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.

Mechanism of Shenqi Yiliu Prescription Combined with Cisplatin on H22 Liver Cancer-bearing Mice Based on NLRP3/Caspase-1/GSDMD Pyroptosis Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10-3 g·kg-1·（3 d）-1］， Shenqi Yiliu prescription group （27 g·kg-1·d-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.

Clinical Effect of Fangfeng Tongshengsan on Post-chemoembolization Syndrome with Primary Liver Cancer or Postoperative Liver Metastases of Colorectal Cancer / 中国实验方剂学杂志

ObjectiveTo observe the effect of the Fangfeng Tongshengsan on post-chemoembolization syndrome with primary liver cancer or postoperative liver metastases of colorectal cancer. MethodSeventy-two patients suffered from post-chemoembolization syndrome after transcatheter hepatic arterial chemoembolization were randomly divided into 2 groups， including a Fangfeng Tongshengsan group and a control group， with 36 patients in each group. The patients in Fangfeng Tongshengsan group orally took the decoction for consecutive 7 d. The patients in the control group were physically cooled down with alcohol rub bath and ice pack for consecutive 7 d. Furthermore， the difference of fever， Karnofsky performance status （KPS）， pain in the liver region， nausea vomiting， constipation， and liver function between these two groups were observed. ResultCompared with the control group， Fangfeng Tongshengsan significantly relieved fever， reduced the body temperature （P<0.05）， and shortened the duration of fever （P<0.05）， indicating that Fangfeng Tongshengsan remarkably improved the KPS （P<0.05）. Meanwhile， Fangfeng Tongshengsan obviously alleviated nausea， vomiting， and constipation status and shortened the duration time compared with the control group （P<0.05）. In addition， the parameters of liver function including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptidase （GGT）， and total bilirubin （TBIL） were significantly decreased in the Fangfeng Tongshengsan group （P<0.05）， which indicated that Fangfeng Tongshengsan alleviated liver dysfunction of patients with post-chemoembolization syndrome. ConclusionFangfeng Tongshengsan can be used to treat post-chemoembolization syndrome with primary liver cancer and postoperative liver metastases of colorectal cancer.

Basic and Clinical Research Progress of Immunotherapy for Hepatocellular Carcinoma / 肿瘤防治研究

Primary liver cancer, especially hepatocellular carcinoma, poses a serious threat to the life and health of the Chinese people. Given the insidious onset of liver cancer, less than 30% of hepatocellular carcinoma patients are considered for radical treatment at the initial diagnosis. Systemic anti-tumor therapy plays an important role in the treatment of advanced hepatocellular carcinoma. Immunotherapy of hepatocellular carcinoma has developed rapidly, and an increasing number of immunotherapy drugs, which can better control the progress of hepatocellular carcinoma and prolong the survival of patients, have become first- and second-line treatment options. This article reviews briefly the progress of immunotherapy for hepatocellular carcinoma in recent years.

Efficacy Evaluation of Biejiajianwan in the Treatment of Primary Liver Cancer Based on Real-world Data of Traditional Chinese Medicine / 中国实验方剂学杂志

