Head and neck cancers (including cancers of the oral cavity, oropharynx, hypopharynx, and larynx) are the sixth most common type of cancer worldwide. Almost all of these cancers are squamous cell carcinomas that develop from the mucosal lining. Due to the lack of specificity of the symptoms and inadequate screening methods, less than half of these tumors are currently discovered, albeit at an early stage. These cancers, therefore, constitute a real public health problem. Smoking, alcohol consumption, certain HPV infections, and chronic betel nut consumption are the main risk factors for developing squamous cell carcinoma of the upper aerodigestive tract. Early diagnosis depends on performing a complete and systematic physical examination of the oral cavity, pharynx, and larynx with a nasofibroscope in populations at risk. However, there are no strict criteria, in terms of alcohol and tobacco consumption, to trigger a physical examination by an ENT specialist, and there are no indications concerning the frequency with which such “screening” should be performed in at-risk populations. Even if such “screening strategies” are used in the absence of an alternative, different approaches are used in practice, depending on the medical system and country, and their efficacy and ideal modes of implementation remain unknown.

Qingfei Paidu decoction (QFPD) is a compounded Chinese herbal medicine used to treat mild and severe cases of COVID-19. Acute lung injury (ALI) is a common clinical manifestation of COVID-19, and this mainly manifests through lung inflammation and epithelial cell damage. However, the mechanism by which QFPD ameliorates ALI remains unclear. The present study aims to determine the role and molecular mechanism of QFPD in lipopolysaccharide (LPS)-induced ALI in mice.

After the administration of QFPD treatment in LPS-induced ALI mice, the therapeutic effect was evaluated through the H&E staining of lung tissues and the level of inflammatory factors in vivo. The RNA sequencing in mouse peritoneal macrophages and subsequent network pharmacological analysis were used to explore the molecular mechanisms of QFPD. Experimental validation was also performed by immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), and western blot.

QFPD inhibited the LPS-induced inflammatory cytokines in macrophages, ameliorated ALI in mice, and prolonged its survival at the lethal dose of LPS. Furthermore, the complement-related pathway was enriched through the network pharmacology and transcriptome analysis of the gene expression. The quantitative real-time PCR and apoptotic analysis further confirmed that QFPD inhibited ALI through the classical complement pathway as no additive changes were observed when its key components were silenced plus QFPD treatment.

QFPD applied for the treatment of COVID-19 can attenuate ALI through the classical complement pathway. The present study provides a practical basis and directional guide for the further exploration of the use of QFPD in treating ALI.

In this paper, the features of ductular reaction (DR) and remodeling of the biliary tract are discussed in models of total and selective biliary occlusion. It has been shown that the intensity of DR, as well as the shape, number, and topography of ductular profiles following common bile duct occlusion (CBDO), are closely related to the duration of the biliary obstruction. In addition, the formation of new ductular profiles can occur by the widening of existing bile ducts/ductules as a result of cholangiocyte proliferation, hepatocyte transdifferentiation, and/or activation and differentiation of stem/progenitor cells. It has been concluded that DR induced by CBDO encompasses the components of all types of DRs, including I, II (A and B), and III, thereby increasing the interest in further studies of this model. In the DR following CBDO, the subsequent “preproliferative” and “proliferative” phases develop alongside cellular differentiation and transdifferentiation (the “para-proliferative” phase) should be distinguished. The dynamics of these phases are crucial for further detailed classification of DRs. During selective biliary obstruction, the full spectrum of DR characteristics for CBDO has not been determined (mainly the events of biliary proliferation and fibrosis are noted). However, the great compensatory potential of the biliary bed has been confirmed, as evidenced by the formation of new collaterals between congested and noncongested bile ducts

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C patients. However, with the introduction and validation of noninvasive tests (NITs) to evaluate advanced fibrosis, and the direct-acting antiviral agents for treatment of chronic hepatitis C virus (HCV), the role of NITs have become even more complex. There is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological response. The aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.

