Objective To establish a quantum dot immunochromatographic test strip for simultaneous detection of central nervous system-specific protein (S100 u03B2) and neuron-specific enolase (NSE), thereby achieving combined detection of both biomarkers. Methods A double-antibody sandwich immunochromatographic assay was developed using S100u03B2 and NSE capture antibodies as the test line and species-specific secondary antibodies as the control line coated on the nitrocellulose membrane. Quantum dot bead-conjugated antibodies targeting S100u03B2 and NSE served as fluorescent probes. The preparation parameters of the strip were optimized, and its performance was systematically evaluated to develop a rapid diagnostic strip for mild traumatic brain injury (mTBI). The diagnostic efficacy of the strip was further validated using clinical samples. Results The total assay time for combined detection of S100u03B2 and NSE was 17 min, with a limit of detection (LOD) of 0.1 ng/mL for S100u03B2 and 2.67 ng/mL for NSE. The inter-batch reproducibility of the strips was excellent (coefficient of variation, CVu0026lt;15%). In clinical validation using 24 mTBI samples, the combined detection strip demonstrated a specificity of 90% and a sensitivity of 92.86%, outperforming single-marker detection. These results prove that the simultaneous quantification of S100u03B2 and NSE enhances diagnostic efficacy for mTBI patients. Conclusion A combined detection method for the biomarkers S100u03B2 and NSE in mTBI, based on quantum dot immunochromatography, has been preliminarily established. This method demonstrates promising clinical application prospects in the auxiliary diagnosis of mTBI.

Tick-borne encephalitis virus (TBEV), a zoonotic pathogen, can cause severe neurological complications and fatal outcomes in humans. Early diagnosis of TBEV infection is crucial for clinical practice. Although serological assays are frequently employed for detection, the lack of antibodies in the early stages of infection and the cross-reactivity of antibodies limit their efficacy. Conventional molecular diagnostic methods such as RT-qPCR can achieve early and accurate identification but require specialized instrumentation and professionals, hindering their application in resource-limited areas. Our study developed a rapid and visual TBEV molecular detection method by combining RT-recombinase-aided amplification, the CRISPR/Cas13a system, and lateral flow dipsticks. The diagnostic sensitivity of this method is 50 CFU/ml, with no cross-reactivity with a variety of viruses. The detection can be carried out within 1 h at a temperature between 37 and 42 °C, and the results can be visually determined without the need for complex instruments and professionals. Subsequently, this assay was used to analyze clinical samples from 15 patients suspected of TBEV infection and 10 healthy volunteers, and its sensitivity and specificity reached 100 %, which was consistent with the results of RT-qPCR. These results indicate that this new method can be a promising point-of-care test for the diagnosis of tick-borne encephalitis.

BackgroundSwift and accurate detection of Vibrio parahaemolyticus, which is a prominent causative pathogen associated with seafood contamination, is required to effectively combat foodborne disease and wound infections. The toxR gene is relatively conserved within V. parahaemolyticus and is primarily involved in the expression and regulation of virulence genes with a notable degree of specificity. The aim of this study was to develop a rapid, simple, and constant temperature detection method for V. parahaemolyticus in clinical and nonspecialized laboratory settings.MethodsIn this study, specific primers and CRISPR RNA were used to target the toxR gene to construct a reaction system that combines recombinase polymerase amplification (RPA) with CRISPR‒Cas13a. The whole-genome DNA of the sample was extracted by self-prepared sodium dodecyl sulphate (SDS) nucleic acid rapid extraction reagent, and visual interpretation of the detection results was performed by lateral flow dipsticks (LFDs).ResultsThe specificity of the RPA-CRISPR/Cas13a-LFD method was validated using V. parahaemolyticus strain ATCC-17802 and six other non-parahaemolytic Vibrio species. The results demonstrated a specificity of 100%. Additionally, the genomic DNA of V. parahaemolyticus was serially diluted and analysed, with a minimum detectable limit of 1 copy/µL for this method, which was greater than that of the TaqMan-qPCR method (102 copies/µL). The established methods were successfully applied to detect wild-type V. parahaemolyticus, yielding results consistent with those of TaqMan-qPCR and MALDI-TOF MS mass spectrometry identification. Finally, the established RPA-CRISPR/Cas13a-LFD method was applied to whole blood specimens from mice infected with V. parahaemolyticus, and the detection rate of V. parahaemolyticus by this method was consistent with that of the conventional PCR method.ConclusionsIn this study, we describe an RPA-CRISPR/Cas13a detection method that specifically targets the toxR gene and offers advantages such as simplicity, rapidity, high specificity, and visual interpretation. This method serves as a valuable tool for the prompt detection of V. parahaemolyticus in nonspecialized laboratory settings.

