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Major research efforts in liver cancer have been devoted to increasing the efficacy and effectiveness of surveillance for hepatocellular carcinoma (HCC). As with other cancers, surveillance programmes aim to detect tumours at an early stage, facilitate curative-intent treatment, and reduce cancer-related mortality. HCC surveillance is supported by a large randomised-controlled trial in patients with chronic HBV infection and several cohort studies in cirrhosis; however, effectiveness in clinical practice is limited by several barriers, including inadequate risk stratification, underuse of surveillance, and suboptimal accuracy of screening tests. There are several proposed strategies to address these limitations, including risk stratification algorithms and biomarkers to better identity at-risk individuals, interventions to increase surveillance, and emerging imaging- and blood-based surveillance tests with improved sensitivity and specificity for early HCC detection. Beyond clinical validation, data are needed to establish clinical utility, i.e. increased early tumour detection and reduced HCC-related mortality. If successful, these data could facilitate a precision screening paradigm in which surveillance strategies are tailored to individual HCC risk to maximise overall surveillance value. However, practical and logistical considerations must be considered when designing and implementing these validation efforts. To address these issues, ILCA (the International Liver Cancer Association) adjourned a single topic workshop on HCC risk stratification and surveillance in June 2022. Herein, we present a white paper on these topics, including the status of the field, ongoing research efforts, and barriers to the translation of emerging strategies. [ABSTRACT FROM AUTHOR]

The last 5 years have witnessed relevant advances in the systemic treatment of hepatocellular carcinoma. New data have emerged since the development of the EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma in 2018. Drugs licensed in some countries now include 4 oral multi-tyrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 4 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, nivolumab and pembrolizumab in monotherapy). Prolonged survival in excess of 2 years can be expected in most patients with sensitive tumours and well-preserved liver function that renders them fit for sequential therapies. With different choices available in any given setting, the robustness of the evidence of efficacy and a correct matching of the safety profile of a given agent with patient characteristics and preferences are key in making sound therapeutic decisions. The recommendations in this document amend the previous EASL Clinical Practice Guidelines and aim to help clinicians provide the best possible care for patients today. In view of several ongoing and promising trials, further advances in systemic therapy of hepatocellular carcinoma are foreseen in the near future and these recommendations will have to be updated regularly. [ABSTRACT FROM AUTHOR]

Hepatitis B and C virus, Opisthorchis viverrini and Clonorchis sinensis, are all individually known to put a person at increased risk for cholangiocarcinoma and hepatocellular carcinoma. This paper seeks to determine if there is any interaction between liver flukes and hepatitis virus infection that are known to put a person at an increased risk for cholangiocarcinoma and hepatocellular carcinoma collectively. This paper seeks to determine whether there is any publicly available articles in English that determine if having a hepatitis viral co-infection along with liver flukes would influence the risk of developing liver cancer. We followed PRISMA systematic review guidelines to conduct a literature review. Three manuscripts fit the search criteria. Two presented evidence in support of a synergistic relationship between liver fluke and viral hepatitis infection while the other found no relationship. One manuscript determined that the interaction between hepatitis B and C. sinensis did not have any significant risk of liver cancer. Studies found that HBV affected progression of co-infection to liver cancer but may have its own disease state worsened by presence of liver flukes. Only one paper was found that presented data on HCV, therefore no conclusion can be drawn due to the lack of evidence discovered. Of the studies, the conclusions and strength of the data were mixed. However, the stronger studies suggested a synergistic relationship between liver flukes and HBV to increase the risk of progressing to liver cancer. [ABSTRACT FROM AUTHOR]

Liver cancer is the second leading cause of cancer death worldwide. Early tumor detection may help identify suitable treatment and increase the survival rate. Medical imaging is a non-invasive tool that can help uncover abnormalities in human organs. Magnetic Resonance Imaging (MRI), in particular, uses magnetic fields and radio waves to differentiate internal human organs tissue. However, the interpretation of medical images requires the subjective expertise of a radiologist and oncologist. Thus, building an automated diagnosis computer-based system can help specialists reduce incorrect diagnoses. This paper proposes a hybrid automated system to compare the performance of 3D features and 2D features in classifying magnetic resonance liver tumor images. This paper proposed two models; the first one employed the 3D features while the second exploited the 2D features. The first system uses 3D texture attributes, 3D shape features, and 3D graphical deep descriptors beside an ensemble classifier to differentiate between four 3D tumor categories. On top of that, the proposed method is applied to 2D slices for comparison purposes. The proposed approach attained 100% accuracy in discriminating between all types of tumors, 100% Area Under the Curve (AUC), 100% sensitivity, and 100% specificity and precision as well in 3D liver tumors. On the other hand, the performance is lower in 2D classification. The maximum accuracy reached 96.4% for two classes and 92.1% for four classes. The top-class performance of the proposed system can be attributed to the exploitation of various types of feature selection methods besides utilizing the ReliefF features selection technique to choose the most relevant features associated with different classes. The novelty of this work appeared in building a highly accurate system under specific circumstances without any processing for the images and human input, besides comparing the performance between 2D and 3D classification. In the future, the presented work can be extended to be used in the huge dataset. Then, it can be a reliable, efficient Computer Aided Diagnosis (CAD) system employed in hospitals in rural areas. [ABSTRACT FROM AUTHOR]

