Regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib / 中国药房

OBJECTIVE To investigate the regulatory effect of autophagy on the resistance of human liver cancer cell Huh7 to lenvatinib. METHODS Using human liver cancer cell Huh7 as subject， the lenvatinib-resist cell model （Huh7-LR） was generated by the low-dose gradient method combined with long-term administration. The sensitivity of parental cell Huh7 and drug-resistant cell Huh7-LR to lenvatinib was detected by using CCK-8 assay and flow cytometry. Western blot assay and GFP-mCherry-LC3 plasmid transfection were performed to detect the expression levels of autophagic protein Beclin-1， autophagic adapter protein sequestosome 1 （p62）， microtubule-associated protein 1 light chain 3 （LC3） and autophagic level. Furthermore， an autophagy activation model was constructed by cell starvation， the protein expression of p62 and autophagy level were detected by using Western blot assay and GFP-mCherry-LC3 plasmid transfection， and the effect of autophagy activation on the sensitivity of Huh7-LR cells to lenvatinib was detected by flow cytometry. RESULTS Compared with parental cells， the drug resistance index of Huh7-LR cells was 6.2； protein expression of p62 was increased significantly， while apoptotic rate， protein expression of Beclin-1 and LC3Ⅱ/ LC3Ⅰ ratio were all reduced significantly （P＜0.05 or P＜0.01）； the level of autophagy was decreased to some extent. Autophagy activation could significantly increase the protein expression of p62 in Huh7-LR cells （P＜0.05） and autophagy level， and significantly increase its apoptotic rate （P＜0.05）. CONCLUSIONS Autophagy is involved in lenvatinib resistance， and activating autophagy can reverse the resistance of liver cancer cells to lenvatinib to some extent.

Renal injury caused by tenofovir disoproxil fumarate in a patient with liver cancer complicated with HBV infection：a case report and literature analysis / 中国药房

Tenofovir disoproxil fumarate （TDF） is a first-line treatment for chronic hepatitis B. With increasing use worldwide， the adverse events of renal injury caused by this drug have also attracted industry attention. This article reports a 61- year-old patient with liver cancer complicated with hepatitis B virus （HBV） infection. The patient started using TDF in mid-March 2022 and developed kidney injury after 2 months of treatment， during which he received 2 courses of donafenib combined with sintilimab chemotherapy and irregular administration of diclofenac for pain relief. In this paper， Naranjo’s assessment scale was used to evaluate the drugs that may be associated with renal injury， including TDF and sintilimab， and the drugs that are suspected to be associated with renal injury are donafenib and diclofenac. The renal injury caused by TDF can be judged according to the changes in the patient’s condition， the incidence of drug-induced renal injury， clinical manifestations， occurrence time， occurrence mechanism， drug combination， and high-risk factors. The changes of serum creatinine in patients with liver cancer complicated with HBV infection after TDF should be dynamically monitored in the clinic， and the dose of antiviral drugs should be adjusted if necessary and other antiviral drugs with less impact on renal function can be selected， to provide individualized medication recommendations for tumor patients， reduce the incidence of TDF-related renal injury.

Epidemiological trend analysis of liver cancer incidence in Luzhou City， Sichuan Province from 2016 to 2022 / 上海预防医学

ObjectiveTo analyze the epidemiological distribution and temporal trends of liver cancer incidence among Luzhou residents from 2016‒2022， and to provide a theoretical basis for improving liver cancer prevention and treatment strategies in Luzhou. MethodsData on liver cancer incidence among Luzhou residents from 2016 to 2022 were collected， and the incidence rate， age-specific incidence rate， and annual percentage change （APC） were calculated. A Joinpoint regression model was used to fit a time series segment to the monthly number of new cases in each district and county of Luzhou to explore the trend of liver cancer incidence rate. ResultsThe incidence rate of liver cancer in Luzhou increased from 22.96/105 in 2016 to 32.31/105 in 2022. The incidence rate of liver cancer in men was higher than that in women in both 2016 and 2022， and the incidence rate of liver cancer in men increased from 34.83/105 in 2016 to 47.95/105 in 2022， with an APC of 3.3%； the incidence rate of liver cancer in women increased from 10.50/105 in 2016 to 15.95/105 in 2022， with an APC of 3.0%， and the differences in the change trends were not statistically significant （P>0.05）.The incidence of liver cancer was low in the age group of 0‒<40 years from 2016 to 2022 and increased with age； the incidence of liver cancer in the age group of 55 years and above was increasing at an average annual rate of 16.4%. ConclusionThe overall incidence of liver cancer in Luzhou is on the rise， and the incidence of liver cancer in men is higher than that in women. Middle-aged and elderly men are the key population for liver cancer prevention and treatment， and liver cancer prevention and treatment should be carried out in a targeted manner， taking into account regional development differences.