结直肠癌是我国常见恶性消化道肿瘤之一,其发病率逐年上升且预后不好,病死率较高.早发现、早诊断可有效降低结直肠癌致死率.目前,临床用于结直肠癌诊断及监测的肿瘤标志物有癌胚抗原(CEA)、糖类抗原19-9(CA199)、糖类抗原242(CA242)等,这些标志物在结直肠癌早期诊断中的临床价值不够理想.因此,探索新的、早期诊断价值更高的肿瘤标志物用于结直肠癌筛查是当前研究的热点之一.SEPT9是一种抑癌基因,SEPT9基因甲基化检测对结直肠癌早期诊断有较高的特异度和灵敏度,该文就SEPT9基因甲基化检测在结直肠癌早期诊断中的研究进展进行综述.

BackgroundUSP51 is a deubiquitinase (DUB), that is involved in diverse cellular processes. Accumulating evidence has demonstrated that USP51 contributes to cancer development. However, its impact on non-small cell lung carcinoma (NSCLC) cell malignancy is largely unknown.MethodsIn this study, we performed bioinformatics analysis on a dataset from The Cancer Genome Atlas to determine the association between USP51 and cell stemness marker expression in NSCLC patients. RT-qPCR, Western blotting, and flow cytometry were performed to examine the effects of USP51 depletion on stemness marker expression. Colony formation and tumor sphere formation assays were used to assess the stemness of NSCLC cells. A cycloheximide chase time-course assay and a polyubiquitination assay were carried out to analyze the effects of USP51 on the TWIST1 protein level. TWIST1 was overexpressed in USP51 knockdown NSCLC cells to determine whether TWIST1 is required. The effect of USP51 on the in vivo growth of NSCLC cells was tested through subcutaneous injections in mice.ResultsWe found that USP51 deubiquitinates TWIST1, which is significantly upregulated in the tissues of patients with NSCLC and is closely associated with poor prognosis. USP51 expression was positively correlated with the expression of stemness marker CD44, SOX2, NANOG, and OCT4 in NSCLC patients. USP51 depletion attenuated mRNA, protein, and cell surface expression of stemness markers and the stemness of NSCLC cells. Ectopic USP51 expression potentiated the stability of the TWIST1 protein by attenuating its polyubiquitination. In addition, TWIST1 re-expression in NSCLC cells reversed the inhibitory effect of USP51 knockdown on cell stemness. Furthermore, the in vivo results confirmed the suppressive effect of USP51 depletion on NSCLC cell growth.ConclusionsOur results show that USP51 maintains the stemness of NSCLC cells by deubiquitinating TWIST1. Knocking it down reduces both cell stemness and growth of NSCLC cells.

创伤性脑损伤(TBI)是一个重要的公共卫生问题,据估计,全球每年有超过5000万患者发生TBI.当前TBI的临床诊断主要依赖于评分量表,筛选客观的TBI生物标志物极为必要.近年相关研究多集中于TBI蛋白标志物的筛选,然而蛋白标志物存在半衰期短、灵敏度低等缺陷,因此筛选新的生物标志物对于TBI的快速诊断评估及后续治疗具有重要意义.TBI缺乏有效的治疗药物,主要依赖对症治疗.microRNA(miRNA)是一类小的非编码RNA,其表达水平变化与包括TBI在内的多种中枢神经系统疾病相关,在神经可塑性调控、神经元损伤修复等方面发挥着重要作用.miRNA分子量小,可穿过血脑屏障,易在外周体液中检测到,具有成为TBI诊断及治疗靶标的潜力.本文对miRNA的主要特征及其与TBI诊断和治疗相关的研究进展进行综述,旨在为相关研究和潜在的临床应用提供参考.

