1.Baricitinib inhibits type Ⅰ IFN-signaling during SARS-CoV-2 infection in vitro
LIANG Wan-xin ; ZHANG Su ; OU Min ; DUAN Lian ; ZHANG Guo-liang ; LIU Shu-yan
China Tropical Medicine 2022;22(11):1056-
Abstract: Objective To explore the antiviral effect of baricitinib in the SARS-CoV-2 infection and influence on cytokine levels. Methods Calu-3 cells were infected with SARS-CoV-2 at MOI of 0.1, and the levels of inflammatory cytokines (IL-6, IL-8, TNF-α and IL-1β), interferon β (IFN-β) and interferon-stimulated gene, IFIT2 in the infected cells were analyzed by qRT-PCR methods. At the same time, Calu-3 cells were infected with SARS-CoV-2 (MOI=0.1) after being treated with baricitinib for 2 hours. Cells were collected at 0, 24, 36, and 48 hours, and analyzed for the mRNA of the above genes in the drug-treated and untreated groups. Results The mRNA levels of IL-6, TNF-a, IL-1β, IFN-β and IFIT2 in Calu-3 infected by SARS-CoV-2 cells were increased significantly. These cytokines were increased by nearly 100-fold post-infection 48 h compared with the control (P<0.000 1), and continued to increase with the infection time (P<0.001 or P<0.000 1). The increase of IL-8 mRNA level was not as significant as IL-6, TNF-α, IL-8, IL-1β, but it also showed a 2-4 folds increase. Baricitinib does not affect the level of viral RNA in Calu-3 cells after SARS-CoV-2 infection (P>0.05). However, baricitinib can significantly inhibit the up-regulation of IL-6 and TNF-α levels induced by SARS-CoV-2 infection (5.25-fold and 3.90-fold down-regulation, respectively, P<0.01), and has little effect on the levels of IL-8 and IL-1β . In addition, the drug could also significantly down-regulate the increase in IFN-β and IFIT2 levels caused by viral infection (10.51-fold and 90.78-fold down-regulation, respectively, P<0.000 1). Conclusions Baricitinib inhibits the release of inflammatory cytokines to some extent, but it drastically down-regulates the expression of interferons and interferon-stimulated genes (ISGs), and has limited antiviral effect on SARS-CoV-2. Considering that interferon signal pathways play important roles on viral infection, caution should be exercised when using baricitinib to treat COVID-19 patients.
2.Study on preventive and therapeutic effects of combined application of yindanxinnaotong soft capsule and exercise on atherosclerotic rats.
Jian-Lu WANG ; Lan WANG ; Long CHENG ; Xiao-Jie YIN ; Hai-Yu XU ; Wan-Dan WANG ; Ri-Xin LIANG
China Journal of Chinese Materia Medica 2014;39(13):2547-2552
To explore the prevention effect of the joint combination of Yindanxinnaotong soft capsule (YDXNT) and exercise (swimming) on atherosclerotic rats. The method of 3 x 3 factorial design, including two factors (YDXNT and swimming) and three levels (0, 1, 2 g x kg(-1) YDXNT; 0, 0.5, 1 h swimming), was mainly adopted. The atherosclerotic rat model was established by ligating their left common carotid arteries and feeding high-fat diet. After 8 weeks, blood samples were collected from their thoracic aorta to determine blood viscosity, plasma viscosity, fibrinogen (FIB), nitric oxide (NO), 6-keto-PGF(1alpha) endothelin (ET) and thromboxane B2 (TXB2). The tissues of left common carotid arteries of the rats were collected to detect the positive expression of SM22alpha and determine the semi-quantitation through the immunohistochemical staining. The result showed that the combination of YDXNT and swimming can significantly decrease the plasma viscosity (F = 3.241, P = 0.017), the high and low shear blood viscosity (F = 6.444, P = 0.001; F = 3.002, P = 0.024) and FIB (F = 4.046, P = 0.005). The increased NO and 6-keto-PGF(1alpha) and the decreased ET and TXB2 indicated a significant interaction (P < 0.05). The swimming showed an obvious main effect in the expression of up-regulated protein SM22alpha (F = 8.088, P = 0.001). The study suggested that the combined administration of YDXNT and swimming could improve the hemorheological parameters of atherosclerotic rats, protect the vascular endothelium, inhibit the vascular remodeling in atherosclerosis and positively prevent the atherosclerosis.
