1.Tanyu Tongzhi Youhua Prescription Regulates cGAS/STING Signaling Pathway to Inhibit Inflammation and Ameliorate No-reflow Phenomenon in Myocardial Ischemia/Reperfusion Injury
Sijia WU ; Yingying LI ; Haonan WU ; Xiang LI ; Lingfeng ZHOU ; Huamin ZHANG ; Danli TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):99-107
ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription(TYTZP) against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, ticagrelor group (32.4 mg·kg-1), RU320521 (RU.521cGAS inhibitors) group (5 mL·kg-1), groups of TYTZP with low dose (3.6 g·kg-1), medium dose (7.2 g·kg-1), and high dose (14.4 g·kg-1), with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin (HE) staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA (dsDNA) levels were detected by using PicoGreen. The protein expression of cGAS, STING, and nuclear factor-κB (NF-κB) p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ (cTNⅠ), cardiac troponin T (cTNT), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham group, the model group showed a significantly increased myocardial no-reflow area (P<0.01). Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01) were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged (P<0.01), and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cTNⅠ, cTNT, and dsDNA were significantly elevated (P<0.01). Western blot results showed that the myocardial protein expressions of cGAS, STING, and NF-κB p65 were upregulated (P<0.01). ELISA results showed that the inflammatory factors in the serum such as IL-6, IL-1β, and TNF-α were increased (P<0.01). Compared with the model group, the group of the TYTZP significantly reduced the levels of myocardial enzyme, troponins, and dsDNA (P<0.01, P<0.05), improved cardiac function and myocardial microcirculation, alleviated histopathological morphology and inflammatory infiltration, inhibited activation of the cGAS/STING pathway, reduced the expression of NF-κB p65 (P<0.01, P<0.05), and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury, and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.
2.Colonization, drug resistance, and molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus among dairy farm workers in Xinjiang
Jiguo JIN ; Zhaojie WANG ; Yanggui CHEN ; Xixiao MA ; Wanting XU ; Xingyu WANG ; Xiangnan WEI ; Fan WU ; Xintao DANG ; Xueying XIANG ; Jianyong WU ; Fuye LI
Journal of Environmental and Occupational Medicine 2026;43(2):201-207
Background Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen for both human bloodstream infections and mastitis in cows. However, little attention has been paid to the cross-host transmission of MRSA from cows to high-risk groups in China. Objective To determine the MRSA colonization rates among dairy cows and dairy farm workers in Xinjiang, identify the antibiotic resistance profiles and molecular characteristics of the isolates, and provide scientific evidence for the formulation of targeted infection control strategies. Method A cross-sectional survey combined with laboratory pathogen analysis was conducted. From June to August 2024, large-scale dairy farms in Xinjiang region were selected as study sites. Nasal swabs (n=96) and skin swabs (n=39) were collected from workers, and bovine nasal swab samples (n=109) were collected simultaneously. All samples were subjected to MRSA isolation, cultivation, and identification, followed by antibiotic susceptibility testing to characterize resistance phenotypes. Staphylococcus aureus protein A (Spa) typing was performed to determine strain genotypes and elucidate MRSA colonization rates and molecular epidemiological patterns. Results A total of 35 MRSA strains was successfully isolated from 244 samples. The MRSA colonization rates among dairy farm workers and dairy cows were 20.83% (20/96) and 12.84% (14/109), respectively, with an overall isolation rate of 14.34% (35/244). Among the workers, the nasal colonization rate was 16.67% (16/96), and the skin colonization rate was 12.82% (5/39). One worker exhibited MRSA colonization at multiple body sites. All MRSA strains were resistant to cefoxitin (100%, 35/35). The resistance rates to erythromycin and clindamycin were 42.86% (15/35) and 34.29% (12/35), respectively. Thirteen strains showed a multidrug-resistant phenotype, whereas all strains were susceptible to vancomycin. The MRSA isolates exhibited high genetic diversity, with 13 Spa types identified, among which t441 was the most prevalent (8 strains). Both t441 and t034 types were detected in samples from both the dairy cows and their handlers. These two Spa types also carried and stably inherited specific resistance combinations, including erythromycin–clindamycin–cefoxitin and ciprofloxacin–erythromycin–clindamycin–gentamicin–cefoxitin–tetracycline, and a statistically significant association was also observed between the two resistance profiles and the bacterial types (P < 0.001). In addition, one novel Spa type strain was identified. Conclusion MRSA colonization rates among dairy cows and dairy farm workers in Xinjiang are relatively high, with evidence of multi-site colonization. The isolates exhibit high levels of multidrug resistance and genetic diversity, indicating a potential risk of cross-host transmission.
