There is a lack of data supporting the notion that antiviral treatments can benefit children with chronic hepatitis B (CHB) having high viremia and normal or mildly elevated serum alanine aminotransferase (ALT) levels. We aimed to analyze the efficacy of antiviral treatments in children with CHB and explore the factors associated with functional cure.

Forty-eight children with CHB having high viremia and normal or mildly elevated serum ALT levels were screened in this real-world study. Thirty-two children received either interferon-alpha (IFN-α) monotherapy, IFN-α therapy with a nucleoside analog (NA) add-on, or IFN-α and NA combination therapy. The 16 children in the control group did not receive antiviral treatment. All 48 children were available for follow-up assessments for the entire 36-month study period. We identified a functional cure with respect to hepatitis B virus (HBV) DNA loss, loss /seroconversion of circulating hepatitis B e antigen (HBeAg), and loss of hepatitis B surface antigen (HBsAg) with or without seroconversion. Cox regression analysis was employed to evaluate the factors that may have influenced the functional cure.

After 36 months, the cumulative functional cure rate was 56.25% (18/32) in the treated group and 0% (0/16) in the control group (p<0.001). In the treated group, the serum HBV DNA levels declined rapidly at the end of a 6-month visit and the cured children achieved a loss rate of 100% (18/18) within 16 months of beginning treatment, compared with 64.29% (9/14) of the uncured children (p<0.001). The rates of HBeAg seroconversion were significantly higher among the cured children than among the uncured children (p<0.001). All 16 children in the control group maintained high levels of serum HBV DNA and were positive for both serum HBeAg and HBsAg during the entire 36 months of the study period. Functional cure was associated with younger ages (1–6 vs. 7–14 years, p=0.013), CD8+ T lymphocyte counts (p=0.013), and B lymphocyte counts (p=0.003). No serious adverse events were observed.

Antiviral treatment achieved a functional cure of CHB in a high proportion of children having high-level viremia and normal or mildly elevated ALT levels. Younger age and high peripheral lymphocyte counts were associated with this functional cure.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high incidence and cancer mortality worldwide. Post-translational modifications (PTMs) of proteins have a great impact on protein function. Almost all proteins can undergo PTMs, including phosphorylation, acetylation, methylation, glycosylation, ubiquitination, and so on. Many studies have shown that PTMs are related to the occurrence and development of cancers. The findings provide novel therapeutic targets for cancers, such as glypican-3 and mucin-1. Other clinical implications are also found in the studies of PTMs. Diagnostic or prognostic value, and response to therapy have been identified. In HCC, it has been shown that glycosylated alpha-fetoprotein (AFP) has a higher detection rate for early liver cancer than conventional AFP. In this review, we mainly focused on the diagnostic and prognostic value of PTM, in order to provide new insights into the clinical implication of PTM in HCC.

The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome (VBDS) have yet to be elucidated. The study aims to investigate these features and identify factors associated with poor prognosis.

This multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022. Clinical and pathological data at time of biopsy were reviewed. Clinical outcomes including cirrhosis, decompensation events, liver transplantation (LT), and liver-related death were recorded. Cox regression analysis was used to identify the risk factors associated with poor outcomes.

A total of 183 patients were included. The median age was 47 years, with 77.6% being women. During a median follow-up of 4.8 years, 88 patients developed compensated or decompensated cirrhosis, 27 died, and 15 received LT. Multivariate Cox regression analysis showed that hepatocellular cholestasis (HR 2.953, 95% CI: 1.437–6.069), foam cells (HR 2.349, 95% CI: 1.092–5.053), and advanced fibrosis (HR 2.524, 95% CI: 1.313–4.851) were independent predictors of LT or liver-related deaths. A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746 (95% CI: 0.706–0.785).

Nearly half of VBDS patients studied progressed to end-stage liver disease and 23% of them had LT or liver-related death within two years of diagnosis. Hepatocellular cholestasis, foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.

Numerous clinical studies over recent years have reported an inverse relationship between benign prostatic hyperplasia (BPH) size and the incidence of prostate cancer (PCa), leading to the clinical hypothesis that the expanding BPH zone damages the glandular tissue where PCa predominately develops. This systematic review aims to establish a historical basis and reference on the zonal origin of BPH and prostate cancer (PCa) within the prostate.

Using the PRISMA guidelines, an in-depth review was conducted of studies published in the PubMed database between January 1978 and November 2022. Due to clinical heterogeneity in type of study designs, meta-analysis was not possible, and a narrative review approach was adopted.

