1.Efficacy and Safety of Small Molecule Drugs in Treatment of Moderate-to-severe Ulcerative Colitis:A Meta-analysis
Jianshu GAO ; Jian LI ; Longxiang ZHANG ; Hongliang GAO
Chinese Journal of Gastroenterology 2024;29(8):459-469
Background:Ulcerative colitis(UC)is a chronic non-specific disease with potential for disability,and clinical treatment mainly relies on drugs.Currently,small molecule drugs(SMDs)have shown good application prospects.Aims:To evaluate the efficacy and safety of SMDs in the treatment of UC.Methods:Randomized controlled trials(RCTs)of SMDs in treatment of moderate-to-severe UC from CNKI,Wanfang Data,VIP,China Biomedical Literature Database,PubMed,Cochrane Library and Embase were searched from the establishment of the database to March 2024.References were screened and data extracted according to inclusion and exclusion criteria,and meta-analysis was performed using RevMan 5.3 software.Results:A total of 16 literatures involving 22 RCTs were finally included.Meta-analysis results suggested that SMDs had better efficacy indicators than placebo,such as clinical response rate(RR=1.86,95%CI:1.60-2.16,P<0.000 01),clinical remission rate(RR=3.01,95%CI:2.17-4.16,P<0.000 01),mucosal healing rate(RR=2.93,95%CI:2.27-3.79,P<0.000 01)and maintained response rate(RR=3.87,95%CI:3.11-4.81,P<0.000 01)were improved,and there was a statistical difference between them.And in terms of safety,SMDs compared to placebos,The incidence of adverse reactions(RR=1.02,95%CI:0.96-1.08,P=0.55),the incidence of serious adverse reactions(RR=0.77,95%CI:0.59-1.00,P=0.05),and the incidence of adverse reactions leading to drug withdrawal(RR=0.78,95%CI:0.59-1.02,P=0.07)were not statistically significant.Conclusions:SMDs are effective and safe in UC patients,which provides a new idea for the treatment of UC.
2.Efficacy and Safety of Small Molecule Drugs in Treatment of Moderate-to-severe Ulcerative Colitis:A Meta-analysis
Jianshu GAO ; Jian LI ; Longxiang ZHANG ; Hongliang GAO
Chinese Journal of Gastroenterology 2024;29(8):459-469
Background:Ulcerative colitis(UC)is a chronic non-specific disease with potential for disability,and clinical treatment mainly relies on drugs.Currently,small molecule drugs(SMDs)have shown good application prospects.Aims:To evaluate the efficacy and safety of SMDs in the treatment of UC.Methods:Randomized controlled trials(RCTs)of SMDs in treatment of moderate-to-severe UC from CNKI,Wanfang Data,VIP,China Biomedical Literature Database,PubMed,Cochrane Library and Embase were searched from the establishment of the database to March 2024.References were screened and data extracted according to inclusion and exclusion criteria,and meta-analysis was performed using RevMan 5.3 software.Results:A total of 16 literatures involving 22 RCTs were finally included.Meta-analysis results suggested that SMDs had better efficacy indicators than placebo,such as clinical response rate(RR=1.86,95%CI:1.60-2.16,P<0.000 01),clinical remission rate(RR=3.01,95%CI:2.17-4.16,P<0.000 01),mucosal healing rate(RR=2.93,95%CI:2.27-3.79,P<0.000 01)and maintained response rate(RR=3.87,95%CI:3.11-4.81,P<0.000 01)were improved,and there was a statistical difference between them.And in terms of safety,SMDs compared to placebos,The incidence of adverse reactions(RR=1.02,95%CI:0.96-1.08,P=0.55),the incidence of serious adverse reactions(RR=0.77,95%CI:0.59-1.00,P=0.05),and the incidence of adverse reactions leading to drug withdrawal(RR=0.78,95%CI:0.59-1.02,P=0.07)were not statistically significant.Conclusions:SMDs are effective and safe in UC patients,which provides a new idea for the treatment of UC.
3. Progress of research on Janus kinase inhibitors in treatment of ulcerative colitis
Chinese Journal of Gastroenterology 2023;28(4):243-248
Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by multiple factors, and its etiology and pathogenesis are not fully understood. Janus kinases (JAK) are non‑transmembrane tyrosine kinases that play a key role in many immune‑related cytokine signaling pathways. JAK‑STATs signaling pathway is a cytokine‑mediated signaling pathway, which is involved in many important biological processes such as cell proliferation, differentiation, apoptosis and immune regulation. JAK inhibitors are small molecule drugs that can be administered orally and are relatively inexpensive, therefore, JAK inhibitors may become a new target for the treatment of UC. This article reviewed progress of research on the efficacy and safety of small molecule JAK inhibitors in treatment of UC.
4. Causal Association Between Unsaturated Fatty Acids and Inflammatory Bowel Disease: A Mendelian Randomization Analysis
Jian LI ; Jianshu GAO ; Keke ZHAO ; Hongliang GAO ; Jianshu GAO ; Keke ZHAO ; Hongliang GAO
Chinese Journal of Gastroenterology 2023;28(1):12-16
Background: Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of gastrointestinal tract including ulcerative colitis (UC) and Crohn's disease (CD). It is unclear whether there is a causal association between unsaturated fatty acids and IBD. Aims: A two⁃sample Mendelian randomization analysis was used to explore the causal association between unsaturated fatty acids and IBD. Methods: The data of the genome⁃wide association study (GWAS) of unsaturated fatty acids and IBD were obtained from web⁃based public databases. Two⁃sample Mendelian randomization analysis was performed by using inverse⁃variance weighted analysis, and weight median estimator and MR⁃Egger regression were conducted to validate the association of the causal effect. The causality of unsaturated fatty acids on the risk of IBD was evaluated by OR and 95% CI. Results: No direct causal association was found between ω⁃6 fatty acids and CD, and a direct causal association was found with UC. Inverse⁃variance weighted analysis showed a 16% increase in the risk of UC for each standard deviation increase in ω⁃6 fatty acid gene levels (OR=1.16, 95% CI: 1.00⁃1.36, P=0.04). However, no causal association was found between ω⁃3 fatty acids, monounsaturated fatty acids and IBD. Conclusions: ω⁃6 fatty acids may be only causally associated with UC, and no causal association is found between ω⁃3 fatty acids, monounsaturated fatty acids and IBD.
5.Crystal structure of E. coli arginyl-tRNA synthetase and ligand binding studies revealed key residues in arginine recognition.
Kelei BI ; Yueting ZHENG ; Feng GAO ; Jianshu DONG ; Jiangyun WANG ; Yi WANG ; Weimin GONG
Protein & Cell 2014;5(2):151-159
The arginyl-tRNA synthetase (ArgRS) catalyzes the esterification reaction between L-arginine and its cognate tRNA(Arg). Previously reported structures of ArgRS shed considerable light on the tRNA recognition mechanism, while the aspect of amino acid binding in ArgRS remains largely unexplored. Here we report the first crystal structure of E. coli ArgRS (eArgRS) complexed with L-arginine, and a series of mutational studies using isothermal titration calorimetry (ITC). Combined with previously reported work on ArgRS, our results elucidated the structural and functional roles of a series of important residues in the active site, which furthered our understanding of this unique enzyme.
Arginine
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chemistry
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Arginine-tRNA Ligase
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chemistry
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Binding Sites
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Catalytic Domain
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Crystallography, X-Ray
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Escherichia coli
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Ligands
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Mutagenesis, Site-Directed
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Protein Binding
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Protein Conformation
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RNA, Transfer
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chemistry
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Structure-Activity Relationship

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