Hepatocellular carcinoma (HCC) being a leading cause of cancer-related death, has high associated mortality and recurrence rates. It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures. Studies have shown that microvascular invasion (MVI) is an independent risk factor for poor prognosis after hepatectomy. The abnormal expression of biomacromolecules such as circ-RNAs, lncRNAs, STIP1, and PD-L1 in HCC patients is strongly correlated with MVI. Deregulation of several markers mentioned in this review affects the proliferation, invasion, metastasis, EMT, and anti-apoptotic processes of HCC cells through multiple complex mechanisms. Therefore, these biomarkers may have an important clinical role and serve as promising interventional targets for HCC. In this review, we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

Men have higher morbidity and mortality from COVID-19 than women, possibly due to androgen receptor-regulated viral entry protein expression. This led to a clinical trial of androgen deprivation therapy (ADT), which has not shown a significant benefit in the outcomes among hospitalized male COVID-19 patients. The aim of this study was to explore biological explanations for the failure of ADT to mitigate clinical outcomes in men with severe COVID-19 by assessing the role of androgen in regulating viral entry protein expression in the upper and lower respiratory tract.

Immunohistochemistry was used to assess the expression of transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2) and how it correlated to androgen receptor expression in the sinonasal epithelium, minor salivary glands of the sinus, lacrimal glands, and lungs from mice pretreated with and without castration and ADT as well as the sinonasal epithelium obtained from healthy human donors and hospitalized COVID-19 patients.

In murine models, castration and ADT treatment downregulated the expression of TMPRSS2 and ACE2 in the sinonasal epithelium, minor salivary glands of the sinus, and lacrimal glands, but not in the lungs. Correlative analyses using human tissue also showed a potential role of ADT in men during the early sinonasal phase but not in the later lung phase of SARS-CoV-2 infection.

Our study suggests a potential benefit of ADT in male patients with early COVID-19 when the virus enters the nasopharynx, but not in those with advanced disease. The downregulation of viral entry proteins in the upper respiratory system following androgen blockade may be a key mechanism for this effect.

Flavin-containing monooxygenases (FMOs) catalyze the oxygenation of a diverse range of sulfur or nitrogen-containing xenobiotics. Recently accumulated evidence has demonstrated the roles of FMOs in physiological and pathological conditions, including neurodegeneration and aging. However, the mechanisms underlying their functions are poorly understood. In this review, we summarize the expression and localization of FMOs in the brain, the endogenous chemicals and xenobiotics metabolized by FMOs, and the consequences of FMO deficiency. The understanding of FMOs activity in the brain is important for fully elucidating the roles of FMOs in pathological mechanisms.

Drug-induced liver injury (DILI) is a major cause of acute liver injury, liver failure, and liver transplantation worldwide. In recent years, immune checkpoint inhibitors have become widely used. This has led to an increase in DILI, for which pathophysiology and management methods differ significantly from the past. As the number of cases of acute liver injury and liver transplantation due to DILI is expected to increase, information about a DILI is becoming more valuable. DILI is classified into two types according to its etiology: intrinsic DILI, in which the drug or its metabolites cause liver damage that is dose-dependent and predictable; and idiosyncratic DILI, in which liver damage is also dose-independent but unpredictable. In addition, depending on the course of the disease, chronic DILI or drug-induced autoimmune hepatitis may be present. The number of DILI cases caused by antimicrobial agents is decreasing, whereas that caused by drugs for malignant tumors and health foods is increasing. The Roussel Uclaf Causality Assessment Method is widely used to assess causality in DILI. Liver injury is a type of immune-related adverse event. The pattern of hepatic injury in immune-related adverse events is mostly hepatocellular, but mixed type and bile stasis have also been reported. Sclerosing cholangitis caused by immune checkpoint inhibitors has also been reported as a unique type of injury. Treatment mainly comprises withdrawal of immune checkpoint inhibitors and steroid administration; however, mycophenolate mofetil may be considered if the disease is refractory to steroids.