ObjectiveTo evaluate the efficacy and influencing factors of Biejiajianwan in the treatment of primary liver cancer based on real-world data of traditional Chinese medicine （TCM）. MethodClinical diagnosis and treatment data of patients with primary liver cancer admitted to five Grade-A tertiary hospitals in Henan Province from January 2015 to December 2020 were collected from the medical electronic database. The patients treated with Biejiajianwan for ≥30 days were assigned to the exposure group and those without treatment with Biejiajianwan or treated with Biejiajianwan for <30 days to the non-exposure group. The propensity score matching model was used to balance confounding factors between the two groups according to the 1∶1 genetic matching method. Kaplan-Meier method was used for survival analysis and survival curve plotting. Log-rank was used to test the difference in survival rate between the two groups. Univariate analysis of Biejiajianwan in the treatment of primary liver cancer was performed by Log-rank test combined with the Kaplan-Meier method. The factors with statistical significance （P<0.05） were combined with unbalanced factors by the propensity score matching model， and at the same time， clinical common sense and relevant prognostic factors by literature search were considered， which were subjected to multivariate analysis by Cox proportional hazards regression model. ResultA total of 2 207 electronic cases were collected，including 174 cases in the exposure group （Biejiajianwan group） and 2 033 cases in the non-exposure group. After propensity score matching， there were 174 cases in the exposure group and 174 cases in the non-exposure group. The Kaplan-Meier method was used for survival analysis on the matched data， and the Log-rank test results showed that the survival rate of patients with primary liver cancer in the Biejiajianwan group was higher than that in the control group （χ2=12.193， P<0.01）. Cox proportional hazards regression model analysis showed that the regression coefficient of Biejiajianwan was -0.916 4 with the hazard ratio （HR） ［95% confidence interval （CI）］=0.4 （0.239 5-0.668 0）， P<0.01， and the regression coefficient of radiofrequency ablation treatment was -0.976 5 with HR （95% CI）=0.376 6 （0.172 8-0.821 1， P<0.05）. Fibrinogen （FIB） abnormal regression coefficient was 0.481 4 with HR （95% CI）=1.618 4（1.022 0-2.562 9），P<0.05. ConclusionBiejiajianwan can prolong the survival period of patients with primary liver cancer. Radiofrequency ablation is an independent protective factor for Biejiajianwan in the treatment of primary liver cancer，while abnormal FIB are independent risk factors for Biejiajianwan in the treatment of primary liver cancer.

Research progress in the preoperative radiotherapy and immunotherapy for primary liver cancer / 中华放射医学与防护杂志

Liver cancer is one of the most common cancers in China. In recent years, liver cancer tends to be treated with comprehensive therapies, including surgery, ablation, interventional embolization, radiotherapy, chemotherapy, targeted therapy, immunotherapy, and liver transplantation. At present, the low surgical resectionrate is one of the main factors affecting the prognosis of liver cancer patients. Preoperative neoadjuvant therapy or conversion therapy for liver cancer can maximize the rate of surgical resection and improve the prognosis. With the rapid development of radiotherapy and immunotherapy in the comprehensive treatment of liver cancer, it has been gradually confirmed that the unique effects of preoperative radiotherapy and immune therapy for liver cancer can improve the prognosis of the patients. Therefore, this paper reviewed the research progress in the preoperative radiotherapy and immunotherapy for liver cancer by searching relevant literature and reports at home and abroad.

Influencing factors of learned helplessness in patients with primary liver cancer treated by interventional therapy / 中国实用护理杂志

Objective:To investigate the influencing factors of learned helplessness in patients with primary liver cancer treated by interventional therapy.Methods:This study was a cross-sectional study. The 221 patients with primary liver cancer treated by interventional therapy in the Second Affiliated Hospital of Air Force Military Medical University from August 2020 to October 2021 were selected as the subjects. General data statistics, Learned Helplessness Scale and Support in Intimate Relationships Rating Scale were used for questionnaire survey.Results:The total score of learned helplessness in the 221 patients with primary liver cancer treated by interventional therapy was 74.12 ± 6.55. Gender, education level, family per capita monthly income, number of interventions and perceived spouse support were the main influencing factors of learned helplessness in patients with primary liver cancer treated by interventional therapy (adjusted R2=0.891, F=65.65, P<0.05). Conclusions:The sense of learned helplessness of patients with primary liver cancer treated by interventional therapy is at a high level. According to patients with features of male, lower education level, lower family per capita monthly income, more number of interventional therapy or lower perceived spouse support, medical staff can use dialectical behavior therapy, symptom group intervention, spouse support intervention and other methods to reduce learned helplessness of patients.

Medication rule of TCM patent compound prescriptions for the treatment of primary liver cancer based on data mining / 国际中医中药杂志

