1.Effect and mechanism of action of 2,5-dihydroxybenzoic acid on an in vitro cell model of metabolic dysfunction-associated fatty liver disease
Junjiao XU ; Tong LIU ; Sutong LIU ; Lihui ZHANG ; Yijia SONG ; Wenjing WU ; Beilei CUI ; Yajie GUAN ; Minghao LIU
Journal of Clinical Hepatology 2026;42(7):1586-1596
ObjectiveTo investigate the potential targets of 2,5-dihydroxybenzoic acid (2,5-DHBA) in the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD) and the molecular mechanism by which it regulates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. MethodsA network pharmacology analysis was performed at first, and related databases were used to obtain the common action targets of 2,5-DHBA and MAFLD, followed by molecular docking and pathway enrichment analysis to predict the potential biological processes and signaling pathways regulated by these targets. Then mouse normal hepatocytes AML-12 were used for cell experiments, and CCK-8 assay was used to determine the three optimal intervention concentrations of 2,5-DHBA. AML-12 cells were divided into control group, model group (cells cultured in a medium containing 2 mmol/L free fatty acid [FFA] to establish a cell model of MAFLD), and three 2,5-DHBA intervention groups (cells cultured with FFA and 2,5-DHBA at the three different concentrations of 1.25, 5, and 20 μmol/L, respectively). Oil red O staining was used to observe intracellular lipid accumulation; the fluorescent probe DCFH-DA was used to measure the level of intracellular reactive oxygen species (ROS); biochemical assays were used to measure the content of triglyceride (TG) and total cholesterol (TC); quantitative real-time PCR and Western Blot were used to measure the expression levels of related genes and proteins. A one-way analysis of variance was used for comparison between multiple groups, and the Tukey’s test was used for further comparison between two groups. ResultsA total of 32 common targets were obtained for 2,5-DHBA and MAFLD. Within a concentration range of 1.25 — 20 μmol/L, 2,5-DHBA treatment, starting from the concentration of 2.5 μmol/L, increased the viability of AML-12 cells in a dose-dependent manner. The minimum effective concentration of 1.25 μmol/L, the intermediate gradient concentration of 5 μmol/L, and the maximum safe concentration within the effective range of 20 μmol/L were selected for low-, middle-, and high-dose intervention, respectively. Compared with the model group, 2,5-DHBA intervention at concentrations of 1.25, 5, and 20 μmol/L could significantly reduce lipid droplet accumulation in cells (all P<0.05), and there were significant differences in TG and TC between the model group and the three intervention groups (all P<0.05). Compared with the control group, the model group had a significant increase in ROS fluorescence intensity (P<0.05), and compared with the model group, there was a dose-dependent reduction in intracellular ROS level after treatment with 5 μmol/L or 20 μmol/L 2,5-DHBA (P<0.05). Compared with the model group, 2,5-DHBA treatment at concentrations of 5 and 20 μmol/L significantly downregulated the mRNA expression levels of the lipogenic genes SREBf1 and FASN and upregulated the mRNA expression levels of the key antioxidant gene Nrf2 and its downstream target gene HO-1 (all P<0.05). Compared with the control group, the expression of p-PI3K/PI3K and p-Akt/Akt in the model group was significantly increased (all P<0.05). Compared with the model group, the protein expression levels of p-PI3K/PI3K and p-Akt/Akt were significantly decreased after 5 μmol/L 2,5-DHBA treatment (P<0.05). Compared with the control group, the expression levels of Nrf2 and HO-1 protein in the model group were significantly decreased (all P<0.05). The protein levels of Nrf2 and HO-1 were significantly increased after treatment with 1.25 μmol/L 2,5-DHBA (P<0.05). ConclusionNetwork pharmacology and cellular experiments confirm that 2,5-DHBA can alleviate lipid deposition and oxidative stress by regulating the PI3K/Akt signaling pathway, thereby exerting a therapeutic effect on MAFLD.
