1.Traditional Chinese Medicine for Hepatocellular Carcinoma Treatment Based on NF-κB Signaling Pathway: A Review
Ren YANG ; Mengge LI ; Zhibo DANG ; Biaobiao GUO ; Shilong LIU ; Zhongqin DANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):327-335
Hepatocellular carcinoma (HCC), the predominant subtype of primary liver cancer, ranks among the top in both incidence and mortality rates of malignant tumors in China. In its early stages, the disease may present with subtle or nonspecific symptoms, often leading to poor clinical prognosis and low patient survival rates, which makes it a significant public health concern. The pathogenesis is associated with multiple factors, including hepatitis virus infection, alcohol consumption, obesity, drug-induced liver injury, and immune disorders, which may interact synergistically to promote disease development. Currently, mainstream therapeutic approaches for HCC in modern medicine encompass surgical resection, liver transplantation, radiofrequency ablation, radiotherapy, and chemotherapy, but they all have certain limitations, such as large side effects and poor prognosis, imposing substantial psychological distress and financial strain on affected individuals. With a rich historical background in hepatic malignancy management, traditional Chinese medicine offers therapeutic benefits characterized by multi-targeted mechanisms, multi-level regulation, minimal adverse effects, and reduced likelihood of disease recurrence. It can not only enhance the curative effect, but also reduce the side effects of radiotherapy, chemotherapy, and surgery. Thus, it has attracted widespread attention. Extensive research has demonstrated that traditional Chinese medicine exhibits significant antitumor properties, along with notable anti-inflammatory and oxidative stress-reducing capabilities, and its mechanism may be related to the regulation of nuclear factor-kappa B (NF-κB) signaling pathway, which can affect multiple stages of hepatocarcinogenesis, such as cell proliferation, invasion, metastasis, and apoptosis. The mechanism of NF-κB signaling pathway in traditional Chinese medicine for HCC treatment has emerged as one of the pivotal research directions in current oncology studies. Based on the existing research foundation, a systematic literature review method was adopted to retrieve and analyze relevant Chinese and English literature in recent years. Integrating the molecular regulatory mechanisms of the NF-κB signaling pathway and its pivotal role in HCC pathogenesis and progression helped further explore the latest research advances in traditional Chinese medicine interventions targeting this pathway for HCC treatment. This approach may provide novel theoretical foundations and translational strategies for the prevention and management of HCC using traditional Chinese medicine.
2.Mechanism of Shoutaiwan in Treatment of Recurrent Spontaneous Abortion: A Review
Xue DANG ; Feixiang LIU ; Yanchen FENG ; Zhiying CHE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):283-291
Recurrent spontaneous abortion (RSA) is a common gynecological disease during pregnancy, clinically characterized by repeated spontaneous abortions, yet its pathological mechanism remains incompletely understood. Traditional Chinese medicine attributes the pathogenesis of RSA to the deficiency of Chong Ren and the lack of fetal solidity. It has amassed experience in treating RSA, with Shoutaiwan being widely utilized for addressing miscarriage symptoms such as habitual abortion due to kidney deficiency, bleeding during pregnancy, and fetal movement. In recent years, there has been a gradual increase in experimental studies on the application of Shoutaiwan in treating RSA and on related experiments. These studies have demonstrated that Shoutaiwan preserves the fetus mainly by modulating hormone balance, alleviating immune inflammation, and enhancing blood coagulation equilibrium during pregnancy. Besides, through the modulation of key signaling pathways such as nuclear factor, erythroid 2 like 2 (Nrf2)/heme oxygenase-1 (HO-1) and Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT), as well as mitogen-activated protein kinase (MAPK), Shoutaiwan has improved cellular antioxidant capacity, adjusted the phenotype of trophoblast and metaphase cells, and inhibited immune rejection, thus improving the pregnancy success rate. These findings not only elucidate the diverse biological foundations underlying Shoutaiwan's efficacy in treating RSA but also offer a scientific rationale for its clinical application and further mechanism research. Nonetheless, there remains a dearth of systematic reviews on RSA treatment with Shoutaiwan. Therefore, this review summarizes and synthesizes existing research findings to systematically analyze existing literature and studies, delving deeply into the principal pharmacological effects and associated signaling pathways of Shoutaiwan in regulating RSA. It aims to establish crucial reference points for its clinical application in RSA treatment and future experiments and research.
3.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.
