Cell damage caused by ionizing radiation is very complex, and has generalities and specificities regarding different ionizing radiation types, characters and radiating methods. These specificities have a complicated molecular mechanism and result in various radiobiological responses; however, the details remain unclear. Ionizing radiation can impair biological macromolecules in cells, such as DNA, RNA, signal proteins. Moreover, different radiation doses, as well as linear energy transfer (LET), cause various effects. Cells show a certain adaptive response to low-dose ionizing radiation (LDIR) when they receive a secondary larger dose of radiation. By contrast, high-dose or LET ionizing radiation can lead a much more serious attack on macromolecules, especially to the molecules involved in gene mutations, DNA single strand breaks (SSBs), DNA double strand breaks (DSBs) and DNA damage repair responses. Under extreme conditions, such as space radiation during a space mission, a large amount of abnormally repaired DNA may vastly affect the cell signal transduction pathway, initiate apoptosis, uncontrolled cell proliferation, and even carcinogenesis. In this mini-review, the molecular mechanism of carcinogenesis induced by high-dose and LET ionizing radiation in cell lifespan is elucidated.

The relationship between quantitative magnetic resonance imaging (MRI) imaging features and gene-expression signatures associated with the recurrence of hepatocellular carcinoma (HCC) is not well studied.

In this study, we generated multivariable regression models to explore the correlation between the preoperative MRI features and Golgi membrane protein 1 (GOLM1), SET domain containing 7 (SETD7), and Rho family GTPase 1 (RND1) gene expression levels in a cohort study including 92 early-stage HCC patients. A total of 307 imaging features of tumor texture and shape were computed from T2-weighted MRI. The key MRI features were identified by performing a multi-step feature selection procedure including the correlation analysis and the application of RELIEFF algorithm. Afterward, regression models were generated using kernel-based support vector machines with 5-fold cross-validation.

The features computed from higher specificity MRI better described GOLM1 and RND1 gene-expression levels, while imaging features computed from lower specificity MRI data were more descriptive for the SETD7 gene. The GOLM1 regression model generated with three features demonstrated a moderate positive correlation (p<0.001), and the RND1 model developed with five variables was positively associated (p<0.001) with gene expression levels. Moreover, RND1 regression model integrating four features was moderately correlated with expressed RND1 levels (p<0.001).

The results demonstrated that MRI radiomics features could help quantify GOLM1, SETD7, and RND1 expression levels noninvasively and predict the recurrence risk for early-stage HCC patients.

Perivascular epithelioid cell neoplasms (PEComas) are a rare type of mesenchymal neoplasm and their preoperative diagnosis is challenging. In this study, we summarized the experience from a single medical center to study the examinations, clinical presentations, and pathological and histological characteristics of PEComas in the liver in order to optimize overall understanding of the diagnosis and treatment of these neoplasms.

We conducted a retrospective analysis to investigate the clinical and pathological characteristics as well as imaging presentations of 75 patients diagnosed with hepatic PEComa in The First Affiliated Hospital of Zhejiang University between April 2010 and April 2020.

Among the 75 patients, 52 were women, and the median age was 48 years. Most patients had no specific symptoms, and two were admitted to the hospital for a second time owing to relapse. All patients underwent surgical resection. Histologically, 38 patients had classical angiomyolipoma (AML) and 37 had epithelioid AML. The PEComas were accompanied by positive immunohistochemical expression of HMB45, Melan-A, and smooth muscle actin. Follow-up data were obtained from 47 of the total 75 patients, through October 2020. Two patients had metastasis after surgery.

AML is the most common type of hepatic PEComa. There are no specific symptoms of hepatic PEComa, and serological examinations and imaging modalities for accurate preoperative diagnosis are lacking. Epithelioid AML should be considered a tumor of uncertain malignant potential; however, the prognosis of PEComa after resection is promising.

Ras-related nuclear (RAN) protein is a small GTP-binding protein that is indispensable for the translocation of RNA and proteins through the nuclear pore complex. Recent studies have indicated that RAN plays an important role in virus infection. However, the role of RAN in hepatitis C virus (HCV) infection is unclear. The objective of this study was to investigate the role and underlying mechanisms of RAN in HCV infection.

Huh7.5.1 cells were infected with the JC1-Luc virus for 24 h and then were incubated with complete medium for an additional 48 h. HCV infection and RAN expression were determined using luciferase assay, quantitative reverse transcription-PCR and western blotting. Small interfering RNA was used to silence RAN. Western blotting and immunofluorescence were used to evaluate the cytoplasmic translocation of polypyrimidine tract-binding (PTB), and coimmunoprecipitation was used to examine the interaction between RAN and PTB.