2.Ameliorative effect of Weiling decoction on metabolic associated fatty liver disease based on the gut-liver axis
Beilei CUI ; Yijia SONG ; Yajie GUAN ; Qizhen ZHANG ; Wenjing WU ; Junjiao XU ; Minghao LIU
China Pharmacy 2026;37(19):2501-2508
OBJECTIVE To investigate the ameliorative effect of Weiling decoction on metabolic associated fatty liver disease (MAFLD) based on the gut-liver axis theory.METHODS Male C57BL/6J mice were divided into a blank group ( n =9) and a modeling group ( n =47). The modeling group was fed a high-fat diet for 12 weeks to establish the MAFLD model. Forty-five modeled mice were randomly divided into a model group, a positive control group [metformin, 0.2 g/(kg·d)], and Weiling decoction low-, medium-, and high-dose groups [6.17, 12.34, 24.68 g/(kg·d), calculated as crude drug], with 9 mice in each group. Mice in each group received intragastric administration of the corresponding drug solution or normal saline once daily for 4 consecutive weeks. After the last administration, the body weight, liver weight, and liver index were compared among groups; the levels of liver function indicators (alanine transaminase, aspartate transaminase), lipid indicators (total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol), inflammatory indicators [tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β], oxidative stress indicators (malondialdehyde, superoxide dismutase, glutathione peroxidase), and intestinal barrier indicators [lipopolysaccharide (LPS), diamine oxidase, D-lactic acid] were measured; hepatic pathological changes were observed; the expressions of tight junction proteins [zonula occludens-1 (ZO-1), occludin] in jejunal tissue and proteins related to lipid metabolism [sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FASN), peroxisome proliferator-activated receptor α (PPARα)] and inflammatory pathways [Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), nuclear factor-κB p65 (NF-κB p65)] in liver tissue were detected; and changes in gut microbiota were analyzed.RESULTS Compared with the model group, hepatic steatosis and inflammatory injury were significantly alleviated in all Weiling decoction dose groups; body weight (at week 16), liver weight, liver index, and the levels of liver function indicators, lipid indicators, inflammation indicators, oxidative stress indicators, and intestinal barrier indicators were all generally improved ( P <0.05). The expressions of SREBP-1, FASN, TLR4, and MyD88 and the phosphorylation level of NF-κB p65 in liver tissue were generally decreased or downregulated ( P <0.05), while the expressions of ZO-1 and occludin in jejunal tissue and PPARα in liver tissue were generally increased or upregulated ( P <0.05). Compared with the model group, the Observed species, Chao1, and Ace indices of gut microbiota in the Weiling decoction high-dose group were significantly increased ( P <0.05), and the relative abundances of Verrucomicrobiota, Akkermansia , etc. were significantly increased, while those of Actinomycetota, Alistipes , Faecalibaculum , etc. were significantly decreased ( P <0.05).CONCLUSIONS Weiling decoction can ameliorate MAFLD, and its effect may be associated with regulating gut microbiota, repairing the intestinal mechanical barrier, reducing LPS translocation, thereby inhibiting the TLR4/MyD88/NF-κB inflammatory pathway, alleviating oxidative stress, and regulating SREBP-1/FASN and PPARα-mediated lipid metabolism.