Vibrio alginolyticus (V. alginolyticus) is a common pathogen in the ocean. In addition to causing serious economic losses in aquaculture, it can also infect humans. The rapid detection of nucleic acids of V. alginolyticus with high sensitivity and specificity in the field is very important for the diagnosis and treatment of infection caused by V. alginolyticus. Here, we established a simple, fast and effective molecular method for the identification of V. alginolyticus that does not rely on expensive instruments and professionals. The method integrates recombinase polymerase amplification (RPA) technology with CRISPR system in a single PCR tube. Using this method, the results can be visualized by lateral flow dipstick (LFD) in less than 50 min, we named this method RPA-CRISPR/Cas13a-LFD. The method was confirmed to achieve high specificity for the detection of V. alginolyticus with no cross-reactivity with similar Vibrio and common clinical pathogens. This diagnostic method shows high sensitivity; the detection limit of the RPA-CRISPR/Cas13a-LFD is 10 copies/µL. We successfully identified 35 V. alginolyticus strains from a total of 55 different bacterial isolates and confirmed their identity by (Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS). We also applied this method on infected mice blood, and the results were both easily and rapidly obtained. In conclusion, RPA-CRISPR/Cas13a-LFD offers great potential as a useful tool for reliable and rapid diagnosis of V. alginolyticus infection, especially in limited conditions.

Tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) is an interesting costimulatory molecule associated with T lymphocyte activation, and it mainly exerts its biological effects by binding to its receptors herpesvirus invasion mediator (HVEM) and lymphotoxin-β receptor. Research shows that TNFSF14 plays a critical regulatory role in immune responses to viral infection, but its role is different in different diseases. TNFSF14 can be a cytokine neutralization target during novel coronavirus infection, and anti-TNFSF14 monoclonal antibody treatment can reduce the risk of respiratory failure and mortality. When the host is infected with adenovirus, TNFSF14 can be used as an inflammatory biomarker to indicate whether there was an adenovirus infection in the host and the degree of disease caused by viral infection. When hosts suffer influenza virus infection, the TNFSF14-HVEM signaling pathway can stimulate the maturation and proliferation of memory CD8+ T cells, which helps the host immune system stimulate a second immune response against respiratory virus infection. TNFSF14 can act as an immune adjuvant and enhance the immunogenicity of the human papillomavirus (HPV) DNA vaccine when the host is infected with HPV. During hepatitis virus infection, TNFSF14 acts as a proinflammatory factor, participates in inflammation and causes tissue damage. In conclusion, TNFSF14 plays different and significant roles in diverse viral infections. This article reviews the current research on TNFSF14 in antiviral immunity.

The outbreak of coronavirus disease 2019 has made nucleic acid detection widely known. Fluorescent quantitative polymerase chain reaction (PCR) technique is the most commonly used nucleic acid detection method in this epidemic control. However, its requirements on operators, instruments and sites limited its application in some scenarios with lower resources or outside laboratories. Isothermal amplification technology, especially recombinase polymerase amplification (RPA) technology, has the advantages of mild reaction conditions, high sensitivity, excellent specificity and short reaction time, which let it has a good application prospect in the rapid detection of a variety of pathogenic microorganisms. In this paper, the development and application of RPA technology are reviewed and summarized to provide a reference for the further research and promotion of this technology. DOI: 10.11855/j.issn.0577-7402.2021.05.13

