Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and a leading cause of cancer-related deaths. Standard treatments, such as surgery, chemotherapy, and radiotherapy, frequently fail to produce positive therapeutic outcomes. Thus, it is essential to identify new treatment modalities with improved survival rates. Extracellular vesicles (EVs) are nanosized lipid bilayer vesicles secreted by cells that mediate intercellular communication. EVs have been used to deliver several non-coding RNAs (ncRNAs), including miRNA, circRNA, and lncRNA. These ncRNAs demonstrate excellent tumor-suppressive effects and serve as new therapeutic candidates for HCC. EVs possess several characteristics, including high biocompatibility, enhanced stability, and limited cytotoxicity, making them promising drug-delivery vehicles. Although these characteristics make them better drug carriers than traditional synthetic delivery vehicles, translating engineered EVs into clinical practice has been challenging. In this review, we summarise the tumor-suppressive roles of ncRNAs, the recent progress of EV-associated ncRNAs in HCC treatment, unique features of EVs relevant to drug delivery, and current challenges in the clinical translation of EVs.

Hepatocellular carcinoma (HCC) is a common and deadly cancer. Accumulating evidence supports modulation of autophagy as a novel approach for determining cancer cell fate. The aim of this study to evaluate the effectiveness of sarmentosin, a natural compound, on HCC in vitro and in vivo and elucidated the underlying mechanisms.

Cell functions and signaling pathways were analyzed in HepG2 cells using western blotting, real-time PCR, siRNA, transmission electron microscopy and flow cytometry. BALB/c nude mice were injected with HepG2 cells to produce a xenograft tumour nude mouse model for in vivo assessments and their tumors, hearts, lungs and kidneys were isolated.

We found that autophagy was induced by sarmentosin in a concentration- and time-dependent manner in human HCC HepG2 cells by western blot assays and scanning electron microscopy. Sarmentosin-induced autophagy was abolished by the autophagy inhibitors 3-methyladenine, chloroquine, and bafilomycin A1. Sarmentosin activated Nrf2 in HepG2 cells, as shown by increased nuclear translocation and upregulated expression of Nrf2 target genes. Phosphorylation of mTOR was also inhibited by sarmentosin. Sarmentosin stimulated caspase-dependent apoptosis in HepG2 cells, which was impaired by silencing Nrf2 or chloroquine or knocking down ATG7. Finally, sarmentosin effectively repressed HCC growth in xenograft nude mice and activated autophagy and apoptosis in HCC tissues.

This study showed sarmentosin stimulated autophagic and caspase-dependent apoptosis in HCC, which required activation of Nrf2 and inhibition of mTOR. Our research supports Nrf2 as a therapeutic target for HCC and sarmentosin as a promising candidate for HCC chemotherapy.

Liver cirrhosis can lead to liver failure and eventually death. Macrophages are the main contributors to cirrhosis and have a bidirectional role in regulating matrix deposition and degradation. Macrophage-based cell therapy has been developed as an alternative to liver transplantation. However, there is insufficient evidence regarding its safety and efficacy. In this study, we aimed to explore the effect of combining insulin-like growth factor 2 (IGF2) with bone marrow-derived macrophages (BMDMs) to treat mice with liver cirrhosis.

We assessed liver inflammation, fibrosis regression, liver function, and liver regeneration in mice with CCl4-induced cirrhosis and treated with BMDM only or IGF2 + BMDM. We performed in vitro experiments in which activated hepatic stellate cells (HSCs) were co-cultured with macrophages in the presence or absence of IGF2. The polarity of macrophages and the degree of inhibition of HSCs were examined. The effect of IGF2 on macrophages was also verified by the overexpression of IGF2.

Combining IGF2 with BMDM reduced liver inflammation and fibrosis and increased hepatocyte proliferation. Combining IGF2 with BMDM was more effective than using BMDM alone. In vitro experiments demonstrated that IGF2 inhibited HSCs activation by upregulating NR4A2 to promote the anti-inflammatory macrophages phenotype. IGF2 also increased the synthesis of matrix metalloproteinases (MMPs) by macrophages, which may explain why administering IGF2 combined with BMDM was more effective than administering BMDM only.

Our study provides a theoretical basis for the future use of BMDM-based cell therapy to treat liver cirrhosis.