3.Tanyu Tongzhi Youhua Prescription Regulates cGAS/STING Signaling Pathway to Inhibit Inflammation and Ameliorate No-reflow Phenomenon in Myocardial Ischemia/Reperfusion Injury
Sijia WU ; Yingying LI ; Haonan WU ; Xiang LI ; Lingfeng ZHOU ; Huamin ZHANG ; Danli TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):99-107
ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription(TYTZP) against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, ticagrelor group (32.4 mg·kg-1), RU320521 (RU.521cGAS inhibitors) group (5 mL·kg-1), groups of TYTZP with low dose (3.6 g·kg-1), medium dose (7.2 g·kg-1), and high dose (14.4 g·kg-1), with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin (HE) staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA (dsDNA) levels were detected by using PicoGreen. The protein expression of cGAS, STING, and nuclear factor-κB (NF-κB) p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ (cTNⅠ), cardiac troponin T (cTNT), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham group, the model group showed a significantly increased myocardial no-reflow area (P<0.01). Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01) were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged (P<0.01), and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cTNⅠ, cTNT, and dsDNA were significantly elevated (P<0.01). Western blot results showed that the myocardial protein expressions of cGAS, STING, and NF-κB p65 were upregulated (P<0.01). ELISA results showed that the inflammatory factors in the serum such as IL-6, IL-1β, and TNF-α were increased (P<0.01). Compared with the model group, the group of the TYTZP significantly reduced the levels of myocardial enzyme, troponins, and dsDNA (P<0.01, P<0.05), improved cardiac function and myocardial microcirculation, alleviated histopathological morphology and inflammatory infiltration, inhibited activation of the cGAS/STING pathway, reduced the expression of NF-κB p65 (P<0.01, P<0.05), and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury, and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.
4.Isochronous substitution effects of 24-hour movement behaviors on self-confidence level of junior high school students
XIONG Zhongjia, XIANG Wei, LI Jinkun, LU Changfen, LUO Xiaobing
Chinese Journal of School Health 2026;47(2):227-231
Objective:
To investigate the effects of 24 hour movement behaviors on the self confidence level of junior high school students, providing empirical evidence for optimizing physical activity intervention strategies and enhancing adolescents mental health.
Methods:
In December 2024, a stratified cluster random sampling method was used to select 350 students from 3 junior high schools in Wuhan City. The ActiGraph wGT3X-BT accelerometer was employed to monitor participants 24 hour movement behaviors, and the Children and Adolescents Self confidence Questionnaire was used to assess their self confidence levels. Compositional isotemporal substitution models were applied to analyze the substitution effects among different movement behaviors and their impact on the self confidence level of junior high school students.
Results:
Among the 24 hour movement behaviors of junior high school students, the compositional means and proportions of moderate to vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SB), and sleep (SP) were 33.91 min (2.35%), 151.64 min (10.53%), 761.12 min (52.86%), and 493.33 min (34.26%), respectively. There were no statistically significant differences were found across grade, parental education level, or family economic status ( t/F =0.62,1.50,-1.22, all P >0.05). Significant differences in self confidence levels were observed between male and female junior high students ( t=3.36, P <0.05). Regarding 24 hour movement behaviors, MVPA, LPA, SB and SP exhibited statistically significant differences across gender, grade, and parental education ( Z/H =-6.76-6.15, all P < 0.05 ). Results of component linear regression analysis indicated that the proportion of MVPA time positively predicted junior high school students self confidence levels ( β =4.38), while the proportion of SP time negatively predicted self confidence levels ( β = -11.20 ) (both P <0.05). Isotemporal substitution analysis revealed that replacing 15 minutes of SB and SP with MVPA increased total self confidence scores by 1.53 and 1.97 units, respectively, while the opposite substitution decreased scores by 2.48 and 2.91 units (all P <0.05). Dose response analysis revealed an asymmetric pattern in the isochronous substitution effects between MVPA and SB/SP.
