1.Establishment and Evaluation of New Mouse Model of Rheumatoid Arthritis Combined with Interstitial Lung Disease
Liting XU ; Qingyu ZHAO ; Chao YANG ; Lianhua HE ; Congcong SUN ; Shuangrong GAO ; Lili WANG ; Chunfang LIU ; Na LIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):81-90
ObjectiveTo establish a mouse model of rheumatoid arthritis with interstitial lung disease (RA-ILD) in DBA/1 mice using Porphyromonas gingivalis (Pg) infection combined with collagen-induced arthritis (CIA), and to comprehensively evaluate pathological characteristics in joints, lungs, and serum. MethodsForty DBA/1 mice were randomly divided into four groups, i.e., Control, Pg infection (Pg), CIA, and Pg infection combined with CIA (Pg+CIA), with 10 mice in each group. Arthritis clinical symptoms were evaluated by recording arthritis incidence and clinical scores. Micro-CT scanning was used to assess knee joint pathology. Histopathological changes and collagen deposition in knee joints and lung tissues were analyzed using hematoxylin-eosin (HE) and Masson staining. Immunohistochemistry was performed to detect protein expression of α-smooth muscle actin (α-SMA), typeⅠ collagen (ColⅠ), and fibronectin (FN) in lung tissues. Real-time quantitative polymerase chain reaction(Real-time PCR)was used to measure mRNA expression levels of α-SMA, ColⅠ, FN, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β in lung tissues. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of Pg, cyclic citrullinated peptide (CCP), and immunoglobulin G (IgG). ResultsJoint lesions: The CIA and Pg+CIA groups showed 100% arthritis incidence, with evident joint redness, swelling, and deformity. The number of affected limbs was 27 and 28, and clinical scores were 68 and 70, respectively. No obvious clinical symptoms were observed in the Pg group. Histopathological and imaging analyses showed severe joint lesions in the CIA and Pg+CIA groups, with significantly increased histopathological scores, bone mineral density, bone volume fraction, trabecular thickness, and trabecular number compared to the Control group (P<0.01). No obvious joint pathology was observed in the Pg group. Lung lesions: The Pg+CIA group exhibited marked alveolar inflammation, interstitial inflammatory cell infiltration, and alveolar wall thickening, with pronounced blue staining of collagen fibers. Histopathological scores and collagen area ratios were significantly higher than those of the Control, Pg, and CIA groups (P<0.05). Lung protein and mRNA expression levels of α-SMA, ColⅠ, and FN were markedly increased, and mRNA levels of IL-6, TNF-α, and IL-1β were significantly elevated compared to the Control group (P<0.05). Serology: The Pg+CIA group showed significantly higher levels of CCP, Pg, and IgG compared with the Control, Pg, and CIA groups (P<0.05). ConclusionDBA/1 mice subjected to Pg infection combined with CIA exhibited pronounced symptoms and pathological features of RA-ILD, along with elevated serum anti-CCP antibody levels. This model represents a novel RA-ILD mouse model, providing a valuable experimental tool for investigating RA-ILD pathogenesis and developing new therapeutics, and serves as a basis for establishing anti-cyclic citrullinated peptide antibody (ACPA)-positive RA-ILD animal models.
2.Mechanism of action of luteolin in treatment of liver injury
Ying JIANG ; Ning GAO ; Xiaxuan WANG ; Jie GONG ; Lili LIU
Journal of Clinical Hepatology 2026;42(2):472-478
Liver injury has become an increasingly serious global health problem, and existing chemical drugs face the limitations in efficacy and adverse reactions, resulting in the urgent need to develop safe and effective drugs. Recent studies have highlighted the potential of flavonoids from natural medicinal plants in the prevention and treatment of liver injury. As a typical natural flavonoid, luteolin shows a good protective effect against liver injury due to various etiologies, but there is still a lack of systematic elaboration on its mechanism of action. This article summarizes related research advances in China and globally and reviews the mechanism of action of luteolin in inhibiting oxidative stress, exerting an anti-inflammatory effect, regulating cell death, alleviating hepatic fibrosis, modulating lipid metabolism disorders, and regulating the gut-liver axis, as well as the application prospect of luteolin in the treatment of liver injury, in order to provide a scientific reference for further research on this compound.
