1.Research Advances on Anti-inflammatory and Anti-oxidation Effect of Medicinal and Edible Herbs Liver-protecting Chinese Medicine
Jinghan ZHAO ; Zhengwang ZHU ; Linlin WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):293-301
The liver is closely associated with inflammation and the redox response, and inflammation is the body's innate defense system for clearing away harmful stimuli and participating in the liver's wound-healing response.Oxidative stress is associated with the activation of inflammatory pathways, and sustained inflammation and the corresponding regenerative wound healing response can induce fibrosis, cirrhosis, progression to end-stage liver disease or hepatocellular carcinoma, and ultimately death.Some "medicine and food homology" traditional Chinese medicine has been used in clinical effect, showing the ability to protect the liver.This paper reviewed the relationship between liver and oxidative stress response and inflammation response, and sorted out 110 "medicine and food same origin" traditional Chinese medicines based on the Chinese Pharmacopoeia(2020 edition) and the Chinese materia medica.The results showed that common floweringqince fruit, licorice root, cassia seed, emblic,seabuckthorn fruit,Chinese date, honeysuckle, ginger, cape jasmine fruit, platycodon root, lotus leaf, dandelion, reed root, honey, mountain honeysuckle, milkvetch root, glossy ganoderma, Gastrodia gastrodia and eucommia leaf were recorded to have liver protection effects.The liver protection mechanism is mainly anti-inflammatory, antioxidant and lipid peroxidation inhibition. Some Chinese herbs can also play a liver protection role by inhibiting the growth of hepatitis virus and liver cancer cells and regulating bile acid metabolism.In addition, the biological mechanism of its liver protection effect through antioxidant and anti-inflammatory effects in animal experiments was analyzed, and it was found that it plays a role through multiple pathways and multiple targets, providing new ideas for the role of "medicine and food homology" traditional Chinese medicine in the treatment strategy of liver diseases.
2.Research Advances on Anti-inflammatory and Anti-oxidation Effect of Medicinal and Edible Herbs Liver-protecting Chinese Medicine
Jinghan ZHAO ; Zhengwang ZHU ; Linlin WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):293-301
The liver is closely associated with inflammation and the redox response, and inflammation is the body's innate defense system for clearing away harmful stimuli and participating in the liver's wound-healing response.Oxidative stress is associated with the activation of inflammatory pathways, and sustained inflammation and the corresponding regenerative wound healing response can induce fibrosis, cirrhosis, progression to end-stage liver disease or hepatocellular carcinoma, and ultimately death.Some "medicine and food homology" traditional Chinese medicine has been used in clinical effect, showing the ability to protect the liver.This paper reviewed the relationship between liver and oxidative stress response and inflammation response, and sorted out 110 "medicine and food same origin" traditional Chinese medicines based on the Chinese Pharmacopoeia(2020 edition) and the Chinese materia medica.The results showed that common floweringqince fruit, licorice root, cassia seed, emblic,seabuckthorn fruit,Chinese date, honeysuckle, ginger, cape jasmine fruit, platycodon root, lotus leaf, dandelion, reed root, honey, mountain honeysuckle, milkvetch root, glossy ganoderma, Gastrodia gastrodia and eucommia leaf were recorded to have liver protection effects.The liver protection mechanism is mainly anti-inflammatory, antioxidant and lipid peroxidation inhibition. Some Chinese herbs can also play a liver protection role by inhibiting the growth of hepatitis virus and liver cancer cells and regulating bile acid metabolism.In addition, the biological mechanism of its liver protection effect through antioxidant and anti-inflammatory effects in animal experiments was analyzed, and it was found that it plays a role through multiple pathways and multiple targets, providing new ideas for the role of "medicine and food homology" traditional Chinese medicine in the treatment strategy of liver diseases.