Objective:To analyze the medication rule of TCM compound prescription in the treatment of Primary Liver Cancer (PLC) in the National Patent Database by the method of data mining.Methods:By searching for the compound prescriptions of TCM which were included in the National Patent Retrieval Platform for the treatment of PLC, and analyzing the frequency, association and cluster of those included compound prescriptions through the inheritance and assistance platform of TCM.Results:A total of 350 patent prescriptions for the treatment of PLC were included, involving 425 Chinese medicines; the top 10 frequently appeared herbal medicines were Hedyotis diffusa, Radix Astragali, Scutellaria barbata, Atractylodes macrocephala, Glycyrrhiza uralensis, Ginseng, Radix Bupleuri, Rhizoma Curcumae, Salvia miltiorrhiza and Angelica sinensis; according to the function of those medicines, the top three frequently appeared herbal medicines were those with deficiency-tonifying heat-clearing and detoxifying, promoting blood circulation and removing blood stasis functions; the property of the medicine were mainly cold, warm and mild; the taste of the medicine were mainly bitter, sweet and acrid; the meridians of the medicines mainly belong to liver, spleen and lung. It was found that there were 12 association rules, and the medicine pair that were closely correlated was " Hedyotis diffusa- Scutellaria barbata", and the most frequently appeared medicines could be grouped into 8 groups. Conclusions:The TCM patent compound prescriptions mainly play the role of replenishing qi and invigorating the spleen, supplemented by the products of clearing heat and detoxification, activating blood circulation and removing blood stasis, which is consistent with the basic treatment principle of PLC "invigorate the upright and dispel the evil, attack the evil and tonify the body". This study explores the basic medication rules of TCM patent compound prescription in the treatment of PLC, in order to provide guidance for clinical practice.

Exploration of the therapeutic mechanism of Yiqi Jiedu recipe for treatment of primary liver cancer based on network pharmacology and molecular docking / 南方医科大学学报

OBJECTIVE@#To explore the effective components of Yiqi Jiedu recipe and the main biological processes and signal pathways involved in the therapeutic mechanism of the recipe in treatment of primary liver cancer through network pharmacology and molecular docking approaches.@*METHODS@#TCMSP, Uniport, Genecards and String databases were searched to obtain the target genes of drugs and disease using Cytoscape 3.8.2 software. GO and KEGG enrichment analyses were performed to identify the common genes in the target genes of the drugs and disease. Using Pubcham, RCSB and Autoduck, the effective components of the drugs were connected with the final core genes. The effects of different concentrations of Yiqi Jiedu recipe on the expressions of the core genes DHX9, HNRNPK, NCL and PABPC1 in HepG2 cells were analyzed with Western blotting and real- time fluorescence quantitative PCR.@*RESULTS@#We finally identified 8 core genes from the drug and disease targets, including DDX5, HNRNPK, PABPC1, DHX9, RPS3A, RPS3, RPL13, and NCL. GO analysis showed that these core genes were involved mainly in the biological processes of adrenaline receptor signal communication, movement of cellular or subcellular components, blood particles, adhesion class and iron ion binding. KEGG analysis showed that the Ras signaling pathway had the greatest gene enrichment. The results of molecular docking suggested that the effective components of the recipe were capable of docking with the core genes under natural conditions, and PABPC1 and stigmasterol had the highest binding energy. In HepG2 cells, treatment with 10% medicated serum for 48 h had the strongest effect on the expression of DHX9, HNRNPK, NCL and PABPC1 (P < 0.05).@*CONCLUSION@#Yiqi Jiedu recipe is capable of regulating viral expression of primary liver cancer multiple effective components that bind to DHX9, HNRNPK, NCL and PABPC1.

Data Mining and Systems Pharmacology to Elucidate Effectiveness and Mechanisms of Chinese Medicine in Treating Primary Liver Cancer / 中国结合医学杂志

OBJECTIVE@#To identify specific Chinese medicines (CM) that may benefit patients with primary liver cancer (PLC), and to explore the mechanism of action of these medicines.@*METHODS@#In this retrospective, singlecenter study, prescription information from PLC patients was used in combination with Traditional Chinese Medicine Inheritance Supports System to identify the specific core drugs. A system pharmacology approach was employed to explore the mechanism of action of these medicines.@*RESULTS@#Taking CM more than 6 months was significantly associated with improved survival outcomes. In total, 77 putative targets and 116 bioactive ingredients of the core drugs were identified and included in the analysis (P<0.05). A total of 1,036 gene ontology terms were found to be enriched in PLC. A total of 75 pathways identified from Kyoto Encyclopedia of Genes and Genomes were also enriched in this disease, including fluid shear stress, interleukin-17 signaling, signaling between advanced glycan end products and their receptors, cellular senescence, tumor necrosis factor signaling, p53 signaling, cell cycle signaling, steroid hormone biosynthesis, T-helper 17 cell differentiation, and metabolism of xenobiotics by cytochrome. Docking studies suggested that the ingredients in the core drugs exert therapeutic effects in PLC by modulating c-Jun and interleukin-6.@*CONCLUSIONS@#Receiving CM for 6 months or more improves survival for the patients with PLC. The core drugs that really benefit for PLC patients likely regulates the tumor microenvironment and tumor itself.