HCV infection significantly induced RAN expression and cytoplasmic redistribution of PTB. Knockdown of RAN dramatically inhibited HCV infection and the cytoplasmic accumulation of PTB. Colocalization of RAN and PTB was determined by immunofluorescence, and a direct interaction of RAN with PTB was demonstrated by coimmunoprecipitation.

PTB in the host cytoplasm is directly associated with HCV replication. These findings demonstrate that the involvement of RAN in HCV infection is mediated by influencing the cytoplasmic translocation of PTB.

Coronaviruses are enveloped positive-strand RNA viruses that belong to the Coronaviridae family. According to the World Health Organization, this virus family has led to an international public health emergency. On the basis of existing clinical outcomes of patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV, it is hypothesized that quercetin can play a potential role in alleviating various symptoms of coronavirus disease 2019 (COVID-19) infection and serve as a supplement to other prescribed anti-viral drugs currently used for the treatment of COVID-19. Quercetin containing medicinal plants can become attractive agents for alleviating various side effects of COVID-19 infection and may potentially affect COVID-19 replication. In this article, we estimated quercetin content, using a RP-HPLC method, in various medicinal plants and propose the possible use of these extracts as health supplements for alleviating different clinical symptoms reported in COVID-19 patients. Also, this article describes the development of a dry powder inhaler (DPI) of quercetin using lactose as a carrier molecule. Moringa oleifera and Glycyrrhiza glabra extracts contain quercetin and can be potentially useful as health supplements for COVID-19 affected patients. The DPI of pure quercetin was found to supply a fine particle fraction of almost 40%, revealing the efficacy of the formulation in the discharge of quercetin into the lungs. Nevertheless, the suggested idea of using quercetin for alleviating side effects of COVID-19 infection does not have any direct experimental evidence. It is therefore believed that these therapeutic strategies may help clinicians to better treat COVID-19 affected patients.

Liver enzyme abnormalities in coronavirus 2019 (COVID-19) are being addressed in the literature. The predictive risk of elevated liver enzymes has not been established for COVID-19 mortality. In this study, we hypothesized that elevated liver enzymes at admission can predict the outcome of COVID-19 disease with other known indicators, such as comorbidities.

This retrospective study included all the consecutive hospitalized patients with confirmed COVID-19 disease from March 4th to May 31st, 2020. The study was conducted in Rajiv Gandhi Government General Hospital, Chennai, Tamil Nadu, India. We assessed demography, clinical variables, COVID-19 severity, laboratory parameters, and outcome.

We included 1,512 patients, and median age was 47 years (interquartile range: 34–60) with 36.9% being female. Liver enzyme level (aspartate aminotransferase and/or alanine aminotransferase) was elevated in 450/1,512 (29.76%) patients. Comorbidity was present in 713/1,512 (47.16%) patients. Patients with liver enzymes’ elevation and presence of comorbidity were older, more frequently hospitalized in ICU and had more severe symptoms of COVID-19 at the time of admission. Presence of liver enzymes’ elevation with comorbidity was a high risk factor for death (OR: 5.314, 95% CI: 2.278–12.393), as compared to patients with presence of comorbidity (OR: 4.096, 95% CI: 1.833–9.157).

Comorbidity combined with liver enzymes’ elevation at presentation independently increased the risk of death in COVID-19 by at least 5-fold.

The liver is frequently affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection. The most common manifestations are mildly elevated alanine aminotransferase and aspartate aminotransferase, with a prevalence of 16-53% among patients. Cases with severe coronavirus disease 2019 (COVID-19) seem to have higher rates of acute liver dysfunction, and the presence of abnormal liver tests at admission signifies a higher risk of severe disease during hospitalization. Patients with chronic liver diseases also have a higher risk of severe disease and mortality (mainly seen in patients with metabolic-associated fatty liver disease). Several pathways of damage have been proposed in the liver involvement of COVID-19 patients; although, the end-cause is most likely multifactorial. Abnormal liver tests have been attributed to the expression of angiotensin-converting enzyme 2 receptors in SARS-CoV-2 infection. This enzyme is expressed widely in cholangiocytes and less in hepatocytes. Other factors attributed to liver damage include drug-induced liver injury, uncontrolled release of proinflammatory molecules (“cytokine storm”), pneumonia-associated hypoxia, and direct damage by the infection. Hepatic steatosis, vascular thrombosis, fibrosis, and inflammatory features (including Kupffer cell hyperplasia) are the most common liver histopathological findings in deceased COVID-19 patients, suggesting important indirect mechanisms of liver damage. In this translational medicine-based narrative review, we summarize the current data on the possible indirect mechanisms involved in liver damage due to COVID-19, the histopathological findings, and the impact of these mechanisms in patients with chronic liver disease.