3.Pharmacological mechanism of hawthorn fruit and its herb pairs for improving metabolic dysfunction-associated fatty liver disease
Yajie GUAN ; Qizhen ZHANG ; Wenjing WU ; Beilei CUI ; Junjiao XU ; Yijia SONG ; Wenxia ZHAO ; Minghao LIU
Journal of Clinical Hepatology 2026;42(9):2203-2208
Metabolic dysfunction-associated fatty liver disease (MAFLD) has become the leading chronic liver disease worldwide. As a classic food-medicine homologous Chinese herb, hawthorn fruit has the functions of promoting digestion to resolve food stagnation and activating blood circulation to resolve blood stasis. Modern pharmacological studies have shown that hawthorn fruit and its active components exert diverse pharmacological activities in regulating lipid metabolism, improving insulin resistance, inhibiting inflammatory response, delaying hepatic fibrosis, and protecting hepatocytes. These effects precisely match the “multiple-hit” pathological features of MAFLD, and thus hawthorn fruit shows significant advantages in the prevention and treatment of MAFLD. Drug pair combination is a key strategy in traditional Chinese medicine to enhance efficacy and reduce toxicity. In clinical practice, hawthorn fruit is often combined with Salvia miltiorrhiza, Alisma orientalis, cassia seed, and Poria cocos, and such combination adheres to the principle of “mutual reinforcement and assistance” to enhance efficacy and expand their application in different syndromes of MAFLD. This article systematically reviews the core pharmacological mechanisms of hawthorn fruit in intervening against MAFLD and the research advances in its classic drug combinations, in order to provide a scientific reference for the in-depth development of hawthorn fruit and its combinations and the precise clinical intervention of MAFLD.
4.Scoping review of financial toxicity assessment tools
Yue XIN ; Renshan CUI ; Yajie SI ; Wenwen HU ; Xiaoqing SUN
Journal of Shenyang Medical College 2025;27(3):276-281,303
Objective:To conduct a scoping review of financial toxicity assessment tools both domestically and internationally,and to summarize their scoring methods,evaluation content,development approaches,reliability/validity,and application status,aiming to provide references for selecting or developing such tools.Methods:Following scoping review methodology,databases including CNKI,VIP,Wanfang,PubMed,Web of Science,Embase,and CINAHL were searched for studies on financial toxicity assessment tools,with the search period spanning from database inception to Oct 8,2024.Results:A total of 34 eligible studies were included,covering 14 financial toxicity assessment tools.These tools primarily focused on economic status,psychosocial responses,or coping behaviors.Tools developed by domestic scholars exhibited strong specificity but lacked generalizability.Conclusions:Existing financial toxicity assessment tools are diverse,yet their reliability and validity in Chinese patient populations require further validation.Most scales lack comprehensive dimensions,and domestically developed tools are overly specific.A universal assessment tool suitable for China's cultural and policy environment needs to be developed.
5.Research progress on sentinel symptoms within symptom clusters in lung cancer patients
Wenwen HU ; Renshan CUI ; Yajie SI ; Yue XIN ; Xiaoqing SUN
Journal of Shenyang Medical College 2025;27(5):522-526
Lung cancer patients frequently experience multiple co-occurring symptoms that manifest as symptom clusters during treatment,severely compromising patients'quality of life.Sentinel symptoms,coexisting with symptom clusters,serve as predictive indicators for the emergence of these clusters.This study focuses on sentinel symptoms within symptom clusters in lung cancer patients,reviewing the current research status,identification methods,related intervention measures,and exist-ing research shortcomings.It summarizes the problems in current studies,with the goal of providing clinical nursing staff to as-sess and manage symptom clusters,as well as to conduct related nursing research.
6.Role and clinical application prospect of epigenetics in lean nonalcoholic fatty liver disease
Junjiao XU ; Sutong LIU ; Qizhen ZHANG ; Yajie GUAN ; Beilei CUI ; Wenjing WU ; Minghao LIU
Journal of Clinical Hepatology 2025;41(6):1161-1166
Epigenetic mechanisms play a crucial role in the development and progression of nonalcoholic fatty liver disease (NAFLD), especially among lean individuals. The research on related epigenetic mechanisms has provided new clues and directions for revealing the underlying causes and treatment strategies of NAFLD. This article introduces the role of epigenetics in the development and progression of NAFLD among lean individuals in recent years, analyzes the latest research advances in the epigenetics of NAFLD in this population, and briefly describes the basic concepts of epigenetics, including DNA methylation, histone modifications, and non-coding RNA regulation. This article also discusses how epigenetic alterations impact the pathogenesis, disease progression, and treatment strategies of NAFLD in lean individuals.