A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Intervention Mechanism of Biejiajian Wan on Primary Liver Cancer by Regulating lncRNA SNHG5/miRNA-26a-5p/GSK-3β Signal Axis / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Biejiajian Wan in the intervention of primary liver cancer based on long non-coding RNA SNHG5 （lncRNA SNHG5）/micro RNA-26a-5p （miRNA-26a-5p）/glycogen synthase kinase-3β （GSK-3β） signal axis. MethodDouble luciferase reporting assay was used to verify the targeted interaction between lncRNA SNHG5 and miRNA-26a-5p， miRNA-26a-5p， and GSK-3β in HepG2 cells. Nude-mouse transplanted tumor model of human HepG2 were established and randomly divided into model group， Biejiajian Wan low-dose group （0.5 g·kg-1）， medium-dose group （1.0 g·kg-1）， and high-dose group （2.0 g·kg-1）， and sorafenib group （100 mg·kg-1）， with 10 mice in each group. The mice were given intragastric administration of normal saline or drug for 28 days， and the tumor volume was measured at different time. Hematoxylin-eosin （HE） staining was used to observe the histological changes of tumors. The nucleic acid levels of lncRNA SNHG5， miRNA-26a-5p， GSK-3β， and β-catenin mPNA in tumor tissue were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of GSK-3β and β-catenin in tumor tissue were detected by western blot. ResultCompared with the SNHG5-WT （wild type） + miRNA NC （negative control） group， the relative luciferase activities of the SNHG5-WT + miRNA-26a-5p mimic group were decreased （P<0.05）. Compared with the GSK-3β-WT + miRNA NC group， the relative luciferase activity of the GSK-3β-WT + miRNA-26a-5p mimic group was decreased （P<0.05）. Compared with the model group， the tumor volume of Biejiajian Wan low-dose， medium-dose， and high-dose groups was significantly decreased （P<0.05， P<0.01）. Compared with the model group， the cells in the tumor tissue of nude mice in each dose group of Biejiajian Wan were sparsely arranged with necrocytosis， which showed concentration-dependent changes. Compared with the model group， the expression levels of lncRNA SNHG5， GSK-3β， and β-catenin were decreased （P<0.05， P<0.01）， while the expression of miRNA-26a-5p was increased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. Compared with the model group， the protein expression levels of GSK-3β and β-catenin were decreased in each dose group of Biejiajian Wan （P<0.05， P<0.01）. ConclusionBiejiajian Wan may affect the necrosis of liver cancer cells through lncRNA SNHG5/miRNA-26a-5p/GSK-3β signal axis and thus play an anti-tumor role. This research will provide more theoretical basis for the clinical application of Biejiajian Wan.

Regressão espontânea do carcinoma hepatocelular: foco nos fatores de risco associados / Spontaneous regression of hepatocellular carcinoma: focusing in the associated risk factors

ABSTRACT Background: Spontaneous regression (SR) is defined as the partial or complete disappearance of a tumor, in the absence of a specific treatment. Evidence of the SR in hepatocellular carcinoma (HCC) is rare. Objective: The authors aimed to review all the cases of SR of HCC in two reference centers of Southern Brazil, highlighting the main characteristics. Methods: Data of all patients with HCC were retrospectively reviewed looking for the occurrence of SR in patients from two tertiary centers in Southern Brazil, in the last five years. The diagnosis of cirrhosis was established according to clinical, laboratory and imaging data, as well as upper endoscopy or histopathological examination when necessary. The diagnosis of HCC was based on typical findings according to radiologic criteria (LIRADS) or histopathological examination. Spontaneous regression was defined as a partial or complete involution of a HCC in the absence of a specific therapy. Results: From all cases of HCC in the last 5 years (n=433), there were five cases of SR. Three (60%) were men, the mean age was 62.6 (50.0-76.0) years, and the etiology was HCV in 3 (60%). Complete regression was observed in three patients (60%), one patient (20%) presented partial regression, and one (20%) relapesed and died. The time of follow-up varied between 12 and 21 months. In this presentation, it was highlighted one case of SR observed after COVID-19 infection in a patient with cirrhosis. The possible mechanisms involved in this situation were reviewed, emphasizing the most common like hypoxia and immunological. There were also one patient submitted to a surgical procedure as a possible fator involved and three patients without obvious risk factors. Conclusion: This phenomenon will possibly contribute to a better understanding of the pathophysiological mechanisms of HCC.