Many liver society guidelines no longer recommend single value alpha-fetoprotein (AFP) for hepatocellular carcinoma (HCC) screening because of poor specificity and sensitivity. Instead, use of longitudinal AFP expression changes is recommended. However, no specific guidance has been provided as to what levels of longitudinal AFP change should be regarded as suspicious. The aim of this study was to determine whether an AFP slope cut-off value exists that could be useful for early diagnosis of HCC.

A retrospective chart review included patients with confirmed HCC as well as patients with cirrhosis but confirmed not to have HCC (control group). Trends in data points for AFP expression peaks (control group) and pre-diagnostic AFP data over time (HCC group) were compared. Additionally, aminotransferase trends were compared to AFP trends (HCC group) to account for possible confounding contribution of inflammation.

Using linear mixed effects models, the slope estimate for log (AFP) significantly differed between groups (p = 0.001), 1.21 (95% CI: 0.44–1.97, p = 0.005) in the HCC pre-diagnosis group versus the cirrhotic non-HCC controls 0.15 (95% CI: 0.08–0.23, p < 0.001). The area under the curve for sensitivity plotted against false positive rate or 1-specificity for log (AFP) of pre-diagnosis HCC was 0.844.

The results suggest that AFP trends do have clinical value compared to a single AFP cut-off. Using a log (AFP) slope cut-off of 0.32 gave a sensitivity of 89% and specificity of 70% for the diagnosis of HCC.

Nanotechnology has revolutionized and improved the potential of drug-delivery systems. Lipidic nanovesicles, termed liposomes, offer several benefits as drug-delivery carriers due to their compositional similarity with human biological membranes. Some of the advantages offered by liposomes include targeted drug delivery and improved pharmacokinetics of an entrapped drug substance, leading to enhanced bioavailability. Additionally, the reduction in the drug dose or dosing frequency, reduced drug toxicity or side effects, longer and controlled therapeutic response of a drug essential for the treatment of chronic diseases, and improved patient acceptance margins are some other benefits offered by liposomes. The easily modifiable surface of liposomes makes it an ideal vehicle for targeting a drug to the desired site. The current review provides insight on liposomes as drug-delivery carriers. This review summarizes the classification of compositional constituents of liposomes based on their chemical nature and structure. Morphology-based classification of liposomes along with methods of preparation and characterization for liposomes are also summarized. The current review emphasizes the medical applications of liposomes, specifically as delivery carriers for therapeutic and diagnostic agents. The article features detailed therapeutic applications of liposomes based on routes of administration and specific disease conditions. Diagnostic applications of liposomes for improving the efficiency of available techniques to treat diseases such as cancer are also discussed. Liposomes are thus reviewed as multifaceted nanovesicular carriers with potential therapeutic and diagnostic medical applications. The prospective multifunctional application of combining imaging functionality with therapeutic agents in a single liposome for diagnosis and real-time treatment is anticipated to be the future of liposomal formulations.

The results of basic research implicate the vascular endothelial growth factor (VEGF) family as a potential target of hepatopulmonary syndrome (HPS). However, the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS. Therefore, we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies.

Clinically, patients with chronic liver disease from two medical centers were enrolled and examined for HPS. Patients were divided into HPS, intrapulmonary vascular dilation [positive contrast-enhanced echocardiography (CEE) and normal oxygenation] and CEE-negative groups. Baseline information and perioperative clinical data were compared between HPS and non-HPS patients. Serum levels of VEGF family members and their receptors were measured. In parallel, HPS rats were established by common bile duct ligation. Liver, lung and serum samples were collected for the evaluation of pathophysiologic changes, as well as the expression levels of the above factors.

In HPS rats, all VEGF family members and their receptors underwent significant changes; however, only soluble VEGFR1 (sFlt-1) and the sFlt-1/ placental growth factor (PLGF) ratio were changed in almost the same manner as those in HPS patients. Furthermore, through feature selection and internal and external validation, sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients.

Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.