4.Transfusion-transmitted hepatitis E
Baixun LI ; Tianxu LIU ; Liqin HUANG ; Yingnan DANG ; Lin WANG
Chinese Journal of Blood Transfusion 2025;38(1):38-42
Hepatitis E is an acute and self-limiting viral hepatitis caused by the hepatitis E virus (HEV). It has a higher mortality rate among immunosuppressed patients and pregnant women infected with HEV. Although HEV infections in humans are mostly caused by contaminated water or food worldwide, the incidence of transfusion-transmitted hepatitis E is continuously rising. Additionally, the prevalence of serum anti-HEV IgG in the blood donors in China is at a relatively high level, making it worth considering screening blood donors for HEV. This article briefly reviews the globally reported cases of transfusion-transmitted hepatitis E and the HEV screening strategies for blood donations.
5.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
Background/Aims:
Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).
Methods:
Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).
Results:
The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively).
Conclusions
We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.
6.Textual Research and Clinical Application Analysis of Classic Formula Fangji Fulingtang
Xiaoyang TIAN ; Lyuyuan LIANG ; Mengting ZHAO ; Jialei CAO ; Lan LIU ; Keke LIU ; Bingqi WEI ; Yihan LI ; Jing TANG ; Yujie CHANG ; Jingwen LI ; Bingxiang MA ; Weili DANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):270-277
The classic formula Fangji Fulingtang is from ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han dynasty. It is composed of Stephaniae Tetrandrae Radix, Astragali Radix, Cinnamomi Ramulus, Poria, and Glycyrrhizae Radix et Rhizoma, with the effects of reinforcing Qi and invigorating spleen, warming Yang and promoting urination. By a review of ancient medical books, this paper summarizes the composition, original plants, processing, dosage, decocting methods, indications and other key information of Fangji Fulingtang, aiming to provide a literature basis for the research, development, and clinical application of preparations based on this formula. Synonyms of Fangji Fulingtang exist in ancient medical books, while the formula composition in the Synopsis of the Golden Chamber is more widespread and far-reaching. In this formula, Stephaniae Tetrandrae Radix, Astragali Radix, Cinnamomi Ramulus, Poria, and Glycyrrhizae Radix et Rhizoma are the dried root of Stephania tetrandra, the dried root of Astragalus embranaceus var. mongholicus, the dried shoot of Cinnamomum cassia, the dried sclerotium of Poria cocos, and the dried root and rhizome of Glycyrrhiza uralensis, respectively. Fangji Fulingtang is mainly produced into powder, with the dosage and decocting method used in the past dynasties basically following the original formula. Each bag is composed of Stephaniae Tetrandrae Radix 13.80 g, Astragali Radix 13.80 g, Cinnamomi Ramulus 13.80 g, Poria 27.60 g, and Glycyrrhizae Radix et Rhizoma 9.20 g. The raw materials are purified, decocted in water from 1 200 mL to 400 mL, and the decoction should be taken warm, 3 times a day. Fangji Fulingtang was originally designed for treating skin edema, and then it was used to treat impediment in the Qing dynasty. In modern times, it is mostly used to treat musculoskeletal and connective tissue diseases and circulatory system diseases, demonstrating definite effects on various types of edema and heart failure. This paper clarifies the inheritance of Fangji Fulingtang and reveals its key information (attached to the end of this paper), aiming to provide a theoretical basis for the development of preparations based on this formula.
7.Textual Research and Clinical Application Analysis of Classic Formula Fangji Fulingtang
Xiaoyang TIAN ; Lyuyuan LIANG ; Mengting ZHAO ; Jialei CAO ; Lan LIU ; Keke LIU ; Bingqi WEI ; Yihan LI ; Jing TANG ; Yujie CHANG ; Jingwen LI ; Bingxiang MA ; Weili DANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):270-277
The classic formula Fangji Fulingtang is from ZHANG Zhongjing's Synopsis of the Golden Chamber in the Eastern Han dynasty. It is composed of Stephaniae Tetrandrae Radix, Astragali Radix, Cinnamomi Ramulus, Poria, and Glycyrrhizae Radix et Rhizoma, with the effects of reinforcing Qi and invigorating spleen, warming Yang and promoting urination. By a review of ancient medical books, this paper summarizes the composition, original plants, processing, dosage, decocting methods, indications and other key information of Fangji Fulingtang, aiming to provide a literature basis for the research, development, and clinical application of preparations based on this formula. Synonyms of Fangji Fulingtang exist in ancient medical books, while the formula composition in the Synopsis of the Golden Chamber is more widespread and far-reaching. In this formula, Stephaniae Tetrandrae Radix, Astragali Radix, Cinnamomi Ramulus, Poria, and Glycyrrhizae Radix et Rhizoma are the dried root of Stephania tetrandra, the dried root of Astragalus embranaceus var. mongholicus, the dried shoot of Cinnamomum cassia, the dried sclerotium of Poria cocos, and the dried root and rhizome of Glycyrrhiza uralensis, respectively. Fangji Fulingtang is mainly produced into powder, with the dosage and decocting method used in the past dynasties basically following the original formula. Each bag is composed of Stephaniae Tetrandrae Radix 13.80 g, Astragali Radix 13.80 g, Cinnamomi Ramulus 13.80 g, Poria 27.60 g, and Glycyrrhizae Radix et Rhizoma 9.20 g. The raw materials are purified, decocted in water from 1 200 mL to 400 mL, and the decoction should be taken warm, 3 times a day. Fangji Fulingtang was originally designed for treating skin edema, and then it was used to treat impediment in the Qing dynasty. In modern times, it is mostly used to treat musculoskeletal and connective tissue diseases and circulatory system diseases, demonstrating definite effects on various types of edema and heart failure. This paper clarifies the inheritance of Fangji Fulingtang and reveals its key information (attached to the end of this paper), aiming to provide a theoretical basis for the development of preparations based on this formula.