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. They originate from the interstitial cells of Cajal and are usually found in extrahepatic gastrointestinal sites. However, a small subset are derived from the liver and are known as primary hepatic gastrointestinal stromal tumors (PHGIST). They have a poor prognosis and are historically difficult to diagnose. Our objective was to review and update the latest evidence-based knowledge concerning PHGIST, with a focus on epidemiology, etiology, pathophysiology, clinical presentation, histopathology, and treatment. These tumors are usually found incidentally, occur sporadically, and are associated with mutations of KIT and PDGFRA genes. PHGIST is a diagnosis of exclusion, as it has the same molecular, immunochemistry and histological appearance as gastrointestinal stromal tumors (GIST). Thus, imaging, such as positron emission tomography-computed tomography (PET-CT) must be used to rule out metastatic GIST before a diagnosis can be made. However, with mutation analysis and pharmacological advances, tyrosine kinase inhibitors are typically pursued with or without surgical intervention. Other potential treatments include transcatheter arterial chemoembolization and tumor ablation. However, these are typically considered palliative options. As there are only a limited number of publications regarding PHGIST, data concerning morbidity and mortality are not yet available. Immunohistopathology can help develop screening guidelines and evaluating resistance to treatment.

The application of Chinese medicine in clinic is based on the classical theory of traditional Chinese medicine (TCM) syndrome differentiation, which remains not fully understood. This study aims to explore and interpret the associations between TCM syndromes and multiple clinical risk factors of hypertension.

A total of 203 patients with hypertension were retrospectively studied. After the regression analysis of confounding factors for different types of hypertension, the potential association between TCM syndrome and risk factors were analyzed.

The comorbidity of left ventricular hypertrophy was probably an independent risk factor for different types of hypertension. The correlation analysis indicated that the disease course was positively correlated with the syndrome differentiation degree (Spearman’s coefficient = 0.185, p < 0.05) and blood stasis syndrome (Spearman’s coefficient = 0.291, p < 0.05). tThe hypertension risk group was positively correlated with the blood stasis syndrome (Spearman’s coefficient = 0.207, p < 0.05). Age was positively correlated with the blood stasis syndrome (Spearman’s coefficient = 0.231, p < 0.05) and qi-deficiency syndrome (Spearman’s coefficient = 0.187, p < 0.05), but was negatively correlated with the liver-yang hyperactivity syndrome (Spearman’s coefficient = −0.167, p < 0.05).

There are correlations between TCM syndromes and the clinical risk factors of hypertension. These findings may help to interpret the TCM syndrome differentiation theory.

Gallbladder carcinoma (GBC) is a malignant tumor of the biliary system that is aggressive, difficult to detect early, and has a low surgical resection rate and poor prognosis. Appropriate in vitro growth models are expected to focus on the study of the biological behavior and assess treatment effects. Nonetheless, cancer initiation, progression, and invasion include spatiotemporal changes and changes in the cell microenvironment intracellular communication, and intracellular molecules, making the development of in vitro growth models very challenging. Recent advances in biomaterial methods and tissue engineering, particularly advances in bioprinting procedures, have paved the way for advances in the creative phase of in vitro cancer research. To date, an increasing number of cultured models of gallbladder disease have emerged, such as two-dimensional (2D) GBC growth cell cultures, three-dimensional (3D) GBC growth cell cultures, xenograft models, and 3D bioprinting methods. These models can serve as stronger platforms, focusing on tumor growth initiation, the association with the microenvironment, angiogenesis, motility, aggression, and infiltration. Bioprinted growth models can also be used for high-throughput drug screening and validation, as well as translational opportunities for individual cancer therapy. This study focused on the exploration, progress, and significance of the development of GBC cultural models. We present our views on the shortcomings of existing models, investigate new innovations, and plan future improvements and application possibilities for cancer models.

In this study, we aimed to evaluate the diagnostic values of alpha-fetoprotein (AFP), soluble AXL (sAXL), des-γ-carboxy prothrombin (DCP), the aspartate aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in hepatocellular carcinoma (HCC) and the possible underlying mechanisms of the correlations between them.

We collected serum samples from 190, 128, and 75 patients with HCC, cirrhosis, and chronic viral hepatitis, and from 82 healthy subjects. Serum levels of AFP, sAXL, and DCP were determined, and APRI and GPR values were calculated. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of single and combined biomarkers.

We detected significant differences between the HCC group and other groups regarding serum AFP, sAXL, DCP, and APRI levels. GPR significantly differed between the HCC group and other groups, except for the liver cirrhosis group. AFP, sAXL, DCP, APRI, and GPR had positive correlations with each other, and AFP showed a higher area under the curve (AUC) and Youden index values, while APRI and DCP showed the highest sensitivity and specificity. Also, when AFP was combined with sAXL, DCP, APRI, and GRP, the highest AUC (0.911) and a higher net reclassification improvement value were obtained compared with those obtained for the individual biomarkers.