With an increasing understanding of hepatitis B, the antiviral indications have been broadening gradually. To evaluate the effectiveness of tenofovir alafenamide (TAF) in chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and detectable hepatitis B virus (HBV) DNA, those who are ineligible for broader antiviral criteria from the Chinese CHB prevention guide (2019).

A total of 117 patients were recruited and their data were collected from paper or electronic medical records. HBV DNA and liver function were measured at baseline and throughout the 24-week follow-up. The effectiveness endpoint was complete virological response. The safety endpoint was the first occurrence of any clinical adverse event during the treatment.

Among the 117 patients, 45 had normal ALT as well as detectable HBV DNA and they were not recommended for antiviral therapy according to Chinese Guidelines (2019). After TAF antiviral therapy, the rates of patients who achieved HBV DNA <20 IU/mL at 4, 12 and 24 weeks were 77.1%, 96.7% and 96.8% respectively. Among them, the undetectable rates of HBV DNA in patients with low baseline viral load at 4, 12 and 24 weeks were 92.3%, 100% and 100%, while the rates of those with high baseline viral load were 68.2%, 94.1% and 94.4%. Compared with 71.4%, 94.4% and 94.7% in the high baseline group, the undetectable rates of HBV DNA at 4, 12 and 24 weeks in the low baseline liver stiffness group were 85.7%, 100% and 100%. There was no statistical significance among the above groups.

CHB patients who had normal ALT and detectable HBV DNA and did not meet “CHB prevention guide (2019)”, could achieve complete virological response in 24 weeks after antiviral treatment by TAF.

In recent years, the prevalence of non-alcoholic fatty liver disease combined with metabolic dysfunction in children has increased rapidly. Current international guidelines for the management of metabolic-associated fatty liver disease do not recommend any specific drug therapy or its exact effect and safety margin. Appropriate drug therapies for children are even more scarce. Traditional Chinese medicine has good advantages in the prevention and treatment of metabolic-associated fatty liver disease. The author reviewed and analyzed a case with complete clinical data treated in our hospital using traditional Chinese medicine alone and discussed the diagnosis and treatment process. This report aimed to provide a reference for clinical practice.

Globally Severe acute malnutrition(SAM) affects more than 29 million children under the age of five. Demographic and Health Survey and Multiple Indicators in Chad (EDS-MICS) of 2014-2015 survey found an acute malnutrition level of 13% out of which 9% was moderate and 4% was severe. The Causes of SAMS are multifactorial, relating to multiple domains such as society, culture, environment, education, livelihoods, agriculture, water, hygiene, etc. Despite this established evidence, the evidence of parental knowledge is unknown.

The objective of our study was to determine the explanatory factors of SAM and its level of knowledge, understanding by the parents.

A prospective descriptive study was conducted in 238 children aged 6-59 months admitted to therapeutic nutritional unit Alerte Santé of Ndjamena from November 15 to December 30, 2017.

During the study, the male sex (58.8%), the age group of 12-17 months (26.9%) and 6-8 months (24.4%) were the most represented and are the majorities in the urban area (72.3%). We were able to identify the various explanatory factors among which the level of education of mothers (62.2%), exclusive breastfeeding (2.3%), the food taboo (81%) are not insignificant. Malnutrition would be decompensated by the breakdown of food access (59%) and digestive diseases (74.8%) and respiratory diseases (73.5%). We found that parents have poor knowledge of malnutrition (87%).

A good understanding of these main factors of malnutrition by parents might help to effectively combat severe acute malnutrition.

Nonalcoholic fatty pancreatic disease (NAFPD) has an incidence of 11.05% −69.7%. Owing to the lack of standardized screening tools, the prevalence of NAFPD widely varies among studies depending on the ethnic groups analyzed and the different diagnostic methods adopted. Obesity is a chronic disease attributable to multiple psychosocial factors, and its prevalence has reached epidemic proportions worldwide, showing doubling in the last 3 decades. Obesity is closely associated with conditions such as hyperlipidemia, type 2 diabetes mellitus (T2DM), cardiovascular disease, metabolic syndrome, and cancer. Diet and exercise are the central components of NAFPD prevention and treatment, whereas the progress in pharmacologic treatment has been lagging. Studies have demonstrated that glucagon-like peptide-1 (GLP-1) can lower blood glucose, and also has effects of reducing body weight and the risk of cardiovascular disease. Thus, the role of GLP-1 in T2DM and NAFPD warrants further investigations.

