Background: High mobility group box 1(HMGB1) overexpression has been reported in a variety of human cancers. However, the role of HMGB1 in hepatocellular carcinoma (HCC) remains unclear. The aim of present study was to analyze HMGB1 protein expression in tumor, para-tumor and normal tissue and to assess its prognostic significance for HCC after curative hepatectomy. Methods: The levels of HMGB1 mRNA and protein in tumor, para-tumor and normal tissue were evaluated in 11 HCC cases by Reverse Transcription-polymerase chain reaction (RT-PCR) and Western blot. Additionally, HMGB1 protein expression in 161 HCC was analyzed by immunohistochemistry and correlated with clinicopathological characteristics and survivals. Student’s t-test, spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model were used to analyze the data. Results: By RT-PCR and Western blot, the levels of HMGB1 mRNA and protein were significantly higher in HCC, compared to that in para-tumor (p < 0.001) and normal tissue (p < 0.001). Immunohistochemical staining revealed that high expression of HMGB1 was detected in 42.9% (69/161) HCC cases. High expression of HMGB1 was significantly associated with incomplete encapsulation (p = 0.035) and advanced TNM stage (p = 0.036). Multivariate analysis showed that high expression of HMGB1 was an independent prognostic factor for both overall (p = 0.009, HR = 1.834, 95%CI: 1.167-2.881) and disease-free survival (p = 0.018, HR = 1.622, 95%CI: 1.088-2.419), along with tumor size. Subgroup analysis revealed that high expression of HMGB1 predicted poorer overall survival only for tumor >5 cm (p = 0.031), but not for tumor ≤5 cm (p = 0.101). Conclusions: HMGB1 protein might contribute to the malignant progression of HCC, high expression of HMGB1 predicts poor prognosis for patients with HCC after curative hepatectomy, especially for patients with tumor >5 cm.

Hepatocellular carcinoma (HCC) remains a global challenge due to its high morbidity and mortality rates as well as poor response to treatment. Local combined systemic therapy is widely used in the treatment of unresectable hepatocellular cancer (uHCC). This retrospective study was to investigate the prognostic effect and prognostic factors of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitors (TKI) with immune checkpoint inhibitors (ICIs) in the treatment of uHCC. A retrospective analysis of 171 patients with uHCC was performed in our hospital from April 27, 2015 to October 18, 2021. According to different treatment options, patients were divided into TACE group (n=45), TACE+TKI group (n=76) and TACE+TKI+ICIs group (n=50). In this study, we found that, the median overall survival (mOS) of TACE+TKI+ICIs group was significantly better than TACE+TKI group and TACE group [24.1 (95% CI 15.1-33.1) months vs 14.9 (95% CI 10.7-19.1) months vs 11.4 (95% CI 8.4-14.5) months, hazard ratio (HR) 0.62; 95% CI 0.47-0.81; P=0.002]. A visible difference in the median progression-free survival (mPFS) interval between the groups was discovered [10.6 (95% CI6.5-14.7) months in TACE+TKI+ICIs group vs. 6.7 (95% CI 5.5-7.9) months in the TACE+TKI group vs. 6 (95% CI 2.3-9.7) months in the TACE group (HR 0.66; 95% CI 0.53-0.83; P<0.001)]. The objective response rates (ORR) in the TACE group, TACE+TKI group, and TACE+TKI+ICIs group were 31.1%, 35.5%, and 42%, and the disease control rate (DCR) were 51.1%, 65.8%, and 80%. There were no adverse events (AEs) of arthralgia, diarrhea, rash, and pruritus in the TACE group. The incidence of grade 3 AEs (Hypertension) in the TACE+TKI+ICIs group was significantly higher than that in TACE+TKI and TACE groups (28% vs 17.1% vs 6.7%, P=0.024), and secondly, the morbidity of rash and pruritus in the TACE+TKI+ICIs group was apparently higher than that in the TACE+TKI group (P<0.05). Multivariate analysis showed that ECOG-PS 2 (HR=2.064, 95%CI 1.335-3.191, P=0.001), Hepatitis B virus (HR=2.539, 95%CI 1.291-4.993, P=0.007), AFP≥400 ng/ml (HR= 1.72, 95%CI 1.12-2.643, P=0.013), neutrophil-lymphocyte ratio (NLR) ≥2.195 (HR=1.669, 95%CI 1.073-2.597, P=0.023) were independent risk factors for OS in uHCC patients. So, TACE+TKI+ICIs therapy can prolong the OS and improve the prognosis of patients effectively, with a well-characterized safety profile.

