1.Role and mechanism of T helper 17 cells/regulatory T cells immune balance regulated by the TGF-β1/Smad signaling pathway mediated in nonalcoholic steatohepatitis
Qian WANG ; Kaiyang LI ; Mei YANG ; Hang ZHANG ; Shengjin ZHU ; Qi ZHAO ; Jing HUANG
Journal of Clinical Hepatology 2025;41(5):942-947
Nonalcoholic steatohepatitis (NASH) is a chronic metabolic disease characterized by hepatocyte fatty degeneration and ballooning degeneration, and it plays an important role in the progression of hepatic steatosis. Recent studies have shown that immune homeostasis imbalance between T helper 17 (Th17) and regulatory T (Treg) cells are closely associated with the pathological process of NASH. Transforming growth factor-β1 (TGF-β1) is a key cytokine for regulating the differentiation and proliferation of Th17/Treg cells, and TGF-β1 binds to its receptor and activates the Smad signaling pathway, thereby regulating the immune balance of Th17/Treg cells and the expression of inflammatory factors and participating in the repair of liver inflammation. This article systematically reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in affecting NASH by regulating the immune balance of Th17/Treg cells, in order to provide a theoretical basis for the research on the pathogenesis of NASH and related treatment strategies.
2.The role of CD8+T cells in nonalcoholic steatohepatitis
Yiming ZHAO ; Kaiyang LI ; Mei YANG ; Qi ZHAO
Journal of Clinical Hepatology 2024;40(10):2087-2091
Nonalcoholic steatohepatitis(NASH)is a liver disease closely associated with metabolic syndrome,and its pathogenesis includes insulin resistance,lipid metabolism disorders,and inflammatory response.This article briefly describes how CD8+T cells exert a cytotoxic effect through the three pathways of the Fas-Fas ligand signaling pathway,the release of perforin and granzymes,and the secretion of tumor necrosis factor-α and other cytokines,and these mechanisms allow CD8+T cells to specifically kill virus-infected cells and tumor target cells,thereby participating in immune regulation.At the same time,this article summarizes that CD8+T cells promote the recruitment of macrophages cooperate with natural killer T cells to participate in the development of adipose tissue inflammation,and lead to liver injury through automatic attack and epigenetic mechanisms,finally promoting the pathogenesis of NASH.It is concluded that CD8+T cells may become a new therapeutic target for NASH,and in-depth research on the specific mechanism of CD8+T cells affecting the pathogenesis in NASH in the future may help to further guide clinical treatment.
3.Research Progress in Intervention of Chinese Materia Medica in Th17/Treg Balance in the Treatment of Ulcerative Colitis
Kaiyang LI ; Mei YANG ; Jing HUANG ; Xiaoyuan LIN ; Jiemin LIU ; Yun TANG ; Zhenfan GUO ; Hui SHI ; Yueyue YANG ; Caiyu HUANG ; Qi ZHAO
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(10):191-196,封3
Pathological mechanism of ulcerative colitis(UC)is not fully clear,which may be the result of Th17/Treg immune imbalance and the interaction of multiple complex factors.Numerous studies have found that classical TCM prescriptions,experienced formulas and TCM active components could regulate Th17/Treg balance by intervening in cytokines,transcription factors,and signaling pathways,restore intestinal mucosal immune function,suppress intestinal mucosal inflammatory response,and repair intestinal mucosal barrier damage.Based on the research status of UC,Th17/Treg balance and TCM treatment,this article reviewed the relationship between Th17/Treg balance and UC,and explained the key role of Th17/Treg balance in the occurrence and development of UC.At the same time,the Chinese materia medica targeting to regulate the balance of Th17/Treg in the treatment of UC in recent years was summarized,in order to provide reference for the treatment of UC.
4.Association of cardiometabolic index with severity of coronary artery stenosis and prognosis in patients with acute myocardial infarction
Kaiyang WANG ; Hongmei LAI ; Jing TAO ; Jiahui YONG ; Guoqing LI ; Yining YANG
Chinese Journal of Endocrinology and Metabolism 2024;40(8):647-653
Objective:To explore the correlation between cardiometabolic index(CMI) and the severity of coronary artery stenosis and long-term prognosis in patients with acute myocardial infarction(AMI).Methods:A total of 712 patients with AMI who were admitted to the Xinjiang Uygur Autonomous Region People′s Hospital from January 2018 to December 2019 were included as the subjects. According to the tertile of CMI, the subjects were divided into high, medium, and low value groups. Gensini score was used to quantitatively assess the degree of coronary artery stenosis. The endpoint event was defined as the occurrence of major cardiovascular adverse events(MACEs). Spearman correlation analysis was conduceted to explore the correlation between CMI and Gensini score. Multivariate Cox regression was utilized to analyze the independent influencing factors of MACEs. A restricted cubic spline plot was employed to analyze the nonlinear relationship between CMI and the risk of MACEs. Kaplan- Meier curve was used to analyze survival differences between groups. Subgroup analysis was performed to evaluate the consistency of the predictive value of CMI for MACEs. Results:Spearman correlation analysis showed that CMI was positively correlated with Gensini score( r=0.13, P<0.001). After adjusting for confounding, multivariate Cox regression analysis showed that CMI was an independent risk factor for MACEs( HR=1.709, 95% CI 1.052-2.778, P=0.031). The restricted cubic spline analysis revealed an L-shaped nonlinear effect relationship between CMI and MACEs risk( P=0.024). Kaplan- Meier survival curve analysis demonstrated that the cumulative incidence of MACEs in AMI patients increased significantly with the increase of CMI( P<0.05). Subgroup analysis indicated that CMI independently predicted the occurrence of MACEs across different subgroups, and had higher predictive value in patients with normal lipids and normal body weight. Conclusion:CMI is closely associated with the severity of coronary stenosis in AMI patients, and is an independent predictor of the risk of long-term MACEs.