Automatic segmentation of the liver in abdominal CT images is critical for guiding liver cancer biopsies and treatment planning. Yet, automatic segmentation of CT liver images remains challenging due to the poor contrast between the liver and surrounding organs in abdominal CT images. In this paper, we propose a novel network for liver segmentation, and the network is essentially a U-shaped network with an encoder–decoder structure. Firstly, the complementary feature enhancement unit is designed in the network to mitigate the semantic gap between encoder and decoder. The complementary feature enhancement unit is based on subtraction, which enhances the complementary features between encoder and decoder. Secondly, this paper proposes a new cross attention model that no longer generates value by convolution, which reduces redundant information and enhances the contextual information of single sparse attention by encoding contextual information by 3 × 3 convolution. The dice score, accuracy, and precision of our network on the LiTS dataset were 95.85 % , 97.19 % , and 97.11 % , and the dice score, accuracy, and precision on the dataset consisted of 3Dircadb and CHAOS were 93.65 % , 94.38 % , and 97.53 % . [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC), recognized as a significant global health concern, ranks as the sixth most prevalent form of cancer and is the third leading cause of cancer-associated mortality. Over half of HCC patients are diagnosed at advanced stages, an unfortunate phenomenon primarily attributed to the liver’s robust compensatory mechanisms. Given the limited availability of donor livers, existing clinical surgical approaches have yet to provide universally applicable treatment strategies offering substantial prognostic improvement for late-stage cancer. Although the past few decades have witnessed significant advancements in chemotherapy and targeted therapy for HCC, the emergence of drug resistance poses a substantial impediment to their successful execution. Furthermore, issues such as diminished quality of life post-treatment and high treatment costs warrant critical attention. Consequently, the imperative for an effective treatment strategy for advanced liver cancer is unequivocal. In recent years, notable progress in the development and application of immunotherapy has sparked a revolution in advanced liver cancer treatment. This study aims to elucidate a more comprehensive understanding of the current landscape, knowledge framework, research focal points, and nascent breakthrough trends in the domain of immunotherapy for hepatocellular carcinoma via bibliometric analysis. Method: Our study involved conducting a comprehensive literature search spanning from 1999 through December 31, 2022, by utilizing the Science Citation Index Expanded (SCI-Expanded) database. Our aim was to amass all the papers and reviews related to immunotherapy for hepatocellular carcinoma. Our search strategy yielded a total of 4,486 papers. After exclusion of selfcitations, we focused our analysis on 68,925 references. These references were cited 119,523 times (excluding 97,941 self-citations), boasting an average citation frequency of 26.64 times per paper, and achieved an h-index of 135. We employed analytical software tools like Citespace and VOSviewer to perform an intricate analysis of the amassed literature, covering various aspects, including geographical location, research institutions, publishing journals, authors, references, and keywords. Our method incorporated timeline analysis, burst detection, and co-occurrence analysis. The application of these tools facilitated a thorough evaluation of research hotspots, knowledge structure, and emerging advancements within the sphere of immunotherapy for hepatocellular carcinoma. Results: Our bibliometric analysis disclosed a noteworthy escalation in the number of publications in the realm of hepatocellular carcinoma immunotherapy during the years 2021-2022, surpassing the aggregate number of papers published in the preceding decade (2011–2020). This surge underscores a sharp upturn in research interest within this field. Additionally, the research hotspot in hepatocellular carcinoma immunotherapy has perceptibly deviated from the preceding decade’s trends. In terms of geographical distribution, China emerged as the leading country, producing 50.08% of the total publications. This was followed by the United States, with 963 papers, and Japan, contributing 335 papers. Among research institutions, Sun Yat-sen University was the most prolific, while Tim F. Greten stood out as the most published author with 42 papers to his credit. A co-reference network examination uncovered a shift in research emphasis within the field of hepatocellular carcinoma immunotherapy, highlighting the evolving nature of this important area of study Conclusion: Our bibliometric study highlights the significant evolution and growth in HCC immunotherapy research over the past two decades. Looking ahead, research will focus on improving the microenvironment post-drug resistance from immune combination therapy, harnessing adoptive cellular immunity (as CAR-T), subclassify the population and developing new tumor markers. Incorporation of technologies such as nanotechnology, microbiology, and gene editing will further advance HCC treatments. This progressive trajectory in the field promises a brighter future for individuals suffering from HCC. [ABSTRACT FROM AUTHOR]