Animals
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Atherosclerosis
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drug therapy
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genetics
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metabolism
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prevention & control
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Blood Viscosity
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drug effects
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Combined Modality Therapy
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Drugs, Chinese Herbal
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administration & dosage
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Exercise Therapy
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Humans
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Male
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Microfilament Proteins
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genetics
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metabolism
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Muscle Proteins
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genetics
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metabolism
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Rats
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Rats, Sprague-Dawley
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Swimming
3.Development and preliminary application of the measurement scale for medical students' professionalism cognition
Minglei SUN ; Libo LIANG ; Mingli JIAO ; Wei LIU ; Siyi TAO ; Yuxin XUE ; Weijian SONG ; Xin WAN ; Yan ZHENG
Chinese Journal of Medical Education Research 2021;20(1):86-90
Objective:To explore the present situation of medical students' professionalism cognition and provide reference for medical personnel training and medical education.Methods:A cross-sectional survey was conducted on medical students among 2 affiliated hospitals of a medical university in H province by cluster sampling. Exploratory factor analysis and reliability and validity test were carried out and a descriptive analysis of the present situation of professionalism was conducted by SPSS 20.0. Amos21.0 software was used for a confirmatory factor analysis on the samples.Results:The measurement scale had good reliability and validity, and the Cronbach alpha coefficient of the scale was 0.901. The average professionalism score of the medical students was about 80 points. The score of "physical and mental status and self-development ability" was the highest (83.65 points), and the lowest score was "academic ability" (72.21 points). There was a little difference in the professionalism cognition between the two hospitals, with significant differences between the dimension "respect and care" and "responsibility".Conclusion:This study has initially formed a medical professionalism measurement scale with good reliability and validity. The professionalism of medical students in the 2 affiliated hospitals of a medical school in Province H is in good condition as a whole. In the future, medical education should pay more attention to the combination of basic professional knowledge and clinical practice of medical students, and change the training model of medical students in order to improve the academic ability of medical students and medical students' overall cognition of professionalism.
4.Tumor immune checkpoint therapy and the drug delivery strategies
Pei-shan LI ; Yi-xuan LIU ; Ying XIE ; Yu-xin REN ; Ming CHEN ; Gui-ling WANG ; Wan-liang LÜ
Acta Pharmaceutica Sinica 2022;57(1):13-24
Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.
5.Evidence of Genetic Instabilities on Chromosome 16q22 24 in Nasopharyngeal Carcinoma
Jian YAN ; Yan FANG ; Jun Bi HUANG ; Wan Qi LIANG ; Xin Yi ZENG
Chinese Journal of Cancer 2001;20(6):588-590
Objective:This study was designed to evaluate the genetic stability on chromosome 16q22 24 in primary nasopharyngeal carcinoma. Methods: Tissue samples from fifty patients with nasopharyngeal carcinoma (NPC) tumors were examined by loss of heterozygosity (LOH) and microsatellite instability (MSI) analysis with a panel of 8 microsatellite polymorphic markers distributed along the chromosome 16q22 24. Results: LOH was observed at one or more loci in 24 cases (48% ) and the prevalence of MSI was detected in 9 cases (18% ). But the genomic alterations scattered along the region, neither common deletion or instability region was found. Conclusions: The status of genetic stability in chromosome 16q22 24 suggests that the genomic alterations on chromosome 16q22 24 may be involved in the development of NPC.
6.Intractable constipation caused by adult dolichocolon
Wei-Liang YANG ; Xin-Chen ZHANG ; Hao-Gang ZHANG ; Wan-Song XU ; Hao-Min ZHANG ; Hui-Liang WANG ; Jian-Guo ZHANG
Chinese Journal of General Surgery 2000;0(12):-
Objective To summarize the diagnosis and surgical treatment for intractable constipation caused by adult dolichocolon.Methods Clinical data of 82 adult dolichocolon cases suffering from intractable constipation were analyzed retrospectively.Results Of the 82 patients,intractable constipation were found in 66 patients(80%),abdominalgia,abdominal distension in 28 patients(34%) and constipation alternatively with diarrhea in 16 patients(19%).Diagnosis was established in 74 patients by barium enema while 8 during the emergency operation.Dolichocolon was divided into 3 types as type Ⅰ in 35 cases,type Ⅱ in 19 and type Ⅲ in 28,in which there were 18 cases of total dolichocolon syndrome. Surgery performed including sigmoidectomy(32 patients),right hemicolectomy(3 patients),right hemicolon and transvers colon resection(4 patients),left side of transvers colon and splenic flexure colon resection(4 patients),descending colon and sigmoid colon resection(15 patients),transvers,descending and sigmoid colon resection(6 patients),pancolectomy with anastomosis of terminal ileum and upper rectum (18 patients).There were no severe postoperative complications such as anastomotic leakage and the recovery was uneventful in all 82 patients.The curative effect was graded as well and up in all 72 cases followed up from 3 months to 4 years,with a follow-up rate of 88%(72/82).Conclusion A history of intractable constipation and barium enema are the mainstay for the diagnosis of dolichocolon,and operation is the effective treatment for intractable constipation caused by adult dolichocolon.
