1.Shaoyaotang Restores Th17/Treg Cell Balance by Regulating Glucose Metabolism Reprogramming in Treatment of Ulcerative Colitis
Yiwen WANG ; Yiling XIA ; Erle LIU ; Shaijin JIANG ; Bo ZOU ; Dongsheng WU ; Youwei XIAO ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):78-85
ObjectiveTo investigate the effect of Shaoyaotang on T helper cell 17/regulatory T lymphocyte(Th17/Treg) cell balance in ulcerative colitis and decipher the intervention mechanism based on glucose metabolism reprogramming. MethodsThe mouse model of ulcerative colitis was established by the dextran sulfate sodium (DSS) method. Forty-eight C57BL/6 mice were randomly allocated into normal, model, Western drug control (mesalazine, 0.39 g·kg-1·d-1), Shaoyaotang (15.54 g·kg-1·d-1), inhibitor (2-deoxy-D-glucose, 2-DG, 100 mg·kg-1·d-1), and inhibitor (2-DG, 100 mg·kg-1·d-1) + Shaoyaotang (15.54 g·kg-1·d-1) groups. Mice were administrated with the corresponding drugs by gavage for 7 days. The general conditions and the colon injury degree were observed 24 h after the last administration. The expression of interleukin (IL)-10 and IL-17 in the colon tissue was detected by immunohistochemical staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were performed to determine the protein and mRNA levels, respectively, of hypoxia-inducing factor-1α (HIF-1α), lactate dehydrogenase (LDHA), and hexokinase 2 (HK2) in the colon tissue. Th17/Treg cell differentiation was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of lactic acid and glucose in the colon tissue and IL-10, IL-17, and IL-6 in the serum. ResultsCompared with the normal group, the model group showed decreases in body weight and disease activity index (DAI) (P<0.05), elevations in levels of HIF-1α, LDHA, HK2, IL-17, IL-6, Th17 cells, lactic acid, and glucose in the colon tissue (P<0.05), and declines in the levels of of IL-10 and Treg cells (P<0.05). Compared with the model group, the drug administration groups showed increases in body weight and DAI (P<0.05), declines in levels of HIF-1α, LDHA, HK2, IL-17, IL-6, Th17 cells, lactic acid, and glucose in the colon tissue (P<0.05), and rises in levels of IL-10 and Treg cells (P<0.05). Shaoyaotang+2-DG group had the most obvious effect. ConclusionShaoyaotang can relieve diarrhea and bloody stool in mice with ulcerative colitis by restoring the Th17/Treg cell balance via regulation of glucose metabolism reprogramming, thus playing a role in the treatment of ulcerative colitis.
2.Shaoyaotang Restores Th17/Treg Cell Balance by Regulating Glucose Metabolism Reprogramming in Treatment of Ulcerative Colitis
Yiwen WANG ; Yiling XIA ; Erle LIU ; Shaijin JIANG ; Bo ZOU ; Dongsheng WU ; Youwei XIAO ; Hui CAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):78-85
ObjectiveTo investigate the effect of Shaoyaotang on T helper cell 17/regulatory T lymphocyte(Th17/Treg) cell balance in ulcerative colitis and decipher the intervention mechanism based on glucose metabolism reprogramming. MethodsThe mouse model of ulcerative colitis was established by the dextran sulfate sodium (DSS) method. Forty-eight C57BL/6 mice were randomly allocated into normal, model, Western drug control (mesalazine, 0.39 g·kg-1·d-1), Shaoyaotang (15.54 g·kg-1·d-1), inhibitor (2-deoxy-D-glucose, 2-DG, 100 mg·kg-1·d-1), and inhibitor (2-DG, 100 mg·kg-1·d-1) + Shaoyaotang (15.54 g·kg-1·d-1) groups. Mice were administrated with the corresponding drugs by gavage for 7 days. The general conditions and the colon injury degree were observed 24 h after the last administration. The expression of interleukin (IL)-10 and IL-17 in the colon tissue was detected by immunohistochemical staining. Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were performed to determine the protein and mRNA levels, respectively, of hypoxia-inducing factor-1α (HIF-1α), lactate dehydrogenase (LDHA), and hexokinase 2 (HK2) in the colon tissue. Th17/Treg cell differentiation was detected by flow cytometry. Enzyme-linked immunosorbent assay was employed to measure the levels of lactic acid and glucose in the colon tissue and IL-10, IL-17, and IL-6 in the serum. ResultsCompared with the normal group, the model group showed decreases in body weight and disease activity index (DAI) (P<0.05), elevations in levels of HIF-1α, LDHA, HK2, IL-17, IL-6, Th17 cells, lactic acid, and glucose in the colon tissue (P<0.05), and declines in the levels of of IL-10 and Treg cells (P<0.05). Compared with the model group, the drug administration groups showed increases in body weight and DAI (P<0.05), declines in levels of HIF-1α, LDHA, HK2, IL-17, IL-6, Th17 cells, lactic acid, and glucose in the colon tissue (P<0.05), and rises in levels of IL-10 and Treg cells (P<0.05). Shaoyaotang+2-DG group had the most obvious effect. ConclusionShaoyaotang can relieve diarrhea and bloody stool in mice with ulcerative colitis by restoring the Th17/Treg cell balance via regulation of glucose metabolism reprogramming, thus playing a role in the treatment of ulcerative colitis.
3.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
4.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
5.Criteria and prognostic models for patients with hepatocellular carcinoma undergoing liver transplantation
Meng SHA ; Jun WANG ; Jie CAO ; Zhi-Hui ZOU ; Xiao-ye QU ; Zhi-feng XI ; Chuan SHEN ; Ying TONG ; Jian-jun ZHANG ; Seogsong JEONG ; Qiang XIA
Clinical and Molecular Hepatology 2025;31(Suppl):S285-S300
Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated death globally. Liver transplantation (LT) has emerged as a key treatment for patients with HCC, and the Milan criteria have been adopted as the cornerstone of the selection policy. To allow more patients to benefit from LT, a number of expanded criteria have been proposed, many of which use radiologic morphological characteristics with larger and more tumors as surrogates to predict outcomes. Other groups developed indices incorporating biological variables and dynamic markers of response to locoregional treatment. These expanded selection criteria achieved satisfactory results with limited liver supplies. In addition, a number of prognostic models have been developed using clinicopathological characteristics, imaging radiomics features, genetic data, and advanced techniques such as artificial intelligence. These models could improve prognostic estimation, establish surveillance strategies, and bolster long-term outcomes in patients with HCC. In this study, we reviewed the latest findings and achievements regarding the selection criteria and post-transplant prognostic models for LT in patients with HCC.
6.Effect of Endoplasmic Reticulum Stress on Intestinal Mucosal Injury in Ulcerative Colitis and TCM Intervention Based on Theory of Sores Depending on Spleen-earth
Youwei XIAO ; Dongsheng WU ; Hui CAO ; Bo ZOU ; Yiqian YU ; Ruoru HUANG ; Qi CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):238-247
In recent years, as the incidence of ulcerative colitis (UC) is growing, intestinal mucosal injury has garnered increasing attention, and it is characterized by high recurrence, risk of inflammation-cancer transformation, and difficulty in repair. Intestinal mucosal injury in UC is centered on persistent inflammation and barrier dysfunction, with its pathological mechanisms involving endoplasmic reticulum stress (ERS)-mediated changes such as abnormal apoptosis, abnormal autophagy, and inflammatory responses. ERS induces apoptosis of intestinal epithelial cells, disrupts tight junction proteins, and exacerbates inflammatory responses through pathways such as protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 alpha (IRE1α), and activating transcription factor 6 (ATF6), ultimately causing intestinal mucosal injury. Traditional Chinese medicine (TCM) has a long history of research on UC. The theory of sores depending on spleen-earth holds that spleen deficiency is the fundamental cause of UC, while pathological products such as dampness-turbidity and blood stasis are the secondary manifestations. Dysfunction