An important issue in interconnected microgrids (MGs) is the realization of balance between the generation side and the demand side. Imbalanced generation and load demands lead to security, power quality, and reliability issues. The load frequency control (LFC) is accountable for regulating MG frequency against generation/load disturbances. This paper proposed an optimized fractional order (FO) LFC scheme with cascaded outer and inner control loops. The proposed controller is based on a cascaded one plus tilt derivative (1+TD) in the outer loop and an FO tilt integrator-derivative with a filter (FOTIDF) in the inner loop, forming the cascaded (1+TD/FOTIDF) controller. The proposed 1+TD/FOTIDF achieves better disturbance rejection compared with traditional LFC methods. The proposed 1+TD/FOTIDF scheme is optimally designed using a modified version of the liver cancer optimization algorithm (MLCA). In this paper, a new modified liver cancer optimization algorithm (MLCA) is proposed to overcome the shortcomings of the standard Liver cancer optimization algorithm (LCA), which contains the early convergence to local optima and the debility of its exploration process. The proposed MLCA is based on three improvement mechanisms, including chaotic mutation (CM), quasi-oppositional based learning (QOBL), and the fitness distance balance (FDB). The proposed MLCA method simultaneously adjusts and selects the best 1+TD/FOTIDF parameters to achieve the best control performance of MGs. Obtained results are compared to other designed FOTID, TI/FOTID, and TD/FOTID controllers. Moreover, the contribution of electric vehicles and the high penetration of renewables are considered with power system parameter uncertainty to test the stability of the proposed 1+TD/FOTIDF LFC technique. The obtained results under different possible load/generation disturbance scenarios confirm a superior response and improved performance of the proposed 1+TD/FOTIDF and the proposed MLCA-based optimized LFC controller. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma accounts for 80% of primary liver cancers, is the most common primary liver malignancy. Hepatocellular carcinoma is the third leading cause of tumor-related deaths worldwide, with a 5-year survival rate of approximately 18%. Chemotherapy, although commonly used for hepatocellular carcinoma treatment, is limited by systemic toxicity and drug resistance. Improving targeted delivery of chemotherapy drugs to tumor cells without causing systemic side effects is a current research focus. Chitosan, a biopolymer derived from chitin, possesses good biocompatibility and biodegradability, making it suitable for drug delivery. Enhanced chitosan formulations retain the anti-tumor properties while improving stability. Chitosan-based biomaterials promote hepatocellular carcinoma apoptosis, exhibit antioxidant and anti-inflammatory effects, inhibit tumor angiogenesis, and improve extracellular matrix remodeling for enhanced anti-tumor therapy. Methods: We summarized published experimental papers by querying them. Results and Conclusions: This review discusses the physicochemical properties of chitosan, its application in hepatocellular carcinoma treatment, and the challenges faced by chitosan-based biomaterials. [ABSTRACT FROM AUTHOR]

Purpose: Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer that could potentially be surrounded by healthy arteries or veins that a surgeon would have to avoid during treatment. A realistic 3D liver model is an unmet need for HCC preoperative planning. Methods: This paper presents a method to create a soft phantom model of the human liver with the help of a 3D-printed mold, silicone, ballistic gel, and a blender. Results: For silicone, the elastic modulus of seven different ratios of base silicone and silicone hardener are tested; while for ballistic gel, a model using 20% gelatin and 10% gelatin is created for the tumor and the rest of the liver, respectively. It is found that the silicone modulus of elasticity matches with the real liver modulus of elasticity. It is also found that the 10% gelatin part of the ballistic gel model is an excellent emulation of a healthy human liver. Conclusion: The 3D flexible liver phantom made from a 10% gelatin-to-water mixture demonstrates decent fidelity to real liver tissue in terms of texture and elasticity. It holds significant potential for improving medical training, preoperative planning, and surgical research. We believe that continued development and validation of such models could further enhance their utility and impact in the field of hepatobiliary treatment planning and education. [ABSTRACT FROM AUTHOR]

A novel cholic acid-conjugated carboplatin (CP-CA) is developed as a liver-targeting prodrug of carboplatin (CP) for liver cancer. Instead of using CP as a raw material, CP-CA was synthesized simultaneously. This paper is focused on the comparison of CP-CA and CP with respect to their pharmacokinetic (PK) and tissue distribution profiles in rats after their intravenous administration. Additionally, their uptake by human liver tumor cell Huh7 and normal human liver cell HL7702 are investigated. The inductively coupled plasma mass spectrometry (ICP-MS) method is applied for the determination of platinum in plasma, tissues, and cells. The PK results show that both the AUC0–t and AUC0–∞ data on Pt for CP-CA are significantly higher than those for CP (p < 0.01), indicating that the plasma exposure of CP-CA is significantly higher than that of CP. The CL1, Vd1, and Vd2 data on Pt for CP-CA are significantly lower than those for CP (p < 0.01), while the MRT0–t is significantly higher (p < 0.01), which is possibly related to a higher PPBR, and can strongly support the higher AUC0–t and AUC0–∞ of Pt for CP-CA compared to for CP. The tissue distribution results show that CP-CA is mainly distributed and accumulated in the liver after its intravenous administration to rats, revealing its liver-targeting profile. Compared to CP, CP-CA is more easily taken up by human liver cancer cells and normal human liver cells. The results suggest that CP-CA has a potential for further development as a new prodrug specific to liver cancer. [ABSTRACT FROM AUTHOR]