Relationship between hepatitis B virus genotyping and primary hepatocellular carcinoma of 182 patients / 公共卫生与预防医学

Objective To analyze the relationship between hepatitis B virus genotyping and primary liver cancer (PHC) in Wuhan, and to provide a theoretical basis for the early prevention and diagnosis of PHC. Methods Patients with chronic hepatitis B (CHB) from Wuhan Sub-heart General Hospital for treatment from February 2020 to February 2021 were selected and divided into PHC group (182 cases) and control group (189 cases) according to whether they were complicated with primary liver cancer. 5ml of fasting elbow venous blood was taken from all subjects at admission. HBV genotyping was determined by real-time fluorescence quantitative PCR. The DNA of CHB virus was determined by fluorescence probe hybridization and PCR amplification, and genotyping and drug-resistant mutation points were detected according to the product sequencing analysis. Spearman linear correlation analysis was used to analyze the correlation between genotyping and mutation rate of PHC patients. Results The proportion of C genotype in PHC group was significantly higher than that in non-PHC group (P0.05). The proportion of HEPATITIS B virus mutation in PHC group (114/182) was significantly higher than that in control group (84/189) (χ2=12.331, P0.05). The proportion of HBV C mutant in PHC group was significantly higher than that in control group (P1=0.349, r2=0.305, P<0.05). Conclusion The HBV genotype of PHC patients is mainly TYPE C, and has a high mutation rate of C genotype. It can be used for diagnosis of PHC by detecting the genotyping of CHB and mutation rate of C genotype in clinic.

Impact of nonsteroidal anti-inflammatory drugs on efficacy of anti-PD-1 therapy for primary liver cancer / 南方医科大学学报

OBJECTIVE@#To assess the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical outcomes of patients receiving anti-PD-1 immunotherapy for hepatocellular carcinoma.@*METHODS@#We conducted a retrospective study among 215 patients with primary liver cancer receiving immunotherapy between June, 2018 and October, 2020. The patients with balanced baseline characteristics were selected based on propensity matching scores, and among them 33 patients who used NSAIDs were matched at the ratio of 1∶3 with 78 patients who did not use NSAIDs. We compared the overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) between the two groups.@*RESULTS@#There was no significant difference in OS between the patients using NSAIDs (29.7%) and those who did not use NSAIDs (70.2%). Univariate and multivariate analyses did not show an a correlation of NSAIDs use with DCR (univariate analysis: OR=0.602, 95% CI: 0.299-1.213, P=0.156; multivariate analysis: OR=0.693, 95% CI: 0.330-1.458, P=0.334), PFS (univariate analysis: HR=1.230, 95% CI: 0.789-1.916, P=0.361; multivariate analysis: HR=1.151, 95% CI: 0.732-1.810, P=9.544), or OS (univariate analysis: HR=0.552, 95% CI: 0.208-1.463, P=0.232; multivariate analysis: HR=1.085, 95% CI: 0.685-1.717, P=0.729).@*CONCLUSION@#Our results show no favorable effect of NSAIDs on the efficacy of immunotherapy in patients with advanced primary liver cancer, but this finding still needs to be verified by future prospective studies of large cohorts.