Conclusions
The overall distribution of 24 hour movement behaviors significantly impacts self confidence level of junior high school students. Insufficient MVPA may constrain the positive development of self confidence.
5.Exploring the mechanism of myofascial trigger points deactivation by Tuina via the TGF-β1/Smad3 signaling pathway
Liya TANG ; Xiaowei LIU ; Jiadong ZANG ; Yuqiao ZHANG ; Xiang FENG ; Wu LI ; Jiangshan LI
Digital Chinese Medicine 2026;9(1):103-113
Objective:
To investigate whether Tuina alleviates fibrotic symptoms in myofascial trigger points (MTrPs) by regulating transforming growth factor (TGF)-β1/Smad3 signaling pathway, thereby deactivating these points.
Methods:
This study comprised two experimental phases. In phase 1, 27 specific pathogen-free (SPF) grade female Sprague-Dawley (SD) rats were randomized into three groups: control 1, model 1, and Tuina 1 groups. Model 1 and Tuina 1 groups underwent an 8-week MTrPs modeling protocol involving blunt impact and eccentric exercise. After successful modeling, rats in Tuina 1 group received manual pressing on nodules or cord-like taut bands on the medial aspect of the left hindlimb. Pain sensitivity and tissue stiffness were evaluated via pressure pain threshold (PPT) and soft tissue tension (STT). Muscle histopathology and fibrosis were observed using hematoxylin and eosin (HE) and Masson staining. Inflammatory factors in muscle were measured by enzyme-linked immunosorbent assay (ELISA), while immunofluorescence (IF) and Western blot (WB) were used to detect the expression levels of α-smooth muscle actin (α-SMA), collagen Ⅲ, and TGF-β1. In phase 2, 45 SPF female SD rats were randomized into five groups: control 2, model 2, Tuina 2, TGF-β1 inhibitor (TI), and Tuina + TGF-β1 agonist (Tuina + TA) groups. All groups except control 2 underwent standardized MTrPs modeling. Rats in Tuina 2 group received consistent pressing manipulation. TI group received intraperitoneal injections of oxymatrine, while Tuina + TA group received intraperitoneal injections of SRI-011381 hydrochloride followed by the same pressing protocol as Tuina 2 group. WB was used to detect the expression of collagen I, collagen III, TGF-β1, and phosphorylated-Smad3 (p-Smad3)/Smad3.
Results:
In phase 1, Tuina significantly improved PPT and STT in MTrPs of rats (P < 0.01), reversed pathological damages including disorganized muscle fiber arrangement, abnormal myocyte morphology, and exacerbated fibrosis. In addition, in MTrPs of rats in model 1 group, expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and fibrosis markers (α-SMA, collagen I, and collagen III) were upregulated, and all exhibited a significant downward trend after Tuina intervention (P < 0.05 or P < 0.01). This indicates that the therapeutic effects of Tuina are directly associated with reduced local inflammation and fibrosis in MTrPs. In phase 2, compared with model 2 group, rats in TI and Tuina 2 groups had decreased expression levels of TGF-β1 and p-Smad3/Smad3 in MTrPs, alongside reduced levels of inflammatory factors (IL-1β, IL-6, NF-κB, and TNF-α) and fibrosis markers (α-SMA, collagen I, and collagen III) (P < 0.05 or P < 0.01). When co-administered with TGF-β1 agonist, the therapeutic effects of Tuina were significantly attenuated, with rebounded TGF-β1 expression and p-Smad3/Smad3 in local MTrPs, and fibrosis and inflammatory responses were re-exacerbated (P < 0.05 or P < 0.01).