Thirty-eight studies met the inclusion criteria, all of which showed that BPH predominantly develops within the transition zone (TZ) and that PCa predominantly develops in the peripheral zone (PZ) of the prostate respectively. This report provides a systemic overview of the historical evolution on the concept of zonal origin for BPH and PCa. The listed studies support the current clinical understanding that BPH mainly originates in the TZ and that the majority of PCa originates in the PZ of the prostate.

To our knowledge, this is the first systemic review on the zonal origin of BPH and PCa and is an important step in the context of evidence-based medicine. This review should encourage other clinicians and investigators to further study the dynamic interactions between the different prostate zones, in particular between the TZ and the PZ, and whether BPH size may be protective against development of PCa.

This study aimed to evaluate the effect of coconut oil (CO) on steatosis and oxidative stress in rats fed a high-fat diet.

Three groups of male Wistar rats were used: the control group (CG, n = 10) received a standard diet for 50 days, the hyperlipidic group (HL, n = 10) received a high-fat diet with 50% lard for 50 days, and the hyperlipidic-CO group (HL+CO, n = 10) received a high-fat diet with 50% lard for 30 days followed by 25% lard and 25% CO for 20 days. Then, the animals were euthanized, and their blood, liver, and adipose tissue were collected for biochemical analyses.

The groups that received a high-fat diet had pronounced liver steatosis. Compared to the CG and HL groups, the HL+CO group had less weight gain, but liver fat and triglycerides were increased, with a significant reduction in liver cholesterol. Glutathione increased significantly and vitamin E decreased in the livers of the experimental groups compared to the control. Lipid peroxidation in the serum and liver was less in the HL+CO group compared to that in the HL group, but it was higher than that in the control group. CO caused significant accumulation of hepatic fat, triglycerides, and fat content, despite decreasing the hepatic cholesterol levels. There was a better hepatic antioxidant response in the CO group, especially compared with the HL group.

CO was not able to prevent or improve liver fat levels, but the HL+CO group had a better antioxidant profile. Additional clinical studies are necessary to verify the efficacy and safety of different CO doses on both hepatic and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease, affecting a quarter of the world’s population. The spectrum of NAFLD ranges from simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and ultimately to hepatocellular carcinoma (HCC). Multiple factors are involved in the pathogenesis and progression of NAFLD, wherein genetic, epigenetic, environmental, gut-microbiome, and dietary factors play a substantial role. Robust genome-wide association studies (GWAS) have recently identified several genetic alterations contributing to NAFLD progression to liver cancer. This review describes the most critical genetic variations identified in various genes that modulate NAFLD pathogenesis. As expected, NAFLD shows gene variations that regulate or influence hepatocyte lipid metabolism. In addition to polymorphisms in genes that regulate insulin signaling, fibrosis, inflammation, and oxidative stress, cytokine/chemokine-expressing genes also participate in NAFLD pathogenesis. GWAS helped us distinguish genetic polymorphisms that modulate steatosis, fibrosis, or both in NAFLD patients. Identifying genetic factors predisposing an individual to NAFLD helps stratify people at high risk and aids in imparting preventive strategies early in life. Such studies should also help in adopting prevention strategies and targeted treatment regimes.

Renal cell tumors with eosinophilic/oncocytic cells include oncocytic papillary renal neoplasm with reverse polarity, oncocytoma, chromophobe renal cell carcinoma, hybrid oncocytic/chromophobe renal tumor, succinate dehydrogenase-deficient renal cell carcinoma, translocation-associated renal cell carcinoma, etc. Recently, several novel and evolving oncocytic renal tumors have been identified, such as eosinophilic solid and cystic renal cell carcinoma, eosinophilic vacuolated tumor, and low-grade oncocytic tumor. In addition, fumarate hydratase-deficient renal cell carcinoma occasionally presents with a low-grade oncocytic morphology. Although these entities demonstrate some overlapping morphological features with oncocytoma and chromophobe renal cell carcinoma, they do have some unique morphological, immunohistochemical, and molecular profiles. In this review, we present an update on selected oncocytic renal cell tumors (eosinophilic vacuolated tumor, low-grade oncocytic tumor, eosinophilic solid and cystic renal cell carcinoma, low-grade fumarate hydratase-deficient renal cell carcinoma, and hybrid oncocytic/chromophobe renal tumor) and discuss their morphologies, immunohistochemical profiles, molecular genetic profiles, and biological behaviors.