3.Mechanism of action of luteolin in treatment of liver injury
Ying JIANG ; Ning GAO ; Xiaxuan WANG ; Jie GONG ; Lili LIU
Journal of Clinical Hepatology 2026;42(2):472-478
Liver injury has become an increasingly serious global health problem, and existing chemical drugs face the limitations in efficacy and adverse reactions, resulting in the urgent need to develop safe and effective drugs. Recent studies have highlighted the potential of flavonoids from natural medicinal plants in the prevention and treatment of liver injury. As a typical natural flavonoid, luteolin shows a good protective effect against liver injury due to various etiologies, but there is still a lack of systematic elaboration on its mechanism of action. This article summarizes related research advances in China and globally and reviews the mechanism of action of luteolin in inhibiting oxidative stress, exerting an anti-inflammatory effect, regulating cell death, alleviating hepatic fibrosis, modulating lipid metabolism disorders, and regulating the gut-liver axis, as well as the application prospect of luteolin in the treatment of liver injury, in order to provide a scientific reference for further research on this compound.
4.Characteristics of cardiometabolic risk in patients with different subtypes of non-alcoholic fatty liver disease
Lili GAO ; Yong WANG ; Huafang YAN ; Xiaoliang WANG ; Yunfeng WANG
Journal of Clinical Hepatology 2025;41(1):63-68
ObjectiveTo investigate the difference in the risk of cardiovascular diseases between patients with different subtypes of non-alcoholic fatty liver disease (NAFLD) from the perspective of metabolism, since cardiovascular events induced by metabolic disorders are the leading cause of death in NAFLD. MethodsThe cluster sampling method was used to conduct a multicenter cross-sectional study among three representative hospitals in Pudong New Area of Shanghai, China. A total of 37 122 sets of physical examination data from July 2022 to June 2023 were collected and stratified according to body mass index (BMI). The chi-square test was used for comparison of continuous data between groups, and a multivariable Logistic regression analysis was used to investigate the association between NAFLD subtypes and cardiometabolic risk factors. ResultsA total of 9 372 cases of NAFLD were detected, with a detection rate of 25.25%, and more than 97% of these patients were diagnosed with metabolic associated fatty liver disease (MAFLD). The subgroup analysis showed that the detection rates of lean, overweight, and obese NAFLD were 7.72%, 33.99%, and 63.56%, respectively. Compared with the patients with lean or overweight NAFLD, the patients with obese NAFLD showed a significantly higher proportion of patients with abnormalities in blood pressure, blood glucose, triglyceride (TG), high-density lipoprotein (HDL) or uric acid (all P<0.001). Among related risk factors, lean NAFLD was associated with the increase in total cholesterol (TC)(P<0.05), while overweight NAFLD and obese NAFLD were not associated with TC abnormalities (P>0.05); obese NAFLD was not associated with TG abnormalities, while lean NAFLD and overweight NAFLD were associated with TG abnormalities (both P<0.05); all types of NAFLD were associated with the abnormalities of waist-hip ratio, blood pressure, blood glucose, low-density lipoprotein, HDL, and uric acid (all P<0.05). ConclusionThe detection rates of different subtypes of NAFLD in Shanghai Pudong are close to those reported in China and globally, and the epidemiologic data of NAFLD can be used analogously for MAFLD. There are certain differences in the distribution and association of cardiometabolic risk factors between different subtypes of NAFLD, and targeted interventions should be formulated based on the metabolic characteristics of each type of NAFLD.
5.Research progress on immunomodulatory effects and role of bile acids and bile acid receptors in the occurrence and development of colorectal cancer
Zhijun LIU ; Lili CUI ; Fengjing XU ; Xinhua SONG ; Zhipeng WANG ; Shouhong GAO
Journal of Pharmaceutical Practice and Service 2025;43(12):583-590
Colorectal cancer is one of the most common malignant tumors, which is a great threat to human life and health. The change of bile acid homeostasis can activate their corresponding receptors to regulate the immune functions, which is closely related to the occurrence of colorectal cancer. In addition, some bile acids can directly induce colorectal cancer and play an important role in the development of colorectal cancer. In this paper, the metabolic process of bile acids in vivo and the immunomodulatory role of bile acid receptors were reviewed, and the evidence of associations between bile acids and colorectal cancer were summarized, which showed the rebalancing the bile acid levels might play a role in the prevention or treatment of colorectal cancer.
