peripheral blood of first degree relatives of pemphigus vulgaris(PV) and healthy control individuals, and to approach the mechanism of the Dsg3-specific autoimmunity in PV. Methods The peripheral blood mononuclear cells (PBMC) from first degree relatives and healthy control was stimulated for72 h with Dsg3 and without Dsg3. Th1/Th2, Tc1/Tc2 was assessed by four-color flow cytometry. Results The mean frequency of Dsg3-spe-cific Th2 cells for PV antibody positive first degree relatives was 10.13%±3.72%, compared with stimula-tion without antigen 7.28%±3.58%, the difference was significant (P<0.05). The percentage Dsg3-spe-cific Th2 was markedly higher in the PV antibody positive first degree relatives group than that in the control group(10.13%±3.72% vs 6.10%±2.82%, P<0.05) , Tc2 was markedly higher also (20.01%± 10.43% v514.91%±8.06%, 20.01%±10.43% vs 9.58%±5.49%, P<0.05). Conclusion When Dsg3 stimulated PBMC were used to stimulate autologous T cells an increased amount of Th2 and Tc2 was observed, it is implied that the imbalance of Th1/Th2, Tc1/Tc2 might play an important role in the initia-tion of PV.

Objective To discuss the clinical value of interventional management before surgical therapy for massive gastrointestinal hemorrhage, and to compare the clinical efficacy and re-bleeding rate between hypophysin infusion group and embolization group. Methods During the period of June 1998-Apr.2009, 31 patients with massive gastrointestinal hemorrhage in our institution underwent preoperative interventional managements before they received surgical treatment. According to DSA manifestations, the patients underwent trunsarterial hypophysin infusion or transcatheter embolization as interventional management. The clinical efficacy of interventional procedures and its influence on the surgery were evaluated, and the hemostasis rate and re-bleeding rate were compared the two kind of intervention managements. The numeration data were analyzed with Fisher's exact test, and the SPSS 11.0 was used as statistical software. Results The interventional managements were successfully performed in all the 31patients, with a total hemostasis rate of 83.9% (26/31) and a total re-bleeding rate 30.7% (8/26). The hemostasis rate and re-bleeding rate of hypephysin infusion group and embolization group were 69.2% (9/13), 94.4% (17/18) and 44.4% (4/9), 23.7% (4/17), respectively. All the 31 patients received surgery after interventional therapy, of which selective operation was carried out in 20. Neither surgery-related or intervention-related serious complications nor death occurred. Conclusion Preoperative interventional managements can provide patients with massive gastrointestinal hemorrhage with valuable chance of a successful surgery, enable the physician to take a selective operation to replace an emergency one, as a result, the surgical risk will be greatly reduced. Therefore, it is worth popularizing the preoperative interventional managements in clinical practice.

Objective To study the mechanism of U937 cell (human histocytic lymphema) apoptosis induced by ATP. Methods ATP (0\^23?g/L) was added into U937 cell cultured medium as experiment group, no ATP adding group as the control. Using immunofluorescent cytochemistry method to demonstrat the expresses of Cx43, F\|actin, vinculin. Results ATP induced U937 cell to form apoptotic bodies. Expresses of Cx43, F\|actin, vinculin were increased in ATP treated U937 cells.Conclusion ATP could induce U937 cell apoptosis. Apoptotic bodies formed from ATP treated U937 cells was correlated closely with express of Cx43, F\|actin, vinculin, It indicats that Cx43, F\|actin, vinculin play important roles in U937 cell apoptosis induced by ATP.