1.Combined Therapy of Traditional Chinese and Western Medicine for Hepatitis B Virus Infection: A Review
Xuan WU ; Hui LI ; Jian HUANG ; Xikun YANG ; Yan ZENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):279-288
Hepatitis B virus (HBV) infection is the primary cause of viral hepatitis and represents a substantial disease burden in China. However, effective and safe agents capable of completely eliminating HBV DNA are still lacking. In modern medicine, anti-HBV strategies mainly target covalently closed circular DNA (cccDNA), among other mechanisms, and multiple novel drugs are currently under clinical investigation. Traditional medicine has been shown to exert anti-HBV effects through direct pathways, such as blocking viral entry, as well as indirect pathways, including the regulation of programmed cell death. Studies have confirmed that the integration of traditional Chinese medicine (TCM) and Western medicine in treating HBV infection and its related complications offers complementary advantages, particularly in enhancing HBV clearance rates, improving liver function, preventing various complications, and delaying the progression from hepatic fibrosis to hepatocellular carcinoma. This review focuses on advances in anti-HBV research involving TCM, Western medicine, and their integrated application, aiming to provide a basis for integrated HBV therapy and new drug development.
2.Effect and mechanism of Biejiajian Pill on subcutaneous xenograft tumor model of hepatocellular carcinoma Huh7 cells
Lu LU ; Huanling CHEN ; Jian XU ; Yuanqin DU ; Xiaoli LIU ; Yingsheng WU ; Chengting WU ; Wei BAN ; Jingjing HUANG ; Hongna HUANG
Journal of Clinical Hepatology 2026;42(1):125-133
ObjectiveTo investigate the inhibitory effect of Biejiajian Pills (BJJW) on the growth of liver cancer, as well as its potential mechanism in mediating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group, BJJW group (2.2 g/kg), and metformin group (250 mg/kg), and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment; HE staining was used to observe histopathological changes; the levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) in tumor tissue were measured; immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the Tukey’s test was used for further comparison between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group, the BJJW group had a tumor inhibition rate of 45.73%, with significant reductions in both tumor volume and weight (P<0.01). Pathological examination showed that compared with the model group, the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group, the BJJW group had a significant increase in ROS level (P<0.001) and a significant reduction in ATP level (P<0.001), as well as significant increases in p-AMPK/AMPK ratio (0.81±0.20 vs 0.13±0.04, P<0.01) and p-ULK1/ULK1 ratio (0.69±0.17 vs 0.18±0.13, P<0.01) and a significant reduction in p-mTOR/mTOR ratio (1.34±0.16 vs 3.20±0.62, P<0.01). ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction, increasing the level of ROS, reducing the level of ATP, and activating the AMPK/mTOR signaling pathway.
3.Ultrasound-guided attenuation parameter for identifying metabolic dysfunction-associated steatotic liver disease: a prospective study
Yun-Lin HUANG ; Chao SUN ; Ying WANG ; Juan CHENG ; Shi-Wen WANG ; Li WEI ; Xiu-Yun LU ; Rui CHENG ; Ming WANG ; Jian-Gao FAN ; Yi DONG
Ultrasonography 2025;44(2):134-144
Purpose:
This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard.
Methods:
Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated.
Results:
Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001).
Conclusion
Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.
4.Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial
Pei SUN ; Hong HAN ; Yi-Kang SUN ; Xi WANG ; Xiao-Chuan LIU ; Bo-Yang ZHOU ; Li-Fan WANG ; Ya-Qin ZHANG ; Zhi-Gang PAN ; Bei-Jian HUANG ; Hui-Xiong XU ; Chong-Ke ZHAO
Ultrasonography 2025;44(2):112-123
Purpose:
The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.
Methods:
This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C). The results of setting C with specialist doctors were considered the gold standard. Carotid intima-media thickness (CIMT) and the features of CPs were measured and recorded. The diagnostic performance of GPs in distinguishing CPs was evaluated using a receiver operating characteristic curve. Inter-observer agreement was compared using the intragroup correlation coefficient (ICC). Questionnaires were completed to evaluate clinical benefits.