RESUMO Contexto: A evidência da regressão espontânea (RE) no carcinoma hepatocelular (CHC) é rara. Objetivo: Revisar todos os casos de RE de CHC em dois centros de referência do Sul do Brasil, destacando as principais características. Métodos: Os dados de todos os pacientes com CHC foram revisados retrospectivamente buscando a ocorrência de RE em pacientes de dois centros terciários do Sul do Brasil, nos últimos 5 anos. O diagnóstico de cirrose foi estabelecido de acordo com dados clínicos, laboratoriais e de imagem, além de endoscopia digestiva alta ou exame histopatológico quando necessário. O diagnóstico de CHC foi baseado em achados típicos de acordo com critérios radiológicos (LIRADS) ou exame histopatológico. A RE foi definida como uma involução parcial ou completa de um CHC na ausência de terapia específica. Resultados: Do total de casos de CHC nos últimos 5 anos (n=433), houve cinco casos de RE. Três (60%) eram homens, a média de idade foi de 62,6 (50,0-76,0) anos, a etiologia foi virus da hepatite C em 3 (60%). A regressão completa foi observada em três pacientes (60%), um paciente (20%) apresentou regressão parcial e um (20%) apresentou recidiva e evoluiu a óbito. O tempo de seguimento variou entre 12 e 21 meses. Nesta apresentação foi destacado um caso (20%) de RE observado após infecção por COVID-19 em paciente com cirrose. Foram revisados os possíveis mecanismos envolvidos nesta situação, enfatizando os mais comuns como hipóxia e imunológicos. Houve também um paciente submetido a procedimento cirúrgico como possível fator envolvido e três pacientes sem fatores de risco evidentes. Conclusão: Este fenômeno possivelmente contribuirá para uma melhor compreensão dos mecanismos fisiopatológicos do CHC.

Effect of serine protease inhibitor Kazal-type 1 on the proliferation of hepatocellular carcinoma cell and its mechanism / 解剖学报

[Abstract] Objective To explore the effect of serine protease inhibitor Kazal-type 1(SPINK1) on the proliferation of hepatocellular carcinoma cells RH-35 and its underling molecular mechanism. Methods Spink1 gene expression in liver cancer and rat liver cancer models were analyzed by Gene Expression Omnibus (GEO) data, RH-35 cells were treated with rrSPINK1 protein, the effect of rrSPINK1 on the proliferation and apoptosis of RH-35 cells was explored by MTT, 2’-deoxy-5-ethynyluridine(EdU) and flow cytometry, the molecular mechanism of SPINK1 regulating liver cancer were detected by Real-time PCR and Western blotting. Results The results showed that Spink1 gene was over-expressed significantly in liver cancer and rat liver cancer models, rrSPINK1-treated RH-35 cells showed increased viability, EdUpositive cell rate, and the proportion of cells in S phase and G

Curative effect of fuzheng xiaoliu granules in the treatment of primary liver cancer and analysis of serum metabolomics / 中国临床药理学与治疗学

AIM: To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics. METHODS: Sixty patients with stage II primary liver cancer who achieved complete remission (CR) after comprehensive interventional therapy were randomly divided into treatment group and placebo group, with 30 patients in each group. They were treated for one year and observed for one year. The one-year recurrence rate, traditional chinese medicine (TCM) syndrome score, alpha-fetoprotein and child-pugh grade were compared between the two groups. The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology, and the metabolic pathways and related biological pathways were analyzed. RESULTS: The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group, and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group (P0.05). Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment, respectively. After enrichment analysis and topological analysis of the different metabolites, it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism, fatty acid metabolism and purine metabolism and other metabolic pathways. Before and after treatment in the treatment group and after treatment in the two groups, there were the same differential metabolites and metabolic pathways in the two comparison results. The same differential metabolites with FOLD CHANGE>1 include Stearic acid, Hypoxanthine, Kynurenic acid, Arachidonic acid, and N-Arachidonoyl Dopamine. The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism. CONCLUSION: Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome. It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids, thereby delaying tumor recurrence.