One of the most frequent malignant tumors seen in clinics is primary liver cancer, also referred to as the "king of cancers." Therefore, the necessity for an effective and precise detection technique is urgent. Compared with the cantilever beam, the double-ended clamped beam has the characteristics of higher resonance frequency and stronger noise immunity, so it has a good application prospect as a biosensor. This paper takes the double-ended clamped beam biosensor as the object and focuses on the method that can be applied to the early diagnosis and detection of liver cancer. The manufacturing process of the double-ended clamped beam and the biofunctional modification of the beam surface were introduced. Meantime, this paper introduces the integration of the composite double-ended clamped beam biosensor system. As a result, a high-sensitivity, high-reliability in situ real-time monitoring technology for early-stage liver cancer is proposed. A composite double-ended clamped beam made of silicon and silicon nitride is used. The size of the double-ended clamped beam is 280 µm × 50µm × 5µm. This paper provides a low-cost, portable, and rapid early diagnosis method for liver cancer, which has very significant application value in the field of early cancer screening. [ABSTRACT FROM AUTHOR]

Tumour development is not only an independent event of genetic mutation and overgrowth of tumour cells but is the result of a synergistic interaction between a malignant tumour and its surrounding tumour stromal microenvironment. In this paper, we address the shortcomings of current tumour therapy by focussing on the tumour itself and the surrounding microenvironment to achieve a two-pronged targeting model. In this paper, a dual-targeting, pH/reactive oxygen species (ROS) sensitive nano-drug delivery system for tumour cells and CAFs was designed. A hyaluronic acid (HA) with CD44 receptor targeting on the surface of tumour cells was selected as the main carrier material, and a dipeptide Z-glycine-proline (ZGP) with specific targeting of fibroblast activating protein (FAP) on the surface of CAFs was modified on HA to achieve precise targeting of CAFs, open the physical barrier of tumour cells and improve the deep penetration effect of the tumour, while introducing thioketone bond and ketone condensation bond to take advantage of the highly reactive ROS and low pH microenvironment at the tumour site to achieve chemical bond breaking of nano micelles encapsulating paclitaxel (PTX), drug release, and thus drug aggregation at the tumour site and improved bioavailability of the drug. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B is a major public health concern as one third of the world's population is infected with hepatitis B virus (HBV). The risk of HBV infection remains primarily through percutaneous or mucosal contact with infected blood or body fluids. Aim: To update the society on hepatitis B immunization strategies and its associated factors. Materials and Methods: The review paper utilized different search engines such as Pubmed Central, Scopus, Web of Science, Google Scholar, and so on to conduct this review paper. Results: Improving immunity through general vaccination recommendations has reduced the number of chronic hepatitis B cases among children and adolescents, but an influx of infections from endemic countries has increased the number of chronically infected adults. This is due to immigration from endemic countries to Hepatitis less burden areas like developed countries. Introduction of infant immunization programs in some countries has reportedly reduced the prevalence of HBV infection and reduced the incidence of liver cancer in children and young adults. Conclusion: While hepatitis B vaccination coverage is low, a significant number of people are not adhering to full hepatitis B vaccination posing a potential hazard to health. [ABSTRACT FROM AUTHOR]

According to a paper released and submitted to WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as a direct result. Hepatitis B virus (HBV) hepatitis C virus (HCV), and hepatitis D virus (HDV) all play critical roles in the pathogenesis of hepatocellular carcinoma (HCC), despite the rising prevalence of HCC due to non-infectious causes. Liver cirrhosis and HCC are devastating consequences of HBV and HCV infections, which are widespread worldwide. Associated with a high mortality rate, these infections cause about 1.3 million deaths annually and are the primary cause of HCC globally. In addition to causing insertional mutations due to viral gene integration, epigenetic alterations and inducing chronic immunological dysfunction are all methods by which these viruses turn hepatocytes into cancerous ones. While expanding our knowledge of the illness, identifying these pathways also give possibilities for novel diagnostic and treatment methods. Nuclear factor erythroid 2-related factor 2 (NRF2) activation is gaining popularity as a treatment option for oxidative stress (OS), inflammation, and metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression is linked to HCC, providing more evidence that Nrf2 is a critical factor in HCC. This aberrant Nrf2 signaling drives cell proliferation, initiates angiogenesis and invasion, and imparts drug resistance. As a result, this master regulator may be a promising treatment target for HCC. In addition, the activation of Nrf2 is a common viral effect that contributes to the pathogenesis, development, and chronicity of virus infection. However, certain viruses suppress Nrf2 activity, which is helpful to the virus in maintaining cellular homeostasis. In this paper, we discussed the influence of Nrf2 deregulation on the viral life cycle and the pathogenesis associated with HBV and HCV. We summed up the mechanisms for the modulation of Nrf2 that are deregulated by these viruses. Moreover, we describe the molecular mechanism by which Nrf2 is modulated in liver cancer, liver cancer stem cells (LCSCs), and liver cancer caused by HBV and HCV. EW1h6cVcK6kCY2-xSiZ8DW Video Abstract [ABSTRACT FROM AUTHOR]

Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods. [ABSTRACT FROM AUTHOR]