Plasma levels of soluble immune checkpoint molecules and their prognostic significance in patients with primary liver cancer / 中华微生物学和免疫学杂志

Objective:To analyze the plasma levels of soluble immune checkpoint molecules in patients with primary liver cancer and their prognostic significance.Methods:The levels of sCD28, sCD80, sCD137, sCD27, sGITR, sTIM3, sCTLA4, sHVEM, IDO, sLAG3, sBTLA, sPD1, sPDL1 and sPDL2 in plasma samples of 58 patients with primary liver cancer and 30 healthy controls were detected by liquid chip technology and compared between different groups. The relationship between the plasma levels of soluble immune checkpoint molecules and tumor recurrence was analyzed.Results:The levels of sCD28 and sCD80 were higher in patients in Barcelona Clinic Liver Cancer (BCLC) stage 0/A and B than in healthy controls and patients in BCLC-C stage ( P<0.05). However, the levels of sCD27 and sHVEM in BCLC-C patients were significantly lower than those in BCLC-0/A and BCLC-B patients, and even lower than healthy control group. The levels of sCD137, IDO and sPD1 in BCLC-0/A and BCLC-B patients were higher than those in healthy controls. The levels of sPDL1 and sPDL2 in different BCLC stages were all higher than those in healthy controls, and maintained at high level in the three stages, but there was no significant difference between different stages. After 24 months of interventional treatment, the preoperative sCD28 level was lower in patients with recurrent tumor recurrence than in patients without recurrence ( t=2.843, P=0.007). The optimal cut-off value of sCD28 based on the receiver operating characteristic (ROC) curve for predicting tumor recurrence was 101.42 pg/ml and the area under the ROC curve was 0.771 (95%CI: 0.611-0.931) with a sensitivity of 0.889 and a specificity of 0.666. The cumulative recurrence rate in patients with high sCD28 level (≥101.41 pg/ml) was 57.9% at 24 months after surgery, which was lower than the rate (95.5%) in patients with low sCD28 level (<101.41 pg/ml). The difference in the cumulative recurrence rate between the two groups was statistically significant (χ 2=15.777, P=0.000). Conclusions:The expression patterns of soluble immune checkpoint molecules varied in patients at different stages of primary liver cancer, suggesting that there were differences in their immune status and sCD28 could be used as a prognostic marker for postoperative recurrence of liver cancer.

Mortality analysis of primary liver cancer in the mainland of China from 2004 to 2018 / 上海预防医学

Objective:To determine the mortality and changing trend of primary liver cancer by using the death data of Chinese mainland from 2004 to 2018. Methods:The death certificate data was collected from China National Mortality Surveillance System from 2004 to 2018. The crude mortality rate（CMR）and age-standardized mortality rate（ASMR）of primary liver cancer in different ages， regions and living environments were calculated by Joinpoint regression model to analyze the basic situation and mortality trend. Results:From 2004 to 2018， there were 556 241 primary liver cancer deaths in China， with a CMR of 25.18/105 and an ASMR of 17.98/105. It suggested that the mortality of primary liver cancer was on a decreasing trend. During the 15 years， the ASMR of primary liver cancer was 15.56/105 in urban areas and 19.29/105 in rural areas. In urban areas， CMR was 32.89/105 in males and 12.14/105 in females， respectively； while in rural areas， CMR was 38.39/105 in males and 14.02/105 in females， respectively. The CMR in eastern， central and western urban regions was 22.25/105， 22.66/105 and 23.50/105， respectively. The CMR in the rural areas of these three regions was 27.82/105， 26.98/105 and 23.85/105， respectively. The patients were divided into four age groups： 0-19 years old， 20-39 years old， 40-59 years old， and more than 60 years old. The CMR of four groups in urban areas was 0.14/105， 2.59/105， 24.51/105 and 91.80/105. In rural areas， the CMR of four groups was 0.17/105， 4.05/105， 32.16/105 and 103.02/105. Conclusion:From 2004 to 2018， the mortality rate of liver cancer in China has a decreasing trend. However， the primary liver cancer death burden is still serious because of the large population base， severe aging population problem， and significant urban-rural and male-female disparities in China.

