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.

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.

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.

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.

Role of PD-1/PD-L1 signaling pathway in immune response of liver transplantation / 器官移植

Primary liver cancer (liver cancer) is one of the main indications of liver transplantation. However, postoperative recurrence of liver cancer severely affects the long-term clinical efficacy of liver transplantation. Programmed cell death protein 1 (PD-1) is an immunosuppressive molecule. Activation of PD-1/programmed cell death protein-ligand 1 (PD-L1) signaling pathway plays a pivotal role in the immune tolerance of grafts. In recent years, immune checkpoint inhibitor(ICI), such as PD-1/PD-L1 inhibitor, has become one of the effective approaches to treat advanced liver cancer, whereas ICI can be applied in liver transplant recipients is highly controversial, and the efficacy and safety remain to be studied. In this article, the expression of PD-1/PD-L1 in liver allograft tissues, the mechanism of PD-1/PD-L1 inducing transplantation immune tolerance and clinical application of PD-1/PD-L1 inhibitor in liver transplantation for liver cancer were reviewed.

Safety of PD-1 inhibitor in preoperative treatment of liver transplantation for liver cancer / 器官移植

Objective To evaluate the safety of programmed cell death protein 1 (PD-1) inhibitor in the treatment of primary liver cancer (liver cancer) before liver transplantation. Methods Clinical data of 7 recipients given with PD-1 inhibitor before liver transplantation for liver cancer were retrospectively analyzed. The incidence of immune-related adverse event (irAE) and clinical prognosis of the recipients were summarized. The safety of PD-1 inhibitor in recipients prior to liver transplantation for liver cancer was evaluated. Results Seven recipients were treated with PD-1 inhibitor with 1-20 courses before liver transplantation for liver cancer. The time interval from drug withdrawal to liver transplantation was 6-120 d. Five recipients suffered from irAE of different degrees, including fatigue in 3 cases, fever in 2 cases, alopecia in 2 cases, rash in 1 case, nausea in 1 case and myocarditis in 1 case, respectively. A majority of these irAE were classified as grade Ⅰ-Ⅱ. One recipient died from grade Ⅴ irAE (fatal myocarditis). One recipient developed rejection at postoperative 7 d, which were mitigated after glucocorticoid pulse therapy combined with increased dosage of tacrolimus. Conclusions PD-1 inhibitor can be applied in preoperative treatment before liver transplantation for liver cancer. Nevertheless, the incidence of irAE and postoperative rejection should be intimately monitored.

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.

Primary liver cancer complicated by hepatic cystic echinococcosis: a case report / 中国血吸虫病防治杂志

A primary liver cancer patient complicated by hepatic cystic echinococcosis was reported. The case was admitted to the hospital due to intermittent upper abdominal discomfort for more than half a month, and an auxiliary examination revealed primary liver cancer complicated by hepatic cystic echinococcosis. Then, hepatic artery infusion and chemoembolization was performed, and no treatment was given to cystic echinococcosis lesions. Following treatment, the patient had remarkable improvements in the liver functions.

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).

Clinical study of microvascular invasion on prognosis of recipients after liver transplantation for liver cancer / 器官移植

Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.

Comparison of clinical efficacy of different anti-tumor therapies for recurrence and metastasis after liver transplantation for liver cancer / 器官移植

Objective To analyze the clinical efficacy of different anti-tumor therapies for recurrence and metastasis after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 145 recipients undergoing liver transplantation for liver cancer were retrospectively analyzed. The overall survival and recurrence and metastasis after liver transplantation for liver cancer were analyzed. The clinical efficacy of different anti-tumor therapies for recipients with recurrence and metastasis were compared. Results Sixty-five recipients (44.8%) developed recurrence and metastasis. The median recurrence time was 6 months. Among them, 1 case underwent secondary liver transplantation after recurrence and died of intestinal perforation. Twenty-four recipients (37%) received targeted drug therapy with a median tumor-bearing survival of 22 months. Eleven recipients (17%) received radiotherapy or chemotherapy with a median tumor-bearing survival of 11 months. Nine recipients (14%) received local treatment (surgical resection or radiofrequency ablation), and the median tumor-bearing survival was 8 months. Twenty recipients (31%) abandoned anti-tumor therapy, and the median tumor-bearing survival was 3 months. The tumor-bearing survival of recipients receiving anti-tumor therapy was significantly longer than that of recipients without anti-tumor therapy (P < 0.001). The tumor-bearing survival of recipients receiving targeted drug therapy was significantly longer than that of those receiving other anti-tumor therapies (P=0.03). The tumor-bearing survival of recipients receiving local treatment, radiotherapy and chemotherapy was considerably longer than that of those who abandoned anti-tumor therapy (P=0.004). Conclusions Surgical resection and radiofrequency ablation are the optimal therapies for recipients with recurrence and metastasis after liver transplantation for liver cancer. For recipients with multi-focal tumors who fail to receive local treatment, those receiving targeted drug therapy obtain the longest survival. In addition, radiotherapy and chemotherapy can also prolong the survival of recipients with recurrence and metastasis.