7.Application of gene sequencing directly to identify the pathogens in specimens.
Xin-Xin LU ; Liang YUAN ; Xiao-Hua WAN ; Jia-Jing GENG
Chinese Medical Journal 2010;123(24):3534-3539
BACKGROUNDAccurate identification of bacterial isolates is an essential task in clinical microbiology. This study compared culturing to analyzing 16S rRNA gene sequences as methods to identify bacteria in clinical samples. We developed a key technique to directly identify bacteria in clinical samples via nucleic acid sequences, thus improving the ability to confirm pathogens.
METHODSWe obtained 225 samples from Beijing Tongren Hospital and examined them by conventional culture and 16S rDNA sequencing to identify pathogens. This study made use of a modified sample pre-treatment technique which came from our laboratory to extract DNA. 16S rDNA was amplified by PCR. The amplified product was sequenced on a CEQ8000 capillary sequencer. Sequences were uploaded to the GenBank BLAST database for comparison.
RESULTSAmong the positively cultivated bacterial strains, seven strains were identified differently by Vitek32 and by 16S rDNA sequencing. Twelve samples that were negative by standard culturing were determined to have pathogens by sequence analysis.
CONCLUSIONThe use of 16S rRNA gene sequencing can improve clinical microbiology by providing better identification of unidentified bacteria or providing reference identification of unusual strains.
Bacteria ; isolation & purification ; DNA, Ribosomal ; chemistry ; Humans ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; genetics ; Sequence Analysis, DNA ; methods
8.Effect of recombinant Sp1 gene on the collagen expression of hypertrophic scar fibroblasts in vitro.
Song-lin YANG ; Wei-dong WAN ; Jiang-hong ZHENG ; Shi-xin ZHANG ; Yun GAO ; Chen-liang DENG
Chinese Journal of Plastic Surgery 2009;25(1):46-49
OBJECTIVETo explore the feasibility of transfecting recombinant Sp1 into hypertrophic scar fibroblasts and investigate the proliferation and collagen I, III synthesis in the transfected cells.
METHODSRecombinant human Sp1 was transfected into hypertrophic scar fibroblasts with the karyocyte expressive vector. The expression of Sp1, collagen I, III mRNA was tested by real time PCR. The change of cell proliferation was observed with CCK8 colorimeter.
RESULTSAbout 30% of transfected hypertrophic scar fibroblasts showed green fluorescence positive. The relative expression of Sp1 mRNA in transfected cells, empty-vector cell or untransfected cells group was 5.26 +/- 0.76, 1.08 +/- 0.18, 1.09 +/- 0.15, respectively, showing a significant difference between thansfected and untransfected cells or between the transfected cells and empty-vector group (P <0.01, n = 5). Expression of collagen I, III mRNA was 2.49 +/- 0.40 and 1.88 +/- 0.30 in transfected cells, 0.96 +/- 0.18 and 0.95 +/- 0.18 in empty-vector cell, and 0.97 +/- 0.15 and 0.93 +/- 0.13 in untransfected cells, respectively, showing a significant difference between thansfected and untransfected cells or between the transfected cells and empty-vector group (P < 0.01, n = 5).
CONCLUSIONSThe hypertrophic scar fibroblasts could be as the target cells of Sp1 gene transfection. Sp1 gene may play an important role in abnormal collagen metabolism in hypertrophic scar.
Cell Proliferation ; Cells, Cultured ; Cicatrix, Hypertrophic ; genetics ; metabolism ; pathology ; Collagen ; metabolism ; Escherichia coli ; genetics ; Fibroblasts ; metabolism ; pathology ; Humans ; RNA, Messenger ; genetics ; Recombinant Proteins ; genetics ; Skin ; metabolism ; Sp1 Transcription Factor ; genetics ; Transfection
9.Effect of interferon neutralization antibody in the treatment of chronic hepatitis B with interferon.