Conclusion
Tuina can effectively reduce inflammatory responses and fibrosis in MTrPs tissue, and its mechanism is closely related to the inhibition of the TGF-β1/Smad3 signaling pathway, which plays a critical role in Tuina-mediated regulation of MTrPs fibrosis.
6.Chinese expert consensus on the diagnosis and treatment of chronic pain after lung surgery with integrated Traditional Chinese and Western medicine (2026 edition)
Jichen QU ; Wentian ZHANG ; Jianqiao CAI ; Zhigang CHEN ; Bin LI ; Wei DAI ; Xiangwu WANG ; Yan LI ; Xiang LÜ ; ; Yongfu ZHU ; Mingran XIE ; Sufang ZHANG ; Lei JIANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(04):522-534
Chronic post-surgical pain (CPSP) is a common long-term complication following lung surgery. Its high incidence significantly impacts patients’ quality of life and functional recovery, and imposes a substantial socioeconomic burden. This consensus aims to systematically establish a standardized integrated Chinese and Western medicine diagnostic and treatment framework for chronic post-lung surgery pain (CPLSP). Based on the latest domestic and international evidence-based medical research and multidisciplinary clinical experience, the working group comprehensively elaborates on core issues regarding CPLSP, including its definition, epidemiology, pathogenesis, clinical assessment, Western medical treatment, traditional Chinese medicine (TCM) treatment, and integrated strategies. The consensus emphasizes a patient-centered approach, adhering to the principles of multimodality, individualization, and stepwise management, highlighting the synergistic advantages of integrating Chinese and Western medicine throughout the entire perioperative management cycle encompassing "perioperative anti-inflammation, acute analgesia, and chronic rehabilitation." Through systematic literature retrieval and evidence integration, a total of 9 core recommendations were established to provide scientifically sound and clinically practical guidance.
7.Predictive value of preoperative plasma fibrinogen combined with lymphocyte-to-monocyte ratio in the prognosis of patients with esophageal squamous cell carcinoma
Xianneng HE ; Yishun XIANG ; Yunfeng LI ; Chengbin LIN ; Weiyu SHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(04):570-577
Objective To investigate the prognostic value of preoperative plasma fibrinogen (FIB) combined with lymphocyte-to-monocyte ratio (LMR) in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Methods A retrospective analysis was conducted on ESCC patients who underwent esophagectomy in the Affiliated Lihuili Hospital of Ningbo University from 2015 to 2018. Based on the cut-off values of preoperative FIB and LMR, the F-LMR scoring system was constructed, and patients were divided into three groups according to the F-LMR score. Kaplan-Meier analysis was used to assess 5-year overall survival (OS) and 5-year progression free survival (PFS), and univariate and multivariate Cox regression analyses were performed to identify prognostic factors. Results Finally 260 patients were collected, including 237 males and 23 females, with a median age of 64 years (IQR: 59-70). The 5-year OS rates for patients with F-LMR score of 0, 1, and 2 were 24.44%, 51.69%, and 67.31%, respectively, and the 5-year PFS rates were 15.56%, 42.37%, and 57.62%, respectively. Lower preoperative F-LMR scores were associated with worse prognosis. Multivariate analysis showed that deeper tumor invasion, presence of lymph node metastasis, larger tumor maximum diameter, and lower preoperative F-LMR score were independent risk factors for OS. Conclusion The F-LMR scoring system based on the preoperative FIB and LMR may serve as an effective tool for predicting the prognosis of patients with ESCC.
8.Antibiotic exposure among third grade primary school students in Shenzhen
NI Yiping, ZHU Bo, ZHANG Wen, WANG Li, JI Xiang
Chinese Journal of School Health 2026;47(3):438-442
Objective:
To investigate the status of antibiotic exposure in third grade primary school students in Shenzhen,so as to provide evidence for the scientific management of antibiotic use and reduction of population health risks.