Background: In the precision medicine era, identifying predictive factors to select patients most likely to benefit from treatment with immunological agents is a crucial and open challenge in oncology. Methods: This paper presents a pan-cancer analysis of Tumor Mutational Burden (TMB). We developed a novel computational pipeline, TMBcalc, to calculate the TMB. Our methodology can identify small and reliable gene signatures to estimate TMB from custom targeted-sequencing panels. For this purpose, our pipeline has been trained on top of 17 cancer types data obtained from TCGA. Results: Our results show that TMB, computed through the identified signature, strongly correlates with TMB obtained from whole-exome sequencing (WES). Conclusion: We have rigorously analyzed the effectiveness of our methodology on top of several independent datasets. In particular we conducted a comprehensive testing on: (i) 126 samples sourced from the TCGA database; few independent whole-exome sequencing (WES) datasets linked to colon, breast, and liver cancers, all acquired from the EGA and the ICGC Data Portal. This rigorous evaluation clearly highlights the robustness and practicality of our approach, positioning it as a promising avenue for driving substantial progress within the realm of clinical practice. [ABSTRACT FROM AUTHOR]

Organoids present substantial potential for pushing forward preclinical research and personalized medicine by accurately recapitulating tissue and tumor heterogeneity in vitro. However, the lack of standardized protocols for cancer organoid culture has hindered reproducibility. This paper comprehensively reviews the current challenges associated with cancer organoid culture and highlights recent multidisciplinary advancements in the field with a specific focus on standardizing liver cancer organoid culture. We discuss the non-standardized aspects, including tissue sources, processing techniques, medium formulations, and matrix materials, that contribute to technical variability. Furthermore, we emphasize the need to establish reproducible platforms that accurately preserve the genetic, proteomic, morphological, and pharmacotypic features of the parent tumor. At the end of each section, our focus shifts to organoid culture standardization in primary liver cancer. By addressing these challenges, we can enhance the reproducibility and clinical translation of cancer organoid systems, enabling their potential applications in precision medicine, drug screening, and preclinical research. [ABSTRACT FROM AUTHOR]

Liver segmentation from abdominal computed tomography (CT) images is a primary step in the diagnosis and treatment of liver cancer, but previous liver segmentation methods have the problems of excessive demand for prior knowledge, under- and oversegmentation, and boundary leakage. To solve these problems, this paper proposes a new method of liver segmentation to assist doctors in medical judgment. Firstly, a liver reconstruction algorithm is proposed to obtain the approximate initial region of the liver, which reduces the requirement of prior knowledge and can reconstruct the liver region closer to the liver boundary. Then, we refine the edge of the liver region based on the reaction diffusion level set (RD level set). This edge refinement method can effectively deal with the weak boundary problem, prevent under- and oversegmentation, and obtain a more accurate liver region. Our method is verified on the clinical and public datasets, respectively. The segmentation results in terms of mean VOE, RVD, ASD, RMSD, and MSD on dataset Sliver07 are 5.1%, −0.1%, 1.0 mm, 2.0 mm, and 18.2 mm, and on dataset 3Dircadb are 8.1%, −0.2%, 1.5 mm, 2.4 mm, and 20.8 mm, respectively. Compared with the previous algorithms, the experiment results show that this method has a great improvement in accuracy with less prior knowledge. The liver reconstruction algorithm proposed in this paper can obtain a more accurate initial liver region, reduce the requirement for prior knowledge, and reduce time costs compared with the level set algorithm. [ABSTRACT FROM AUTHOR]

Background: Liver cancer (LC) is one of the most common malignancies. Currently, nanotechnology has made great progress in LC research, and many studies on LC nanotechnology have been published. This study aims to discuss the current status, hot spots, and research trends in this field through bibliometric analysis. Methods: The Web of Science Core Collection (WoSCC) database was searched for papers related to hepatocellular carcinoma (HCC) included from January 2000 to November 2022, and its research hotspots and trends were visualized and analyzed with the help of VOSviewer. In addition, a search was conducted to find LC papers related to nanotechnology. Then we used the visual analysis software VOSviewer and CiteSpace to evaluate the contributions of countries/ regions, authors, and journals related to the topic and analyze keywords to understand the research priorities and hot spots in the field as well as the development direction. Results: There are 1908 papers in the highly cited literature on LC, and its research hotspots are pathogenesis, risk factors, and survival rate. The literature on the application of nanotechnology in LC had 921 papers. Among them, China (n=560, 60.8%) and the United States (n=170, 18.5%) were the countries with the highest number of published papers. Wang Yan (n=11) and Llovet JM (n=131) were the first authors and co-cited authors, respectively. The International Journal of Nanomedicine was the most prolific academic journal (n=41). In addition to “hepatocellular carcinoma” and “nanoparticles”, the most frequent keyword was “drug delivery”. In recent years, “metastasis” and “diagnosis” appeared in the keyword bursts. This indicates that the application of nanoparticles in the early diagnosis and drug delivery of LC (including liver metastasis) has a good prospect. Conclusion: Nanotechnology has received more and more attention in the medical field in recent years. As nanoparticles are easily localized in organelles and cells, they can increase drug permeability in tumor tissues, improve drug delivery efficiency and reduce drug toxicity. Our research results were the first scientific evaluation of the application of nanotechnology in LC, providing scholars with research hotspots and development trends. [ABSTRACT FROM AUTHOR]