of the spleen-earth leads to insufficient production and transformation of Qi and blood, malnutrition of the intestinal mucosa, and invasion of external pathogens. In the active phase of UC, spleen deficiency is often accompanied by excessive pathogenic factors such as dampness-heat and heat-toxin, leading to acute intestinal mucosal damage. In the remission phase, however, it is mainly characterized by spleen deficiency and healthy Qi deficiency, accompanied by residual pathogens, resulting in weak intestinal mucosal repair. Studies have shown that the endoplasmic reticulum, as a key site for protein synthesis and folding, has functions highly similar to the TCM concept of the spleen governing transportation and transformation. From a TCM perspective, the endoplasmic reticulum can be regarded as the carrier of spleen transportation, and ERS is a microcosmic manifestation of spleen dysfunction, leading to intestinal mucosal injury. ERS impairs the structure and function of the endoplasmic reticulum, induces the generation of abnormal Qi, and triggers pathological changes, making inflammation difficult to be reduced and causing the aggravation of ERS, forming a vicious cycle of spleen deficiency-pathological products-intestinal injury. TCM has unique advantages in regulating ERS to prevent and treat intestinal mucosal injury. According to the theory of sores depending on spleen-earth and the modern medical understanding of ERS, this paper delves into the TCM and Western medicine pathogenesis of intestinal mucosal injury in UC. Furthermore, this paper discusses the roles of TCM active components and compound formulas in reducing intestinal mucosal injury in UC by regulating ERS under the guidance of the treatment principles of invigorating the spleen and replenishing Qi as the key and dispelling dampness and removing blood stasis as the supplementation, aiming to provide new ideas and methods for the prevention and treatment of UC.
7.Prognostic value of quantitative flow ratio measured immediately after percutaneous coronary intervention for chronic total occlusion.
Zheng QIAO ; Zhang-Yu LIN ; Qian-Qian LIU ; Rui ZHANG ; Chang-Dong GUAN ; Sheng YUAN ; Tong-Qiang ZOU ; Xiao-Hui BIAN ; Li-Hua XIE ; Cheng-Gang ZHU ; Hao-Yu WANG ; Guo-Feng GAO ; Ke-Fei DOU
Journal of Geriatric Cardiology 2025;22(4):433-442
BACKGROUND:
The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined.
METHODS:
All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI.
RESULTS:
Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70).
CONCLUSIONS
Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.
8.Chemical synthesis and antibody affinity of epitope fragments from Helicobacter pylori lipopolysaccharide
Hui ZHAO ; Xiaopeng ZOU ; Lei XIAO ; Jing HU ; Jian YIN
Journal of China Pharmaceutical University 2024;55(5):645-656
Helicobacter pylori(Hp)is responsible for chronic gastritis,peptic ulcers,and even gastric cancers.Currently,there is no vaccine to prevent or treat Hp infections.Here,we described the chemical synthesis of α-1,6-glucans with different lengths(di-to hexasaccharide),which are present in the core oligosaccharide of Hp lipopolysaccharide(LPS).The 1,2-cis-glucosidic bonds were constructed successfully using a synergistic glycosylation strategy based on acyl remote participation and solvent effects.The results of glycan microarrays indicated that all synthesized α-1,6-glucan fragments possessed a strong binding to IgG antibodies in both rabbit serum immunized with Hp O1 LPS and patient serum infected with Hp.The α-1,6-linked trisaccharide exhibited strong binding affinity to anti-LPS rabbit IgG antibodies.The α-1,6-glucan trisaccharide and pentasaccharide elicited a strong response to IgG antibodies in sera of most Hp-infected patients.Some patients'sera exhibited strong binding activity with α-1,6-linked disaccharide.The results suggest that the α-1,6-glucan disaccharide,trisaccharide and pentasaccharide could be important carbohydrate antigen fragments in Hp lipopolysaccharide.