7.Scoping review of financial toxicity assessment tools
Yue XIN ; Renshan CUI ; Yajie SI ; Wenwen HU ; Xiaoqing SUN
Journal of Shenyang Medical College 2025;27(3):276-281,303
Objective:To conduct a scoping review of financial toxicity assessment tools both domestically and internationally,and to summarize their scoring methods,evaluation content,development approaches,reliability/validity,and application status,aiming to provide references for selecting or developing such tools.Methods:Following scoping review methodology,databases including CNKI,VIP,Wanfang,PubMed,Web of Science,Embase,and CINAHL were searched for studies on financial toxicity assessment tools,with the search period spanning from database inception to Oct 8,2024.Results:A total of 34 eligible studies were included,covering 14 financial toxicity assessment tools.These tools primarily focused on economic status,psychosocial responses,or coping behaviors.Tools developed by domestic scholars exhibited strong specificity but lacked generalizability.Conclusions:Existing financial toxicity assessment tools are diverse,yet their reliability and validity in Chinese patient populations require further validation.Most scales lack comprehensive dimensions,and domestically developed tools are overly specific.A universal assessment tool suitable for China's cultural and policy environment needs to be developed.
8.Research progress on sentinel symptoms within symptom clusters in lung cancer patients
Wenwen HU ; Renshan CUI ; Yajie SI ; Yue XIN ; Xiaoqing SUN
Journal of Shenyang Medical College 2025;27(5):522-526
Lung cancer patients frequently experience multiple co-occurring symptoms that manifest as symptom clusters during treatment,severely compromising patients'quality of life.Sentinel symptoms,coexisting with symptom clusters,serve as predictive indicators for the emergence of these clusters.This study focuses on sentinel symptoms within symptom clusters in lung cancer patients,reviewing the current research status,identification methods,related intervention measures,and exist-ing research shortcomings.It summarizes the problems in current studies,with the goal of providing clinical nursing staff to as-sess and manage symptom clusters,as well as to conduct related nursing research.
9.Efficacy and safety profile of repetitive transcranial magnetic stimulation versus modified electroconvulsive therapy in combination with antidepressants in patients with major depressive disorder
Meijie WANG ; Yajie SHI ; Peng YANG ; Jianjun WANG ; Yingyin LI ; Jian CUI ; Xiaoming ZHANG
Sichuan Mental Health 2024;37(2):108-113
BackgroundMajor depressive disorder is one of the most disabling mental diseases. Currently, medication in combination with physiotherapy and psychotherapy remains the most commonly used treatment modality for the disease, whereas only a few randomized controlled studies have been conducted on physiotherapy, and even fewer studies have focused on medication combined with physiotherapy. ObjectiveTo explore the efficacy and safety profile of repetitive transcranial magnetic stimulation (rTMS) versus modified electroconvulsive therapy (MECT) in combination with antidepressants in the treatment of major depressive disorder, so as to provide an optimized treatment plan for patients with major depressive disorder. MethodsPatients with major depressive disorder (n=335) hospitalized in Shandong Daizhuang Hospital from January 1, 2019 to April 30, 2023 were included, all of whom met the diagnostic criteria of the International Classification of Diseases, tenth edition (ICD-10). Depending on their disease condition, patients were subjected to either MECT in combination with drugs (n=141) or rTMS in combination with drugs (n=194) after admission. Depressive symptoms were assessed using Hamilton Depression Scale-24 item (HAMD-24) at the baseline and the end of the 1st, 2nd, 3rd and 4th week of treatment, and the adverse reactions were documented in patient's medical records. ResultsAnalysis of variance on HAMD-24 revealed a significant effect of time (F=3.081, P=0.042), but no effect of group (F=1.023, P=0.313), and the interaction effect between the time and the groups was not statistically significant (F=1.642, P=0.191). No statistical difference was reported between two groups in response rate and full remission rate (P>0.05). Throughout the course of treatment, 58 cases (41.13%) of recent memory impairment and 74 cases (52.48%) of headache or neck muscle pain occurred in MECT combined with drugs group, and 27 cases (13.92%) in rTMS combined with drugs group experienced headache or head skin discomfort. ConclusionAntidepressants in combination with rTMS or MECT show equivalent efficacy in the treatment of major depressive disorder, while rTMS combined with antidepressants demonstrates a superior safety profile compared to MECT.
