1.Correlations of plasma cyclin-dependent kinase 9 level with disease progression and prognosis in patients with acute large artery atherosclerotic cerebral infarction
Xueqin TIAN ; Jiahao WANG ; Linling JI ; Gege ZHAO ; Jing JIANG ; Yingge WANG
Journal of Clinical Medicine in Practice 2025;29(1):6-12
Objective To investigate the influencing factors of disease progression and prognosis in patients with large artery atherosclerotic(LAA)cerebral infarction and analyze the value of plasma cyclin-dependent kinase 9(CDK9)level in the diagnosis and treatment of LAA cerebral infarction.Methods Patients with acute cerebral infarction admitted to the Department of Neurology of the Affili-ated Hospital of Yangzhou University between March 1,2022,and November 20,2023,were select-ed.According to the diagnostic criteria,98 patients with acute LAA(LAA group)and 33 patients with acute small artery occlusion(SAO)cerebral infarction(SAO group)were selected.Additionally,40 healthy individuals matched for age and gender from the Health Examination Center were included as control group.Based on whether the condition of LAA cerebral infarction patients progressing,they were divided into progressive cerebral infarction(PCI)group(39 patients)and the non-pro-gressive cerebral infarction(NPCI)group(59 patients).During the 3-month follow-up period,6 patients from the 98 LAA cerebral infarction patients were lost.According to the modified Rankin Scale(mRS)score at 90 days of follow-up,patients were divided into good prognosis group(mRS score≤2,59 patients)and poor prognosis group(mRS score>2,33 patients).Fasting lipid in-dices[total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),glucose(GLU),glycated hemoglobin(HbA1c),and homocysteine(Hey)]were collected on the second day after admission.The National Institutes of Health Stroke Scale(NIHSS)was used to assess the degree of neurological impairment in cerebral infarction patients.Enzyme-linked immunosorbent assay(ELISA)was used to measure plasma CDK9 levels in different groups;factors influencing disease progression in patients with acute LAA cerebral infarction were explored;and receiver operating characteristic curves were plotted to evalu-ate the predictive value of CDK9 in patients with acute LAA cerebral infarction.Results Compared with the control group,the LAA group had lower HDL-C level and higher CDK9 level(P<0.05).The LAA group had a higher proportion of diabetes history,larger infarction volume,higher NIHSS score at admission,and higher CDK9 level compared with the SAO group(P<0.05).Binary Logistic regression analysis showed that diabetes history and plasma CDK9 levels were influencing factors for LAA cerebral infarction.There were statistically significant differences in the proportion of diabetes history,HbA1c,random GLU,and CDK9 levels between the NPCI and PCI groups(P<0.05).Diabetes history and plasma CDK9 levels were influencing factors for disease progression in patients with acute LAA cerebral infarction.The area under the ROC curve for CDK9 in predicting acute LAA cerebral infarction was 0.854 5(95%CI,0.794 1 to 0.9148).When the CDK9 level was 602.1 ng/L,the Youden index was maximum(0.604),with a corresponding sensitivity of 0.849 and specificity of 0.755.The NIHSS score,infarction volume,and plasma CDK9 level were higher in the poor prognosis group compared with the good prognosis group(P<0.01).Correlation analysis showed a positive correlation between mRS scores and CDK9 levels(r=0.485,P<0.01).Conclusion Plasma CDK9 levels are significantly elevated,and is an influencing factor.It is positively correlated with disease progression and poor prognosis in acute cerebral infarction and has certain predictive value for the progression of LAA cerebral infarction.
2.Effect of Quzhi Ruangan prescription on the farnesoid X receptor-fibroblast growth factor 19 pathway in rats with nonalcoholic steatohepatitis
Enrui XIA ; Gege TIAN ; Suyan ZHANG ; Shunzhen ZHANG
Journal of Clinical Hepatology 2022;38(5):1069-1074
Objective To investigate the effect of Quzhi Ruangan prescription on the farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) pathway in rats with nonalcoholic steatohepatitis (NASH). Methods Male Sprague-Dawley rats were randomly divided into normal group (Control group with 8 rats), model group (HFD group with 12 rats), simvastatin group with 8 rats, high-dose Quzhi Ruangan prescription group (QH group with 8 rats), and low-dose Quzhi Ruangan prescription group (QL group with 8 rats). The rats in the Control group were fed with a normal diet and those in the other groups were fed with a high-fat diet. Related samples were collected at the end of week 10 to observe liver pathological changes and measure the serum levels of liver function parameters, the level of FGF19 in the liver and the small intestine, and the level of bile acid (BA) in the liver. The expression levels of FXR in the small intestine and cholesterol 7α-hydroxylase (CYP7A1) in the liver were also measured. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison bewteen two groups. Results Compared with the Control group, the HFD group showed the pathological manifestations of marked inflammatory lesions and steatosis. Compared with the HFD group, all administration groups had a significant increase in high-density lipoprotein cholesterol and significant reductions in alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, and low-density lipoprotein cholesterol (all P < 0.05). Compared with the Control group, the HFD group had a significant reduction in FGF19 in the small intestine and a significant increase in BA in the liver (both P < 0.05). Compared with the HFD group, all administration groups had a significant increase in FGF19 in the small intestine and a significant reduction in BA in the liver (all P < 0.05). Compared with the Control group, the HFD group had a significant reduction in the mRNA expression of FXR in the small intestine and a significant increase in the mRNA expression of CYP7A1 in the liver (both P < 0.05). Compared with the HFD group, the QH group had a significant increase in the mRNA expression of FXR in the small intestine, while the QL group had a significant reduction (both P < 0.05), and the QH group had a significant reduction in the mRNA expression of CYP7A1 in the liver ( P < 0.05). Compared with the Control group, the HFD group had a significant reduction in the positive rate of FXR in the small intestine and a significant increase in the positive rate of CYP7A1 in the liver (both P < 0.05). Compared with the HFD group, the simvastatin group and the QH group had a significant increase in the positive rate of FXR in the small intestine (both P < 0.05), and the simvastatin group, the QH group, and the QL group had a significant reduction in the positive rate of CYP7A1 in the liver (all P < 0.05). Conclusion Quzhi Ruangan prescription can activate the FXR-FGF19 pathway in NASH rats and may exert a preventive and therapeutic effect on NASH through this pathway.
3.Research advances in traditional Chinese medicine in improving nonalcoholic steatohepatitis by regulating the Toll-like receptor 4/nuclear factor-kappa B signaling pathway
Gege TIAN ; Enrui XIA ; Suyan ZHANG ; Shunzhen ZHAGN ; Furong XU
Journal of Clinical Hepatology 2021;37(12):2957-2962
Nonalcoholic steatohepatitis (NASH) is a serious type of nonalcoholic fatty liver disease (NAFLD) and can develop into life-threatening liver cirrhosis and liver cancer. Toll-like receptor 4 (TLR4) is a type of pattern recognition receptor in innate immunity, and after being activated, it can trigger a cascade reaction and activate nuclear factor-κB (NF-κB) which mediates inflammatory response. The TLR4/NF-κB signaling pathway is a classic inflammatory pathway. In clinical practice, traditional Chinese medicine has achieved a good effect in the treatment of NASH, and the TLR4/NF-κB signaling pathway is one of the approaches for traditional Chinese medicine to treat NASH. By searching the relevant literature, this article summarizes the active components and compounds of traditional Chinese medicine that can regulate the TLR4/NF-κB signaling pathway to alleviate NASH, so as to provide ideas for future research and medication.

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