9.Clinical trial of rituximab and leflunomide in the treatment of patients with systemic lupus erythematosus
Jia-Hui GUO ; Jun-Jie ZOU ; Yang-Yang WANG ; Jin-Long ZHANG ; Dan-Dan PANG ; Xiao-Yan XU
The Chinese Journal of Clinical Pharmacology 2024;40(11):1547-1550
Objective To observe the clinical efficacy and safety of rituximab injection combined with leflunomide tablets in the treatment of patients with systemic lupus erythematosus(SLE).Methods The SLE patients were divided into control and treatment groups according to cohort method.The control group received leflunomide with 50 mg·d-1 after meal in the first 3 days of treatment and was adjusted to 20 mg·d-1 thereafter.On the basis of control group,the treatment group was combined with rituximab,375 mg·m-2 was given intravenously every 2 weeks in the first 3 times of treatment,and adjusted to once every 4 weeks from the 4th dose.Two groups were treated for 24 weeks.The clinical efficacy,systemic lupus erythematosus disease activity index(SLEDAI)scores,serological indicators,24-hour urinary protein and adverse drug reactions were compared between two groups.Results The treatment and control groups were enrolled 74 cases and 72 cases,respectively.After treatment,the total effective rates of treatment and control groups were 91.89%(68 cases/74 cases)and 79.17%(57 cases/72 cases)with significant difference(P<0.05).After treatment,the SLEDAI scores of treatment and control groups were(7.21±1.67)and(9.03±1.35)points;the levels of anti-Smith/ribonucleoprotein antibodies were(81.43±18.25)and(59.38±14.61)U·mL-1;the levels of immunoglobulin G were(12.04±2.15)and(17.28±2.64)g·L-1;the levels of interleukin-10 were(33.39±7.13)and(39.87±9.02)pg·mL-1;24-hour urinary protein quantification were(1.46±0.32)and(2.67±0.54)g·24 h-1;all the differences were statistically significant(all P<0.05).The drug adverse reactions of two groups were liver and kidney function injury and digestive tract reactions.The total incidences of drug adverse reactions in the treatment and control groups were 13.51%and 5.56%without significant difference(P>0.05).Conclusion Rituximab injection combined with leflunomide tablets has a definitive clinical efficacy in the treatment of SLE patients,which can significantly reduce disease activity and inflammatory reactions,improve immune function,without increasing the incidence of drug adverse reactions.
10.Predictive Ability of Hypertriglyceridemic Waist,Hypertriglyceridemic Waist-to-Height Ratio,and Waist-to-Hip Ratio for Cardiometabolic Risk Factors Clustering Screening among Chinese Children and Adolescents
Li Tian XIAO ; Qian Shu YUAN ; Yu Jing GAO ; S.Baker JULIEN ; De Yi YANG ; Jie Xi WANG ; Juan Chan ZHENG ; Hui Yan DONG ; Yong Zhi ZOU
Biomedical and Environmental Sciences 2024;37(3):233-241
Objective Hypertriglyceridemic waist(HW),hypertriglyceridemic waist-to-height ratio(HWHtR),and waist-to-hip ratio(WHR)have been shown to be indicators of cardiometabolic risk factors.However,it is not clear which indicator is more suitable for children and adolescents.We aimed to investigate the relationship between HW,HWHtR,WHR,and cardiovascular risk factors clustering to determine the best screening tools for cardiometabolic risk in children and adolescents. Methods This was a national cross-sectional study.Anthropometric and biochemical variables were assessed in approximately 70,000 participants aged 6-18 years from seven provinces in China.Demographics,physical activity,dietary intake,and family history of chronic diseases were obtained through questionnaires.ANOVA,x2 and logistic regression analysis was conducted. Results A significant sex difference was observed for HWHtR and WHR,but not for HW phenotype.The risk of cardiometabolic health risk factor clustering with HW phenotype or the HWHtR phenotype was significantly higher than that with the non-HW or non-HWHtR phenotypes among children and adolescents(HW:OR = 12.22,95%CI:9.54-15.67;HWHtR:OR = 9.70,95%CI:6.93-13.58).Compared with the HW and HWHtR phenotypes,the association between risk of cardiometabolic health risk factors(CHRF)clustering and high WHR was much weaker and not significant(WHR:OR = 1.14,95%CI:0.97-1.34). Conclusion Compared with HWHtR and WHR,the HW phenotype is a more convenient indicator with higher applicability to screen children and adolescents for cardiovascular risk factors.

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