Objective To investigate the efficacy of continuous hepatic arterial infusion chemotherapy (HAIC) with the FOLFOX regimen and its multimodality therapeutic regimen in the treatment of patients with advanced hepatocellular carcinoma, as well as the influencing factors for prognosis. Methods A retrospective analysis was performed for the clinical data of 66 patients with advanced hepatocellular carcinoma who received continuous HAIC with FOLFOX regimen in Nanfang Hospital, Southern Medical University, from September 2018 to November 2021. The patients were observed in terms of objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) after treatment, and treatment-related adverse reactions were recorded. For the patients with portal vein tumor thrombus, the effect of the treatment on portal vein tumor thrombus was assessed. The Kaplan-Meier method was used for survival analysis, and the Cox regression analysis was used to investigate the influencing factors for prognosis. Results According to the RECIST1.1 criteria, FOLFOX-HAIC and its multimodality therapeutic regimen achieved an ORR of 33.3% (22/66) and a DCR of 86.4% (57/66) in the treatment of 66 patients with advanced hepatocellular carcinoma, with an mPFS time of 8.2 months and an mOS time of 22.1 months. Among the 39 patients with portal vein tumor thrombus, 2 achieved complete remission, 8 achieved partial remission, 24 achieved stable disease, and 5 had disease progression, with an ORR of 25.6% (10/39) and a DCR of 87.2% (34/39). The main adverse reactions included gastrointestinal reactions (16.7%, 11/66), pyrexia (12.1%, 8/66), liver area pain (10.6%, 7/66), bone marrow suppression (3.0%, 2/66), and contrast agent allergy (3.0%, 2/66), and there were no grade > Ⅳ toxic or side effects or deaths caused by such complications. The Cox regression analysis showed that extrahepatic metastasis (hazard ratio [ HR ]=2.668, 95% confidence interval [ CI ]: 1.357-5.245, P < 0.05) and prothrombin time (PT) ( HR =1.282, 95% CI : 1.080-1.630, P < 0.05) were independent risk factors for PFS, and aspartate aminotransferase level ( HR =1.008, 95% CI : 1.002-1.013, P < 0.05) and PT ( HR =1.303, 95% CI : 1.046-1.630, P < 0.05) were independent risk factors for OS. Conclusion FOLFOX-HAIC and its multimodality therapeutic regimen has a certain clinical effect with controllable adverse reactions in the treatment of advanced hepatocellular carcinoma.

Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.

Objective:To explore the value of the aMAP risk score (age, male, albumin -bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods:This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors.Results:Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group ( P=0.001). Conclusions:The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..

Objective:To analyze the epidemiological characteristics and track probable imported sources of the local dengue outbreak in Zhangzhou city, Fujian province, 2019.Methods:Serum samples of patients with suspected dengue fever at acute phases were collected for virus detecting and serotyping by real-time fluorescence quantitative RT-PCR. For the positive specimens of local cases, full-length fragments of E gene were amplified by RT-PCR, and were sequenced and analyzed.Result:In 2019, there were 98 local cases of dengue fever in Zhangzhou city, which were concentrated in Zhao’an county, Longhai district and Yunxiao county. In this study, fourteen dengue virus E gene sequences representing different sources in different districts and counties were selected. The amino acid sequence virulence site analysis showed that the local epidemic strains were relatively virulent strains. The gene sequence alignment and phylogenetic analysis showed that all the local strains were classified as DENV-I subgenotype genotype I, divided into a, b and c three different branches. The evolutionary branch a contained all Zhao’an and Longhai sequences and was divided into three sub-branches, the b and c evolutionary branches were both the sequences of Yunxiao. There was a high correlation between the Shenqiao Town in Zhao’an and the Haicheng Town in Longhai. The other areas of the strains were limited to the towns, and the evolutionary branches were close to the other areas in China and countries in Southeast Asia.Conclusions:The indigenous dengue outbreaks in Zhangzhou, 2019 were caused by multiple sources of introduction and originated from other areas in China or from Southeast Asian countries and there was also the possibility of local cross-county transmission.