5.Correlation of novel anthropometric indicators with long-term prognosis in patients with acute myocardial infarction
Kaiyang WANG ; Jing TAO ; Tingting WU ; Jiahui YONG ; Guoqing LI ; Xiang XIE ; Yining YANG
The Journal of Practical Medicine 2024;40(21):3040-3046
Objective To explore the predictive value of novel anthropometric indicators for the long-term prognosis in patients with acute myocardial infarction(AMI).Methods A total of 712 patients diagnosed with AMI in the People's Hospital of Xinjiang Uygur Autonomous Region from January 2018 to December 2019 were selected as research subjects,and divided into an event group and a non-event group according to whether major cardiovascular adverse events(MACEs)occurred during the period of follow-up.Gensini score was used to quanti-tatively assess the degree of coronary artery stenosis.Spearman correlation analysis was used to explore the correla-tion between the new anthropometric indicators and Gensini score.Receiver operating characteristic(ROC)curve was used to evaluate the ability of new anthropometric indicators to predict MACEs,and the patients were grouped according to the optimal cut-off value.Kaplan-Meier curve was used to analyze the survival difference between the groups.Multivariate Cox regression was used to analyze the independent risk factors of MACEs.Results During a median follow-up of 27(20,39)months,a total of 125 patients developed MACEs.As compared with those in the non-event group,the patients in the event group had a higher proportion of hypertension,diabetes and abdominal obesity,higher HbA1c and FBG levels,and longer body weight and waist circumference.The LAP index,CMI index,BRI index and Gensini score were significantly increased,and the differences were statistically significant(P<0.05).Spearman correlation analysis showed that LAP index,CMI index and BRI index were positively corre-lated with Gensini score(r=0.233,0.126,0.272,P<0.001).ROC curve analysis showed that the AUC of LAP index,CMI index,VAI index,BRI index and ABSI index were 0.745,0.640,0.490,0.874 and 0.506 respec-tively;Kaplan-Meier curve analysis showed that the cumulative incidence of MACEs in LAP index,CMI index and BRI index was significantly increased in the high-value group(Log-rank test,P<0.05).The results of multivariate Cox regression analysis after adjusting confounding showed that CMI index(HR=1.430,95%CI:1.049~1.952,P=0.024)and BRI index(HR=1.332,95%CI:1.234~1.439,P<0.001)were independent risk factors for MACEs.Conclusions CMI index and BRI index of new anthropometric indicators are independent risk factors for long-term prognosis in patients with AMI.
6.Progress of research into natural products that regulate TGF-β1/Smad pathway for the treatment of hepatic fibrosis
Kaiyang LI ; Xiaomei WU ; Jing HUANG ; Yun TANG ; Weixin GUO ; Qi ZHAO ; Mei YANG
Acta Laboratorium Animalis Scientia Sinica 2024;32(10):1320-1331
TGF-β1 is considered a key mediator in the formation of hepatic fibrosis and mainly acts by activating the downstream Smad signaling pathway.Smad2 and Smad3 are two major downstream regulators that promote TGF-β1-mediated tissue fibrosis,while Smad7 is a negative-feedback regulator of the TGF-β1/Smad pathway and inhibits TGF-β1-mediated hepatic fibrosis.A growing number of studies are showing that natural products can delay the progression of hepatic fibrosis by regulating the TGF-β1/Smad pathway,inhibiting HSC activation,and reducing ECM deposition.This article reviews the molecular mechanism of the TGF-β1/Smad signaling pathway in hepatic fibrosis,and summarizes the natural products that target the regulation of this pathway,providing a reference for research into the treatment of hepatic fibrosis.
7.Role of vitamin D in non-alcoholic fatty liver disease
Kaiyang LI ; Si SHI ; Qi ZHAO ; Mei YANG
Chinese Journal of Pathophysiology 2024;40(10):1963-1968
Non-alcoholic fatty liver disease(NAFLD)is one of the common chronic liver diseases in the world.The molecular mechanism of NAFLD is complex,involving many signal molecules,and the vitamin D(VD)/VDBP/vitamin D receptor(VDR)axis is also involved.VD is a lipid-soluble steroid,which can participate in the regula-tion of lipid metabolism,insulin secretion,immune function,inflammatory response and other biological processes.Stud-ies have shown that VD deficiency is closely related to liver lipid accumulation,inflammation,insulin resistance,oxida-tive stress,intestinal flora imbalance,autophagy,apoptosis,pyroptosis and fibrosis,and plays an important role in the oc-currence and development of NAFLD.This paper reviews the research progress on Vitamin D in recent years in the field of NAFLD,including the physiological characteristics of VD and its role in the NAFLD mechanism,so as to provide referenc-es for the prevention and treatment of NAFLD.
