In Europeans, variants in the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene impact liver histology in metabolic-associated fatty liver disease (MAFLD). The impact of these variants in ethnic Chinese is unknown. The aim of this study was to investigate the potential associations in Chinese patients.

In total, 427 Han Chinese with biopsy-confirmed MAFLD were enrolled. Two single nucleotide polymorphisms in HSD17B13 were genotyped: rs72613567 and rs6531975. Logistic regression was used to test the association between the single nucleotide polymorphisms and liver histology.

In our cohort, the minor allele TA of the rs72613567 variant was related to an increased risk of fibrosis [odds ratio (OR): 2.93 (1.20–7.17), p=0.019 for the additive model; OR: 3.32 (1.39–7.91), p=0.007 for the recessive model], representing an inverse association as compared to the results from European cohorts. In contrast, we observed a protective effect on fibrosis for the minor A allele carriers of the HSD17B13 rs6531975 variant [OR: 0.48 (0.24–0.98), p=0.043 for the additive model; OR: 0.62 (0.40–0.94), p=0.025 for the dominant model]. HSD17B13 variants were only associated with fibrosis but no other histological features. Furthermore, HSD17B13 rs6531975 modulated the effect of PNPLA3 rs738409 on hepatic steatosis.

HSD17B13 rs72613567 is a risk variant for fibrosis in a Han Chinese MAFLD population but with a different direction for allelic association to that seen in Europeans. These data exemplify the need for studying diverse populations in genetic studies in order to fine map genome-wide association studies signals.

Endothelial dysfunction plays a crucial role in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and has recently been proposed to be connected with acute thrombosis, hyper-inflammation, cytokine storm syndrome, immune cell recruitment, platelet aggregation, vasoconstriction and endothelial apoptosis. Importantly, certain mediators and pro-inflammatory cytokines such as galectin (Gal) 1, Gal3 and Gal8 act in a concerted manner through the N- and O-linked glycans located on the SARS-CoV-2 S protein. We hypothesize that the presence of these factors may cause the ACE2 receptor, integrin β1, and CD44 to generate a Gal-glycan lattice on the surface of SARS-CoV-2 virus. This lattice, in addition to endothelial cells (ECs), may not only influence EC behavior and the inflammatory response, but may also induce conformational changes in the viral structure that can facilitate attachment and entry into the ECs. We believe that further basic science research is necessary to elucidate the composition and role of the Gal-glycan lattices in the SARS-CoV-2 infection.

The rearrangement during transfection (RET) encodes a receptor tyrosine kinase (RTK), which is involved in the development of various tissues and cells. The rearrangements and mutations of RET contribute to the development of a variety of human malignancies. Therefore, RET alterations are novel therapeutic targets. Inhibitors for RET and other kinases have been approved for the treatment of RET-altered tumors and have demonstrated their benefits for some types of cancer patients in clinics. However, due to off-target effects, these inhibitors have some adverse effects and dose-limiting toxicity. Therefore, long-term treatment with these inhibitors has potential limitations. Novel highly selective inhibitors (pralsetinib and selpercatinib) that target the RET pathway are well tolerated and have significant and long-lasting antitumor activity. They have been accelerated for approval by the FDA. This article will focus on the role of highly selective inhibitors targeting the RET and their efficacy and safety in therapy for RET-associated cancers.

Patients with cirrhosis and acute-on-chronic liver failure (ACLF) may have bleeding complications and need for invasive procedures. Point-of-care (POC) coagulation tests like thromboelastography (TEG) and Sonoclot may be better for guiding patient management than the standard coagulation tests (SCTs), like prothrombin time, platelet count and international normalized ratio.

We prospectively compared and validated the POC tests and SCTs in 70 persons with ACLF and 72 persons with decompensated cirrhosis who had clinical bleeding and checked for episodes of re-bleeding and transfusion requirements. We assessed pre-procedure requirement of blood components when correction was done based on an SCT or POC strategy.

Episodes of bleeding were seen in 45% and 28% of ACLF and cirrhosis patient, respectively (p=0.036), with the major site of bleeding being gastrointestinal (31% and 16%, respectively). Platelet counts correlated with TEG-maximum amplitude in cirrhosis (p=0.045) and prothrombin time correlated positively with TEG-reaction (R) time (p=0.032), TEG-Clot kinetics (K) time (p=0.042), Son-activated clotting time (p=0.038) and negatively with clot rate (p=0.043) in ACLF, making these correctable target variables in POC transfusion algorithms. Of 223 procedures, transfusion of fresh frozen plasma and platelet concentrate was reduced by 25% (p=0.035) and 20.8% (p=0.045) by using a POC strategy in 76 patients. Correction of deranged Son-activated clotting time and TEG-reaction time was noted in 68% and 72% after 24 h of fresh frozen plasma transfusion in ACLF and 85% and 80% in cirrhosis, respectively.