Results:
Among the 111 community residents, 80, 96, and 112 CPs were detected in settings A, B, and C, respectively. Setting B exhibited better diagnostic performance than setting A for detecting CPs (area under the curve, 0.856 vs. 0.749; P<0.01). Setting B had better consistency with setting C than setting A in CIMT measurement and the assessment of CPs (ICC, 0.731 to 0.923). Moreover, measurements in setting B required less time than the other two settings (44.59 seconds vs. 108.87 seconds vs. 126.13 seconds, both P<0.01).
Conclusion
Using an intelligent handheld US device, GPs can perform CP screening and achieve a diagnostic capability comparable to that of specialist doctors.
5.Treatment response to nucleos(t)ide analogs in chronic hepatitis B with mildly elevated alanine aminotransferase: Letter to the editor on “Antiviral therapy for chronic hepatitis B with mildly elevated aminotransferase: A rollover study from the TORCH-B trial”
Jian WANG ; Fei CAO ; Chuanwu ZHU ; Chao WU ; Rui HUANG
Clinical and Molecular Hepatology 2025;31(2):e140-e142
6.Presence of liver fibrosis in chronic hepatitis B patients with varying serum hepatitis B virus DNA levels: Letter to the editor on “Non-linear association between liver fibrosis scores and viral load in patients with chronic hepatitis B”
Jian WANG ; Shaoqiu ZHANG ; Chuanwu ZHU ; Yuanwang QIU ; Chao WU ; Rui HUANG
Clinical and Molecular Hepatology 2025;31(1):e27-e30
7.Applications of Vaterite in Drug Loading and Controlled Release
Xiao-Hui SONG ; Ming-Yu PAN ; Jian-Feng XU ; Zheng-Yu HUANG ; Qing PAN ; Qing-Ning LI
Progress in Biochemistry and Biophysics 2025;52(1):162-181
Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.
8.Role and Mechanism of Cucurbitacin B in Suppressing Proliferation of Breast Cancer 4T1 Cells via Inducing Ferroptosis
Yidan RUAN ; Huizhong ZHANG ; Huating HUANG ; Pingzhi ZHANG ; Aina YAO ; Yongqiang ZHANG ; Xiaohan XU ; Shiman LI ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):91-97
ObjectiveTo explore the role of cucurbitacin B (CuB) in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB(0.2, 0.4, 0.8 μmol·L-1)on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium (MTT) assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay, and the levels of lactate dehydrogenase (LDH) in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species (ROS) levels in 4T1 cells were detected by flow cytometry, and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells, solute carrier family 7 member 11 (SCL7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), transferrin receptor protein 1 (TFR1), and ferritin heavy chain 1 (FTH1). ResultsCompared with that in the blank group, the survival rate of 4T1 cells in CuB groups was significantly decreased (P<0.05), and the number of cell clones in CuB groups was significantly reduced (P<0.01). In addition, compared with that in the blank group, the leakage of LDH in cells in CuB groups was significantly increased (P<0.01), and the mitochondrial membrane potential of cells in CuB groups decreased significantly (P<0.01). Cellular ROS levels were significantly elevated in CuB groups (P<0.01). The mitochondria of cells in CuB groups were obviously wrinkled, and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group, the protein expression of p53, ACSL4, and TFR1 were significantly up-regulated in CuB groups (P<0.05), and that of SLC7A11, GPX4, and FTH1 were significantly down-regulated (P<0.05). ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53, which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe3+ and down-regulates the expression of FTH1 to reduce the ability of iron storage, resulting in an elevated free Fe2+ level. It catalyzes the Fenton reaction, generates excess ROS, imbalances the antioxidant system and iron metabolism, and then induces ferroptosis in 4T1 cells.