The gut microbiota are frequently reported to be associated with colorectal cancer, while less attention has been paid to precancerous tumors. This study aimed to characterize the intestinal bacteria in patients with colorectal lesions and to assess the potential of bacteria as noninvasive biomarkers of colorectal tumors

We prospectively collected and sequenced 463 fecal samples from Zhongshan Hospital, Xiamen University, by targeting 16S rRNA V3_V4 on a Hiseq instrument with PE250 reagents. We analyzed the gut bacterial communities, determined the bacterial characteristics, and constructed models to classify colorectal tumors after feature selection, especially for precancerous lesions.

There was a significant difference in fecal bacterial communities among the controls with normal colons (healthy subjects; HS) and the four stages of colorectal tumors. The fecal bacterial diversity increased in colorectal tumors. The phylum Firmicutes was significantly decreased, while Bacteroidetes was increased in colorectal tumors vs. HS. Correspondingly, a total of 81 genera, 589 operational taxonomic units, and 157 predicted pathways were remarkably different in relative abundances among the five groups. Relatively weak differences were observed among colorectal hyperplastic or inflammatory polyps (CRP), small adenomas (CRA), and advanced adenomas (Adv_CRA). Based on feature selection from genera, operational taxonomic units, pathways, and age, the models achieved an area under the receiver operating characteristic curve of 0.92 for classifying colorectal tumors vs. HS, 0.91 for the precancerous tumors vs. CRC, 0.80 for Adv_CRA vs. CRP, and 0.70 for CRA vs. CRP.

Alterations in the bacterial diversity, composition, and predicted pathways were identified across multistep colorectal tumorigenesis. The selected bacterial features represent potential noninvasive predictors of colorectal tumors, especially in discriminating benign polyps and adenomas.

The liver maintains important homeostatic functions such as metabolism and detoxification. Failure to remove toxic intermediates can cause hepatic damage, liver fibrosis, and even cancer development. This review focuses on acetaldehyde dehydrogenases (ALDHs), a group of key enzymes within the ALDH superfamily with the ability to convert highly reactive aldehyde substrates to the corresponding carboxylic acids in NAD(P)-dependent manners. These enzymes participate in a diverse array of biological processes such as detoxification, biosynthesis, antioxidant, and regulatory functions. ALDH dysfunction can disrupt homeostasis, leading to toxic buildup, tissue damage, and cancer. Here, we examine the expression patterns of hepatic ALDHs in adult normal human livers and two types of liver cancers—hepatocellular carcinoma and cholangiocarcinoma. We also investigated their distributions related to liver zonation. These observations provide deep insights into previously unrecognized spatial and temporal regulation of ALDHs in liver zonation.

Health risks from exposure to asbestos fibers have been evaluated based on professional histories, when fiber concentrations at workplaces were greater than today. A linear no-threshold model was used for risk estimation, although its relevance has not been proven. Asbestos fibers are often detected in lungs and pleura during autopsy, but finding evidence of fibers does not prove that a disease has been caused by asbestos. Thus, targeted detection of mesothelioma and other conditions associated with asbestos exposures has resulted in an increase in the reported incidence of mesothelioma among high-risk groups. Histological and immunochemical characteristics of malignant mesothelioma partially overlap with other cancers, which may also contribute to the overdiagnosis in exposed populations. Differences in carcinogenicity of various asbestos types are discussed here. Prohibitions of asbestos in some developed countries must be reconsidered on the basis of independent research. Life-long bioassays are the most promising way to obtain reliable information regarding asbestos-related malignancy. It should be stressed that non-use of asbestos contributes to an increase of harm from fires, armed conflicts, and traffic accidents.

Psoralea corylifolia L. (PCL) is widely used in clinical practice and is commonly used in the treatment of osteoporosis, tumors, and dermatosis. However, in recent years, adverse reactions of PCL and its related preparations have been frequently reported, and there are even case reports of acute liver injury caused by taking PCL alone, which seriously affects the safe and rational clinical application of PCL. In this paper, the main chemical components, pharmacology, and toxicology of PCL are analyzed and summarized, and the effect-toxicity relationship of PCL and its main active components are sorted out and compared. On this basis, the active components of PCL for treating osteoporosis and causing hepatotoxicity are further systematically compared and summarized, to clarify its effect-toxicity relationship, reduce the toxicity risk of PCL, increase the benefit/risk ratio and provide evidence for the safe clinical application of PCL.