OBJECTIVE:Breast cancer is a common type of malignant tumour worldwide and the second leading cause of death in women. The present study aims to investigate the clinical significance of serum soluble intercellular adhesion molecule-1 (sICAM-1) in differentiating benign breast lesions from breast cancer.METHODS:Plasma samples were obtained from 200 breast cancer patients, 47 patients with benign breast lesions and 50 age- and sex-matched healthy individuals as controls. Plasma levels of sICAM-1 were measured in all the samples using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. The serum levels of carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) were detected by the UniCel® DxI 800 Immunoassay System with matched kits.RESULTS:The plasma levels of CEA and CA15-3 were 1.22±0.2 (ng/mL) and 6.39±1.5 (ng/mL) in the healthy control group, 1.40±0.3 (ng/mL) and 5.81±2.1 (ng/mL) in the benign breast lesion (BBL) group, and 5.29±0.6 (ng/mL) and 27.08±5.7 (ng/ mL) in the breast cancer (BC) group. Plasma levels of CEA and CA15-3 in the BC group were significantly higher than those in the BBL and healthy control groups (all P<0.05), but the plasma levels of CEA and CA15-3 were not significantly different between the BBL group and the healthy control group, P=0.548 and P=0.2976, respectively. The diagnostic sensitivity and specificity were 13.4% and 98.0% for CEA and 22.2% and 100.0% for CA15-3. For plasma sICAM-1, the diagnostic sensitivity and specificity were 98% and 94% at a cut-off value of 20.0 (ng/mL), with an area under the receiver operating characteristic (ROC) curve of 0.99, which could be used to distinguish between healthy controls and the BC group; the diagnostic sensitivity and specificity were 95.5% and 94.0% at a cut-off value of 20.0 (ng/mL) with an area under the ROC curve of 0.98, which could be used to distinguish between healthy controls and the BBL group; and the diagnostic sensitivity and specificity were 44.6% and 94.1% at a cut-off value of 40.0 (ng/mL), with an area under ROC curve of 0.68, which could be used to distinguish between the BBL group and the BC group. The plasma levels of sICAM-1 were 15.43±2.3 (ng/mL) in healthy controls, 29.8±3.5 (ng/ mL) in the BBL group, and 50.07±12.2 (ng/mL) in the BC group. The plasma level of sICAM-1 in the BC group was the highest among all three groups (all P<0.05).CONCLUSIONS:The CEA, CA15-3 and sICAM-1 levels were increased in breast cancer patients, especially in those with node and/or organ metastasis. After diagnosis, CEA, CA15-3 and sICAM-1 levels are closely related to tumour metastasis. sICAM-1 has great potential value in the clinical diagnosis of benign breast lesions and breast cancer.

Objective. To investigate the clinical significance of serum let-7a-5p and miR-21-5p in the diagnosis of breast cancer. Methods. We examined 32 healthy people and 30 patients with benign breast lesions as controls and 90 breast cancer patients as study subjects. The expression of let-7a-5p and miR-21-5p were detected in all subjects' samples, and Cel-miR-39-3p was used as a spike-in reference. Serum miRNAs were extracted by the TRIzol method, and reverse transcription was performed with specific primers for let-7a-5p, miR-21-5p and Cel-miR-39-3p, and 2-mu L reverse transcription products were used as PCR templates. A SLAN-96P fluorescent quantitative PCR instrument was used for quantitative PCR detection. Results. (1) The serum levels of carcinoembryonic antigen (CEA)and carbohydrate antigen 15-3 (CA15-3) in the breast cancer group were higher than those in the healthy controls and patients with benign breast lesions; (2) The expression level of let-7a-5p in the serum of the breast cancer group was lower than that in the healthy control group (P<0.05), but there was no significant difference compared to the breast benign lesion group (P>0.05); (3) The serum expression level of miR-21-5p in the breast cancer group was lower than that in the healthy control group (P<0.05) but was not significantly different from that in the patients with benign breast lesions (P>0.05). Conclusion. Reduced expression of Let-7a-5p and miR-21-5p levels is of little value for early diagnosis of breast cancer; however reduced expression of Let-7a-5p and miRNA-21-5p may serve as non-invasive biomarkers for the diagnosis of breast cancer metastasis, and combination of these markers with CEA and CA15-3 can help to distinguish benign breast lesions from breast cancer.

Proinflammatory macrophage (M1) is now being suggested as a potential therapeutic strategy for cancer because of its tumoricidal capacity. However, few studies have been focused directly on the effects of M1 macrophages on cancer cells. Here, we found that M1 induced a subpopulation of CD44high/CD24−/low or ALDH1+ cells with CSC-like phenotypes from different types of breast cancer cells (BCCs) in a paracrine manner. Stat3/NF-κB pathways in BCCs were activated by proinflammatory cytokines, igniting Lin-28B-let-7-HMGA2 axis to induce CSC through epithelial-mesenchymal transition (EMT). Previously, we reported that Stat3-coordinated Lin-28B-let-7-HMGA2 axis initiated EMT in BCCs. Here, inhibition of Stat3/NF-κB pathways or Lin-28B-let-7-HMGA2 axis suppressed EMT/CSCs program. Notably, HMGA2 knockdown directly repressed M1-induced CSC formation and expression of Klf-4 and Nanog. Meanwhile, prolonged coculture with BCCs endowed M1 with M2 properties. M1 supernatant induced CSC from non-stem cancer cells, while M2 supernatant sustained a higher proportion of ALDH1+ cells. Our data suggest that macrophages might modulate CSC formation and maintenance by transferring between M1/M2 phenotype. Given that M1 are being considered as a promising immunotherapy tool, it is important to inhibit their CSC-inducing potential by targeting key molecules and pathways.