9.Role and Mechanism of Cucurbitacin B in Suppressing Proliferation of Breast Cancer 4T1 Cells via Inducing Ferroptosis
Yidan RUAN ; Huizhong ZHANG ; Huating HUANG ; Pingzhi ZHANG ; Aina YAO ; Yongqiang ZHANG ; Xiaohan XU ; Shiman LI ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):91-97
ObjectiveTo explore the role of cucurbitacin B (CuB) in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB(0.2, 0.4, 0.8 μmol·L-1)on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium (MTT) assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay, and the levels of lactate dehydrogenase (LDH) in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species (ROS) levels in 4T1 cells were detected by flow cytometry, and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells, solute carrier family 7 member 11 (SCL7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), transferrin receptor protein 1 (TFR1), and ferritin heavy chain 1 (FTH1). ResultsCompared with that in the blank group, the survival rate of 4T1 cells in CuB groups was significantly decreased (P<0.05), and the number of cell clones in CuB groups was significantly reduced (P<0.01). In addition, compared with that in the blank group, the leakage of LDH in cells in CuB groups was significantly increased (P<0.01), and the mitochondrial membrane potential of cells in CuB groups decreased significantly (P<0.01). Cellular ROS levels were significantly elevated in CuB groups (P<0.01). The mitochondria of cells in CuB groups were obviously wrinkled, and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group, the protein expression of p53, ACSL4, and TFR1 were significantly up-regulated in CuB groups (P<0.05), and that of SLC7A11, GPX4, and FTH1 were significantly down-regulated (P<0.05). ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53, which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe3+ and down-regulates the expression of FTH1 to reduce the ability of iron storage, resulting in an elevated free Fe2+ level. It catalyzes the Fenton reaction, generates excess ROS, imbalances the antioxidant system and iron metabolism, and then induces ferroptosis in 4T1 cells.
10.Effect of Biejia Decoction Pill on aerobic glycolysis in hepatocellular carcinoma by regulating the protein kinase B/mammalian target of rapamycin signaling pathway
Qinwen TAN ; Jingjing HUANG ; Ruixi ZHONG ; Yuanqin DU ; Jian XU ; Jinli NONG ; Yujiao PENG
Journal of Clinical Hepatology 2025;41(2):300-306
ObjectiveTo investigate the inhibitory effect of Biejia Decoction Pill on the proliferation, migration, and aerobic glycolysis of hepatocellular carcinoma (HCC) using cell experiments, as well as related mechanisms. MethodsHuman liver cancer cell line Huh7 was selected, and Sprague-Dawley rats were randomly divided into blank serum group, inhibitor group, and high-, middle-, and low-dose Biejia Decoction Pill groups. Rat serum containing the drug was prepared for the incubation of Huh7 cells. CCK8 assay and scratch assay were used to explore the effect of Biejia Decoction Pill on the proliferation and migration of HCC cells; glycolytic rate-limiting enzymes and metabolites were measured to explore the effect of Biejia Decoction Pill on aerobic glycolysis of liver cancer cells; RT-qPCR and Western blot were used to explore the effect of Biejia Decoction Pill on the mRNA expression, related proteins, and phosphorylation of the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test or the Dunnett’s T3 test were used for further comparison between two groups. ResultsCompared with the blank serum group, the Biejia Decoction Pill groups had significant reductions in OD value, migration rate during different periods of time, glycolytic rate-limiting enzymes (hexokinase, phosphofructokinase, pyruvate kinase), and glycolytic metabolites (pyruvate, lactic acid, ATP) (all P<0.05). RT-qPCR results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of mTOR, and the high- and low-dose Biejia Decoction Pill groups had a significant reduction in the mRNA expression level of AKT (all P<0.05). Western blot results showed that compared with the blank serum group, the high-, middle-, and low-dose Biejia Decoction Pill groups had significant reductions in the expression levels of mTOR-related proteins and phosphorylated proteins, and the high- and middle-dose Biejia Decoction Pill groups had significant reductions in the expression levels of AKT-related proteins and phosphorylated proteins (all P<0.05). ConclusionThis study preliminarily verifies that the serum containing Bijia Decoction Pill can inhibit the aerobic glycolysis of human hepatoma Huh7 cells, thereby inhibiting their proliferation and migration, possibly by inhibiting the expression of the proteins related to the AKT/mTOR signaling pathway.

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