With the improvement of living standards in recent years, up to 90% of obese patients have nonalcoholic fatty liver disease (NAFLD). The number of nonalcoholic steatohepatitis (NASH)-related deaths will gradually increase, and NASH is expected to be the most common cause of liver-related deaths in the future. Therefore, there is an urgent need to find effective and reliable serum biomarkers to distinguish simple hepatic steatosis (SS) from NASH. Liver cell regeneration, oxidative stress-induced DNA methylation, and biliary epithelial cell proliferation were reported to increase serum alpha-fetoprotein (AFP) levels. AFP has long been used as a tool to monitor liver cancer. However, the function of AFP in NAFLD, especially NASH, has not been clarified. Moreover, whether an elevated AFP level indicates the occurrence of NASH or serves as a serum biomarker remains to be elucidated. The miRNA-122 pathway, DNA methylation and DNA damage, and activation of resident stem cells and/or progenitor cells in the liver, as well as necrosis, regeneration, and repair of liver cells, may contribute to slight increases in AFP levels in the development of NASH in patients with NAFLD. Furthermore, mildly elevated AFP levels may indicate the development of NASH. This review explores the role of elevated AFP levels in the development of NASH, with a specific focus on the underlying molecular mechanisms and the clinical significance.

Surgical site infections are the most common and significant epidemiological burden worldwide. Despite implementing modern surgical techniques, appropriate antibiotic prophylaxis, sterilization techniques, and aseptic and antiseptic practices, surgical site infections continue to pose a significant challenge. As a result, patients who experience these infections may require increased antibiotic use, extended hospital stays, and higher treatment costs. This is particularly concerning given that such infections are largely preventable. The financial and social burden imposed by the costs of surgical site infections remains a significant problem for many countries. Evidence-based preventive practices should be integrated into the preoperative, intraoperative, and postoperative periods to prevent these infections. It is estimated that approximately half of all surgical site infections can be prevented by applying evidence-based practices.

Drug-induced liver injury (DILI) can present as a chronic phenotype or acute course. However, there is a lack of research on the underlying mechanisms of chronic DILI as well as the definition of cut-off point. We aimed to profile holistic metabolic characteristics of chronic DILI and provide evidence for the cut-off point by serum metabolomics.

The sera of DILI patients were divided into Group I (0–6 months), Group II (6–12 months), and Group III (>12 months) based on the duration of liver injury. In total, 2,105 metabolites associated with the DILI duration were screened out as the holistic metabolomic signature (HMS). By unsupervised principal component analysis on the HMS dataset, the samples spontaneously represented a two-cluster pattern of the three groups, i.e., Group I as the first cluster and Group II/III as the second cluster, which suggested six months as the potential metabolomic cut-off point of DILI chronicity. Then, the differentiation ability of the metabolomic signature was validated in an independent cohort. We further screened out 23 most-associated metabolites as the metabolic fingerprint (MFP) for the DILI duration and constructed an eigenmetabolite by dimension reduction.

The eigenmetabolite was significantly different in chronic versus acute DILI and was not related to the severity grade of liver injury. Pathway enrichment analysis underlined the enhanced metabolic pathways of lipids in chronic DILI, which are associated with energy metabolism remodeling and immune regulation balance.

MFP was different between chronic and acute DILI. Six months might be the potential metabolomic cut-off point in defining chronicity of DILI.

The Bethesda System for Reporting Thyroid Cytopathology is the first reporting system established in non-gynecologic cytopathology after the Bethesda System for Reporting Cervical Cytopathology. It adopts the same concept of providing a uniform reporting system for all pathologists and clinicians to follow in thyroid cytology. The reporting system is composed of six diagnostic categories. There are defined diagnostic criteria, estimated risk of malignancy, and management recommendations for each category. The reporting system has undergone two revisions upon the emergence of a new entity, updated terminology in histology, and development and refinement of molecular testing. The third edition is soon to be published in 2023. This review will provide an updated summary of the reporting system. Potential diagnostic pitfalls and molecular testing are also discussed.