Effect of Gupi Xiaoji Decoction on mitochondrial structure and function of human hepatoma cell line HepG2 / 中国药理学通报

Aim To observe the effect of Gupi Xiaoji Decoction (GPXJY) on the structure and function of mitochondria of human hepatoma cell HepG2 cells and explore its possible mechanism. Methods CCK8 was used to detect cell proliferation, Mito-Tracker Green fluorescence staining was used to observe the mitochondrial structure, flow cytometry was used to detect the membrane potential, Elisa was used to detect the ATP content, fluoroscopic electron microscopy was used to observe the microstructure changes, and high-content screening(HCS) was used to detect the related proteins. Results Fluorescence staining showed that GPXJY damaged the mitochondria of HepG2 cells and decreased the content of ATP. The results of flow cytometry showed that GPXJY could reduce the mitochondrial membrane potential of HepG2 cells. The results of electron microscope showed that GPXJY made the mitochondria of cancer cells swell and so on. HCS found that GPXJY significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells, and significantly increased the average fluorescence intensity of apoptosis promoting proteins Bax, cytochrome-c, caspase-3 and cleaved-caspase-3, which was statistically significant. Conclusion GPXJY can regulate the structure and function of mitochondria in HepG2 cells.

Research progress of circular RNA in drug resistance of liver cancer / 中国药理学通报

Circular RNAs are novel non-coding RNAs with multiple biological functions, which can participate in biological processes such as the occurrence, development, invasion, and metastasis of liver cancer, as well as drug resistance of liver cancer. This article reviews the roles and mechanisms of circR-NAs in chemotherapy resistance, targeted therapy resistance and immunotherapy resistance in liver cancer, in order to provide new ideas for solving liver cancer resistance.

Effects of salidroside on proliferation, migration, invasion and apoptosis of 97H cells / 中国药理学通报

Aim To study the effect of salidroside on the proliferation, migration, invasion and apoptosis of human highly metastatic liver cancer cells ( 97 H cells) . Methods Multifunctional cell analyzer was used to determine the effect of salidroside on the proliferation of 97H cells. Scratch assay was used to determine the effect of salidroside on the migration ability of 97H cells. Transwell assay was used to determine the effect of salidroside on the invasion ability of 97 H cells. Inverted microscope was used to observe the effect of salidroside on the morphology of 97H cells. Transmission electron microscope was employed to observe the effect of salidroside on mitochondria in 97 H cells. Flow cytometry was used to analyze the effect of salidroside on apoptosis and cycle distribution of 97 H cells. q-PCR was used to determine the effect of salidroside on related apoptosis genes in 97H cells.Western blot was used to determine the effect of salidroside on related migration, invasion and apoptosis proteins in 97H cells. Results Compared to blank group, salidroside treatment inhibited the proliferation, migration and invasion of 97H cells, and induced apoptosis of 97H cells. Salidroside could up-regulate the relative expression of Caspase-3 (P <0.05). Salidroside could up-regulate the levels of E-cad, Bax, Caspase-3 and Caspase-9 proteins (P <0.05), and down-regulate the levels of N-cad, Girdin and Bcl-2 proteins (P < 0. 05 ). Conclusions Salidroside has inhibitory effects on the proliferation, migration and invasion of 97H cells, and induces apoptosis of 97H cells through mitochondrial pathway.