AFP, sAXL, DCP, APRI, and GPR are independent risk factors for HCC, and the diagnostic performance of AFP combined with sAXL, DCP, APRI, and GPR for HCC diagnosis was superior to that of the individual biomarkers.

Liver damage in cholestasis is multifactorial, yet bile acid-mediated hepatotoxicity is pivotal. Honey consumption has many physiological effects; it influences detoxification process (phase I, II and III), has antioxidant, anti-inflammatory, immune-stimulant, anti-ulcer, wound/burn healing effects and others. The bile acid ursodeoxycholic acid (UDCA) is currently used off-label to treat neonatal cholestasis. This study aimed to assess the effectiveness of spore-free natural honey to treat neonatal nonobstructive cholestasis.

Thirty infants with cholestasis received spore-free natural honey. Their progression was compared to a control group with cholestasis (28 infants) and a historical group (31 infants) on UDCA.

The mean ± standard deviation (SD) follow-up duration was 29.68 ± 18.68 months. At presentation, the total bilirubin concentrations were 9.5 ± 5.9 mg/dL, 10.9 ± 7 mg/dL and 14 ± 9 mg/dL in the honey, control and UDCA groups, respectively (p = 0.064), and their direct bilirubin concentrations were 6 ± 4 mg/dL, 6.7 ± 4 mg/dL and 8.4 ± 6.9 mg/dL, respectively (p = 0.169). The final total bilirubin concentrations were 1.2 ± 1.7 mg/dL, 4.6 ± 8.2 mg/dL and 7.3 ± 8.9 mg/dL, (p = 0.006), and their final direct bilirubin concentrations were 0.8 ± 1 mg/dL, 2.77 ± 5.2 mg/dL and 5.1 ± 7.2 mg/dL (p = 0.008), with cure achievement in 25, 16 and 16 (p = 0.023), improvement in 3, 5 and 3 (p = 0.565), failure in 2, 3 and 10 (p = 0.016), and death in 0, 4 and 2, respectively (p = 0.095). None suffered from botulism or flaccid paralysis.

Spore-free honey is effective in clearing cholestasis in neonates and infants. UDCA use in cholestasis in pediatric age should be abandoned as it is less effective and is associated with a worse outcome.

In order to study the regulating effect of electroacupuncture at specific acupoints on the depression level of drug addicts, we randomly selected 42 drug addicts from Sichuan drug rehabilitation center of women and divided them into treatment group (13), comfort group (10) and control group (19) from April to August 2019. Venous blood was taken before and after treatment, and the serum samples such as Noradrenalin (NA) and brain-derived neurotrophic factor (BDNF) were systematically detected. At the same time, Beck Depression Scale was used to detect the level of depression before and after treatment. Results showed that the level of depression in the real acupuncture group decreased significantly after treatment (p < 0.05). The contents of NA and BDNF in the serum of the real acupuncture group increased after treatment, but did not reach a significant level. In a word, the combination therapy of electroacupuncture can improve the levels of BDNF and NA in drug addicts and adjust their depression level, which is worthy of clinical promotion.

Helicobacter pylori (H. pylori) infection is widely prevalent worldwide. H. pylori infection has been reported to be a risk factor for the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Because treatment for NAFLD, other than weight loss is limited, the treatment for H. pylori infection is well established. It is important to determine whether screening and treatment for H. pylori infection should be considered in patients with no gastrointestinal symptoms. The aim of this mini-review is to evaluate the association between H. pylori infection and NAFLD including epidemiology, pathogenesis, and the evidence for H. pylori infection as a modifiable risk factor for preventing or treating NAFLD.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies. It has high mortality and poor clinical outcomes, but the molecular mechanisms in the pathogenesis of HCC are not understood. The tumor immune microenvironment (TIME) is a highly intricate system with distinct populations of innate and adaptive immune cells, as well as other stromal cells. They interact and evolve with tumor cells to influence tumor growth, migration, invasion, immune evasion, and response to therapy. Emerging evidence has shown noncoding RNAs (ncRNAs) are prominent regulators of TIME in HCC. In this review, we elaborate on the functions and molecular mechanisms of ncRNAs in remodeling TIME of HCC and discuss their diagnostic and therapeutic potential for HCC treatment.