目的 通过对180株金黄色葡萄球菌临床分离株MecA、Nuc基因的检测,以期选择出一种适合临床的并能简便、快速、准确检测耐甲氧西林金黄色葡萄球菌(methicillin resistant Staphylococcus aureus,MRSA)的方法.方法 细菌鉴定及药敏采用全自动细菌鉴定和药敏分析仪.MecA、Nuc基因检测采用荧光定量聚合酶链反应(fluorescence quantitative polymerase chain reaction,FQ-PCR)法.结果 FQ-PCR对180株金黄色葡萄球菌MecA、Nuc基因检出率为75.0%,全自动细菌鉴定和药敏分析仪对180株金黄色葡萄球菌的MRSA检出率为72.8%,2种检测方法比较差异无统计学意义(P>0.05).全自动细菌鉴定和药敏分析仪对MRSA的检测正确率为94.8%.结论 FQ-PCR检测MRSA正确率高,只需要1~2 h即可完成.该方法快速、简便、准确,值得推广应用.

The aim of this study was to develop a rapid detection assay to identify methicillin-resistant Staphylococcus aureus by simultaneous testing for the mecA, nuc, and femB genes using the loop-mediated isothermal amplification (LAMP) method. LAMP primers were designed using online bio-software (http://primerexplorer.jp/e/), and amplification reactions were performed in an isothermal temperature bath. The products were then examined using 2% agarose gel electrophoresis. MecA, nuc, and femB were confirmed by triplex TaqMan real-time PCR. For better naked-eye inspection of the reaction result, hydroxy naphthol blue (HNB) was added to the amplification system. Within 60 min, LAMP successfully amplified the genes of interest under isothermal conditions at 63 °C. The results of 2% gel electrophoresis indicated that when the Mg2+ concentration in the reaction system was 6 μmol, the amplification of the mecA gene was relatively good, while the amplification of the nuc and femB genes was better at an Mg2+ concentration of 8 μmol. Obvious color differences were observed by adding 1 μL (3.75 mM) of HNB into 25 μL reaction system. The LAMP assay was applied to 128 isolates cases of methicillin-resistant Staphylococcus aureus, which were separated from the daily specimens and identified by Vitek microbial identification instruments. The results were identical for both LAMP and PCR. LAMP offers an alternative detection assay for mecA, nuc, and femB and is faster than other methods.

Tuberculosis is caused by mycobacterium, a potentially fatal infectious bacterium. In recent years, TB cases increased in the whole world. WHO statistics data shows that the world's annual tuberculosis incidence was 8~10 million with about 3 million deaths. Several studies have shown that susceptibility to tuberculosis may be associated with IFNGR1 gene polymorphisms. Here, we report the distribution frequency of IFNGR1 gene polymorphisms in 103 cases of IGA-negative patients and 100 cases of IGA-positive patients from China by sequencing the IFNGR1 proximal ~750 bp promoter region. We found a total of 5 types of site mutations: -611 (G/A), -56 (T/C), -255 (C/T), -359 (T/C), and -72 (C/T). The two main types of gene polymorphisms among the IGA-negative and IGA-positive groups were -611 (G/A), with mutation rates of 88.3% and 78.4%, respectively, and -56 (T/C), with mutation rates of 84.5% and 83.8%, respectively, which had no statistical significance, and there was no correlation with the incidence of tuberculosis.

BACKGROUND:To examine whether the combined detection of serum tumor markers (CEA, CA72-4, CA19-9, CA15-3 and CA12-5) improves the sensitivity and accuracy in the diagnosis of gastric cancer (GC). MATERIALS AND METHODS:An automatic chemiluminescence immune analyzer with matched kits was used to determine the levels of serum CEA, CA72-4, CA19-9, CA15-3, and CA12-5 in 87 patients with gastric cancer (GC group), 60 patients with gastric benign diseases (GBD group) who were hospitalized during the same period, and 40 healthy subjects undergoing a physical examination. The values of these 5 tumor markers in the diagnosis of gastric cancer were analyzed. RESULTS:The levels of serum CEA, CA72-4, CA19-9, and CA12-5 were higher in the GC group than in the GBD group and healthy subjects, and these differences were significant (P<0.001). Although the level of CA15-3 was higher than those of benign lesion and healthy control groups, the difference was not statistically significant (P>0.05). The combined detection of CEA, CA72-4, CA19-9, and CA12-5 had a higher diagnostic value for gastric cancer than did single detection, and the positive detection rate of the combined detection of the four tumor markers was 60.9%. The diagnostic power when using the combined detection of CA72-4, CEA, CA19-9, and CA12-5 was the best. CONCLUSIONS:The combined detection of serum CA72-4, CEA, CA19-9 and CA12-5 increases the sensitivity and accuracy in the diagnosis of GC and can thus be considered an important tool for early diagnosis.