8.Relationship Among Fungal Diversity at Different Levels of Root System of Stellaria dichotoma var. lanceolata, Soil Properties, and Main Components of Medicinal Materials in Lithosol Habitats
Wangsuo LIU ; Kaiyang QIU ; Darifu BA ; Xuehua GAO ; Zhiming YANG ; Min GAO ; Fang ZHANG ; Bo ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):160-168
ObjectiveTo explore the interaction among root fungi of Stellaria dichotoma var. lanceolata, soil factors, and main components of medicinal materials in lithosol habitats. MethodHigh-throughput sequencing technology was employed to determine the fungal community of the root system of S. dichotoma var. lanceolata at different levels (bulk soil, rhizosphere soil, rhizoplane soil, and root interior) and the soil properties of the root system (bulk and rhizosphere), and the relationship among the fungal community, soil properties, and the main components of medicinal materials was analyzed. ResultThe total phosphorus, available phosphorus, alkaline nitrogen, dissolved organic carbon, and soil water content in the rhizosphere soil of S. dichotoma var. lanceolata were slightly higher than those in the rhizosphere, but the difference was not significant. Ascomycota is the dominant phylum of root fungi in S. dichotoma var. lanceolata. In the progressive level of bulk-rhizosphere-rhizoplane-root interior system, although the fungal diversity gradually decreased, the abundance of Hypocreales, a new phylum (unclassified_ k_ Fungi), Helotiales, and Natipusilales gradually increased, among which Hypocreales is the most important fungal group in the root system of S. dichotoma var. lanceolata. The structural equation model (SEM) shows that the physicochemical factors of the root-soil play an important regulatory role in the fungal community and the main components of medicinal herbs, with soil total nitrogen, alkaline nitrogen, soil water content, and pH being the main regulatory factors. Soil nitrogen content is the key to promoting the main components of the medicinal herbs, and Penicillium fungi are the key fungal group to regulate the main components of the medicinal herbs. ConclusionIt highlights that the physicochemical properties of the soil of S. dichotoma var. lanceolata play a crucial role in the fungal community and the components of medicinal materials. Hypocreales fungi in the root of S. dichotoma var. lanceolata were an important group, and Penicillium fungi had a certain role in mediating the components of medicinal materials.
9.Research Progress in the Treatment of Ulcerative Colitis with Sishen Pills
Kaiyang LI ; Mei YANG ; Qi ZHAO ; Jing HUANG ; Xiaoyuan LIN ; Jiemin LIU ; Zhenfan GUO ; Hui SHI ; Yueyue YANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(3):180-185
Sishen Pills is a classic prescription for the treatment of spleen and kidney diarrhea,which has the effect of warming the kidney and the spleen,astringent intestine and antidiarrheal.In modern clinical application,the modified prescriptions based on Sishen Pills,combined with other treatments of TCM and integrated traditional Chinese and Western medicine are often used to treat ulcerative colitis with spleen-kidney yang deficiency syndrome,and the curative effect is remarkable.Experimental pharmacological studies have shown that Sishen Pills may achieve the purpose of ulcerative colitis by regulating the expression of related signaling pathway proteins,regulating inflammatory factors,inhibiting inflammatory response,regulating autophagy,regulating intestinal flora,improving intestinal mucosal permeability,repairing intestinal mucosal barrier,regulating cellular energy metabolism,anti-oxidative stress,regulating cellular immune function,etc.In this article,the research status of Sishen Pills in the treatment of ulcerative colitis was sorted out and summarized,in order to provide reference for further study of its mechanism and clinical application.
10.Efficacy and safety of mitoxantrone hydrochloride liposome injection in treatment of peripheral T-cell lymphomas: a multicenter, non-interventional, ambispective cohort, real-world study (MOMENT)
Huiqiang HUANG ; Zhiming LI ; Lihong LIU ; Liang HUANG ; Jie JIN ; Hongyan TONG ; Hui ZHOU ; Zengjun LI ; Zhenqian HUANG ; Wenbin QIAN ; Kaiyang DING ; Quande LIN ; Ming HOU ; Yunhong HUANG ; Jingbo WANG ; Pengcheng HE ; Xiuhua SUN ; Xiaobo WANG ; Zunmin ZHU ; Yao LIU ; Jinhai REN ; Huijing WU ; Liling ZHANG ; Hao ZHANG ; Liangquan GENG ; Jian GE ; Ou BAI ; Liping SU ; Guangxun GAO ; Xin LI ; Yanli YANG ; Yijian CHEN ; Aichun LIU ; Xin WANG ; Yi WANG ; Liqun ZOU ; Xiaobing HUANG ; Dongping HUANG ; Shujuan WEN ; Donglu ZHAO ; Jun MA
Journal of Leukemia & Lymphoma 2023;32(8):457-464
Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

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