3.Clinical efficacy of donafenib combined with PD-1 inhibitor and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma
Lan SU ; Jinghan ZHU ; Mingming LIU ; Yarong YANG ; Yu ZHANG ; Zutao CHEN
China Pharmacy 2025;36(21):2692-2698
OBJECTIVE To observe the clinical efficacy of donafenib combined with programmed death-1 (PD-1) inhibitors and vascular intervention therapy in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS This retrospective study included 165 patients with unresectable HCC who were treated at the Fourth and First Affiliated Hospitals of Soochow University between June 2022 and March 2023. Among them, 89 patients received PD-1 inhibitors (tislelizumab or sintilimab, similarly hereinafter) plus vascular intervention (control group) and 76 patients received donafenib in combination with PD-1 inhibitors and vascular intervention (observation group). Short-term efficacy (3 months after treatment), long-term efficacy (2 years after treatment), the levels of liver function indexes [serum alanine amino-transferase (ALT), aspartate transferase (AST), and total bilirubin (TBil)] and tumor biomarkers [alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and des-gamma-carboxy prothrombin (DCP)] before treatment and after 3 months of treatment, as well as the occurrence of adverse drug reaction (ADR) during treatment, were compared between the two groups. In addition, overall response rate (ORR) stratified by PD-1 inhibitor type was analyzed. RESULTS After treatment, the ORR was significantly higher in the observation group than in the control group (P<0.05); although the disease control rate was higher in the observation group compared to the control group, the difference was not statistically significant (P>0.05). The median overall survival of patients in the observation group was 16.9 months [95% confidence interval (CI): 14.2 to 19.1 months], which was significantly longer than that in the control group (12.4 months, 95%CI: 10.1 to 15.3 months) (P<0.05). Subgroup analysis result indicated that therapeutic advantage was consistent across both sintilimab and tislelizumab subgroups, with no significant heterogeneity (P>0.1, I 2<0.001%). Before treatment, there were no significant differences in liver function indexes or tumor marker levels between 2 groups (P>0.05). After treatment, both groups showed significant declines in these indicators compared with baseline (P<0.05), with greater reductions observed in the observation group (P<0.05). There were no statistically significant differences in overall incidence of ADR and grade ≥3 ADRs between the two groups (P>0.05). CONCLUSIONS For patients with unresectable HCC, the combination of donafenib, PD-1 inhibitors and vascular intervention therapy may achieve superior clinical outcomes without increasing the risk of treatment-related ADR.
4.Tuihuang Mixture improves α‑naphthylisothiocyanate-induced cholestasis in rats by inhibiting NLRP3 inflammasomes via regulating farnesoid X receptor.
Zhengwang ZHU ; Linlin WANG ; Jinghan ZHAO ; Ruixue MA ; Yuchun YU ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Journal of Southern Medical University 2025;45(4):718-724
OBJECTIVES:
To study the therapeutic mechanism of Tuihuang Mixture against cholestasis.
METHODS:
Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining.
RESULTS:
The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models.
CONCLUSIONS
Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals
;
NLR Family, Pyrin Domain-Containing 3 Protein
;
Rats
;
Receptors, Cytoplasmic and Nuclear/metabolism*
;
Cholestasis/drug therapy*
;
Rats, Wistar
;
Inflammasomes/metabolism*
;
1-Naphthylisothiocyanate
;
Drugs, Chinese Herbal/therapeutic use*
;
Male
;
Interleukin-18/metabolism*
;
Caspase 1/metabolism*
;
Interleukin-1beta/metabolism*
;
Liver/metabolism*
5.The regulatory role and mechanism of microRNA in cholestasis
Linlin WANG ; Zhengwang ZHU ; Jinghan ZHAO ; Ruixue MA ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Journal of Clinical Hepatology 2025;41(10):2187-2194
As a type of endogenous small non-coding RNA, microRNA (miRNA) can regulate gene expression and thereby intervene against the development and progression of cardiovascular diseases, neurodegenerative diseases, metabolic diseases, and autoimmune diseases. The pathogenesis of cholestasis is complex and is mainly associated with the metabolism and transport of bile acids, oxidative stress, inflammatory response, and intestinal flora. Currently, ursodeoxycholic acid is the preferred drug for the clinical treatment of cholestasis, but it may cause adverse reactions and exhibit poor efficacy in some patients. Studies have shown that miRNA can intervene in the disease process of cholestasis through multiple mechanisms such as regulating bile acid metabolism and transport, alleviating oxidative stress, inhibiting inflammatory response, improving cholangiocyte proliferation, and regulating intestinal flora. It can be used as a new biomarker and action target for cholestasis, with high research potential and value. Therefore, this article summarizes the role and mechanisms of miRNA in regulating cholestasis in recent years, in order to provide a reference for further research on the prevention and treatment of cholestasis by targeting miRNA.