Our study clinically validates that POC tests can better detect coagulation defects and transfusion thresholds in ACLF and cirrhosis, whereas use of conventional tests appear to be less suitable in patients with clinical bleeding.

NCT04332484.

Plants are a rich source of bio-functional phytochemicals. The present study was designed to investigate the methanol extracts of selected plants for their phytochemicals, antioxidant activity, urease and acetylcholine esterase (AChE) inhibitory potential.

Crude methanol extracts of selected ethnopharmacological plants were prepared by a simple maceration procedure. Antioxidant assays, total phenolic and total flavonoid content were determined using colorimetric methods. The urease and AChE inhibitory potential of the extract was investigated using spectroscopy techniques.

Most of the extracts tested positive for alkaloids, saponin, glycosides and terpenoids. The total phenolic and flavonoid content in the extracts ranged from 62.7 ± 6.07 – 172.25 ± 11.8 µg gallic acid equivalent (GAE) and 9.7–60.1 µg quercetin equivalent (QE) per gram dry weight (DW). The maximum GAE and QE content was found in Coruns officinalis and Prunus armeniaca, at 164.9 ± 5.6 and 60 ± 0.65 g/mg DW, respectively. All medicinal plants showed significant antioxidant activity. M. kobus exhibited significant antiradical (DPPH) potential (IC50 = 30.77 µg/ml). F. koreana showed the maximum total antioxidant capacity when expressed as ascorbic acid equivalent (AAE) (119.1 µg AAE/mg DW). The extracts were evaluated for their inhibitory potential against urease and AChE enzymes. Among all plants, G. biloba and P. mume exhibited the maximum urease and AChE inhibitory activity with IC50 of 45.25 and 16.58 µg/mL, respectively.

The present study showed that methanol extracts of plants can be considered as potential sources of pharmacological importance in terms of phyto-constituents for the treatment of oxidative stress associated ailments, ulcer and Alzheimer’s disease.

Lymphoepithelioma-like hepatocellular carcinoma (LEL-HCC) is a very rare neoplasm, with distinct epidemiologic, morphologic and clinical characteristics. Molecular mechanistic insight into the pathogenesis of this carcinoma suggests a pivotal role for the host immune system in the proliferation and progression of this tumor. However, while detailed genomic profiling of these hepatic tumors have revealed an intra-tumoral inflammatory mutational signature that may predispose to immune checkpoint inhibitor efficacy, no published report has described their use in this tumor type. Unfortunately, with near 100 cases of LEL-HCC reported in the literature to date and the majority of cases confined to localized and resectable disease, current evidence-based practices in the unresectable setting are lacking, with unknown benefit of chemotherapy or immunotherapy. We report on the case of a 68 year-old man with unresectable, advanced LEL-HCC who had evidence of disease stability after starting on the immune checkpoint inhibitor nivolumab. His disease response persisted off therapy for over a year and was potentially augmented by radiotherapy at the site of local progression. For this extremely rare tumor subtype, this case highlights the potential efficacy and safety of immune checkpoint blockade in LEL-HCC and reinforces the need for more robust, large-scale analysis of patients with these rare tumors to better evaluate treatment strategies and outcomes.

A 36-year-old male, diagnosed with atopic dermatitis and allergy to egg white when he was a baby, was diagnosed in adolescence with Bird-Egg Syndrome and seasonal rhinoconjunctivitis with bronchial asthma. Five years later, he developed rhinosinusitis, nasosinusal polyposis and persistent bronchial asthma. At the age of 27, this individual presented with eosinophilic esophagogastroduodenitis and peripheral eosinophilia with a total IgE of 1,989 KU/mL and repeatedly tested negative for antineutrophil cytoplasmic antibodies. When he was 31-year-old, the patient was admitted to the hospital due to an exacerbation of his asthma, the onset of fever, bilateral migratory lung infiltrates and maculopapular lesions in the ankles (leukocytoclastic vasculitis). He was also diagnosed with motor-sensory polyneuritis. Finally, this patient met the criteria of allergic granulomatosis with polyangiitis and was treated with Omalizumab (monthly) with effective recovery.