Application of an extreme learning machine network with particle swarm optimization in syndrome classification of primary liver cancer / 中西医结合学报

OBJECTIVE@#By optimizing the extreme learning machine network with particle swarm optimization, we established a syndrome classification and prediction model for primary liver cancer (PLC), classified and predicted the syndrome diagnosis of medical record data for PLC and compared and analyzed the prediction results with different algorithms and the clinical diagnosis results. This paper provides modern technical support for clinical diagnosis and treatment, and improves the objectivity, accuracy and rigor of the classification of traditional Chinese medicine (TCM) syndromes.@*METHODS@#From three top-level TCM hospitals in Nanchang, 10,602 electronic medical records from patients with PLC were collected, dating from January 2009 to May 2020. We removed the electronic medical records of 542 cases of syndromes and adopted the cross-validation method in the remaining 10,060 electronic medical records, which were randomly divided into a training set and a test set. Based on fuzzy mathematics theory, we quantified the syndrome-related factors of TCM symptoms and signs, and information from the TCM four diagnostic methods. Next, using an extreme learning machine network with particle swarm optimization, we constructed a neural network syndrome classification and prediction model that used "TCM symptoms + signs + tongue diagnosis information + pulse diagnosis information" as input, and PLC syndrome as output. This approach was used to mine the nonlinear relationship between clinical data in electronic medical records and different syndrome types. The accuracy rate of classification was used to compare this model to other machine learning classification models.@*RESULTS@#The classification accuracy rate of the model developed here was 86.26%. The classification accuracy rates of models using support vector machine and Bayesian networks were 82.79% and 85.84%, respectively. The classification accuracy rates of the models for all syndromes in this paper were between 82.15% and 93.82%.@*CONCLUSION@#Compared with the case of data processed using traditional binary inputs, the experiment shows that the medical record data processed by fuzzy mathematics was more accurate, and closer to clinical findings. In addition, the model developed here was more refined, more accurate, and quicker than other classification models. This model provides reliable diagnosis for clinical treatment of PLC and a method to study of the rules of syndrome differentiation and treatment in TCM.

Network Meta-analysis of oral Chinese patent medicine for adjuvant treatment of primary liver cancer / 中国中药杂志

Network Meta-analysis was used to evaluate the efficacy and safety of different oral Chinese patent medicines combined with transcatheter arterial chemoembolization(TACE) in the treatment of primary liver cancer. Randomized controlled trials of oral Chinese patent medicines for primary liver cancer were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library and EMbase databases from inception to May 2020. According to the Cochrane recommendation standard, the quality of the included articles was evaluated, and the data were analyzed by RevMan, R software and GeMTC software. A total of 10 kinds of oral Chinese patent medicines and 68 RCTs were included. Network Meta-analysis results showed that: as compared with TACE alone, 10 kinds of oral Chinese patent medicines combined with TACE showed advantages in effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence. In the pairwise comparison of oral Chinese patent medicines, the results showed that Cidan Capsules were superior to Jinlong Capsules and Xihuang Pills in 1-year survival rate. According to the probabi-lity ranking results: Shenyi Capsules and Ganfule were more obvious in improving the effective rate; Cidan Capsules and Shenyi Capsules were more effective in improving the 1-year survival rate; Pingxiao Capsules and Shenyi Capsules had better efficacy in improving 2-year survival rate; Huaier Granules and Shenyi Capsules had better efficacy in improving the quality of life; Huisheng Oral Liquid and Ganfule were more effective in reducing the incidence of adverse reactions(such as nausea, vomiting and leukocytosis). The current evidence showed that oral Chinese patent medicine combined with TACE was superior to TACE alone in efficacy and safety. In terms of the effective rate, 1-year survival rate, 2-year survival rate, KPS score improvement rate and reduced adverse reaction incidence, the optimal treatment measures were Shenyi Capsules, Cidan Capsules, Pingxiao Capsules, Huaier Granules and Huisheng Oral Liquid in turn. However, due to the limitations of the research, the current level of evidence is not high, and clear conclusions and evi-dence strength still need to be further verified and improved by high-quality researches.