Objective:To analyze the epidemiologic characteristics of environmental samples of avian influenza virus in Fujian province from 2017 to 2021, and provide a reference for the prevention and control of avian influenza.Methods:Six types of specimens were collected from four types of environments in six cities in Fujian province. And the specimens were subjected to nucleic acid detection for influenza A, subtypes H5, H7 and H9 by fluorescence quantitative PCR, and the results were analyzed statistically with descriptive epidemiological methods.Results:From 2017 to 2021, a total of 4 214 samples were collected from 6 cities, of which the positive rate of avian influenza virus was 41.53%, and the positive rates of H5, H7 and H9 subtypes were 2.33%, 1.16% and 23.16%, respectively. The positive rate for mixed subtypes of H5 and H7 was 0.05%, the positive rate for mixed subtypes of H5 and H9 was 1.83%, the positive rate for mixed subtypes of H7 and H9 was 0.83%, the positive rate for mixed subtypes of H5, H7 and H9 was 0.09%, and the positive rate of A-type unclassified was 12.08%. The difference in avian influenza virus detection among different monitoring places ( χ2=517.57, P<0.001), different types of specimens( χ2= 51.58, P<0.001), and different cities ( χ2=458.34, P<0.001) was statistically significant. Among different monitoring places, the positive rate of avian influenza virus in urban and rural live poultry markets was the highest. The highest rate of positive detection was found in specimens from the cage surface, cleaning poultry sewage and poultry chopping board surface, with 48.09%, 47.34% and 45.66%, respectively. In terms of different cities, Sanming city had the highest positivity rate (56.00%), while Zhangzhou city had the lowest positivity rate(3.34%). And the positive rate was higher from November to February of the next year and June to August each year. Conclusions:The overall positive rate of avian influenza viruses in Fujian province was relatively high, with H9 subtype accounting for the main proportion. The monitoring of avian influenza viruses in winter, spring and summer should be strengthened. And effective measures should be taken to deal with avian influenza especially in urban and rural live poultry markets.

Objective:To compare the postoperative liver function injury condition in patients with intermediate-and advanced-stage hepatocellular carcinoma (HCC) treated with hepatic artery infusion chemotherapy (HAIC) and hepatic artery chemoembolization (TACE) combined with immune checkpoint inhibitors (ICIs) and multi-target tyrosine kinase inhibitors (TKIs).Methods:Patients with intermediate-and advanced-stage HCC who were admitted and treated with HAIC/TACE+ICIs+TKIs therapy at Nanfang Hospital of Southern Medical University from January 2019 to November 2021, with follow-up up to July 2023, were retrospectively enrolled. The results of liver function tests within one week before interventional surgery and on the first day after surgery were recorded. The degree of postoperative liver injury was graded according to the common terminology criteria for adverse events 5.0 (CTCAE 5.0). The treatment efficacy was evaluated according to RECIST 1.1 criteria. Measurement data were compared between groups using a t-test or a non-parametric rank sum test. Enumeration data were compared between the groups using the χ2 test or Fisher's exact probability method. The survival condition differences were analyzed by the log-rank method. Results:This study included 82 and 77 cases in the HAIC and TACE groups. There were no statistically significant differences between the two groups of patients in terms of gender, age, physical condition score, number of tumors, presence or absence of liver cirrhosis, Child-Pugh grade, albumin-bilirubin (ALBI) grade, and combined ICIs and TKIs . The HAIC group had later tumor staging, a greater tumor burden, poorer liver reserve function, and a larger proportion of patients in stage C (81.7% vs. 63.6%), χ2=6.573, P = 0.01). There were 53 cases (64.6% vs. 32.5%) with a maximum tumor diameter of ≥ 10cm, χ2=16.441, P < 0.001), and more patients had a retention rate of ≥ 10% for indocyanine green (ICG) at 15 minutes (68.3% vs. 51.9%, P = 0.035). The postoperative incidence rate of increased levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin was significantly lower in the HAIC group than that in the TACE group (28.0% vs. 63.6%, χ2=20.298, P < 0.001, 54.9% vs. 85.7%, χ2=17.917, P < 0.001;40.2% vs. 55.8%, χ2=3.873, P = 0.049). The number of patients with postoperative ALBI grade 3 was significantly lower in the HAIC group than that in the TACE group (6.1% vs. 16.9%, χ2=4.601, P = 0.032). There was no statistically significant difference in the incidence rate of postoperative hypoalbuminemia, activated partial thromboplastin time, or increased international standardized ratio between the two groups of patients. There was no statistically significant difference in median progression-free survival (7.3 months vs. 8.2 months, P = 0.296) or median overall survival (16.5 months vs. 21.9 months, P = 0.678) between the two groups of patients. Conclusion:The incidence rate of postoperative liver injury is higher in patients with intermediate-and advanced-stage HCC treated with TACE combined with ICIs and TKIs than in patients with HAIC combined with ICIs and TKIs.