High-intensity interval training (HIIT) is a therapeutic option for people with nonalcoholic steatohepatitis (NASH). However, the perspectives and experiences of HIIT for people with NASH are unknown, limiting translation of research. We explored the experiences and perspectives of both professionally supervised and self-directed HIIT in people with NASH and evaluated participant-reported knowledge, barriers, and enablers to commencing and sustaining HIIT.

Twelve participants with NASH underwent 12 weeks of supervised HIIT (3 days/week, 4×4 minutes at 85–95% maximal heart rate, interspersed with 3 minutes active recovery), followed by 12-weeks of self-directed (unsupervised) HIIT. One-on-one, semistructured participant interviews were conducted by exercise staff prior to HIIT and following both supervised and self-directed HIIT to explore prior knowledge, barriers, enablers, and outcomes at each stage. Interviews were audio-recorded, transcribed, coded, and thematically analyzed by two independent researchers.

Four dominant themes were identified: (1) no awareness of/experience with HIIT and ambivalence about exercise capabilities; (2) multiple medical and social barriers to commencing and continuing HIIT; (3) exercise specialist support was a highly valued enabler, and (4) HIIT was enjoyed and provided holistic benefits.

People with NASH may lack knowledge of and confidence for HIIT, and experience multiple complex barriers to commencing and continuing HIIT. Exercise specialist support is a key enabler to sustained engagement. These factors need to be addressed in future clinical programs to augment the uptake and long-term sustainability of HIIT by people with NASH so they can experience the range of related benefits.

Over the past decades, cervical cancer has been a worldwide public health problem. Population-based early cancer risk detection and prevention approaches, including vaccination, cytology screening and human papilloma virus (HPV) detection, with the aligned clinical management, have formed a well-rounded high-quality implementation system for cervical cancer control, and revolutionarily improved the quality of life of women: (1) the success of cervical cancer screening practices, (2) standardization of The Bethesda system for reporting cervicovaginal cytology, (3) improvement in the understanding of HPV pathogenesis in cervical cancer, and (4) the development of appropriate management approaches have significantly decreased the disease burden of cervical cancer worldwide. This scoping review aimed to understand the evolvement of cervical cancer screening and management guidelines, describe the Bethesda cervical cytology reporting system, and HPV vaccines and tests, and highlight the key information of present policies and practices.

Metastasis is a major factor associated with high recurrence and mortality in hepatocellular carcinoma (HCC) patients while the underlying mechanism of metastasis remains elusive. In our study, procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was shown to be involved in the process of metastasis in HCC.

The Cancer Genome Atlas (TCGA) database and HCC tissue microarrays were used to evaluate the expression of genes. In vitro migration, invasion, in vivo subcutaneous tumor model and in vivo lung metastasis assays were used to determine the role of PLOD2 in tumor growth and metastasis in HCC. RNA sequencing and gene set enrichment analysis were performed to uncover the downstream factor of PLOD2 in HCC cells. A luciferase reporter assay was performed to evaluate the interaction between PLOD2 and interferon regulatory factor 5 (IRF5).

The expression of PLOD2 in HCC tissues was higher than that in adjacent tissues, and increased PLOD2 expression was often found in advanced tumors and was correlated with poor prognosis in HCC patients. In vitro experiments, knockdown of PLOD2 reduced the migration and invasion of human HCC cells. Loss of PLOD2 suppressed human HCC growth and metastasis in a subcutaneous tumor model and a lung metastasis model. Baculoviral IAP repeat containing 3 (BIRC3) was proven to be the downstream factor of PLOD2 in human HCC cells. In addition, PLOD2 was transcriptionally regulated by IRF5 in HCC cells.

High expression of PLOD2 was regulated by IRF5, which was correlated with the poor survival of HCC patients. PLOD2 enhanced HCC metastasis via BIRC3, suggesting that PLOD2 might be a valuable prognostic biomarker for HCC treatment.