Systematic evaluation of Huaier Granules adjuvant treatment of primary liver cancer / 中国中药杂志

To systematically evaluate the efficacy and safety of Huaier Granules in the adjuvant treatment of primary liver cancer. The databases of CNKI, Wanfang, VIP, CBMdisc, PubMed, Cochrane Library and EMbase were searched by computer to screen out the randomized controlled trial on Huaier Granules combined with Western medicine in the treatment of primary liver cancer from the establishment of the databases to January 2020. Data extraction and quality evaluation were conducted for the included literature. Meta-analysis was conducted with RevMan 5.3 software, and evidence quality evaluation was conducted for the outcomes by GRADE profiler software. A total of 24 articles were included, with a total sample size of 2 664 cases. Meta-analysis showed that as compared with Western medicine alone, Huaier Granules combined with Western medicine could improve the objective remission rate(RR=1.38, 95%CI[1.26, 1.51], P<0.000 01), disease control rate(RR=1.29, 95%CI[1.10, 1.52], P=0.002) and 6-month survival rate(RR=1.20, 95%CI[1.10, 1.32], P<0.000 1), 1-year survival rate(RR=1.39, 95%CI[1.23, 1.58], P<0.000 01), 2-year survival rate(RR=1.95, 95%CI[1.28, 2.96], P=0.002), KPS score(MD=17.15, 95%CI[6.47, 27.83], P=0.002) and the improvement rate of KPS score(RR=2.02, 95%CI[1.47, 2.77], P<0.000 1), AFP decline rate(RR=1.40, 95%CI[1.20, 1.62], P<0.000 1), CD3~+(MD=17.34, 95%CI[9.28, 25.40], P<0.000 1), CD4~+(MD=8.62, 95%CI[1.59, 15.64], P=0.02), CD8~+(MD=1.95, 95%CI[-3.93, 7.82], P=0.52), CD4~+/CD8~+(MD=0.42, 95%CI[-0.33, 1.17], P=0.27); reduce the level of AFP(MD=-71.57, 95%CI[-80.42,-62.72], P<0.000 01), recurrence rate(RR=0.76, 95%CI[0.67, 0.85], P<0.000 01), and incidence of adverse reactions(RR=0.60, 95%CI[0.41, 0.89], P=0.01) in patients with primary liver cancer. According to the GRADE system, the evidence for outcome measures was low to very low. The results show that Huaier Granules have certain efficacy and high safety in adjuvant treatment of primary liver cancer, but its effect in reducing adverse reactions and improve immunity remains to be verified. Due to the poor quality of the included studies and evidences, the conclusions still need to be further verified by multi-center, large sample, and randomized double-blind controlled studies.

Effect of Dahuang Zhechong Pills combined with TACE on VEGF, MMP-2, TGF-β1 and immune function of patients with primary liver cancer (blood stasis and collaterals blocking type) / 中国中药杂志

To investigate the effects of Dahuang Zhechong Pills combined with hepatic arterial chemoembolization(TACE) on tumor index and immune function of patients with primary liver cancer(blood stasis and collaterals blocking type), observe its application values in treatment of such patients, and provide effective treatment means for this disease. From June 2019 to December 2019, 79 patients with confirmed primary liver cancer(blood stasis and collaterals blocking type) treated in Wenzhou Hospital of Traditional Chinese Medicine were included in this study, all of which were grouped with random number table method before inclusion in this study. 40 patients in the control group were treated with TACE, while 39 patients in the observation group were treated with Dahuang Zhechong Pills combined with TACE. The efficacy was compared between two groups after 4 weeks of treatment. The immune function indexes of serum CD4~+ cells, CD4~+/CD8~+, CD3~+ cells of the observation group were higher than those in control group after treatment(P<0.05), and tumor indexes such as serum alpha-fetoprotein(AFP), carbohydrate antigen 199(CA199) and glutamic-pyruvic transaminase(ALT), total bilirubin(TBiL) levels were lower than those in the control group, with statistically significant differences(P<0.05). Plasma vascular endothelial growth factor(VEGF), transforming growth factor-β1(TGF-β1), and matrix metalloprotei-nase-2(MMP-2) levels in the observation group were lower than those in the control group after treatment, with statistically significant differences(P<0.05). The total effective rate of the observation group was 87.18%, higher than 67.50% in the control group, and the benefit rate was 94.87% in the observation group, higher than 85.00% in the control group(P<0.05). The total incidence of adverse reactions such as bone marrow suppression, gastrointestinal reaction, fever, renal function injury and peripheral nerve injury in the observation group was 48.72%, lower than 82.50% in the control group, with statistically significant difference(P<0.05). In summary, the combination of Dahuang Zhechong Pills with TACE could improve immunity, protect liver function, and reduce the risk of metastasis and the incidence of adverse reactions from chemotherapy, so it is worth popularizing for patients with primary liver cancer(blood stasis and collaterals blocking type).