The incidence and mortality of HCC in China account for approximately 50% of all cases worldwide. Low early diagnosis rate and high postoperative recurrence rate are two major causes for poor 5-year survival rate of HCC patients in China. At present, multiple problems such as low performance and compliance of screening technology and lack of effective markers for predicting postoperative recurrence, remain to be resolved. Due to the simplicity and accuracy, new molecular markers, such as liquid biopsy, are expected to serve as supplementary tools to traditional screening and early warning approaches, thereby realizing early detection and accurate treatment of HCC. In this article, research progress upon the clinical application of liquid biopsy in early screening and prediction of postoperative recurrence of HCC was reviewed, and prospects the future research.
Biomarkers ; Carcinoma, Hepatocellular/pathology* ; Humans ; Liquid Biopsy ; Liver Neoplasms/pathology* ; Mass Screening ; Neoplasm Recurrence, Local

Advanced hepatocellular carcinoma (HCC) has limited treatment options and poor prognosis. Only two tyrosine kinase inhibitors have been approved as single agents for first-line treatment over the last decade. In 2020, atezolizumab combined with bevacizumab was appro-ved for first-line treatment of advanced HCC. As the first brand-new therapy to surpass sorafenib, atezolizumab combined with bevacizumab showed good safety and life quality in patients. The authors introduced the diagnosis and treatment of a China Liver Cancer Staging Ⅲb HCC patient receiving atezolizumab combined with bevacizumab, in order to provide references for patient management.

Objective:To analyze the clinical efficacy and safety of camrelizumab combined with apatinib as a second-line therapy for unresectable hepatocellular carcinoma (HCC).Methods:Ninety-four cases with mid-and advanced-stage HCC who received camrelizumab combined with apatinib as second-line treatment were enrolled. Routine blood test, blood biochemical indexes, tumor stage, tumor imaging characteristics, previous treatment strategies and other clinical data before treatment were documented. Imaging examination follow-up results and adverse reactions during treatment were followed up until the end of follow-up or loss of follow-up or death. Kaplan-Meier method was used to analyze the clinical efficacy.Results:As of the last follow-up, 94 cases with mid-and advanced-stage HCC had received camrelizumab combined with apatinib as second-line treatment. Among them, 15 cases were lost to follow-up, 31 cases died, and 48 cases survived. The overall remission rate was 31.9%. The overall disease control rate was 71.3%. The median time to disease-free progression was 6.6 months. The median time to disease progression was not yet available. The 1-year cumulative survival rate was 62.3%. Grade 3 and above adverse reactions mainly included were thrombocytopenia (7.4%), abdominal pain (4.3%), active hepatitis (4.3%), leukopenia (4.3%), diarrhea (3.2%), hand-foot syndrome (3.2%). All adverse reactions were effectively controlled.Conclusion:Camrelizumab combined with apatinib can effectively prolong the survival period of patients with mid-and advanced-stage HCC, and it is well tolerated.

Molecular targeted drugs are the first choice for systemic treatment of liver cancer. In the past decade, several anti-liver cancer targeted drugs have been launched. More recently, immunotherapy has become a dazzling nova in the field of systemic treatment of liver cancer. Nivolumab and pembrolizumab have been approved as second-line treatments for patients with advanced hepatocellular carcinoma treated with sorafenib. However, the effect of single-agent treatment is always unsatisfactory in advanced liver cancer. An increasing number of evidences suggests that molecular targeted drugs have important immunomodulatory effects for liver cancer, and several targeted combined immunotherapies have also shown promising clinical effectiveness. This paper reviews the immunomodulatory effects of several molecular targeted drugs in the field of liver cancer.