Functional dyspepsia is a common health problem found in society. Few of multifactorial aspects which become the underlying cause of functional dyspepsia are anxiety and psychosocial problem. Esophagogastroduodenoscopy (EGD) examination can display exact information to patient with functional dyspepsia and expected to increase patient's quality of life. It is still necessary to evaluate the advantages of EGD examination in improving patient's quality of life.A Randomized double blind controlled trial was conducted to compare between group of patients who have been given an empiric treatment(Proton pump inhibitor and prokinetic agents) and other who have been given a placebo for 2 weeks after underwent EGD examination in patients with functional dyspepsia. The primary outcome of this study is the decrease of NDI-SF score on both of groups at the end of study.A total of 42 patients (22 in EGD+placebo group [Group I] and 20 in EGD + treatment group[Group II]) were enrolled. NDI-SF score decreased significantly in both groups, Group I (26.23±8.43 vs 19.59±7.62, P=0.001) and Group II (27.32±7.57 vs 19.21±5.68, P=0.002), 15 days after underwent EGD examination. NDI-SF score improvement between two groups 15 days after EGD was not significantly different (P=0.814). This study showed improvement in quality of life of patients whom diagnosed with functional dyspepsia after EGD examination in both groups. This improvement was not significantly different between two groups and showed the placebo effect of EGD on functional dyspepsia patient.

To investigate the mechanism of the active ingredients of Smilax china L. in the treatment of hepatic fibrosis (HF).

The targets of the active ingredients of Smilax china L. were predicted using the TCMSP database, PubChem database, Babel software, Swiss Target Prediction platform, SEA platform, and UniProt database. The targets for HF were obtained using the DisGeNET database. Venn diagram platforms were used to intersect the active ingredients of Smilax china L. and HF targets. The key targets were selected using the STRING database to construct a protein-protein interaction network model. The key compounds were selected using the Cytoscape software to construct an active Smilax china L. ingredient-action target network. The intersection target was used for GO enrichment analysis and KEGG metabolic pathway analysis by ClueGO. The DockThor program was used to connect the important active ingredients and compounds of Smilax china L. with the corresponding intersection targets by calculating the binding energy and using the PyMOL software to create visual images.

A total of 9 active ingredients, 209 targets, 56 targets, and 15 key targets related to HF were identified from Smilax china L. The biological processes associated with Smilax china L. for preventing HF mainly included collagen metabolism, positive regulation of vascular endothelial cell migration, muscle cell proliferation, and smooth muscle cell proliferation. The pathways mainly included the IL-17 signaling pathway, estrogen signaling pathway, prolactin signaling pathway, and pancreatic cancer pathway.

The mechanism of Smilax china L. in the treatment of HF was preliminarily explored. Smilax china L. has multi-component and multi-target characteristics, through which it can be used to treat HF.

Change of gut microbiota composition is associated with the outcome of hepatitis B virus (HBV) infection, yet the related mechanisms are not fully characterized. The objective of this study was to investigate the immune mechanism associated with HBV persistence induced by gut microbiota dysbiosis.

C57BL/6 mice were sterilized for gut-microbiota by using an antibiotic (ABX) mixture protocol, and were monitored for their serum endotoxin (lipopolysaccharide [LPS]) levels. An HBV-replicating mouse model was established by performing HBV-expressing plasmid pAAV/HBV1.2 hydrodynamic injection (HDI) with or without LPS, and was monitored for serum hepatitis B surface antigen, hepatitis B e antigen, HBV DNA, and cytokine levels. Kupffer cells (KCs) were purified from antibiotic-treated mice and HBV-replicating mice and analyzed for IL-10 production and T cell suppression ability.

ABX treatment resulted in increased serum LPS levels in mice. The KCs separated from both ABX-treated and LPS-treated HBV-replicating mice showed significantly increased IL-10 production and enhanced ability to suppress IFN-γ production of TCR-activated T cells than the KCs separated from their counterpart controls. HDI of pAAV/HBV1.2 in combination with LPS in mice led to a delayed HBV clearance and early elevation of serum IL-10 levels compared to pAAV/HBV1.2 HDI alone. Moreover, IL-10 function blockade or KC depletion led to accelerated HBV clearance in LPS-treated HBV-replicating mice.

Our results suggest that dysbiosis of the gut microbiota in mice leads to endotoxemia, which induces KC IL-10 production and strengthens KC-mediated T cell suppression, and thus facilitates HBV persistence.