Immunotherapy of recurrence and metastasis after liver transplantation for liver cancer / 器官移植

Primary liver cancer (liver cancer) is one of the main indications of liver transplantation in China. Nevertheless, the 5-year survival rate of liver transplant recipients is lower than 50%. Recurrence and metastasis after operation are the main causes affecting the long-term survival of the recipients. At present, immunotherapy, represented by programmed cell death protein 1(PD-1)/programmed cell death protein-ligand 1(PD-L1) immune checkpoint inhibitor, has achieved remarkable clinical efficacy in the treatment of middle-stage and advanced liver cancer. However, whether it can be applied in recipients with recurrence and metastasis after liver transplantation for liver cancer remains controversial. The main reason is that it may cause acute rejection at the same time. In this article, the research progresses on the application of immunotherapy in recipients with recurrence and metastasis after liver transplantation for liver cancer were reviewed, aiming to improve the survival rate of recipients undergoing liver transplantation forliver cancer.

Curative efficacy of retetrexel combined with laparoscopic hepatectomy in treatment of patients with primary liver cancer and its effects on liver function and CIART, AFP-L3 and GP73 / 中国临床药理学与治疗学

AIM: To study the curative efficacy of retetrexel combined with laparoscopic hepatectomy in treatment of patients with primary liver cancer and its effects on liver function and the effects of diurnal transcription suppressor (CIART), fetoprotein heterosomes (AFP-l3), golgi membrane protein-73 (GP73). METHODS: A total of 100 patients with primary liver cancer who were treated in our hospital from July 2012 to July 2019 were selected as study subjects, the patients were divided into observation group (n=52) and control group (n=48) according to the order of admission. The control group was treated with laparoscopic hepatectomy, and the observation group was treated with retetroxel on the basis of the control group. Serum CIART, AFP-L3, GP73, ALT, AST, TBIL, 1-year, 3-year, 5-year tumor recurrence rates and adverse reactions were compared between the two groups before and after treatment. RESULTS:Before treatment, CIART, AFP-L3, GP73, ALT, AST and TBIL levels were not significantly different between the two groups. After treatment, the levels of CIART, AFP-L3 and GP73 in the observation group were significantly lower than those in the control group (P0.05). The 5-year recurrence rate in the observation group was significantly lower than that in the control group (P0.05). The total incidence of adverse reactions in the two groups was 53.84% and 52.08%, respectively, with no significant difference (P>0.05). CONCLUSION:Laparoscopic resection combined with letetrexed in the treatment of primary liver cancer can effectively reduce the level of ciart, AFP-L3 and GP73, and it is safe.

The therapeutic effect of fluorouracil combined with radiotherapy on patients with primary liver cancer and its effect on serum LPO and MDA levels / 公共卫生与预防医学

Objective To explore the therapeutic effect of fluorouracil combined with radiotherapy on patients with primary liver cancer and its effect on the levels of serum lipid peroxide (LPO) and malondialdehyde (MDA). Methods From March 2016 to March 2017, a total of 108 patients with primary liver cancer were randomly divided into two groups: radiotherapy group and combined treatment group, with 54 cases in each group. The patients in the radiotherapy group were treated with radiotherapy, while the patients in the combined treatment group were treated with fluorouracil combined with radiotherapy. Biochemical assays were used to detect the levels of aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), alanine aminotransferase (ALT), fibrinogen (FIB), activated partial thromboplastin time (APTT), and prothrombin time (PT). The enzyme-linked immunosorbent assay was used to detect serum hyaluronidase (HA), laminin (LN), and type III procollagen (PCIII) levels. The flow cytometry was used to detect T lymphocyte subgroup levels. LPO and MDA were detected by immunoturbidimetry. The total effective rate was compared between the two groups. Results The levels of AST, GGT and ALT in the combined treatment group were significantly lower than those in the radiotherapy group (P<0.05). After treatment, the FIB level in the combined treatment group was higher than that in the radiotherapy group, and the APTT and Pt levels were lower than those in the radiotherapy group (P<0.05). The levels of HA, LN and PCIII in the combined treatment group were lower than those in the radiotherapy group (P<0.05). After treatment, the CD8+ level in the combined treatment group was lower than that in the radiotherapy group, while the CD4+ and CD3+ levels were higher than those in the radiotherapy group (P<0.05). The level of LPO and MDA in the combined treatment group was lower than that in the radiotherapy group (P<0.05). The total effective rate of the combined treatment group was higher than that of the radiotherapy group (P<0.05). Conclusion The treatment of primary liver cancer patients with fluorouracil combined with radiotherapy could improve the liver function and coagulation function, improve the immune function, and reduce the severity of liver fibrosis and oxidative stress response of patients. The effect of the combination treatment was significant.