Effects of extracts from Arnebia euchroma (Royle) Johnst on apoptosis of HepG2 and its anti-hepatocellular carcinoma in mice / 中国药理学通报

Aim To study the apoptosis of human hep-atoma cell line ( HepG2 ) induced by different polar parts of Arnebia euchroma ( Royle ) Johnst ( AE ) and to verify its anti-hepatoma effect by a mouse orthotopic liver cancer model so as to explore the anti-cancer effect of AE extract. Methods Firstly, MTT method and Annexin V-FITC/PI double staining method were used to detect the anti-proliferative and pro-apoptotic effects of each polar part of AE on HepG2 cells, and Western blot was used to detect the expression of Bcl-2 apoptosis family proteins incells. Based on the above experimental results, the effective parts with significant pro-apoptotic effect were screened out for anti-in situ liver cancer experiments in mice, and the organ indexes, liver function indexes and tissue sections of mice with orthotopic liver cancer before and after administration were evaluated. Results With the decrease of the polarity of AE extract,the anti-proliferation and pro-apoptotic effects on HepG2 cells were enhanced, and the anti-proliferation and apoptosis-inducing effects of AE petroleum ether fraction ( AEP) were the most significant. When AEP dose was 1.56 (μg • L

The molecular mechanism of Qizhu anti-cancer prescription in treatment of primary liver cancer based on network pharmacology and experimental verification / 中国药理学通报

Aim To investigate the mechanism of Qizhu anti-cancer prescription ( QZACP) inthe treatment of primary liver cancer using network pharmacology and molecular docking. Methods Drugs and primary liver cancer ( PLC) -related targets were found according to TCMSP database and disease databases such as GeneCard, the key chemical components and core targets were screened by Cytoscape 3. 9. 1 and String platform respectively, and a network relationship diagram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9. 1. GO functional analysis and KEGG pathway analysis were performed using DAVID platform, visualized by R 4. 1. 1 software, and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets, and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments. Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin, glycyrrhizin, Denudatin B, isoflavanone, sanguinarol, etc. ; the potential targets were STAT3, EGFR, AKT1 etc. ; the related pathways were mainly PI3K-Akt signaling pathway,MAPK signaling pathway,etc. ; molecular docking showed that the core compounds had better integrating conformation with the key targets. In addition, QZACP could inhibit the growth of tumor in nude mice and decrease the expression of STAT3, EGFR and AKT1. Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer, which may be related to the regulation of PI3K/Akt signaling pathway.

Transthoracic Echocardiography Revealed Inferior Vena Cava and Right Atrial Occupation:Report of One Case / 中国医学科学院学报

One case with ascites and lower limb edema as the initial manifestations was reported.The echocardiography revealed inferior vena cava and right atrial occupation,which combined with increased alpha fetoprotein and imaging examination,suggested liver malignant tumor combined with tumor thrombus of inferior vena cava and right atrium.After targeted therapy combined with immunotherapy,the tumor shrank and alpha fetoprotein decreased significantly,suggesting that the treatment was effective.The median survival time of the patient was 3 months.This patient had a clear history of cirrhosis due to hepatitis B and was clinically diagnosed with advanced liver cancer,which suggested the importance of early liver cancer screening.

Serum metabolomics study on benign liver lesions and hepatic malignancies by central carbon pathway metabolites / 药学实践杂志

Objective To screen potential metabolites and significantly altered metabolic pathways of liver lesions by central carbon pathway metabolites. Methods 32 healthy volunteers (HC), 23 patients with biliary cysts (CYST), 19 patients with biliary stones (Stone), 45 patients with hepatocellular carcinoma (HCC), and 50 patients with hilarcholangiocarcinoma (HCCA) were recruited. Their serum samples were collected for UPLC-QQQ-MS analysis and further MPP statistical analysis. Pattern recognition was further used to discovery the differences in metabolome between groups, and to explore the significantly altered metabolic pathway and possible pathogenic mechanism of liver diseases. Results A total of 15, 7, 7, and 3 metabolites and a total of 8, 4, 4, and 1 metabolic pathway that were significantly different in serum between CYST, Stone, HCC, HCCA and healthy controls were identified and enriched through serum metabolomics analysis, respectively. Conclusion According to the above identified differential metabolites and enriched metabolic pathway results, it is shown that liver lesions mainly involved in the energy metabolism and amino acid metabolism & transport, in addition, inositol phosphate metabolism were significantly changed both in CYST, Stone, HCC and HCCA.