This article reviews the emergence and development of translational medicine, ana-lyzes the current domestic background of translational medicine, explains the definition and transla-tional medicine mode, and puts forward the key points and measures of strengthening the translational medicine practice. The laboratory medicine is one of the most active field of translational medicine, the hospital collaboration with scientific research colleges and universities to carry out the strategy of translational medicine have been discussed.

Structure–activity relationships (SAR) in 2,5-dichloro-N-(2-methyl-4-nitrophenyl)benzenesulfonamide (FH535) were examined as part of a program to identify agents that inhibit the Wnt/β-catenin signaling pathway that is frequently upregulated in hepatocellular carcinoma (HCC). FH535 was reported as an inhibitor of both β-catenin in the Wnt signaling pathway and the peroxisome proliferator-activated receptor (PPAR). A β-catenin/T-cell factor (TCF)/Lymphoid-enhancer factor (LEF)-dependent assay (i.e., luciferase-based TOPFlash assay) as well as a [3H]-thymidine incorporation assay were used to explore SAR modifications of FH535. Although replacing the 2,5-dichlorophenylsulfonyl substituent in FH535 with a 2,6-dihalogenation pattern generally produced more biologically active analogs than FH535, other SAR modifications led only to FH535 analogs with comparable or slightly improved activity in these two assays. The absence of a clear SAR pattern in activity suggested a multiplicity of target effectors for N-aryl benzenesulfonamides.

Activation of the Wnt/β-catenin pathway has been observed in at least 1/3 of hepatocellular carcinomas (HCC), and a significant number of these have mutations in the β-catenin gene. Therefore, effective inhibition of this pathway could provide a novel method to treat HCC. The purposed of this study was to determine whether FH535, which was previously shown to block the β-catenin pathway, could inhibit β-catenin activation of target genes and inhibit proliferation of Liver Cancer Stem Cells (LCSC) and HCC cell lines. Using β-catenin responsive reporter genes, our data indicates that FH535 can inhibit target gene activation by endogenous and exogenously expressed β-catenin, including the constitutively active form of β-catenin that contains a Serine37Alanine mutation. Our data also indicate that proliferation of LCSC and HCC lines is inhibited by FH535 in a dose-dependent manner, and that this correlates with a decrease in the percentage of cells in S phase. Finally, we also show that expression of two well-characterized targets of β-catenin, Cyclin D1 and Survivin, is reduced by FH535. Taken together, this data indicates that FH535 has potential therapeutic value in treatment of liver cancer. Importantly, these results suggest that this therapy may be effective at several levels by targeting both HCC and LCSC.

BACKGROUND/AIMThe aim of this study is to find synergistic effect using FH535 and sorafenib by targeting the RAS/RAF/MAPK and WNT/β-catenin pathways.MATERIALS AND METHODS3H-Thymidine incorporation assays were performed to address Huh7 and liver cancer stem cell (LCSC) inhibition using FH535 and sorafenib, alone and in combination. Calcusyn analysis was used to calculate the combination index (CI). A western blot assay was performed to check for potential targets.RESULTSFH535 and sorafenib caused inhibition of Huh7 and LCSC. Combination therapy was significantly better than monotherapy in inhibition of HuH7. Combination with sorafenib and FH535 was found to be synergistic in inhibition of LCSC with a CI of less than 1. The western blot assay demonstrated enhanced cleaved poly (ADP-ribose) polymerase (PARP) and inhibition of cyclin D1, B-cell lymphoma 2 (Bcl2), survivin and cellular myelocytomatosis oncogene (c-MYC).CONCLUSIONFH535 and sorafenib combination produced synergistic effect on inhibition of HCC and LCSC. Our study demonstrated that FH535 can induce apoptosis in these two different hepatocellular carcinoma (HCC) cell lines.