Currently, infection with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during pregnancy is a problem worthy of attention, especially in patients with underlying diseases. In this case report, we present a case of chronic active hepatitis B with COVID-19 in pregnancy. A 31-year-old woman at 29 weeks of gestation who had a history of chronic hepatitis B virus infection discontinued antiviral treatment, was admitted to the hospital with chronic active hepatitis B, and tested positive for SARS-CoV-2 infection. In this case, we applied liver protective and antiviral agents, and low-dose dexamethasone therapy to successfully treat the critically ill pregnant woman suffering from chronic active hepatitis B combined with COVID-19.

Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease, including decompensated cirrhosis and hepatocellular carcinoma. Over 95% of patients with HCV infection have achieved sustained virologic response at 12 weeks under the treatment of several pan-genotypic regimens approved for patients with HCV infection. The glecaprevir/pibrentasvir (G/P) regimen has some features that distinguish it from others and is the only 8-week regimen approved for treatment-naive patients and patients experienced in regimens containing (peg)interferon, ribavirin, and/or sofosbuvir, without an HCV NS3/4A protease inhibitor or NS5A inhibitor (except those with genotype 3). This review aims to summarize the efficacy and safety of G/P in HCV-infected patients from clinic trials and real-world studies, including those who have historically been considered difficult to cure.

Lung cancer is the leading cause of cancer morbidity and mortality. Surgery, chemotherapy and radiotherapy techniques have been developed over many years, and anti-angiogenic therapy, molecular targeted therapy and immune-checkpoint inhibitors have become increasingly effective for treating lung cancer. However, the overall disease-free and survival rates of lung cancer remain quite low. MicroRNAs are small, non-coding RNAs that consist of an average of 22 nucleotide molecules. MicroRNAs play an important role in the development, progression, metastasis, diagnosis and prognosis of lung cancer. This review summarizes the recent publications abnormally expressed miRNAs and the abnormal expression of their target genes in the biological process of lung cancer. This review aims to shed light on the recent advances in this field and to provide perspectives for future directions.

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme of alcohol metabolism and it is involved in the cellular mechanism of alcohol liver disease. ALDH2 gene mutations exist in about 8% of the world’s population, with the incidence reaching 45% in East Asia. The mutations will result in impairment of enzyme activity and accumulation of acetaldehyde, facilitating the progression of other liver diseases, including non-alcoholic fatty liver diseases, viral hepatitis and hepatocellular carcinoma, through adduct formation and inflammatory responses. In this review, we seek to summarize recent research progress on the correlation between ALDH2 gene polymorphism and multiple liver diseases, with an attempt to provide clues for better understanding of the disease mechanism and for strategy making.

As coronavirus disease 2019 (COVID-19) vaccines continue to be reviewed and approved by regulatory bodies for emergency use, mass vaccination against COVID-19 is on the horizon. This will significantly reduce the incidence and mortality of COVID-19. However, the unintended consequences of mass vaccination and their associated challenges could be urgent and severe. To effectively prepare for and meet these challenges, we propose three guiding principles and share cautionary perspectives on the mass vaccination against COVID-19. These opinions could help shape policy-making and the implementation of the mass vaccination.

Great efforts have been made towards increasing our understanding of the pathogenesis involved in hepatocellular carcinoma (HCC), but the rapid growth inherent to such tumor development remains to be explored.

We identified distinct gene coexpression modes upon liver tumor growth using weighted gene coexpression network analysis. Modeling of tumor growth as signaling activity was employed to understand the main cascades responsible for the growth. Hub genes in the modules were determined, examined in vitro, and further assembled into the growth signature.

We revealed modules related to the different growth states in HCC, especially the fastest growth module, which is preserved among different HCC cohorts. Moreover, signaling flux in the cell cycle pathway was found to act as a driving force for rapid growth. Twenty hub genes in the module were identified and assembled into the growth signature, and two genes (NCAPH, and RAD54L) were tested for their growth potential in vitro. Genetic alteration of the growth signature affected the global gene expression. The activity of the signature was associated with tumor metabolism and immunity in HCC. Finally, the prognosis effect of the growth signature was reproduced in nine cancers.

These results collectively demonstrate the molecule organization of rapid tumor growth in HCC, which is a highly synergistic process, with implications for the future management of patients.