China accounts for nearly half of liver cancer deaths globally. A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver cancer. The study aimed to explore and predict the mortality burden of liver cancer in China.

Data were extracted from the Disease Surveillance Point system of the Chinese Center for Disease Control and Prevention from 2008 to 2020. Crude and age-standardized liver cancer mortality rates were reported by sex, urban or rural residence, and region. Trends in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change (AAPC). The changing trend of live cancer mortality in the future is also predicted.

In 2020, the crude mortality of liver cancer was 25.57/100,000, and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban areas. Crude mortality and age-standardized mortality rates in southwest provinces (Guangxi, Sichuan, Tibet) and in a northeast province (Heilongjiang) were higher than that in other provinces, and age-specific mortality rates increased with age. From 2008 to 2020, liver cancer mortality rates decreased, but people under 50 years of age had a higher AAPC than those over 50 years of age, possibly because of the adoption of hepatitis B virus vaccination in newborns and children. Furthermore, the mortality of liver cancer in 2021–2030 is predicted to have a downward trend.

Liver cancer mortality rates declined in China from 2008 to 2020. Future interventions to control liver cancer mortality need to focus on people of male sex, older age, and living in rural areas or less developed provinces.

Essential oils, known for their pleasant aromas, not only calm the mind and elevate the mood but also captivate the interest of researchers aiming to unveil their vast potential. Various methodologies are employed to explore the diverse capabilities of essential oils, often yielding promising and significant outcomes. This review aims to elucidate the molecular mechanisms of essential oils at the cellular level. It identifies multiple mechanisms through which essential oils exhibit their therapeutic effects across various systems. However, a comprehensive understanding of their fundamental mechanisms still necessitates extensive research. In this review, we discuss the mechanisms underlying the biological activities of essential oils, specifically their antioxidant, antimicrobial, anticarcinogenic, anti-diabetic, and anti-inflammatory properties.

Nodular lymphocyte predominant Hodgkin lymphoma was termed “nodular lymphocyte predominant B-cell lymphoma” in the International Consensus Classification (ICC), to emphasize clinical and biological differences from classic Hodgkin lymphoma (CHL). The abbreviation “NLP” represents both terms in the ICC and World Health Organization classifications. Variations in the growth pattern, originally reported as Fan patterns A-F, are designated as either grade 1 or grade 2 in the ICC. NLP is uncommon, and in some cases an accurate diagnosis is challenging. The objectives of this article were to review the histopathologic features of NLP and the differential diagnosis from other key entities including de novo T-cell/histiocyte-rich large B-cell lymphoma (THRLBL) and lymphocyte-rich classic Hodgkin lymphoma (LRCHL). Histologically, NLP Fan pattern E (THRLBL-like) can be indistinguishable from de novo THRLBL. However, focal nodular areas, clustering of tumor cells, presence of few admixed small B-cells or FDC meshworks, and T-cell rosettes favor NLP Fan pattern E and argue against de novo THRLBL. NLP may also be confused with LRCHL. Patients with NLP are younger than those with LRCHL, and LRCHL may show mediastinal involvement. In LRCHL, the nodular pattern often contains eccentrically located small regressed germinal centers and intact small dense FDC meshworks, in contrast to the expanded, and fragmented FDC meshworks in NLP. Neoplastic cells that are positive for CD30 and CD15 but negative for CD20 and CD79a are characteristic of LRCHL. Additionally, Fascin and Gata3 are commonly positive in LRCHL but usually negative in NLP.

Breast cancer is one of the greatest global health concerns for women, with rising incidence rates and mortality projections, while affordability and access to mammography screening and diagnosis, especially in low- and middle-income countries, remain a challenge. This retrospective clinical validation study evaluated a breast cancer pre-screening solution (BCPS) based on a commercially available smartphone with a thermal imaging sensor powered by artificial intelligence. The purpose was to measure the performance of the BCPS tool compared to mammography, the gold standard for first-pass examination in breast cancer screening.

The evaluation was conducted in the Erebouni Medical Center Breast Unit in Armenia over a period of six months. We tested a cohort of 478 women of whom 45 were finally diagnosed with breast cancer after biopsy. Participants were first screened with the BCPS before undergoing the standard breast screening pathway. After studying the mammography results, if malignancy was discovered, a biopsy was performed and taken as the ground truth when comparing with BCPS artificial intelligence results.