Hepatocellular carcinoma (HCC) is becoming one of the major health problems, and the leading cause of cancer-related mortality globally. Its multifactorial risk factors remain as paramount challenges to the treatment of this deadly disease. The conventionally known risk factors that trigger HCC include hepatitis C virus (HCV), hepatitis B virus (HBV), excess alcohol consumption, and environmental toxins, such as aflatoxin, aristolochic acid, etc. All these risk factors activate the oncogenic signaling in the liver, and transform the normal liver into an HCC liver. Recently, globalization and the Western sedentary lifestyle have newly emerged as risk factors for HCC, which include obesity, metabolic syndrome, and associated clinical and pathological modalities. In addition, a number of cellular signaling pathways are derailed in HCC, and these pathways, which are altered in HCC, are known to be directly controlled by oncogenes, such as KRAS, BRAF, c-MYC, astrocyte elevated gene-1 (AEG-1), staphylococcal nuclease domain containing 1 (SND1), late SV40 factor (LSF), apoptosis-antagonizing transcription factor (AATF), WNT/β-catenin, TGF-β, etc. All these oncogenes activate the oncogenic signaling in HCC, and suppress the important cellular tumor suppressor protein activity, playing a prominent role in hepatocarcinogenesis, and its development and progression. The present review established a novel interconnected network between all these oncogene-associated proteins, in order to determine its role in deregulating normal cellular signaling pathways, and transforming these into oncogenic signaling. A number of these oncogenes regulate the miRNA-RISC-associated oncogenic signaling, and trigger oncogenic miRNA singling by downregulating various tumor suppressor genes. Therefore, therapeutically targeting these oncogenes and associated proteins would aid in the development of new drugs to treat HCC.

Hepatocellular carcinoma (HCC) is among the most common malignant tumors globally. Circular RNAs (circRNAs), as a type of noncoding RNAs, reportedly participate in various tumor biological processes. However, the role of circHDAC1_004 in HCC remains unclear. Thus, we aimed to explore the role and the underlying mechanisms of circHDAC1_004 in the development and progression of HCC.

Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect circHDAC1_004 expression (circ_0005339) in HCC. Sanger sequencing and agarose gel electrophoresis were used to determine the structure of circHDAC1_004. In vitro and in vivo experiments were used to determine the biological function of circHDAC1_004 in HCC. Herein, qRT-PCR, RNA immunoprecipitation, western blotting, and a luciferase reporter assay were used to explore the relationships among circHDAC1_004, miR-361-3p, and NACC1.

circHDAC1_004 was upregulated in HCC and significantly associated with poor overall survival. circHDAC1_004 promoted HCC cell proliferation, stemness, migration, and invasion. In addition, circHDAC1_004 upregulated human umbilical vein endothelial cells (HUVECs) and promoted angiogenesis through exosomes. circHDAC1_004 promoted NACC1 expression and stimulated the epithelial-mesenchymal transition pathway by sponging miR-361-3p.

We found that circHDAC1_004 overexpression enhanced the proliferation, stemness, and metastasis of HCC via the miR-361-3p/NACC1 axis and promoted HCC angiogenesis through exosomes. Our findings may help develop a possible therapeutic strategy for HCC.

Primary melanomas of the penis are extremely rare, accounting for 0.18% of all melanomas and less than 2% of all primary penile malignancies. We present a case of primary mucosal melanoma of the penile urethra in an 82-year-old man. His partial penectomy revealed sheets of spindling and epithelioid tumor cells with pale eosinophilic granular cytoplasm and indistinct cell borders, which invaded the corpus spongiosum. Multi-foci of melanoma in situ was identified at the mucosal surface of the urethra meatus. Both positron emission tomography (PET) and magnetic resonance imaging (MRI) scan one month after the partial penectomy showed no evidence of metastatic disease. Five months later, an F18-fluorodeoxyglucose-PET/computed tomography scan demonstrated mildly increased F18-fluorodeoxyglucose avidity along the ventral penis and a marked avidity of a right inguinal lymph node. Subsequent excision confirmed an ulcerated melanoma and a metastatic melanoma in one inguinal lymph node, respectively. Molecular analysis revealed a unique BRAF c.1780G>A mutation, resulting in the D594N alteration, which is the first report in penile urethral melanoma. The patient was miserable from the first infusion of immunotherapy (Keytruda), and a PET scan showed that the tumor continued to grow, with extensive metastatic pulmonary disease leading to massive pleural effusion. Unfortunately, the patient died of the disease 18 months after his first presentation.

Cirrhosis is the precursor lesion for most hepatocellular carcinoma (HCC) cases. However, no biomarker effectively predicted HCC initiation before diagnosis by imaging. We aimed to investigate the hallmarks of immune microenvironments in healthy, cirrhotic livers and HCC tumor tissues and to identify immune biomarkers of cirrhosis-HCC transition.