6.Diagnostic value of endoscopic submucosal dissection for primary gastrointestinal lymphoma
Hua GAO ; Liping YANG ; Xiaoquan HUANG ; Zhenjian JIANG ; Jie HE ; Zheng WEI ; Dou WANG ; Lili MA
Chinese Journal of Digestive Endoscopy 2025;42(11):871-874
Objective:To analyze and explore the diagnostic value of endoscopic submucosal dissection (ESD) for primary gastrointestinal lymphoma (PGIL).Methods:A retrospective analysis was conducted on the clinical and pathological data from 37 patients with suspected PGIL and admitted to Zhongshan Hospital, Fudan University and Xiamen Hospital, Zhongshan Hospital, Fudan University between January 2021 and December 2023. The diagnostic accuracy for PGIL of initial endoscopic conventional biopsies was compared with that of ESD biopsies.Results:Among these patients, 6 were diagnosed as having primary gastrointestinal lymphoma by routine endoscopic biopsy, with a diagnostic rate of 16.22% (6/37). Of the 22 patients who underwent ESD, 20 were diagnosed as having primary gastrointestinal lymphoma, achieving a diagnostic rate of 90.91% (20/22), which was significantly higher than that of initial endoscopic routine biopsies ( χ2=31.228, P<0.05). Conclusion:ESD demonstrates significant diagnostic value for PGIL.
7.Association between liver radiodensity and the degree of liver fibrosis in patients with chronic hepatitis B
Zheyu LI ; Lili WANG ; Xiaoyue ZHANG ; Cuifang HE ; Min LI ; Shan WANG ; Xiaoqin GAO ; Longzhen SHI ; Jianjun JIN ; Liting ZHANG ; Junfeng LI
Journal of Clinical Hepatology 2025;41(7):1358-1363
Objective To investigate the association of liver radiodensity with the degree and progression of liver fibrosis in patients with chronic hepatitis B(CHB).Methods A retrospective cohort study was conducted among 114 CHB patients who were hospitalized in The First Hospital of Lanzhou University from January to December 2019,and related clinical data were collected,including laboratory tests and abdominal CT.The metabolic characteristics of the patients were assessed,and liver radiodensity was measured.An analysis of variance was used for comparison of normally distributed continuous data between three groups,and the Kruskal-Wallis H rank sum test was used for comparison of continuous data with skewed distribution between three groups;the chi-square test or the Fisher's exact test was used for comparison of categorical data between three groups.A logistic regression analysis was used to investigate the influencing factors for the degree of liver fibrosis,and the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for the progression of liver fibrosis in CHB.Results Among the 114 patients enrolled,43(37.72%)had no liver cirrhosis,30(26.32%)were suspected of liver cirrhosis,and 41(35.96%)had liver cirrhosis,with a median follow-up time of 538.5(322.75-1 031.50)days.Liver radiodensity on plain scan(odds ratio[OR]=0.81,95%confidence interval[CI]:0.68-0.97,P=0.025),liver radiodensity on contrast-enhanced scan(OR=0.95,95%CI:0.90-0.99,P=0.037),and liver volume(OR=0.99,95%CI:0.98-0.99,P<0.001)were independent influencing factors for the degree of liver fibrosis.The univariate Cox regression analysis showed that the low level of HDL(hazard ratio=2.81,95%CI:1.04-7.54,P=0.041)was associated with the progression of liver fibrosis in CHB patients,and the degree of liver fibrosis,liver volume,and liver radiodensity showed no significant association with the progression of liver fibrosis(all P>0.05).Conclusion In CHB patients,liver radiodensity is an independent influencing factor for the degree of liver fibrosis,and low HDL has a marked influence on the progression of liver fibrosis.