When combined with patient-reported or clinical symptoms, the BCPS tool achieved a sensitivity of 89% and a specificity of 83% compared to mammography. When clinical or patient-reported symptoms were not taken into account, sensitivity was considerably lower (60%), while specificity was higher (88.2%).

The BCPS tool, in combination with basic clinical exams and patient-reported symptoms, may serve as a robust triaging tool for breast cancer detection where mammography is not available or affordable, identifying the majority of women who need further diagnostic assessment.

Hepatic ischemia-reperfusion injury (HIRI) is a prevalent complication of liver transplantation, partial hepatectomy, and severe infection, necessitating the development of more effective clinical strategies. Receptor activity–modifying protein 1 (RAMP1), a member of the G protein–coupled receptor adapter family, has been implicated in numerous physiological and pathological processes. The study aimed to investigate the pathogenesis of RAMP1 in HIRI.

We established a 70% liver ischemia-reperfusion model in RAMP1 knockout (KO) and wild-type mice. Liver and blood samples were collected after 0, 6, and 24 h of hypoxia/reperfusion. Liver histological and serological analyses were performed to evaluate liver damage. We also conducted in-vitro and in-vivo experiments to explore the molecular mechanism underlying RAMP1 function.

Liver injury was exacerbated in RAMP1-KO mice compared with the sham group, as evidenced by increased cell death and elevated serum transaminase and inflammation levels. HIRI was promoted in RAMP1-KO mice via the induction of hepatocyte apoptosis and inhibition of proliferation. The absence of RAMP1 led to increased activation of the extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and yes-associated protein (YAP) phosphorylation, ultimately promoting apoptosis. SCH772984, an ERK/MAPK phosphorylation inhibitor, and PY-60, a YAP phosphorylation inhibitor, reduced apoptosis in in-vitro and in-vivo experiments.

Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction, highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.

The correlation between gut, secreted metabolites, and hepatic diseases has strengthened over the last decade. Interactions of intestinal permeability, gut microbes, and derived metabolites influence the development and progression of nonalcoholic fatty liver disease (NAFLD), a prevalent disease that affects more than 30% of the global population. NAFLD is now called metabolic dysfunction-associated steatotic liver disease (MASLD) to better reflect the disease process. Here, we describe mechanisms of NAFLD development, the role of gut bacteria, gut metabolites, interventions for diagnosis, and the prognosis of NAFLD. We discuss new paradigms that challenge the conventional, addressing disease etiology and translational approaches in a new dimension. Previous studies shed light on intricate relationships of the gut microbiome with the liver, or the gut-liver axis. Bidirectional communication between the gut and the liver involves exchange of metabolites, immune signaling, and inflammatory responses that has potential for novel NAFLD/nonalcoholic steatohepatitis (NASH) treatments. In this review, we propose exploring functional metagenomics to develop NAFLD diagnostic methods and risk assessment. The prospects of genetic engineering, fecal transplants, and specialized diet as targets of novel therapeutic regimes to combat NAFLD/NASH are discussed. Changes in lifestyle and diet in the population, combined with genetic predisposition, have led to an increasing number of cases of NAFLD. The microbiome responds to diet, exercise, and the environment, and can modulate NAFLD in cases with surgical impediments. It is thus vital to explore its emerging roles in human healthcare and not only liver disease.

Disease progression of chronic hepatitis B virus (HBV) infection is driven by the interactions between viral replication and the host immune response against the infection. This study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease progression.

Two cross-sectional, one validation cohort, and meta-analyses were used to explore the relationship between HBV replication and liver inflammation. Spearman analysis, multiple linear regression, and logistic regression were used to explore the relationship between variables.

In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients, Spearman analysis revealed a negative relationship between HBV replication (such as HBV DNA) and liver inflammation (such as ALT) in HBeAg-positive patients with higher HBV DNA >2×106 IU/mL (rho=−0.160 and −0.042) which turned to be positive in HBeAg-positive patients with HBV DNA ≤2×106 IU/mL (rho=0.278 and 0.260) and HBeAg-negative patients (rho=0.450 and 0.363). After adjustment for sex, age, and anti-HBe, results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels; the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort; the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis (overall R: −0.004 vs 0.481).

These results suggested a negative relationship between viral replication and liver inflammation in HBeAg-positive patients with high HBV DNA, which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×106 IU/mL and HBeAg-negative patients.