Effect of 1M3S nursing management mode combined with interventional surgery on intestinal microecological distribution in patients with primary liver cancer / 中国实用护理杂志

Objective:To investigate the effect of 1M3S nursing management mode combined with transcatheter arterial chemoembolization (TACE) on intestinal microecological distribution in patients with primary liver cancer.Methods:A total of 115 patients with primary liver cancer in Hai′an people′s Hospital from January 2017 to January 2020 were enrolled. Patients were divided into two groups according to the admission time. Patients ( n=56) receiving routine nursing care from January 2017 to December 2018 were set as control group, patients ( n=59) receiving 1M3S nursing management from January 2019 to January 2020 were set as observation group. Another 34 healthy individuals were set as healthy group from January 2017 to January 2020 in Hai′an People′s Hospital. The general data were collected in all three groups, and the serum levels of endotoxin (ET), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Fecal samples were collected, and 16S rDNA sequencing method was used to analyze the fecal flora structure and species relative abundance among groups, and alpha diversity was analyzed. Results:At the level of phylum, the dominant phylum of the three groups were Bacteroidetes, Proteobacteria and Firmicutes. After TACE, the ET, ALT and AST levels were (9.67±2.12) ng/L, (53.24±8.47) U/L, (55.48±8.15) U/L in the control group, (4.36±2.15) ng/L, (45.31±8.36) U/L, (47.25±8.21) U/L in the observation group ( t value was 13.328, 5.052, 5.392, P<0.05). Compared with the control group, there was an increase in the relative abundance percentage of Firmicutes( t value was 16.426, P<0.01) and Lachnospiraceae in the observation group ( t value was 4.527, P<0.01), and a decrease in the relative abundance percentage of Proteobacteria ( t value was 8.462, P<0.001) after intervention. Conclusions:TACE can affect the intestinal bacteria in patients with primary liver cancer, resulting in a decrease in the relative abundance of Proteobacteria, Lachnospiraceae, and an increase in the relative abundance of Firmicutes, while application of 1M3S nursing management mode can effectively reduce the level of endotoxin, improve liver function, and reduce the imbalance of intestinal flora caused by TACE.

Data Mining-Based Macroscopic Exploration of Clinical Medication of Chinese Medicine for Liver Cancer / 中国实验方剂学杂志

Objective:To explore the macroscopic medication rule of Chinese medicine for the treatment of primary liver cancer and provide references for clinical medication. Method:The databases of CNKI，VIP， and Wanfang Data were searched for research articles published from September 1959 to June 2019 with the terms of "Chinese medicine" and "liver cancer". A database was established based on the collected Chinese medicinal prescriptions for the treatment of primary liver cancer. The frequency，clustering， and association rules were analyzed by Excel， etc. Result:In this study，106 effective articles were included，and after the modified prescriptions were removed， 92 effective prescriptions were screened out，involving 281 Chinese herbal medicines used for 1 181 times in total. The top 5 high-frequency drugs were Poria （deficiency-tonifying），Astragali Radix （heat-clearing），Bupleuri Radix （blood-activating and stasis-resolving），Paeoniae Radix Alba （urination-promoting and dampness-draining）， and Codonopsis Radix （Qi-regulating）. The analysis of drug flavor with a frequency higher than 10 showed that most of the drugs were sweet，bitter， and pungent in flavor，cold，warm， and plain in nature，and acted on spleen and liver meridians. Four combinations and 10 herbal pairs were obtained by the cluster analysis of high-frequency drugs and association analysis， respectively. The high-frequency drugs and potential herbal pairs were classified targeting the specific clinical syndromes in different stages of liver cancer. Conclusion:Replenishing Qi， invigorating spleen，clearing heat， removing toxin，activating blood， and resolving stasis were the basic principles for the treatment of primary liver cancer. The combination of those drugs was the main therapeutic strategy. In addition，the resulting 10 potential herbal pairs from high-frequency drugs and cluster analysis could inspire the clinical treatment of primary liver cancer in different clinical stages with various clinical syndromes， which was of reference value for the clinical medication.