Methods:
From 1 September to 30 October 2021, 200 third grade students from 8 primary schools in Luohu District of Shenzhen were selected by cluster random sampling as research subjects. The body composition was measured, urine samples were collected, and the contents of 35 antibiotics in the samples were detected by mass spectrometry. Relevant dietary habit information of the subjects was collected via questionnaires. The Chi square test was used to compare the detection rate of antibiotics among different genders and weight grades. The Logistic regression model was adopted to evaluate the correlation between the target antibiotic detection rate and dietary habits.
Results:
At least one type of antibiotic was detected in 198 of the subjects with an overall detection rate of 99.0% . Among the 35 target antibiotics, 23 were detected with detection rates ranging from 0.5%-69.5%. Quinolones had the highest detection rate of 86.5% , followed by macrolides and sulfonamides with detection rates of 77.5% and 76.5%, respectively. The detection rate of antibiotics was 98.3% in boys and 100.0% in girls with no statistically significant difference ( χ 2=1.35, P >0.05). The detection rates of quinolones, macrolides, and sulfonamides varied significantly among children with different BMI categories ( χ 2=38.18, 12.45, 9.76 , all P <0.05). The multivariate Logistic regression model analysis showed that the macrolide detection rate was affected by genders( OR =0.42) and the sulfonamide detection rate was significantly correlated with the frequency of dairy product consumption and being overweight( OR =2.01)(both P <0.05). Enrofloxacin was associated with the weekly consumption frequency of livestock meat such as pork, beef and mutton, as well as the weekly consumption frequency of poultry meat such as chicken, duck and goose ( OR = 2.81,2.17,both P <0.05). Trimethoprim was associated with the weekly frequency of drinking pure milk ( OR =5.49, P < 0.05 ).
Conclusions
Third grade primary school students in Shenzhen are generally exposed to low dose antibiotics. Macrolides, quinolones, and sulfonamides may be associated with the risk of obesity in primary school students.
9.Correlation between liver fibrosis degree and carotid plaque in patients with lean metabolic dysfunction-associated fatty liver disease
Shuai ZHANG ; Shoulu JIN ; Wanqing LI ; Xijing SHI ; Hao LIANG ; Hao DONG ; Dailong LU ; Ying ZHU ; Xiaoxing XIANG ; Jun LIU
Journal of Clinical Hepatology 2026;42(2):319-325
ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque (CP) in patients with lean metabolic dysfunction-associated fatty liver disease (MAFLD), and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort, with the presence or absence of CP as the outcome, and fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis, the restricted cubic spline analysis, the receiver operating characteristic curve, and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group(n=607), the CP group (n=350) had a significantly higher proportion of male patients, a significantly higher proportion of patients with smoking/diabetes/hypertension, and significantly higher levels of age, creatinine, blood urea nitrogen, triglycerides, fasting blood glucose, aspartate aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio, NFS, and FIB-4 index, as well as significantly lower levels of platelet count and albumin (all P<0.05). The multivariate logistic regression analysis showed that after adjustment for confounding factors, FIB-4 index (odds ratio[OR]=2.979, 95% confidence interval[CI]:2.141 — 4.219, P<0.001) and NFS (OR=1.747, 95%CI: 1.499 — 2.046, P<0.001) were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers, and its mediating effect accounted for 39.5% — 40.8% of the total effect (P<0.001). ConclusionIn patients with lean MAFLD, NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP, and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.
10.Epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer
Minggang WANG ; Jiamei DONG ; Zhihua YE ; Xiang GAO ; Qi CHEN ; Xiaoqiao YU ; Hanmin LI
Journal of Clinical Hepatology 2026;42(2):362-371
ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation, and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group, model group, and Diwu Yanggan Capsule group using a random number table, with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage, and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention; DNA methylation chips were used to analyze the change in DNA methylation in liver tissue, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for data analysis. In addition, the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB, ADCK2, ERLIN2, SEMA3B, and TPH2 in the liver tissue of rats, and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups, while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group, the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group, the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes, and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation, apoptosis, and microenvironment regulation, such as the calcium ion signaling pathway, the cAMP signaling pathway, and the extracellular factor signaling pathway. Compared with the model group, the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene (P<0.05) and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes (all P<0.05). Compared with the model group, the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 (all P<0.05). ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.


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