Hepatitis B virus (HBV) reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy. Paclitaxel (PTX) treatment has been identified as a potential trigger for HBV reactivation. This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo, which may inform new strategies for HBV antiviral treatment.

The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay, dual-luciferase reporter assay, quantitative real-time PCR, chromatin immunoprecipitation, and immunohistochemical staining. Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice.

PTX enhanced the levels of HBV 3.5-kb mRNA, HBV DNA, HBeAg, and HBsAg both in vitro and in vivo. PTX also promoted the activity of the HBV core promoter and transcription factor AP-1. Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation. Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17, NF-κB, and MAPK signaling pathways, with the pivotal common key molecule being AP-1. The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota.

PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1. These findings propose a novel molecular mechanism, underscoring the critical role of AP-1 in PTX-induced HBV reactivation.

Voriconazole (VRC), a widely used antifungal drug, often causes hepatotoxicity, which presents a significant clinical challenge. Previous studies demonstrated that Astragalus polysaccharide (APS) can regulate VRC metabolism, thereby potentially mitigating its hepatotoxic effects. In this study, we aimed to explore the mechanism by which APS regulates VRC metabolism.

First, we assessed the association of abnormal VRC metabolism with hepatotoxicity using the Roussel Uclaf Causality Assessment Method scale. Second, we conducted a series of basic experiments to verify the promotive effect of APS on VRC metabolism. Various in vitro and in vivo assays, including cytokine profiling, immunohistochemistry, quantitative polymerase chain reaction, metabolite analysis, and drug concentration measurements, were performed using a lipopolysaccharide-induced rat inflammation model. Finally, experiments such as intestinal biodiversity analysis, intestinal clearance assessments, and Bifidobacterium bifidum replenishment were performed to examine the ability of B. bifidum to regulate the expression of the VRC-metabolizing enzyme CYP2C19 through the gut–liver axis.

The results indicated that APS does not have a direct effect on hepatocytes. However, the assessment of gut microbiota function revealed that APS significantly increases the abundance of B. bifidum, which could lead to an anti-inflammatory response in the liver and indirectly enhance VRC metabolism. The dual-luciferase reporter gene assay revealed that APS can hinder the secretion of pro-inflammatory mediators and reduce the inhibitory effect on CYP2C19 transcription through the nuclear factor-κB signaling pathway.

The study offers valuable insights into the mechanism by which APS alleviates VRC-induced liver damage, highlighting its immunomodulatory influence on hepatic tissues and its indirect regulatory control of VRC-metabolizing enzymes within hepatocytes.

Acute liver failure (ALF) is a life-threatening clinical problem with limited treatment options. Administration of human umbilical cord mesenchymal stem cells (hUC-MSCs) may be a promising approach for ALF. This study aimed to explore the role of hUC-MSCs in the treatment of ALF and the underlying mechanisms.

A mouse model of ALF was induced by lipopolysaccharide and d-galactosamine administration. The therapeutic effects of hUC-MSCs were evaluated by assessing serum enzyme activity, histological appearance, and cell apoptosis in liver tissues. The apoptosis rate was analyzed in AML12 cells. The levels of inflammatory cytokines and the phenotype of RAW264.7 cells co-cultured with hUC-MSCs were detected. The C-Jun N-terminal kinase/nuclear factor-kappa B signaling pathway was studied.

The hUC-MSCs treatment decreased the levels of serum alanine aminotransferase and aspartate aminotransferase, reduced pathological damage, alleviated hepatocyte apoptosis, and reduced mortality in vivo. The hUC-MSCs co-culture reduced the apoptosis rate of AML12 cells in vitro. Moreover, lipopolysaccharide-stimulated RAW264.7 cells had higher levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β and showed more CD86-positive cells, whereas the hUC-MSCs co-culture reduced the levels of the three inflammatory cytokines and increased the ratio of CD206-positive cells. The hUC-MSCs treatment inhibited the activation of phosphorylated (p)-C-Jun N-terminal kinase and p-nuclear factor-kappa B not only in liver tissues but also in AML12 and RAW264.7 cells co-cultured with hUC-MSCs.

hUC-MSCs could alleviate ALF by regulating hepatocyte apoptosis and macrophage polarization, thus hUC-MSC-based cell therapy may be an alternative option for patients with ALF.