To determine whether liver stiffness measurement (LSM) indicates liver inflammation in chronic hepatitis B (CHB) with different upper limits of normal (ULNs) for alanine aminotransferase (ALT).

We grouped 439 CHB patients using different ULNs for ALT: cohort I, ≤40 U/L (439 subjects); cohort II, ≤35/25 U/L (males/females; 330 subjects); and cohort III, ≤30/19 U/L (males/females; 231 subjects). Furthermore, 84 and 96 CHB patients with normal ALT (≤40 U/L) formed the external and prospective validation groups, respectively. We evaluated the correlation between LSM and biopsy-confirmed liver inflammation, and determined diagnostic accuracy using area under the curve (AUC). A noninvasive LSM-based model was developed using multivariate logistic regression.

Fibrosis-adjusted LSM values significantly increased with increasing inflammation. The AUCs of LSM in cohorts I, II, and III were 0.799, 0.796, and 0.814, respectively, for significant inflammation (A≥2) and 0.779, 0.767, and 0.770, respectively, for severe inflammation (A=3). Cutoff LSM values in all cohorts for A≥2 and A=3 were 6.3 and 7.5 kPa, respectively. Internal, external, and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3, and no significant differences in AUCs among the four groups. LSM and globulin independently predicted A≥2. The AUC of an LSM-globulin model for A≥2 exceeded those of globulin, ALT, and AST, but was similar to that of LSM.

LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

Prostate cancer is a heterogeneous disease with a wide spectrum of pathological, clinical, and molecular features. The diagnosis and classification of prostate cancer have been constantly modified with the incorporation of new data. The 5th edition of the World Health Organization (WHO) Classification of Urinary and Genital Tumors was recently published six years after the 4th edition. In this new edition, the classification of prostate cancer has been refined in the diagnostic criteria, grading, nomenclature, and genomics. This review summarizes significant updates to the new WHO classification of prostate cancer, including high-grade prostatic intraepithelial neoplasia, acinar adenocarcinoma, intraductal carcinoma, ductal carcinoma, and neuroendocrine tumors. Controversial issues in the Gleason grading are discussed, such as intraductal carcinoma and tertiary grade. We also highlight distinct genetic and epigenetic alterations in prostate cancer that may contribute to its diverse clinicopathologic features. Overall, the 5th edition of the WHO classification provides a comprehensive assessment of prostate cancer with morphologic, immunohistochemical, genomic, and clinical data, which may represent an optimal paradigm for diagnosing and treating prostate cancer.

As for resection for colorectal liver metastasis (CRLM), securing an adequate surgical margin is important for achieving a better prognosis. However, it is often difficult to achieve adequate margins for the resection of CRLM. So the current survival impact of sub-centi/millimeter surgical margins in hepatectomy for CRLM should be evaluated. In the current era of multidisciplinary treatment options, this review focused on the prognostic impact of a sub-centi/millimeter surgical margin width in hepatectomy for CRLM. We systematically reviewed retrospective studies that clearly described the surgical margin width for hepatectomy for CRLM. We selected studies conducted since 2000 that involved patients diagnosed as having CRLM. We focused on studies that investigated not only surgical margins, but also microscopic surgical curability such as R0 (microscopically complete resection) or R1 (microscopically incomplete resection), which clearly describe their definitions. Based on our literature review, 1, 2, or 5 mm was considered the minimum surgical margin width for hepatectomy for CRLM. Although a surgical margin width of 1 mm is acceptable for hepatectomy for CRLM, submillimeter margins, which are defined as R1 in many reports, are only acceptable for limited patients such as those who have undergone preoperative chemotherapy. Zero-mm margins are also acceptable in limited patients such as those who show a good response to preoperative chemotherapy. New chemotherapy agents have been reported to reduce the prognostic impact of a narrow surgical margin width. The incidence of margin recurrence, which is a major concern regarding R1 resection of CRLM, is about 20–30% according to the majority of earlier reports. As evaluations of the actual prognostic impact of the surgical margin remain difficult, further study is warranted.

Cervical cancer has caused numerous deaths in women worldwide over the past few decades. It is a serious clinical problem that needs to be solved, though its morbidity and mortality have declined in recent years. The current treatments against cervical cancer are hysterectomy, radiotherapy, and chemotherapy, with certain limitations. Meanwhile, progress has been made in the screening and prevention of cervical cancer, focusing on human papillomavirus (HPV) infection, which is considered a necessary but insufficient cause. This review summarizes our current knowledge of screening and prevention of cervical cancer and its relation to HPV.