Background: Disseminating disease knowledge through concise videos on various platforms is an innovative and efficient approach. However, it remains uncertain whether pancreatic neuroendocrine tumor (pNET)-related videos available on current short video platforms can effectively convey accurate and impactful information to the general public. Objective: Our study aims to extensively analyze the quality of pNET-related videos on TikTok and Bilibili, intending to enhance the development of pNET-related social media content to provide the general public with more comprehensive and suitable avenues for accessing pNET-related information. Methods: A total of 168 qualifying videos pertaining to pNETs were evaluated from the video-sharing platforms Bilibili and TikTok. Initially, the fundamental information conveyed in the videos was documented. Subsequently, we discerned the source and content type of each video. Following that, the Global Quality Scale (GQS) and modified DISCERN (mDISCERN) scale were employed to appraise the educational value and quality of each video. A comparative evaluation was conducted on the videos obtained from these two platforms. Results: The number of pNET-related videos saw a significant increase since 2020, with 9 videos in 2020, 19 videos in 2021, 29 videos in 2022, and 106 videos in 2023. There were no significant improvements in the mean GQS or mDISCERN scores from 2020 to 2023, which were 3.22 and 3.00 in 2020, 3.33 and 2.94 in 2021, 2.83 and 2.79 in 2022, and 2.78 and 2.94 in 2023, respectively. The average quality scores of the videos on Bilibili and Tiktok were comparable, with GQS and mDISCERN scores of 2.98 on Bilibili versus 2.77 on TikTok and 2.82 on Bilibili versus 3.05 on TikTok, respectively. The source and format of the videos remained independent factors affecting the two quality scores. Videos that were uploaded by professionals (hazard ratio=7.02, P=.002) and recorded in specialized popular science formats (hazard ratio=12.45, P<.001) tended to exhibit superior quality. Conclusions: This study demonstrates that the number of short videos on pNETs has increased in recent years, but video quality has not improved significantly. This comprehensive analysis shows that the source and format of videos are independent factors affecting video quality, which provides potential measures for improving the quality of short videos.

Determining an effective biomarker for predicting the prognosis of patients with hepatocellular carcinoma (HCC) may improve patient survival rates. The present study aimed to investigate the expression of glucose transporter 3 (GLUT‑3) in HCC and to determine its predictive value for the survival of patients with HCC. Immunohistochemistry was used to detect GLUT‑3 expression in HCC tissues of 275 and 140 patients with HCC from training and validation cohorts, respectively. The association between GLUT‑3 expression and the clinicopathological characteristics of patients with HCC, and between GLUT‑3 expression and patient survival rates were analyzed. The predictive value of GLUT‑3 expression was confirmed using the validation cohort. The results demonstrated that the high GLUT‑3 expression in HCC tissues was significantly associated with elevated α‑fetoprotein level, large tumor size, poor histological differentiation and Tumor‑Node‑Metastasis stages III and IV (P<0.05). In addition, GLUT‑3 high expression was also significantly associated with reduced overall survival of patients with HCC in the training and validation cohorts. In conclusion, the results from the present study suggested that GLUT‑3 may be considered as a potential independent prognostic factor for predicting the survival of patients with HCC.

Purpose: Monocarboxylate transporter 4 (MCT4) is an important component of cancer cell glycolytic metabolism. It has been confirmed that MCT4 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues and is significantly associated with poor prognosis of HCC patients. However, research on its downstream molecules that affect HCC is still insufficient. The aim of current research was to investigate the MCT downstream molecule and its role of in HCC development. Patients and Methods: After MCT4 expression was knocked down by RNA interference, RNA sequencing and quantitative real-time PCR were used to screen for differentially expressed genes in an HCC cell line (HCCLM3). Immunohistochemistry in HCC tissue microarray was carried out to evaluate the Trafficking Protein Particle Complex Subunit 5 (TRAPPC5) expression. Cell proliferation, migration, and invasion were evaluated by CCK-8 assay, colony formation assay, transwell and wound-healing test, respectively. Xenograft experiment was employed to investigate the function of TRAPPC5 on tumor growth in vivo. Related signaling pathway proteins were evaluated by Western blot. Results: TRAPPC5 expression was significantly downregulated after knocking down of MCT4 in HCCLM3. TRAPPC5 was highly expressed in HCC tissues, and it could enhance the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) process of HCC cells. In vivo experiment showed that TRAPPC5 could promote HCC tumorigenesis. Conclusion: In the process of MCT4 affecting the progression of HCC, TRAPPC5 is one of the most important related molecules. TRAPPC5 suppression could significantly reduce HCC cell proliferation, migration and invasion and could serve as a therapeutic target in HCC.

The incidence of non-alcoholic fatty liver (NAFLD) remains high, and many NAFLD patients suffer from severe ischemia-reperfusion injury (IRI). Currently, no practical approach can be used to treat IRI. Puerarin plays a vital role in treating multiple diseases, such as NAFLD, stroke, diabetes, and high blood pressure. However, its role in the IRI of the fatty liver is still unclear. We aimed to explore whether puerarin could protect the fatty liver from IRI. C57BL/6J mice were fed with a high‐fat diet (HFD) followed by ischemia reperfusion injury. We showed that hepatic IRI was more severe in the fatty liver compared with the normal liver, and puerarin could significantly protect the fatty liver against IRI and alleviate oxidative stress. The PI3K-AKT signaling pathway was activated during IRI, while liver steatosis decreased the level of activation. Puerarin significantly protected the fatty liver from IRI by reactivating the PI3K-AKT signaling pathway. However, LY294002, a PI3K-AKT inhibitor, attenuated the protective effect of puerarin. In conclusion, puerarin could significantly protect the fatty liver against IRI by activating the PI3K-AKT signaling pathway.