6.Study on the Distribution of Traditional Chinese Medicine Syndrome Types and Medication Rules of Functional Dyspepsia Based on Data Mining
Zhengwang ZHU ; Linlin WANG ; Jinghan ZHAO ; Pingsheng ZHU ; Mingsan MIAO
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(9):1437-1444
Objective To explore syndrome differentiation of traditional Chinese medicine(TCM)and medication rules of functional dyspepsia,and to provide reference for modern TCM clinical treatment.Methods The clinical research literature on the treatment of functional dyspepsia with TCM were searched from CNKI,Wanfang,VIP,PubMed and Web of Science databases,TCM compounds were collected and database was established.Excel 2019,Clementine 12.0 and SPSS 21.0 were used for frequency analysis of TCM syndrome types,drug frequency,efficacy classifications,properties,tastes,and meridian tropisms of functional dyspepsia,and association rule analysis,factor analysis and cluster analysis were performed on high-frequency drugs.Results A total of 428 articles were included,and 442 prescriptions were extracted,involving 225 Chinese medicines and 24 high-frequency drugs,among which Codonopsis Radix,Poria,Citri Reticulatae Pericarpium and Bupleuri Radix were most frequently used.Tonic deficiency drugs and regulating qi drugs were the most common efficacy categories.The property was mainly warm,the tastes were mainly bitter,pungent and sweet,most of which belonged to spleen,lung and stomach meridians.Twenty drug combinations were obtained by association rule analysis,nine common factors were extracted by factor analysis,and drugs could be divided into four categories by cluster analysis.Functional dyspepsia with the liver-stomach disharmony is the most common syndrome.Twelve drug combinations were obtained by association rule analysis,three common factors were extracted by factor analysis,and drugs could be divided into two categories by cluster analysis.Conclusion The clinical treatment of functional dyspepsia in TCM is mainly to replenish qi and invigorate spleen,dredge liver and promote qi,replenish deficiency with sweet and warm drugs,disperse pungent and descend bitter,which were compatible with drugs for resolving dampness,relieving external symptoms and clearing heat according to syndrome differentiation.
7.Characteristics and Application Analysis of Animals Model of Cholelithiasis Based on Data Mining
Linlin WANG ; Zhengwang ZHU ; Jinghan ZHAO ; Mingsan MIAO ; Pingsheng ZHU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(10):1621-1627
Objective To summarize the existing animal models of cholelithiasis,and to explore a pathological model that can better reflect the characteristics of clinical syndromes of traditional Chinese and western medicine and meet the needs of the development of clinical and basic research of traditional Chinese medicine. Methods The animal models for experimental research on cholelithiasis at home and abroad were collected and sorted out by searching CNKI,Wanfang,VIP,SinoMed,PubMed and other databases. The animal types,modeling methods,modeling cycles,detection indicators and positive drugs of the models were statistically analyzed. Results Among the 128 articles included,the animal types of cholelithiasis models were mainly guinea pigs,rabbits and C57BL/6J mice. The most used modeling method is high-fat diet,and the feeding cycle takes eight weeks to complete. High-frequency detection indicators were stone formation rate,total cholesterol,phospholipids,total bilirubin,total bile acid,etc. The commonly used intervention methods are traditional Chinese medicine compound,western medicine and single Chinese medicine or extract. Ursodeoxycholic acid (UDCA) is mainly used for western medicine intervention,whereas the intervention of traditional Chinese medicine mainly includes traditional Chinese medicine compound,acupuncture,exercise,diet and other methods. The positive control drug in the experiment was mostly UDCA. Conclusion With the continuous improvement and development of cholelithiasis animal model,there are many kinds of modeling methods to simulate the clinical manifestations of cholelithiasis in Chinese and western medicine,but there are also some limitations. This paper aims to provide reference for the selection,application and improvement of cholelithiasis model through data mining and characteristic analysis.
8.Role and Mechanism of Chinese Herbal Saponins in Ameliorating Metabolism-associated Fatty Liver Disease: A Review
Linlin WANG ; Zhengwang ZHU ; Jinghan ZHAO ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):273-281
Saponins are widely found in various Chinese medicines such as Ginseng Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Bupleuri Radix. They possess multiple biological activities, including anti-inflammatory, antioxidant, antitumor, hepatoprotective, lipid-lowering, and hypoglycemic effects. They play an important role in the prevention and treatment of diseases such as acute lung injury, hyperlipidemia, and diabetic cardiovascular complications, and hold significant research potential and value. Metabolism-related fatty liver disease is a prevalent chronic liver disease characterized by excessive lipid accumulation in hepatocytes. According to the "multiple hit" theory, its occurrence is the result of systemic homeostasis disorder, influenced by abnormal lipid metabolism, oxidative stress, inflammation, insulin resistance, mitochondrial dysfunction, and intestinal microbiota. However, there is currently no effective treatment available in clinical practice. Recent studies have found that Chinese herbal saponins can alleviate metabolism-related fatty liver disease through various pathways, including regulating abnormal lipid metabolism, inhibiting inflammatory responses, alleviating oxidative stress, reducing insulin resistance, improving mitochondrial dysfunction, modulating intestinal flora, inhibiting hepatocyte programmed death, regulating liver autophagy, and correcting immune imbalances. Therefore, this review summarized the pharmacological effects and related mechanisms of Chinese herbal saponins in improving metabolism-related fatty liver disease in recent years, aiming to provide a theoretical reference for the clinical application and experimental research of Chinese herbal saponins in the prevention and treatment of metabolism-related fatty liver disease.