Objective: Traditional Chinese medicine (TCM) has been used as a complementary treatment for cancer patients, but there has been no quantitative comprehensive analysis of TCM's efficacy. The purpose of this paper is to explore the current status and hotspots of TCM in cancer research from 2002 to 2022 and to provide a reference for future research. Methods: We retrieved articles published between 2002 and 2022 from the Web of Science database and analyzed them using R software, VOSviewer, and CiteSpace software. Results: A total of 7,129 articles were included in this study. The publication rate of TCM cancer research increased steadily from 2002 to 2022, with a rapid increase from 2010 to 2021. China was the country with the most published articles, followed by the United States, Republic of Korea, Germany, and Japan. China was also the country with the most international collaborations, and China Medical University and Shanghai University of Traditional Chinese Medicine were the most representative cooperation centers. The Journal of Ethnopharmacology was the most published and cited journal. Apoptosis, expression, in vitro, activation, and other related keywords were commonly used in these articles. Breast cancer, colorectal cancer, gastric cancer, liver cancer, and lung cancer were the most studied cancer types in TCM research. Pathway-related apoptosis, antiinflammation, and oxidative stress were the hotspots and trends of TCM's anticancer mechanism. Metabolomics combined with network pharmacology was the main research method. Conclusion: Traditional Chinese medicine as an anti-cancer drug has received increasing attention from researchers worldwide, and it is expected to be a hotspot for developing new anti-cancer drugs in the future. Our study provides a comprehensive analysis of the current status and hotspots of TCM cancer research, which could serve as a valuable reference for future studies. [ABSTRACT FROM AUTHOR]

This article aims to develop an aspirin-loaded double-modified nano-delivery system for the treatment of hepatocellular carcinoma. In this paper, mesoporous silica nanoparticles (MSN) were prepared by the "one-pot two-phase layering method", and polydopamine (PDA) was formed by the self-polymerization of dopamine as a pH-sensitive coating. Gal-modified PDA-modified nanoparticles (Gal-PDA-MSN) were synthesized by linking galactosamine (Gal) with actively targeted galactosamine (Gal) to PDA-coated MSN by a Michael addition reaction. The size, particle size distribution, surface morphology, BET surface area, mesoporous size, and pore volume of the prepared nanoparticles were characterized, and their drug load and drug release behavior in vitro were investigated. Gal-PDA-MSN is pH sensitive and targeted. MSN@Asp is different from the release curves of PDA-MSN@Asp and Gal-PDA-MSN@Asp, the drug release of PDA-MSN@Asp and Gal-PDA-MSN@Asp accelerates with increasing acidity. In vitro experiments showed that the toxicity and inhibitory effects of the three nanodrugs on human liver cancer HepG2 cells were higher than those of free Asp. This drug delivery system facilitates controlled release and targeted therapy. [ABSTRACT FROM AUTHOR]

The term "Liver disease" refers to a broad category of disorders affecting the liver. There are a variety of common liver ailments, such as hepatitis, cirrhosis, and liver cancer. Accurate and early diagnosis is an emergent demand for the prediction and diagnosis of liver disease. Conventional diagnostic techniques, such as radiological, CT scan, and liver function tests, are often time-consuming and prone to inaccuracies in several cases. An application of machine learning (ML) and deep learning (DL) techniques is an efficient approach to diagnosing diseases in a wide range of medical fields. This type of machine-related learning can handle various tasks, such as image recognition, analysis, and classification, because it helps train large datasets and learns to identify patterns that might not be perceived by humans. This paper is presented here with an evaluation of the performance of various DL models on the estimation and subtyping of liver ailment and prognosis. In this manuscript, we propose a novel approach, termed CNN+LSTM, which is an integration of convolutional neural network (CNN) and long short-term memory (LSTM) networks. The results of the study prove that ML and DL can be used to improve the diagnosis and prognosis of liver disease. The CNN+LSTM model achieves a better accuracy of 98.73% compared to other models such as CNN, Recurrent Neural Network (RNN), and LSTM. The incorporation of the proposed CNN+LSTM model has better results in terms of accuracy (98.73%), precision (99%), recall (98%), F1 score (98%), and AUC (Area Under the Curve)-ROC (Receiver Operating Characteristic) (99%), respectively. The use of the CNN+LSTM model shows robustness in predicting the liver ailment with an accurate diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Metastasis is one of the leading causes of cancer-related deaths. A comprehensive comparison of the differences between primary and metastatic cancers within the same organ can aid in understanding the growth mechanisms of cancer cells at metastatic sites, thereby helping to develop more effective targeted treatment strategies. Primary liver cancer is one of the most common types of cancer, and the liver is also one of the main metastatic sites. In this paper, we utilize single-cell RNA-Seq data to compare primary liver cancer and colorectal liver metastases from multiple perspectives, including cell types and proportions, activity of various cell types, cell–cell communication, mRNA expression differences within the same types of cells, key factors associated with cell proliferation, etc. Our analysis results show the following: (i) Compared to primary tissue, metastatic tissue contains more cytotoxic T cells and exhausted T cells, and it retains some specific characteristics of the primary site. (ii) Cells of the same type exhibit functional differences between primary and metastatic cancers, with metastatic cancer cells showing lower metabolism levels and immune cells exhibiting stronger immune activity. (iii) Interactions between monocytes and hepato-associated cells are strong in primary cancer, while depleted T cells frequently communicate with hepatocytes in metastatic cancer. (iv) Proliferation-related genes in primary and metastatic cancers are mainly involved in cell energy supply and basic metabolism activity, respectively. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) cancers comprise a significant number of cancer cases worldwide and contribute to a high percentage of cancer-related deaths. To improve survival rates of GI cancer patients, it is important to find and implement more effective therapeutic strategies with better prognoses and fewer side effects. The development of new drugs can be a lengthy and expensive process, often involving clinical trials that may fail in the early stages. One strategy to address these challenges is drug repurposing (DR). Drug repurposing is a developmental strategy that involves using existing drugs approved for other diseases and leveraging their safety and pharmacological data to explore their potential use in treating different diseases. In this paper, we outline the existing therapeutic strategies and challenges associated with GI cancers and explore DR as a promising alternative approach. We have presented an extensive review of different DR methodologies, research efforts and examples of repurposed drugs within various GI cancer types, such as colorectal, pancreatic and liver cancers. Our aim is to provide a comprehensive overview of employing the DR approach in GI cancers to inform future research endeavors and clinical trials in this field. [ABSTRACT FROM AUTHOR]