10.Screening Effective Sites of Momordicae Semen-Epimedii Folium and Anti-lung Cancer Mechanism of Its Prescription
Yuanlong ZANG ; Jun LI ; Rui ZENG ; Xihe CUI ; Qing YANG ; Xiaoxin ZHU ; Yajie WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):17-25
ObjectiveTo preliminarily confirm the effective anti-lung cancer sites of Momordicae Semen and Epimedii Folium and study their mechanism of action. MethodOn the basis of preliminary research, the extraction method of Momordicae Semen and Epimedii Folium was optimized and the effective parts were screened under the guidance of pharmacological effects. Different ethanol elution and water elution sites of Momordicae Semen and Epimedii Folium were obtained through adsorption and elution with D101 macroporous resin. The methylthiazolyldiphenyl-tetrazolium bromide (MTT) colorimetric assay was used to detect the effects of total drug extracts and different elution sites on the proliferation of various tumor cell lines, and to screen for the optimal elution site and tumor sensitive strains. Flow cytometry was used to detect the effect of the elution sites of Momordicae Semen and Epimedii Folium on intracellular reactive oxygen species (ROS) and apoptosis in A549 cells. Western blot was used to compare the expressions of tumor protein 53 (p53), Bcl-2-associated X protein (Bax), cysteinyl aspartate specific proteinase-3 and 9 (Caspase-3 and Caspase-9) proteins in A549 cells. ResultThe inhibitory effect of Momordicae Semen on the proliferation of A549 cells was better than the kernel of Momordicae Semen, with 50% inhibitory concentration (IC50) being (86.83±2.88) mg·L-1 and (95.10±18.13) mg·L-1, respectively. The effect of total extracts of Epimedii Folium on A549 anti proliferation IC50 value was (4.71±0.81) mg·L-1. The IC50 values of the 40%, 60%, and 80% ethanol and anhydrous ethanol eluted macroporous resins of the total extracts of Momordicae Semen and Epimedii Folium inhibiting A549 proliferation were (45.32±4.38)、 (14.95±0.73)、 (17.07±1.76)、 (14.46±2.35)、 (51.7±2.26)、 (12.37±0.67)、 (20.29±0.93)、 and (3.43±0.91) mg·L-1, respectively. Compared with the normal group, the 1∶1 combination of Momordicae Semen and Epimedii Folium inhibited A549 cell proliferation in a time-dependent and concentration-dependent manner. Compared with the normal group, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased intracellular ROS expression (P<0.01). Compared with the normal group, 12.5, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of A549 cell apoptosis (P<0.01). Compared with the normal group, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of p53 in A549 cells (P<0.01). Compared with the normal group, 12.5, 25, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly increased the expression of Bax (P<0.01). Compared with the normal group, 50 mg·L-1 of the combination of Momordicae Semen and Epimedii Folium significantly reduced the expressions of Caspase-3 and Caspase-9 (P<0.01). ConclusionThe anti-tumor effect of Momordicae Semen is better than that of the kernel of Momordicae Semen. The anti-tumor substances of Momordicae Semen and Epimedii Folium mainly concentrate in the 60% ethanol to anhydrous ethanol elution site. A549 cells are sensitive to the 1∶1 combination of Momordicae Semen and Epimedii Folium, which can effectively inhibit the cell proliferation. The mechanism may be related to increasing the generation of ROS in A549 cells, promoting their apoptosis, increasing the expressions of apoptotic proteins such as p53 and Bax, and reducing the expressions of Caspase-3 and Caspase-9.

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