Expression matrices of single-cell RNA sequencing studies were downloaded and integrated with Seurat package vignettes. Clustering was performed to analyze the immune cell compositions of different sample types.

The cirrhotic liver and HCC tumors had distinct immune microenvironments, but the immune landscape of cirrhotic livers was not markedly modified compared with healthy livers. Two subsets of B cells and three subsets of T cells were identified in the samples. Among the T cells, naïve T cells were more prominent in the cirrhotic and healthy liver samples than in the HCC samples. In contrast, the neutrophil count was lower in cirrhotic livers. Two macrophage clusters were identified, one that actively interacted with T cells and B cells and was enriched in cirrhotic blood compared with HCC blood samples.

Decreased naïve T cell infiltration and increased neutrophil infiltration in the liver may indicate the development of HCC in cirrhotic patients. Alterations in blood-resident immune cells may also be a sign of HCC development in cirrhotic patients. The dynamics of the immune cell subsets may serve as novel biomarkers to predict the transition from cirrhosis to HCC.

The liver has a vital role in many metabolic and regulatory processes in the body. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, is a chronic cholestatic autoimmune disease of the intrahepatic bile ducts associated with loss of tolerance to mitochondrial antigens. At this time there is no definitive cure for PBC; however, ursodeoxycholic acid (UDCA) has been shown to reduce injury when administered as the first line of treatment. Additional therapeutics can be given concurrently or as an alternative to UDCA to manage the symptoms and further curb disease progression. Currently, a liver transplant is the only potentially curative option when the patient has developed end-stage liver disease or intractable pruritus. This review aims to delineate the pathogenesis of primary biliary cholangitis and shed light on current therapeutic strategies in the treatment of PBC.

Lung cancer (LC), with its high incidence and less effective treatment strategies, is often not detected until it is in an advanced stage, which contributes to its high mortality rate. Hence, screening the DNA and RNA content in exosomes offers a promising method for its early diagnosis. New technologies for the early detection of LC are absolutely necessary to improve patient outcomes. Such an approach could be the exploitation of exosomes and their content. Exosomes contain DNA, different RNA species, proteins, ceramides, and cholesterol. They can transport their oncogenetic cargo derived from tumor cells to healthy cells over a range of distances to help propagate genetic information that could contribute to the initiation of cancer. This review provides an overview of the involvement of exosomes and their DNA/RNA together with cell-free DNA, summarizes potential biomarkers and describes the application of technologies for the characterization of exosomes with their possible tumor markers. Current radiological and scanning methods for the early detection of LC are also described and compared with nucleic acid analysis. The strengths and weaknesses of both approaches are considered.

We previously reported that carboxylesterase 1 (CES1) expression was suppressed following liver injury. The study aimed to explore the role of interleukin (IL)-33 in liver injury and examine the mechanism by which IL-33 regulates CES1.

IL-33 and CES1 levels were determined in the livers of patients and lipopolysaccharide (LPS)-, acetaminophen (APAP)-treated mice. We constructed IL-33 and ST2 knockout (KO) mice. ST2-enriched immune cells in livers were screened to identify the responsible cells. Macrophage-derived exosome (MDE) activity was tested by adding exosome inhibitors. Micro-RNAs (miRs) were extracted from control and IL-33-stimulated MDEs (IL-33-MDEs) and subjected miR sequencing (miR-Seq). Candidate miR was tested in vitro and in vivo and its binding of a target gene was assessed by luciferase reporter assays. Lentivirus-vector cellular transfection and transcript silencing were used to examine pathways mediating IL-33 suppression of miR-27b-3p.

Patient liver IL-33 and CES1 expression levels were inversely correlated. CES1 downregulation in liver injury was rescued in both IL-33–deficient and ST2 KO mice. Macrophages were shown to be responsible for IL-33 effects. IL-33-MDEs reduced CES1 levels in hepatocytes. Exosomal miR-Seq and qRT-PCR demonstrated increased miR-27b-3p levels in IL-33-MDEs; miR-27b-3p was implicated in Nrf2 targeting. IL-33 inhibition of miR-27b-3p was found to be GATA3-dependent.

IL-33–ST2–GATA3 pathway signaling increases miR-27b-3p content in MDEs, which upon being internalized by hepatocytes reduce CES1 expression by inhibiting Nrf2. The elucidation of this mechanism in this study contributes to a better understanding of CES1 dysregulation in liver injury.