9.Prevalence of tinnitus in noise-exposed workers and its influencing factors
Jianying ZHENG ; Jinghan ZHU ; Xuhui ZHANG
Journal of Environmental and Occupational Medicine 2023;40(3):317-322
Background Tinnitus is a common symptom in workers exposed to noise, and no specific treatment is available yet. Paying attention to the influencing factors of tinnitus is very important to prevent tinnitus. Objective To investigate the situation of tinnitus among noise-exposed workers and its influencing factors. Methods Using a cross-sectional study design, 1011 noise-exposed male workers in Hangzhou were studied. Tinnitus status, age, education, personal protection, smoking history, drinking history, and family history of the participants were surveyed by questionnaires. Binaural pure tone hearing threshold test was performed on all study subjects. The environmental noise in the workplace was measured. The relationships of tinnitus with noise exposure intensity, noise exposure time, noise exposure category, cumulative noise exposure, and wearing hearing protectors among the noise-exposed workers were analyzed by logistic regression. Results The prevalence of tinnitus among the noise-exposed workers was 36.1%. The mean hearing thresholds at 500, 3000, 4000, and 6000 Hz in the right and left ears were higher in the tinnitus group than in the non-tinnitus group (P<0.05); the hearing threshold at 2000 Hz in the right ear was higher in the tinnitus group than in the non-tinnitus group (P<0.05). There was no statistically significant difference between the two groups in the prevalence of monaural speech-frequency hearing loss or monaural high-frequency hearing loss (P>0.05). The on-site noise intensity was divided into three groups: <85, 85-<95, and ≥95 dB(A); the prevalence of tinnitus in the three groups was 19.6%, 40.5%, and 66.7% respectively. The years of noise exposure was divided into three groups: <1, 1-<5, and ≥5 years; the prevalence of tinnitus in the three groups was 17.9%, 34.0%, and 45.4% respectively. The cumulative noise exposure was divided into six groups: <80, 80-<85, 85-<90, 90-<95, 95-<100, and ≥100 dB(A)·year; the prevalence of tinnitus in the six groups was 6.8%, 25.0%, 31.0%, 39.6%, 43.1%, and 46.7% respectively. The prevalence of tinnitus was higher in the non-stationary noise group (42.5%) than in the stationary noise group (26.8%) (χ2=26.18, P<0.01), and the prevalence in the group without or with hearing protection was 39.7% and 35.5% respectively. The results of logistic regression showed that workers exposed to higher intensity, longer noise exposure, higher cumulative noise exposure, and non-stationary noise (reference: stationary noise) resulted in a higher risk of tinnitus (Ptrend<0.01 or P<0.01); workers wearing of hearing protection device versus those not showed a lower risk of tinnitus (P<0.05). Conclusion Higher intensity, longer exposure to noise, and more cumulative noise exposure associate with a higher risk of tinnitus. Wearing hearing protective device can reduce the risk of tinnitus. Tinnitus in noise-exposed workers can precede the presentation of abnormal hearing loss.
10.Progress on Immunotherapy of Gastrointestinal Cancer
Weichang CHEN ; Tongguo SHI ; Jinghan ZHU ; Linqing SUN ; Juntao LI
Cancer Research on Prevention and Treatment 2022;49(7):639-643
Gastrointestinal cancers are the common malignant tumors of the digestive system, and their morbidity and mortality are in the forefront of malignant tumors. Currently, cancer immunotherapy is the hottest topic in cancer research field. Although cancer immunotherapy has achieved some results in the fundamental research and clinical application of gastrointestinal tumors, there are still a series of problems that need to be resolved. In this article, we review the fundamental and clinical research progress of several common methods of cancer immunotherapy in the field of gastrointestinal tumors.

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