Cancer is a devastating and deadly disease, and liver cancer is one of the leading causes of cancer deaths. Early detection of liver tumor is important to choose a treatment plan, get an accurate prognosis, and gain a deep understanding of the tumor to determine its severity. Despite a lot of research, performing automatic segmentation and classification liver tumor is still a challenging task due to the low tissue contrast between the surrounding organs and the deformable shape of the CT image. Therefore, this paper introduces the unified learning multi-task model network for combined automatic liver tumor segmentation and classification. The first step is to build a multi-task deformable attention U-Net (MDAUnet) technique to segment the liver tumor and capture the features for classification. Here, an attention-based deformable module is used instead of convolution to learn the irregular and inconspicuous appearance of tumors by combining context attention and deformable convolution. Further, a residual skip connection is used to avoid duplicate transmission of low-resolution data by introducing a residual path. In the second step, the segmented liver tumor features from MDAUnet are fed into the deep DenseNet (DDNet) model and concatenation layer. Based on the segmented liver tumor features, DDNet learns distinguishable features for classification. The concatenation layer combines the learned features of the MDAUnet and DDNet models for liver tumor classification. Finally, a fully connected layer classifies primary and secondary liver tumors. Therefore, our proposed ULM-net model outperforms single models in terms of precision, F-1 measure, recall, classification accuracy, and kappa coefficient. [ABSTRACT FROM AUTHOR]

Liver cancer is one of the most common cancers in the world and a primary cause of cancer-related death. In recent years, despite the great development of diagnostic methods and targeted therapies for liver cancer, the incidence and mortality of liver cancer are still on the rise. As a universal post-transcriptional modification, N6-methyladenosine (m6A) modification accomplishes a dynamic and reversible m6A modification process, which is executed by three types of regulators, methyltransferases (called writers), demethylases (called erasers) and m6A-binding proteins (called readers). Many studies have shown that m6A RNA methylation has an important impact on RNA metabolism, whereas its regulation exception is bound up with the occurrence of human malignant tumors. Aberrant methylation of m6A RNA and the expression of related regulatory factors may be of the essence in the pathogenesis and progression of liver cancer, yet the precise molecular mechanism remains unclear. In this paper, we review the current research situations of m6A methylation in liver cancer. Among the rest, we detail the mechanism by which methyltransferases, demethylases and m6A binding proteins regulate the occurrence and development of liver cancer by modifying mRNA. As well as the potential effect of m6A regulators in hepatocarcinogenesis and progression. New ideas and approaches will be given to the prevention and treatment of liver cancer through the following relevant research results. [ABSTRACT FROM AUTHOR]

Quercetin is a flavonoid with significant biological and pharmacological activity. In this paper, quercetin was modified at the 3-OH position. Rutin was used as a raw material. We used methyl protection, Williamson etherification reactions, and then substitution reactions to prepare 15 novel quercetin derivatives containing a quinoline moiety. All these complexes were characterized by 1H NMR, 13C NMR, IR and HRMS. Of these, compound 3e (IC50 = 6.722 μmol·L−1) had a better inhibitory effect on human liver cancer (HepG-2) than DDP (Cisplatin) (IC50 = 26.981 μmol·L−1). The mechanism of the action experiment showed that compound 3e could induce cell apoptosis. [ABSTRACT FROM AUTHOR]