Xian-rui CHEN ; Hui-liang WANG ; Mei-xiang XUAN ; Xin-gang MAO ; Jian-guo SUN ; Bao-mei WAN
Chinese Journal of Hepatology 2009;17(5):385-386
Adult
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Antibodies
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blood
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Antiviral Agents
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therapeutic use
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DNA, Viral
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blood
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Female
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Hepatitis B Surface Antigens
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blood
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Hepatitis B e Antigens
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blood
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Hepatitis B virus
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drug effects
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Hepatitis B, Chronic
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blood
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drug therapy
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virology
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Humans
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Interferons
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immunology
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therapeutic use
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Liver Function Tests
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Male
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Middle Aged
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Young Adult
10.Protection effect of Yindan Xinnaotong capsule and main compositions compatibility on myocardial ischemia/reperfusion injury.
Wan-Dan WANG ; Lan WANG ; Long CHENG ; Xiao-Jie YIN ; Hai-Yu XU ; Jian-Lu WANG ; Ri-Xin LIANG ; Hong-Jun YANG
China Journal of Chinese Materia Medica 2014;39(9):1690-1694
OBJECTIVETo study the protected effect of Yindan Xinnaotong capsule (YDXNTC) and main components compatibility on myocardium ischemia/reperfusion injury.
METHODGlobal ischemia/reperfusion was adopted to induce myocardial ischemia/reperfusion injury (MIRI) in isolated rat heart. Sprague-Dawley (SD) rats were divided into control, model, YDXNTC, Ginkgo biloba extract (GBE) group, ethanol extract of Salvia miltiorrhiza (SM-E) group, aqueous extract of Salvia miltiorrhiza (SM-H) group, mixed compatibility of other components in YDXNTC (MC), GBE and SM-E compatibility (GSEC), GBE and SM-H compatibility (GSHC), and SM-E and SM-H compatibility (SEHC). During the experiment, electrocardiogram was recorded to observe cardiac arrest time, heart resuscitation time, regaining normal rhythm time, the incidence and duration of arrhythmias (VT/VF). At the end of reperfusion, hearts were arrested and homogenated to assay the activity of superoxide dismutase (SOD), and the content of malondialdehyde (MDA), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), cardiac troponin I.
RESULT(1) YDXNTC, SM-E, SM-H and MC elevated cardiac arrest time, also reduced rebeating time, restoring normal rhythm time as well as the duration of arrhythmia, but no remarkable impact on VT/VF occurrence. GBE was effective for incidence of VT/VF, also achieved good effect on shortening rebeating time, restoring normal rhythm time and arrhythmia duration. Likewise, obviously reduced rebeating time, restoring normal rhythm time and arrhythmia duration, and evaluated cardiac arrest time were also exhibited in compatibility groups except that no lengthened cardiac arrest time was detected in GSHC. And the incidence of VT/VF was decreased by GSEC. (2) YDXNT, ginkgo biloba extract (GBE), ethanol extract of salvia miltiorrhiza (SM-E), GBE and SM-E compatibility (GSEC), and SM-E and aqueous extract of salvia miltiorrhiza (SM-H) compatibility (SEHC) could improved SOD and decreased MDA level SM-H, mixed compatibility of other elements in YDXNTC (MC) and GBE and SM-H compatibility (GSHC) showed a role on MDA reduction. (3) LDH was declined by YDXNT and SM-H. CK-MB was reduced by GBE, SM-E, SM-H, and GSEC. (4) The release of cTnI was only inhibited by GSEC.
CONCLUSIONYDXNTC, primary materials and main components compatibility has a certain protection effect on MIRI, its mechanism may be related to antioxidant and calcium overload reduction.
Animals ; Arrhythmias, Cardiac ; physiopathology ; prevention & control ; Capsules ; Creatine Kinase, MB Form ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Electrocardiography ; Ginkgo biloba ; chemistry ; Heart ; drug effects ; physiopathology ; In Vitro Techniques ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; metabolism ; physiopathology ; prevention & control ; Myocardium ; metabolism ; pathology ; Phytotherapy ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Salvia miltiorrhiza ; chemistry ; Superoxide Dismutase ; metabolism ; Troponin I ; metabolism