Study on the regularity of traditional Chinese medicine in treatment of postembolization syndrome after TACE based on data mining / 药学实践杂志

Objective To explore the regularity of traditional Chinese medicine (TCM) in the treatment of postembolization syndrome (PES) after transcatheter arterial chemoembolization (TACE). Methods CNKI, WANFANG and VIP were used as data sources to search the journals and literatures related to TCM treatment from January 2000 to December 2021. Then, relevant TCM formula or Chinese patent medicines preparations were screened out. The Chinese medicinal materials contained were entered into Excel 2019 table database, and the data were analyzed by SPSS Statistics 21.0 and SPSS Modeler 18.0 statistical software. Results 86 qualified prescriptions were included, containing 181 Chinese medicinal materials, with a total frequency of 942 times. Of the 181 Chinese herbs included, there were 28 herbs with frequency ≥10%, with a total frequency of 587. The top 5 Chinese medicinal materials of frequency were licorice, Poria, Atractylodes, Bupleurum and Astragalus. Among the efficacy classifications, tonifying deficiency drugs, heat-clearing drugs and diuretics were most used. In four properties and five tastes, the top three of four properties were warm, flat and cold, and the top three of five tastes were sweet, bitter and pungent. In the classification of meridians, the first three meridians were spleen meridian, lung meridian and liver meridian. 30 association rules were obtained in association rules analysis, 11 common factors were obtained by factor analysis, 6 clustering combinations were obtained by cluster analysis, and 4 commonly used drug combinations were obtained. Conclusion The prescription drugs for the treatment of PES after TACE were mainly tonic drugs, heat-clearing drugs and diuresis and dampness-draining drugs. The treatment methods were mainly invigorating spleen and replenishing qi, clearing heat and dampness and detoxification.

Chinese expert consensus on Co-Ablation System for the treatment of primary liver cancer （2023 edition） / 临床肝胆病杂志

@#Clinically， the recurrence and metastasis of liver cancer after local ablation therapy have been the main factors affecting the long-term survival of patients with liver cancer. As a new generation of composite cryoablation and thermal ablation system， Co-Ablation System creatively integrates the advantages of profound hypothermia cryoablation and thermal ablation， which can maximize the release of tumor antigen while completely destroying liver cancer in situ， thus， the purpose of controlling liver cancer recurrence and metastasis can be achieved. Co-Ablation System treatment is usually carried out through percutaneous puncture under ultrasound or CT guidance. The selection of local anesthesia or general anesthesia is based on the size and location of the liver cancer. Co-Ablation System treatment is mainly suitable for single tumor with diameter <5 cm and multiple tumors（≤3 tumor lesions） with a maximum diameter <3 cm. After ablation， protection of liver function and symptomatic treatment are employed according to patient’s condition. About one month after ablation， MRI or contrast-enhanced CT examination is performed to evaluate the therapeutic efficacy， then， the patients are followed up regularly. In order to standardize the application of Co-Ablation System in treating liver cancer， the Committee of Minimally Invasive Therapy in Oncology and the Committee of Ablation Therapy in Oncology， Chinese Anti-Cancer Association， have organized domestic experts engaged in liver cancer ablation therapy to make a professional and in-depth discussion and to compose this expert consensus on Co-Ablation System for the treatment of primary liver cancer.

Anti-liver Cancer Mechanisms of Biejiajian Wan and Clinical Research： A Review / 中国实验方剂学杂志

Biejiajian Wan， a classical formula for liver diseases， originated from Synopsis of the Golden Chamber. It has been applied in clinical settings for more than 2 000 years. According to modern pharmacological studies， it has anti-tumor， anti-fibrosis， and immunity-enhancing effects and thus is widely used for the treatment of liver fibrosis， hepatitis， liver injury， and other diseases. In recent years， accumulating evidence has proven the efficacy of this formula in the treatment of malignant tumors， especially liver cancer. This paper summarizes relevant papers in the last 20 years and summed up the anti-liver cancer mechanisms of Biejiajian Wan as regulating biological behaviors of liver cancer cells， anti-precancerosis， inhibiting tumor angiogenesis， modulating signaling pathways， suppressing activity of relevant enzymes， and regulating immunity. Moreover， this prescription can inhibit the proliferation， invasion， and metastasis of liver cancer cells， promote apoptosis of cells， suppress tumor angiogenesis， and boost immunity. In addition， it regulates Wnt/β-catenin， interleukin-6/signal transducer and activator of transcription 3 （IL-6/STAT3）， NOD-like receptor protein 3 （NLRP3）， Janus kinase-signal transducers and activators of transcription （JAK-STAT）， Delta-like ligand 4-Notch （DLL4-Notch）， nuclear factor-κB （NF-κB）， Rho-associated kinase （Rho/ROCK）， transforming growth factor-β/Smad （TGF-β/Smad）， phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase-3β （PI3K/Akt/GSK-3β）， and other signaling pathways. Thus， Biejiajian Wan is confirmed to have anti-liver cancer effect based on the molecular mechanisms. According to the summary of Biejiajian Wan in anti-liver cancer treatment， Biejiajian Wan alone or in combination with other drugs can significantly alleviate the symptoms， reduce adverse reactions， prolong the survival time with definite efficacy. Thus， it is safe with no adverse reactions in long-term use， which should be further promoted in clinical application. This paper analyzed Biejiajian Wan in the treatment of liver cancer based on the molecular mechanisms and clinical studies， summarized the limitations in current research， and put forward suggestions， which can lay a basis for the future in-depth research on and clinical application of Biejiajian Wan and development of anti-tumor drugs.