8.Asiaticoside inhibits the malignant biological behavior of hepatocellular carcinoma Huh7 cells via the cAMP/PKA/CREB signaling pathway
LIU Zhichao1 ; DANG Tongke1 ; MAN Gaoya1 ; CHEN Peng2
Chinese Journal of Cancer Biotherapy 2025;32(3):294-300
[摘 要] 目的:探讨积雪草苷(ASI)是否通过环磷酸腺苷/蛋白激酶A/环磷酸腺苷反应成分结合蛋白(cAMP/PKA/CREB)信号通路调节肝细胞癌Huh7细胞的恶性生物学行为。方法:MTT筛选合适的ASI及时间后,将Huh7细胞分为对照组、ASI低剂量组(ASI-L组,20 μmol/L ASI)、ASI中剂量组(ASI-M组,40 μmol/L ASI)、ASI高剂量组(ASI-H组,80 μmol/L ASI)及ASI-H+Forskolin组(80 μmol/L ASI+100 μmol/L cAMP激活剂-Forskolin),按照上述分组处理48 h后,MTT及细胞克隆实验检测Huh7细胞增殖;Transwell实验分析Huh7细胞迁移、侵袭变化;膜联蛋白V-FITC凋亡试剂盒检测细胞凋亡变化;ELISA实验、WB法检测Huh7细胞的cAMP分泌水平及p-PKA、p-CREB蛋白的表达水平;将Huh7细胞经皮下注射于裸鼠右腹部,建立肝癌异种移植模型,以5、15和45 mg/kg的ASI灌胃干预4周,分离肿瘤组织并称质量。结果:以接近IC50的40 μmol/L ASI处理48 h为合适的浓度和时间。ASI-L组、ASI-M组、ASI-H组Huh7细胞增殖及克隆数、迁移数、侵袭数、cAMP水平、p-PKA/PKA和p-CREB/CREB表达均显著低于对照组(均P < 0.05),而凋亡率均显著高于对照组(均P < 0.05);ASI-H+Forskolin组Huh7细胞增殖及克隆数、迁移数、侵袭数、cAMP水平、p-PKA/PKA、p-CREB/CREB表达均显著高于ASI-H组(均P < 0.05),而Huh7细胞凋亡率显著低于ASI-H组(P < 0.05);在裸鼠移植瘤实验中,5、15和45 mg/kg ASI处理组的移植瘤质量均显著低于对照组(均P < 0.05)。结论:ASI可通过下调cAMP/PKA/CREB信号通路蛋白表达抑制Huh7细胞的恶性生物学行为、促进其凋亡,以及抑制裸鼠移植瘤的生长。
9.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
Background/Aims:
Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).
Methods:
Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).
Results:
The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively).
Conclusions
We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.
10.Aberrant fragmentomic features of circulating cell-free mitochondrial DNA enable early detection and prognosis prediction of hepatocellular carcinoma
Yang LIU ; Fan PENG ; Siyuan WANG ; Huanmin JIAO ; Kaixiang ZHOU ; Wenjie GUO ; Shanshan GUO ; Miao DANG ; Huanqin ZHANG ; Weizheng ZHOU ; Xu GUO ; Jinliang XING
Clinical and Molecular Hepatology 2025;31(1):196-212
Background/Aims:
Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA).
Methods:
Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC).
Results:
The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively).
Conclusions
We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

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