Yes-associated protein-1 (YAP1) is a potent transcriptional co-activator and functions as an important downstream effector of the Hippo signaling pathway, which is key to regulating cell proliferation, apoptosis, and organ growth. YAP1 has been implicated as an oncogene for various human cancers including gastrointestinal cancers and hepatocellular carcinoma (HCC). YAP1 promotes tumorigenesis and cancer progression by multiple mechanisms, such as by promoting malignant phenotypes, expanding cancer stem cells, and inducing epithelial-mesenchymal transition. YAP1 overexpression or its activated forms are associated with advanced pathological grades and poor prognosis of cancer, and therefore targeting YAP1 may open a fertile avenue for cancer therapy. In this review, we summarize the recent evidence regarding the role of YAP1 in the carcinogenesis of gastrointestinal cancers and HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and liver transplantation (LT) is the only potentially curative treatment. Over the years, Milan criteria has been used for patient selection. There is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future treatment. Furthermore, newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant list. In addition, combination therapies for better outcome are under investigation. Interestingly, the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ pool. However, there is a conflict of opinion between different centers regarding its efficacy and data is scarce. The aim of this review article is to outline the various selection criteria for LT, discuss the outcomes of LT in HCC patients, and explore future directions of LT for HCC. Therefore, a comprehensive PubMed/MEDLINE review was conducted. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies, the authors independently reviewed them to identify the relevant studies. After careful evaluation 120 studies relevant to out topic are cited in the manuscript. Three tables and two figures are also included. In conclusion LT for HCC has evolved over the years. With the introduction of several expanded criteria beyond Milan, the introduction of bridging therapies, such as transcatheter arterial chemoembolization and radiofrequency ablation, and the approval of newer systemic therapies, it is evident that there will be more LT recipients in the future. It is promising to see ongoing trials and the continuous evolution of protocols. Prospective studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent, clarify the role of LDLT, and determine the optimal bridging therapies to LT.

Fibroblast growth factor (FGF)19 has been implicated in the pathogenesis of murine hepatocellular carcinoma. Whether it plays a role in the development or course of human cholangiocarcinoma remains to be determined. The aim of this study was to determine whether prolonged exposure to FGF19 results in the transformation of non-malignant human cholangiocytes into cells with malignant features.

Human SV-40 transfected non-malignant H69 cholangiocytes were cultured with FGF19 (0-50 ng/mL) for 6 weeks, followed by 6 weeks with medium alone. Cell proliferation, invasion, stem cell surface markers, oncofetoprotein expression, state of differentiation, epithelial-mesenchymal transition (EMT) and interleukin (IL)-6 expression were documented at various time intervals throughout the 12-week period.

FGF19 exposure was associated with significant increases in cell proliferation, de-differentiation, EMT and IL-6 expression. However, each of these effects returned to baseline or control values during the 6-week FGF19 free follow-up period. The remaining cell properties remained unaltered.

Six weeks of FGF19 exposure did not result in the acquisition of permanent malignant features in non-malignant, human cholangiocytes.

Liver penetration by a confined perforation of peptic ulcer is a rare but severe event. Its clinical and pathological features are unclear.

In total, 41 qualified English publications were identified using the PubMed database and one in-house case.

Among the 42 patients, 20 patients had liver involvement by a perforated duodenal ulcer and 22 by a gastric ulcer. Among the 23 cases of known ulcer histology, 2 ulcers were malignant and were adenocarcinomas in the gastric remnant and the remaining 21 ulcers were confirmed as histologically benign (for frequency of malignancy in duodenal versus gastric ulcers, p = 0.48). The presence of hepatocytes was the clue of diagnosis for 19 cases. The median ages of the patients were 64.5 years (95% Confidence Intervals [CI] 53.40–71.90) for duodenal ulcer and 65.5 years (95% CI: 59.23–70.95) for gastric ulcer, respectively. The male to female ratio was 1.5:1 for duodenal ulcers and 2:1 for gastric ulcers. Patients with liver involvement of a perforated gastric ulcer were more likely to have a larger ulcer (median largest dimension, 4.75 cm versus 2.5 cm, p = 0.014). Female patients with liver involvement of a gastric ulcer were older than male patients (median age 72 versus 60 years, p = 0.045). There were no differences in gender, region (Asia, Europe, America versus others), use of non-steroidal anti-inflammatory drugs (n = 15), H. Pylori positivity (n = 10), possible history of peptic ulcer disease (n = 19) or mortality (n = 32) between duodenal and gastric ulcers.

Careful histologic examination, clinicopathological correlation, and immunohistochemistry are critical to establish the diagnosis and avoid misdiagnosing liver involvement as malignancy.