Minutes of seminar on 2023 multi-center cooperation project of liver transplantation for metastatic liver cancer in China / 器官移植

Led by Zheng Shusen, Academician of Chinese Academy of Engineering (CAE) from Zhejiang University, the first multi-center cooperation project of liver transplantation for metastatic liver cancer in China, gathering 28 liver transplantation centers nationwide, was launched in Shanghai. All participating experts conducted in-depth exchanges and discussions regarding four topics including inclusion criteria of liver transplantation for metastatic liver cancer, the risk assessment and prognostic evaluation of liver transplantation for metastatic liver cancer, perioperative medication of liver transplantation for metastatic liver cancer, and the implementation details of multi-center cooperation project. Questionnaires were distributed to reach consensus and pinpoint the directions, aiming to carry out high-quality and standardized clinical researches on liver transplantation for metastatic liver cancer in China.

Clinical observation of Ruyi jinhuang powder combined with ICIs in the treatment of advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder / 中国药房

OBJECTIVE To explore the clinical efficacy and safety of Ruyi jinhuang powder for external application combined with immune checkpoint inhibitors （ICIs） in the treatment of patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder. METHODS All patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder were admitted to our hospital from January 2018 to June 2022 and assigned into observation group and control group according to random number table method. Patients in the control group （n＝56） were treated with ICIs （Navulizumab injection/Sintilimab injection/Camrelizumab for injection） 200 mg， ivgtt， 21 days as a treatment cycle. Patients in the observation group （n＝56） were additionally treated with Ruyi jinhuang powder for external application， once a day， on the basis of control group. The therapeutic effects of 2 groups were compared after a treatment cycle. The levels of interleukin-6 （IL- 6）， matrix metalloproteinase-9 （MMP-9）， cyclooxygenase-2 （COX-2）， prostaglandin E2 （PGE2）， carbohydrate antigen 199 （CA199）， alpha-fetoprotein （AFP） and vascular endothelial growth factor （VEGF） in serum were compared between 2 groups before and after treatment. Karnofsky functional status （KPS） score， digital rating scale （NRS） score， total symptom score of traditional Chinese medicine， and the occurrence of adverse reactions were recorded for both groups of patients. RESULTS After treatment， the levels of IL-6， MMP-9， COX-2， PGE2， CA199， AFP， VEGF， NRS score and total symptom score of traditional Chinese medicine in observation group were significantly lower than control group （P＜0.05）， KPS score was significantly higher than the control group （P＜0.05）. The zypp-04） total effective rate and remission rate of the observation group were 64.29% and 80.36%， those of control group were 60.71% and 73.21%. There was no statistical significance between two groups （P＞0.05）. The adverse drug reactions of both groups were mainly nausea and vomiting， liver function injury， fever hlshli@yeah.net and so on； the incidence of adverse reaction in observation group was significantly lower than that of control group （P＜0.05）. CONCLUSIONS In patients with advanced liver cancer complicated with dampness and heat syndrome of liver and gallbladder， the combination of Ruyi jinhuang powder for external application and ICIs can help inhibit the secretion of pain mediators， regulate vascular endothelial function， reduce the inflammatory response， promote the recovery of cardiopulmonary function， improve clinical efficacy and has good safety.