8.Long-term protective efficacy of recombinant CHO cell-derived hepatitis B vaccine:A 26-year follow-up study in Zhengding county
Qiudong SU ; Zhiyong HAO ; Feng QIU ; Lili QIAO ; Huijuan JIA ; Shuang ZHANG ; Pengpeng YUAN ; Juan CHU ; Zhiyong ZHANG ; Junfang YAO ; Jinling WEI ; Yan WANG ; Peiqi ZHAO ; Yujiao LIU ; Zhao GAO ; Jingchen MA ; Feng WANG ; Haisong ZHOU
Chinese Journal of Experimental and Clinical Virology 2025;39(4):434-440
Objective:To evaluate the long-term protective efficacy of the recombinant Chinese hamster ovary cell-derived hepatitis B vaccine(CHO-HepB)26 years post-vaccination in the rural China.Methods:Zhengding county,Hebei province was designated as a rural monitoring site for CHO-HepB efficacy. Study participants included individuals born between 1997 and 1999 who had completed the three-dose CHO-HepB primary series without booster doses. A cross-sectional survey was conducted in late 2024 using random sampling. Demographic and vaccination history data were collected via questionnaires,and hepatitis B virus(HBV)serological markers were detected using chemiluminescence. Historical surveillance data were integrated to infer infection statuses of HBsAg-positive individuals and evaluate longitudinal trends in anti-HBs seropositivity and antibody titers.Results:Among 178 participants(mean time since vaccination:26.2 years),the seroprevalence rates were 0.6% for HBsAg(95% CI:0.0%-1.6%),64.6% for anti-HBs(95% CI:57.6%-71.6%),and 1.1% for anti-HBc(95% CI:0.0%-2.7%). Compared to the pre-vaccination baseline HBsAg positivity of 11.3% in children under 10 years of age,the estimated vaccine protection rate was 95%. Two notable cases were identified:one with concurrent HBsAg and anti-HBc positivity and one with anti-HBs and anti-HBc positivity,suggestive of transient HBV exposure(1999—2009)without chronicity. Natural immune boosting was inferred for the latter case based on anti-HBs titer dynamics. Longitudinal analysis of four prior cross-sectional surveys(2005,2009,2013,and 2017)revealed no significant upward trends in HBsAg and anti-HBc positivity(both P>0.05)over 26 years,while anti-HBs seropositivity declined significantly( P<0.05)from 6 to 26 years post-vaccination. Conclusion:The CHO-HepB vaccine demonstrates sustained immunological persistence and robust long-term protection up to 26 years post-immunization. Continued emphasis on rigorous implementation of mother-to-child transmission prevention strategies is critical for future hepatitis B control.
9.Effect of periodic feedback method in pelvic floor function exercise for patients with low anal preservation
Yuejun HUA ; Weiwei GAO ; Ziyan HU ; Lili JIANG
China Modern Doctor 2025;63(32):4-7
Objective To explore the application effect of periodic feedback method in pelvic floor function exercise for patients with low anal preservation.Methods A total of 83 rectal cancer patients with low anal preservation admitted to Zhejiang Cancer Hospital from December 2023 to February 2024 were selected as subjects.They were divided into control group(n=42)and experimental group(n=41)by using a random number table method.The control group received routine health education,while experimental group received guidance on periodic feedback method-based pelvic floor exercises.The compliance with pelvic floor muscle exercises,symptom scores for low anterior resection,and quality of life improvement were compared between two groups.Results After intervention,compliance with pelvic floor exercises was higher,symptom scores for low anterior resection was reduced,overall quality of life was improved in experimental group compared to control group(P<0.05).Conclusion Periodic feedback method can enhance compliance with pelvic floor exercises and improve overall quality of life for rectal cancer patients with low anal preservation.
10.The effect of piceatannol on inflammatory response in hepatitis B virus infected rats by regulating Notch signaling pathway
Qi LIU ; Jing ZHENG ; Lili GAO ; Jiagang ZHANG
Chinese Journal of Infection and Chemotherapy 2025;25(4):418-424
Objective To examine the effect of piceatannol on inflammatory response in hepatitis B virus(HBV)infected rats by regulating Notch signaling pathway.Methods Wistar rats were randomly assigned to control group,model group,low dose piceatannol group,high dose piceatannol group,high dose piceatannol+Jagged1 group to receive injection of HBV antigen solution via tail vein to induce HBV infection model.After intervention with piceatannol and Notch signal activator Jagged1,HBV infection and liver function of rats in each group were tested.ELISA was applied to measure the levels of inflammatory biomarkers in serum and liver tissue.Immunoblotting was applied to detect the expression of Notch signaling pathway related proteins[Notch1,Delta-like ligand 4(DLL4),hairy and enhancer of split 1(Hes1)]in the liver tissues.Results Compared with the control group,the aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels,iNOS and TNF-α levels,Notch1,DLL4,and Hes1 protein expression increased(P<0.05),IL-10 level decreased(P<0.05)in model group.AST and ALT,iNOS and TNF-α levels,liver tissue Notch1,DLL4,and Hes1 protein expression decreased,hepatitis B surface antigen(HBsAg)and hepatitis B e antigen(HBeAg)seroconversion rate,IL-10 levels increased(P<0.05)in the low and high dose piceatannol groups compared with the model group(P<0.05).High dose piceatannol was associated with stronger beneficial effect on various pathological indicators in HBV infected rats.Jagged1 could reduce the beneficial effect of piceatannol on various pathological indicators in HBV infected rats.Conclusions Piceatannol can reduce the production of proinflammatory factors and increase the production of anti-inflammatory factors by blocking Notch signal transduction,thereby inhibiting inflammation,alleviating liver injury,and improving liver function in HBV-infected rats.

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