One area of cancer research is the interaction between cancer cells and immune cells, in which chemokines play a vital role. Despite this, a comprehensive summary of the involvement of C-X-C motif ligand 1 (CXCL1) chemokine (also known as growth-regulated gene-α (GRO-α), melanoma growth-stimulatory activity (MGSA)) in cancer processes is lacking. To address this gap, this review provides a detailed analysis of CXCL1's role in gastrointestinal cancers, including head and neck cancer, esophageal cancer, gastric cancer, liver cancer (hepatocellular carcinoma (HCC)), cholangiocarcinoma, pancreatic cancer (pancreatic ductal adenocarcinoma), and colorectal cancer (colon cancer and rectal cancer). This paper presents the impact of CXCL1 on various molecular cancer processes, such as cancer cell proliferation, migration, and invasion, lymph node metastasis, angiogenesis, recruitment to the tumor microenvironment, and its effect on immune system cells, such as tumor-associated neutrophils (TAN), regulatory T (Treg) cells, myeloid-derived suppressor cells (MDSCs), and macrophages. Furthermore, this review discusses the association of CXCL1 with clinical aspects of gastrointestinal cancers, including its correlation with tumor size, cancer grade, tumor–node–metastasis (TNM) stage, and patient prognosis. This paper concludes by exploring CXCL1's potential as a therapeutic target in anticancer therapy. [ABSTRACT FROM AUTHOR]

Background: Ranitidine is a generic antacid most commonly sold as Zantac. Ranitidine was popular in the United States even without a prescription until April 2020. The Food and Drug Administration (FDA) came to the conclusion that NDMA levels in ranitidine increased under ordinary storage settings, and that these thresholds increased significantly at higher temperatures. NDMA has been found to be a possible human carcinogen by independent testing, after being reported to become an efficacious carcinogen in experimental animals. Methods: A number of databases, such as PubMed, Cochrane Central Register and EMBASE, were searched to locate all qualified trials for Ranitidine contained NDMA, a carcinogen. In a PubMed search, 664 papers were identified till October 31, 2022, identical articles were removed, and lastly, 8 papers were included for the systemic review and meta-analysis. Results: Figures and tables were used to sum up Meta-regression results and the NDMA ddose-responseanalysis results. Relative Risk (R.R.) was used to assess the relationship between dietary intake of NDMA nitrates and nitrites and cancer risk. In this study, we take a look at the findings from other studies that have been done previously that showed NDMA (nitrosamines) use increased the risk of cancer by a lot. Several studies have also looked at the link between working with or eating NDMA and taking Ranitidine, which has been linked to cancers of the liver, GI tract, esophagus, pancreas, and colon. Conclusions: This study provided a summary of an article on dietary NDMA, including Ranitidine contamination exposure related with a significant statistical increased incidence of gastrointestinal cancers. [ABSTRACT FROM AUTHOR]

Since 1986, the first microcantilever applied in atomic force microscope, the device manufacturing technology, driving method and readout technology have improved significantly. In this paper, five readout technologies will be introduced in detail, and they are optical readout, piezoelectric readout, piezoresistive readout, capacitance readout and electron tunneling readout, respectively. Among them, the piezoresistive readout technology attracts a large number of researchers due to simple detection equipment, easy integration, and lower cost. In order to improve the detection accuracy of the piezoresistive microcantilever, a detection system based on FPGA is proposed in this paper. Output signal of the piezoresistive microcantilever array sensor for alpha-fetoprote (AFP) detection was researched. The detection accuracy of 0.05 Hz is achieved, the system stability is within 0.6 Hz, and it has a precise detection level for AFP with concentration of 50 pg/ml, which makes microcantilever has potential in early diagnosis and detection of liver cancer. [ABSTRACT FROM AUTHOR]

α-Fetoprotein (AFP) is a kind of fetal protein that is related to tumor, the increasing concentration of which gives birth to a large variety of diseases, such as liver cancer. Therefore, the detection method with super sensitivity, high selectivity, and less time consumption under trace concentrations in early stage of diseases is becoming a necessity. In recent years, nanomaterials have been regarded as significant resources for the exploration of efficient biosensors with high sensitivity, selectivity, speed, as well as simple process, due to their excellent optical, electrical, and chemical properties. In this paper, we reviewed the research progress of AFP biosensors with enhanced sensitivity and selectivity by nanoparticles. Representative examples have also been displayed in this paper to expound the nanotechnologies utilized in the early detection of AFP. Furthermore, challenges of the clinical application of AFP biosensors based on nanotechnology have been elaborated, as well as the development opportunity in this field in the future. This review provides a comprehensive overview on the various nano-biosensor for AFP detection based on functional nanotechnology. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer is a common clinical malignant tumor disease that seriously endangers human health and lacks effective treatment methods. As part of the innate immune defense of many organisms, antimicrobial peptides not only have broad-spectrum antibacterial activity but also can specifically kill tumor cells. The positive charge of antimicrobial peptides under neutral conditions determines their high selectivity to tumor cells. In addition, antimicrobial peptides also have unique anticancer mechanisms, such as inducing apoptosis, autophagy, cell cycle arrest, membrane destruction, and inhibition of metastasis, which highlights the low drug resistance and high specificity of antimicrobial peptides. In this review, we summarize the related studies on antimicrobial peptides in the treatment of digestive tract tumors, mainly oral cancer, esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, and colorectal cancer. This paper describes the therapeutic advantages of antimicrobial peptides due to their unique anticancer mechanisms. The length, net charge, and secondary structure of antimicrobial peptides can be modified by design or modification to further enhance their anticancer effects. In summary, as an emerging cancer treatment drug, antimicrobial peptides need to be further studied to realize their application in gastrointestinal cancer diseases. [ABSTRACT FROM AUTHOR]